INTERNAL MEDICINE

INPATIENT HOUSESTAFF HANDBOOK 2008-2009 V2.1

RRUCLAMC Wards To Call a Code in RRUCLAMC ............................................................................................................................#36 Bed Control ...................................................................................................................................................... x56922 Transfer center................................................................................................................................................. x49805 Emergency Room ................................................................................................................................. x78400/78407 Observation Unit .............................................................................................................................................. x79523 4-MICU small nurse stn/main nurse stn .............................................................................................. x77437/x77424 4-South Psych.................................................................................................................................................. x77430 5-East Clerk/main nurse stn................................................................................................................ x77515/x77511 6-East J-Med Clerk/main nurse stn .................................................................................................. x77610/x77611 6-ICU Neuro sm nurse stn/lrg nurse stn.............................................................................................. x77641/x77656 6-North Clerk/main nurse stn .............................................................................................................. x77660/x77661 6-West Clerk .................................................................................................................................................... x77630 7-ICU CT surg sm nurse stn/lrg nurse stn........................................................................................... x77741/x77727 7-East Clerk/main nurse stn................................................................................................................ x77710/x77711 7-East small nurse stn south corner................................................................................................................. x77784 7-East small nurse stn north corner ................................................................................................................. x77713 7-East Hoteling office (Post-call work rm)...................................................................................................... x79537 7-East 7134 Large Rounding room .................................................................................................................. x77789 7-East 7132 Small Roundng room ................................................................................................................... x77787 7-East/West Hall Medicine Library ................................................................................................................... x79655 7-West Clerk/main nurse station ......................................................................................................... x77730/x77799 7-North COU/CCU .............................................................................................................................. x77271/x77765 8-ICU Liver Tx sm nurse stn/lrg nurse stn........................................................................................... x77841/x77840 8-West Clerk .................................................................................................................................................... x77830 Dialysis 8th floor............................................................................................................................................... x77820 OR Front Desk ................................................................................................................................................. x78800 OR Scheduling................................................................................................................................................. x78846 PACU............................................................................................................................................................... x79850 PTU.................................................................................................................................................................. x79800 Medicine Services Virtual Pagers Chiefs Pager ...................................................................................................................................................#91010 Medicine Float..................................................................................................................................................#91903 A Medicine Resident ........................................................................................................................................#91895 B Medicine Resident ........................................................................................................................................#91914 C Medicine Resident........................................................................................................................................#91920 D Medicine Resident........................................................................................................................................#93370 E Medicine Resident ........................................................................................................................................#93380 J-Medicine On-call ...........................................................................................................................................#90050 Observation/Overflow Resident .......................................................................................................................#96450 Geriatrics Resident ..........................................................................................................................................#91907 Hospitalist Resident .........................................................................................................................................#90016 CCU On-Call Resident.....................................................................................................................................#90080 CCU On-call Intern...........................................................................................................................................#90089 MICU On-Call Resident ...................................................................................................................................#90090 MICU On-Call Intern ........................................................................................................................................#90040 Internal Medicine Consult Service Resident.....................................................................................................#91200 Renal Consult ..................................................................................................................................................#96110

Renal Transplant ..............................................................................................................................................#96220 Endocrine Consult ............................................................................................................................................#95876 Infectious Disease Consult...............................................................................................................................#98771 Transplant ID consult .......................................................................................................................................#93424 GI Consult .............................................................................................................................................. Call Page Op Pulmonary Consult ................................................................................................................................. Call Page Op Ethics Consult (page ETHIC).........................................................................................................................#38442 Palliative Care Consult ........................................................................................................................... Call Page Op Other Services Virtual Pagers L-Surgery Consult ............................................................................................................................................#95550 Neurosurgery Consult ......................................................................................................................................#94320 Pain Service Consult ........................................................................................................................................#93600 Psychiatry Consult..........................................................................................x50173 (8-5 M-F); #95722 (after hours) Geri-Psychiatry....................................................................................................................................... Call Page Op Diabetic Teaching.............................................................................................................................................#91331 Ophthalmology Consult ....................................................................................................................................x53090 Anesthesia Team Captain ...................................................................................................................#93851/x70023 Radiology/Other Procedures ER Radiology Resident On-Call ..........................................................................................................#93580/x78426 Inpatient Radiology Resident On-Call (5pm-8am)............................................................................................#97612 Radiology-General .............................................................................................................................. x78703/x78700 Film Library ......................................................................................................................................................x78731 X-ray Tech Area ...............................................................................................................................................x78703 Chest Radiology Resident................................................................................................................................x78704 GI Reading Room.............................................................................................................................................x78737 GU Reading Room ...........................................................................................................................................x78737 EEG Tech/Reading Room................................................................................................................... x79543/x79464 Nuclear Medicine Reading Room (Myoviews)............................................................................................................. Nuclear Medicine Scheduling...........................................................................................................................x41005 Echo-scheduling...............................................................................................................................................x78037 Echo/Dobutamine Echo results ........................................................................................................................x78042 U/S-reading room .............................................................................................................................................x79796 U/S-scheduling.................................................................................................................................................x79781 CT-scheduling ..................................................................................................................................................x78786 MRI-scheduling ................................................................................................................................................x78745 EKG-reading ....................................................................................................................................................x78040 Interventional radiology-scheduling ..................................................................................................................x78754 Pulmonary function tests .............................................................................................x57887/x78744 (reading room) Neuroradiology.................................................................................................................................................x78729 EEG Tech/Reading Room................................................................................................................... x79543/x79464 Echo-scheduling...............................................................................................................................................x78042 EKG-reading ....................................................................................................................................................x78040 Interventional radiology-scheduling ..................................................................................................................x78700 Nuclear Medicine Scheduling .......................................................................................................................................................x41005 Fax ...................................................................................................................................................................x70227 General Nuc Med .............................................................................................................................................x31425

PET/CT and SPECT/CT................................................................................................................................... x31388 Imaging Library ................................................................................................................................................ x31420 Reading Room ................................................................................................................................................. x31436 RRUCLA Pharmacies B-level Outpatient Pharmacy ........................................................................................................................... x78524 2nd Floor Inpatient Pharmacy............................................................................................................................ x77221 th 4 Floor Inpatient Pharmacy ............................................................................................................................ x77421 6th Floor Inpatient Pharmacy ............................................................................................................................ x77621 7th Floor Inpatient Pharmacy ............................................................................................................................ x77721 CHS UCLA Outpatient Pharmacies A-Level Pharmacy, CHS .................................................................................................................................. x64242 1st Floor Pharmacy, 200 Med Plaza ................................................................................................................. x41174 4th Floor Pharmacy, 200 Med Plaza................................................................................................................. x47456 RRUCLA Laboratories Inpatient (Main) ................................................................................................................................................ x78100 Urinalysis ......................................................................................................................................................... x78132 Chemistry......................................................................................................................................................... x78141 Hematology...................................................................................................................................................... x78130 Coagulation...................................................................................................................................................... x78134 Surgical Pathology ........................................................................................................................................... x78192 Microbiology..................................................................................................................................................... x42758 Virology ............................................................................................................................................................ x42767 Bacteriology ..................................................................................................................................................... x42757 Outpatient Laboratory ...................................................................................................................................... x41298 Blood and Platelet Center ................................................................................................................................ x50888 Additional Staff Admissions....................................................................................................................................................... x78010 Care Coordination............................................................................................................................................ x79700 Durable medical equipment ............................................................................................. John Henry (310) 901-4950 Home Health .................................................................................................................................................... x41400 Interpreter Services............................................................................................................................. x78001/x79110 Medical Records .............................................................................................................................................. x78044 PICC line nurse.........................................................................................................pgr92788 (RR)/pgr90102 (SMH) Paula Stoessel, Resident Mental Health and counseling ...........................................................................x68976 Rehab/Physical Therapy.................................................................................................................................. x55650 Prosthetics and Orthotics ................................................................................................................................. x41323 Respiratory Therapy ........................................................................................................................................ x78900 Social Work...................................................................................................................................................... x79760 Spiritual Care ................................................................................................................................................... x78190 TB Compliance Office ...................................................................................................... Annemarie Flood pgr94168 USEFUL PHONE/PAGER NUMBERS UCLA Page Operatordirect line for staff ....................................................................................................... x66766 UCLA Page Operatornumber for patients to use............................................................................... 310-825-6301 UCLA prefixes........................................................................................................................... 794-, 206-, 267-, 825Medicine Housestaff Office Teresa Roth, Housestaff Coordinator .............................................................................................................. x57375

Crystal Riley, Assistant Housestaff Coordinator (backline for doctors only) ...........................................................................x79642 (doctor line) x61814 (patient line) Crystal Riley Fax ..............................................................................................................................................x73594 Libby Shin, Outpatient Coordinator ..................................................................................................................x79647 Ronald Lopez ...................................................................................................................................................x79648 Program Directors Office Jodi Friedman, Program Director .....................................................................................................................x79656 Jan Tillisch MD, Program Director....................................................................................................................x79644 Dale Best, Assistant to Program Director ............................................................................................ x79649/x62006 Chief Residents Office Kathy Oka, Assistant to Chief Residents..........................................................................................................x79650 Chief Residents Office......................................................................................................................................x56549 Chiefs Fax Machine.........................................................................................................................................x73592 Chiefs Pager....................................................................................................................................................#91010 Housestaff Office Rose Ziff, Housestaff Coordinator ....................................................................................................................x58307 Internal Medicine Suite Front Desk........................................................................................................................................................x58038 Patient Appointment Line .................................................................................................................... x64083/x61814 Patient Check-Out ............................................................................................................................................x49191 Tony Michaelis, IMS Clinic Manager ................................................................................................................x49822 IMS Fax#..........................................................................................................................................................x46565 Romie Angelich ................................................................................................................................................x49801 Coumadin Clinic (Lorrie/Lily) ........................................................................................................................... x44054 Miscellaneous EmergenciesPolice/Fire....................................................................................................................................x911 Security ............................................................................................................................................................x77100 Transport..................................................................................................................................................................... Computer HELP desk.......................................................................................................................................x44357 Needlestick Hotline.............................................................................................................................. (800) 925-4698 West LA VA......................................................................................................................................... (310) 478-3711 Harbor/UCLA....................................................................................................................................... (310) 222-2345 Oliveview Medical Center.................................................................................................................... (818) 364-1555

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CONTRIBUTORS ....................................................................................................................................................16 ACKNOWLEDGEMENTS........................................................................................................................................17 INTRODUCTION......................................................................................................................................................18 GENERAL INFORMATION .....................................................................................................................................19 HOSPITAL MAPS....................................................................................................................................................20 MEDICINE WARD BASICS .....................................................................................................................................30 Pagers ................................................................................................................................................................30 Dictating..............................................................................................................................................................30 Admit Orders.......................................................................................................................................................30 Admit Notes ........................................................................................................................................................31 Prerounds ...........................................................................................................................................................31 Daily Questions...................................................................................................................................................31 End of Day Checklist...........................................................................................................................................31 How to call a consult ...........................................................................................................................................32 Transferring Patients...........................................................................................................................................32 Discharging Patients ...........................................................................................................................................32 Procedure Notes .................................................................................................................................................33 Code Team .........................................................................................................................................................33 Code Team .........................................................................................................................................................33 Declaring A Patient Deceased ............................................................................................................................33 How To Float (Nuts and Bolts)............................................................................................................................34 How To Float (General Tips)...............................................................................................................................34 Outpatient Clinic Codes ......................................................................................................................................35 CARDIOLOGY .........................................................................................................................................................37 EKG Tutorial .......................................................................................................................................................37 Bradycardia.........................................................................................................................................................37 Tachycardia ........................................................................................................................................................38 Narrow complex tachycardia, regular ............................................................................................................38 Narrow complex tachycardia, irregular ..........................................................................................................39 Wide complex tachycardia, regular................................................................................................................40 Wide complex tachycardia, irregular..............................................................................................................41 Hypertension.......................................................................................................................................................41 Hypertensive Emergency ..............................................................................................................................42 Hypertensive Urgency ...................................................................................................................................42 Hypotension........................................................................................................................................................42 Vasopressors and Vasodilators (Table 1) ...........................................................................................................45 Vasopressors and Vasodilators (Table 2) ...........................................................................................................46 Chest Pain ..........................................................................................................................................................47 TIMI Score .....................................................................................................................................................47 GRACE (Global Registry of Acute Coronary Events) ....................................................................................48 Chest Pain Algorithm (Diagram) ....................................................................................................................49 Acute Myocardial Infarction.................................................................................................................................50 Goal Lipid Levels by CAD Risk (Table) .........................................................................................................53

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EKG Diagnosis in Ischemia, Infarction and Injury............................................................................................... 53 Rough Angiographic Correlation of EKG diagnosis of MI (Table) ................................................................. 53 Congestive Heart Failure .................................................................................................................................... 54 ACE Protocol................................................................................................................................................. 56 Pulmonary Artery (Swan-Ganz) Catheter Tracing .............................................................................................. 57 Early Pacemaker Complications......................................................................................................................... 57 Chronic Valvular Disease ................................................................................................................................... 57 Chronic Aortic Stenosis ................................................................................................................................. 57 Chronic Aortic Regurgitation ......................................................................................................................... 58 Chronic Mitral Stenosis ................................................................................................................................. 58 Chronic Mitral Regurgitation.......................................................................................................................... 58 Syncope.............................................................................................................................................................. 58 Preoperative Clearance For Noncardiac Surgery ............................................................................................... 60 Revised Goldman Cardiac Risk Index (RCRI) Stratification .......................................................................... 63 Dosing of Common Cardiovascular Drugs (Table) ............................................................................................. 65 Goal Immunosuppression Levels (Table) ........................................................................................................... 65 ENDOCRINOLOGY................................................................................................................................................. 67 Diabetes Mellitus ................................................................................................................................................ 67 Types of Insulin (Table)................................................................................................................................. 67 Insulin Sliding Scale (Table).......................................................................................................................... 67 Perioperative insulin management ................................................................................................................ 68 Diabetic Ketoacidosis (DKA) ......................................................................................................................... 68 Hyperosmolar Nonketotic Coma (HONC)...................................................................................................... 69 Non-Insulin Diabetic Medications (Table)...................................................................................................... 70 Adrenal Insufficiency .......................................................................................................................................... 70 Adrenal Function Testing.................................................................................................................................... 71 Cosyntropin Stimulation Test ........................................................................................................................ 72 Metyrapone Test ........................................................................................................................................... 72 Adrenal Replacement Therapy ........................................................................................................................... 72 Adrenal Incidentaloma ........................................................................................................................................ 73 Pheochromocytoma............................................................................................................................................ 73 Thyrotoxicosis..................................................................................................................................................... 74 Thyroid Storm ..................................................................................................................................................... 74 Myxedema Coma ............................................................................................................................................... 75 Non-Thyroidal Illness Syndrome......................................................................................................................... 75 Thyroid Function Tests ....................................................................................................................................... 76 GASTROENTEROLOGY......................................................................................................................................... 78 Acute GI Bleed ................................................................................................................................................... 78 Nasogastric Lavage ............................................................................................................................................ 80 Abdominal Pain .................................................................................................................................................. 80 Acute Pancreatitis............................................................................................................................................... 81 Ransons Criteria for Acute Pancreatitis (Table) ........................................................................................... 83 Small Bowel Obstruction..................................................................................................................................... 83 Acute Nausea ..................................................................................................................................................... 84 Constipation........................................................................................................................................................ 84 Acute Diarrhea.................................................................................................................................................... 85 Helicobacter Pylori.............................................................................................................................................. 86

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Regimens for Treatment of H. Pylori Infection (Table)...................................................................................87 Abdominal Radiography......................................................................................................................................87 HEPATOLOGY ........................................................................................................................................................88 Ascites ................................................................................................................................................................88 Etiology of Ascites Based On SAAG (Table) .................................................................................................88 Paracentesis .......................................................................................................................................................89 Spontaneous Bacterial Peritonitis (SBP).............................................................................................................89 Hepatic Encephalopathy .....................................................................................................................................90 Abnormal Liver Function Tests ...........................................................................................................................91 Hepatitis Serologies (Table)................................................................................................................................92 HEMATOLOGY/ONCOLOGY..................................................................................................................................93 Guidelines for DVT/PE Prophylaxis ....................................................................................................................93 Anemia................................................................................................................................................................94 Reticulocyte Index (Equation)........................................................................................................................95 Microcytic Anemia (Table) .............................................................................................................................96 Normocytic Anemia (Table) ...........................................................................................................................96 Macrocytic Anemia (Table) ............................................................................................................................97 Hemolytic Anemia (Table) ...........................................................................................................................100 Pancytopenia ....................................................................................................................................................101 Sickle Cell Anemia ............................................................................................................................................101 Bleeding Disorders............................................................................................................................................102 Characteristic Bleeding Patterns (Table) .....................................................................................................102 von Willebrands Disease ............................................................................................................................103 Hemophilia A and B.....................................................................................................................................103 Thrombocytopenia ............................................................................................................................................103 Idiopathic Thrombocytopenic Purpura (ITP) ................................................................................................104 Heparin-Induced Thrombocytopenia (HIT) ..................................................................................................104 Thrombotic Thrombocytopenic Purpura (TTP) ............................................................................................105 Disseminated Intravascular Coagulopathy (DIC) ..............................................................................................105 Hypercoagulable States....................................................................................................................................106 Anticoagulation .................................................................................................................................................107 Initiating Warfarin Dosing (Table) ................................................................................................................108 Transfusion Practices .......................................................................................................................................109 RBC Transfusion .........................................................................................................................................110 Platelet Transfusion.....................................................................................................................................111 Fresh Frozen Plasma (FFP) ........................................................................................................................112 Cryoprecipitate ............................................................................................................................................112 Intravenous Immunoglobulin (IVIG) .............................................................................................................112 Vitamin K ..........................................................................................................................................................113 Growth Factors .................................................................................................................................................113 Transfusion Reactions ......................................................................................................................................114 Acute Hemolysis..........................................................................................................................................114 Anaphylaxis .................................................................................................................................................114 Acute Lung Injury.........................................................................................................................................114 Delayed Hemolysis......................................................................................................................................114 Febrile, Non-Hemolytic Transfusion Reaction .............................................................................................115 Neutropenia ......................................................................................................................................................115

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Neutropenic Fever ............................................................................................................................................ 116 Bone Marrow Transplantation........................................................................................................................... 117 Allogeneic BMT ........................................................................................................................................... 117 Autologous BMT.......................................................................................................................................... 118 Timeline of Frequent Complications After Bone Marrow Transplantation (Chart) ....................................... 118 BMT Complications and Prevention ................................................................................................................. 118 Graft Versus Host Disease (GVHD) ............................................................................................................ 119 Acute Graft Versus Host Disease Clinical Grading (Table).................................................................... 120 Chronic Graft Versus Host Disease Organ Involvement and Complications (Table) ............................. 120 Veno-occlusive Disease (VOD)................................................................................................................... 120 Acute Renal Failure..................................................................................................................................... 121 Oncologic Emergencies.................................................................................................................................... 121 Hypercalcemia ............................................................................................................................................ 121 Superior Vena Cava Syndrome (SVCS)...................................................................................................... 121 Tumor Lysis Syndrome ............................................................................................................................... 122 Spinal Cord Compression ........................................................................................................................... 123 Increased Intracranial Pressure .................................................................................................................. 123 Pericardial Tamponade ............................................................................................................................... 123 Antiemetics For Chemotherapy Patients (Table) .............................................................................................. 124 Common Tumor Markers (Table) ..................................................................................................................... 125 Common Chemotherapeutic Agents (Table) .................................................................................................... 126 Novel Chemotherapeutic Agents (Table).......................................................................................................... 127 INFECTIOUS DISEASE ........................................................................................................................................ 128 Key Concepts of Anti-Microbial Therapy........................................................................................................... 128 Therapeutic drug monitoring............................................................................................................................. 128 Fever ................................................................................................................................................................ 128 Pneumonia ....................................................................................................................................................... 130 Community acquired Pneumonia in Immunocompetent Hospitalized Patient ............................................. 130 Hospital acquired Pneumonia ..................................................................................................................... 131 Pneumonia in HIV positive patient .............................................................................................................. 131 Tuberculosis ..................................................................................................................................................... 132 Criteria for a Positive Tuberculin Skin Test ................................................................................................. 132 Active Tuberculosis ..................................................................................................................................... 132 Meningitis ......................................................................................................................................................... 133 Cerebral Spinal Fluid Studies (Table).......................................................................................................... 134 CSF Findings in Various Types of Meningitis (Table) ................................................................................. 134 Bacterial Endocarditis....................................................................................................................................... 135 Prophylaxis.................................................................................................................................................. 136 Clostridium Difficile ........................................................................................................................................... 137 Line Infections .................................................................................................................................................. 138 Urinary Tract Infections..................................................................................................................................... 138 Acute, uncomplicated cystitis in women ...................................................................................................... 139 Acute, uncomplicated pyelonephritis in women........................................................................................... 139 Complicated UTI ......................................................................................................................................... 139 Asymptomatic Bacteriuria............................................................................................................................ 139 Pyuria .......................................................................................................................................................... 139 Candiduria................................................................................................................................................... 140 Lactose Fermenting Status of Gram Negative Organisms (Table) ................................................................... 140

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Quick Guide to empiric antibiotic management (Table) ....................................................................................141 Antibiotic Dosing In Renal Replacement Therapy (Figure)..........................................................................144 HIV AND AIDS .......................................................................................................................................................145 Human Immunodeficiency Virus (HIV) Testing .................................................................................................145 Laboratory Diagnosis of HIV .............................................................................................................................145 The CDC Definition of AIDS..............................................................................................................................146 Initial Work-Up of HIV+ Patient .........................................................................................................................146 Vaccinations and Prophylaxes for HIV Infected Individuals ..............................................................................148 HIV Complications By CD4+ Count ..................................................................................................................148 Any CD4+ Count: ........................................................................................................................................148 CD4+ Counts <500......................................................................................................................................148 CD4+ Counts <200......................................................................................................................................149 CD4+ Count <100 (Table) ...........................................................................................................................149 AIDS Indicator Conditions.................................................................................................................................149 Antiretroviral Therapy Initiation and Treatment Considerations ........................................................................150 Antiretroviral Regimens.....................................................................................................................................150 Nucleoside Reverse Transcriptase Inhibitors (Table) ..................................................................................150 Non-Nucleoside Reverse Transcriptase Inhibitors (Table) ..........................................................................151 Protease Inhibitors (Table) ..........................................................................................................................151 Fusion Inhibitors (Table)..............................................................................................................................151 Combination Drugs (Table)..........................................................................................................................151 Recommended Combinations .....................................................................................................................151 Pregnancy Considerations ..........................................................................................................................152 Complications of Highly Active Antiretroviral Therapy.......................................................................................152 Post Exposure Prophylaxis (PEP).....................................................................................................................153 Pulmonary Disease in HIV ................................................................................................................................153 Mycobacterium Tuberculosis .......................................................................................................................154 Mycobacterium Avium-Intracellulare............................................................................................................155 Pneumocystis Jiroveci (formally PCP).........................................................................................................155 CMV Pneumonitis........................................................................................................................................157 Fungal Infections .........................................................................................................................................158 Malignancies................................................................................................................................................158 NEPHROLOGY......................................................................................................................................................160 Guide to Intravenous Fluids (Table)..................................................................................................................160 Urinalysis Interpretation ....................................................................................................................................160 Urine Dipstick ..............................................................................................................................................160 Urine Microscopy.........................................................................................................................................161 Proteinuria ........................................................................................................................................................161 Nephrotic Syndrome .........................................................................................................................................162 Decreased Urine Output ...................................................................................................................................163 GFR Estimation.................................................................................................................................................164 MDRD Equation...........................................................................................................................................164 Cockroft-Gault Equation ..............................................................................................................................164 Acute Renal Failure (ARF)/Acute Kidney Injury (AKI) .......................................................................................165 RIFLE Classification for Acute Renal Failure (Table) ..................................................................................165 Dialysis ........................................................................................................................................................166 Hemodialysis..........................................................................................................................................166

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Continuous Renal Replacement Therapy .............................................................................................. 166 Peritoneal Dialysis ................................................................................................................................. 167 Evaluation of urinary composition in ARF.................................................................................................... 167 Fractional Excretion of Sodium (Equation)............................................................................................. 167 Fractional Excretion of Urea (Equation) ................................................................................................. 167 Evaluation of Urinary Composition in Acute Renal Failure (Table) ........................................................ 167 Hepatorenal syndrome (HRS) .......................................................................................................................... 167 Chronic Kidney Disease ................................................................................................................................... 168 Requirements for Outpatient Hemodialysis ...................................................................................................... 169 Hyponatremia ................................................................................................................................................... 169 Syndrome of Inappropriate ADH Secretion (SIADH) ........................................................................................ 171 Hypernatremia .................................................................................................................................................. 171 Polyuria............................................................................................................................................................. 172 Hypokalemia..................................................................................................................................................... 173 Hyperkalemia.................................................................................................................................................... 174 Hypocalcemia ................................................................................................................................................... 175 Differential Diagnosis of Hypocalcemia Based On Lab Findings (Table) .................................................... 176 Hypercalcemia.................................................................................................................................................. 176 Treatments for Hypercalcemia (Table) ........................................................................................................ 178 Other Electrolyte Replacement......................................................................................................................... 178 Magnesium.................................................................................................................................................. 178 Phosphate ................................................................................................................................................... 178 Identifying Acid/Base Disorders........................................................................................................................ 179 Acid/Base Formulas ......................................................................................................................................... 179 Acid/Base Differential Diagnoses ..................................................................................................................... 180 Metabolic Acidosis....................................................................................................................................... 180 Metabolic Alkalosis...................................................................................................................................... 181 Respiratory Acidosis.................................................................................................................................... 181 Respiratory Alkalosis................................................................................................................................... 181 Renal Tubule Acidoses..................................................................................................................................... 181 Diuretic Therapy ............................................................................................................................................... 184 Rhabdomyolysis ............................................................................................................................................... 184 Contrast-Induced Nephropathy......................................................................................................................... 185 Vascular Access for Hemodialysis.................................................................................................................... 186 Complications associated with hemodialysis access .................................................................................. 186 Renal Transplant .............................................................................................................................................. 188 Differential of Renal Transplant Graft Dysfunction ...................................................................................... 188 Work-up of renal allograft dysfunction ......................................................................................................... 189 Immunosuppressive Medications In Renal Transplant ................................................................................ 190 Renal Transplant Rejection ......................................................................................................................... 192 NEUROLOGY........................................................................................................................................................ 194 Glasgow Coma Scale (Table)........................................................................................................................... 194 Folstein Mini-Mental Status Exam (Table) ........................................................................................................ 194 Delirium Versus Dementia (Table).................................................................................................................... 195 Delirium Prophylaxis ......................................................................................................................................... 195 Altered Mental Status ....................................................................................................................................... 195 Status Epilepticus ............................................................................................................................................. 196 Phenytoin .................................................................................................................................................... 197

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Adjustment Formula for Low Albumin ....................................................................................................197 Adjustment Formula for Renal Failure....................................................................................................197 Acute Stroke .....................................................................................................................................................198 Ischemic Strokes .........................................................................................................................................198 Criteria for Determining Thrombolytic Use (tPA) In Ischemic Strokes (Table)........................................198 Hemorrhagic Strokes...................................................................................................................................199 Brain Death Criteria ..........................................................................................................................................199 Headaches........................................................................................................................................................200 Headache Alarms and Workup (Table) .......................................................................................................200 HIV and Headaches ....................................................................................................................................200 Primary Headache Disorders.......................................................................................................................200 Migraines................................................................................................................................................200 Tension Headaches ...............................................................................................................................201 Cluster Headaches.................................................................................................................................201 Temporal Arteritis...................................................................................................................................201 Pseudotumor Cerebri .............................................................................................................................201 Medications and Chemicals Known to Cause Headaches (Table) ..............................................................202 Peripheral Neuropathy ......................................................................................................................................202 Dermatome Map ...............................................................................................................................................204 NUTRITION............................................................................................................................................................205 Oral Diets..........................................................................................................................................................205 Disease Specific Modifications ....................................................................................................................205 Nutritional Supplements ..............................................................................................................................205 Enteral Nutrition ................................................................................................................................................205 Parenteral Nutrition ...........................................................................................................................................206 Approved Diet Orders (Table)...........................................................................................................................206 PULMONARY AND CRITICAL CARE...................................................................................................................208 Pulmonary Function Tests ................................................................................................................................208 Normal Flow-Volume Loop (Diagram) .........................................................................................................208 Asthma..............................................................................................................................................................209 Asthma Severity Classification (Table) ........................................................................................................209 Asthma Treatment (Table)...........................................................................................................................209 GINA Levels of Asthma Control (Table) ......................................................................................................210 Chronic Obstructive Pulmonary Disease (COPD).............................................................................................211 GOLD Staging Criteria for COPD (Table)....................................................................................................211 COPD Exacerbation Triaging (Table) ..........................................................................................................212 Pulmonary Embolism ........................................................................................................................................212 Simplified Wells Criteria for Pretest Probability of PE (Table)......................................................................214 V/Q Scan and Clinical Probability in Predicting PE from PIOPED (Table)...................................................214 CTA and Clinical Probability in Predicting PE from PIOPED II (Table)........................................................214 Algorithm for Diagnosis of PE (Diagram).....................................................................................................215 Inferior Vena Cava Filters ............................................................................................................................216 Pulmonary Hypertension...................................................................................................................................217 Pleural Effusions ...............................................................................................................................................218 Lights Criteria for Diagnosing a Pleural Effusion as an Exudate (Table) ....................................................219 Chest Tubes .....................................................................................................................................................219 Water Seal (Diagram)..................................................................................................................................219

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Complications.............................................................................................................................................. 220 Differential Diagnosis of Shock (Table) ............................................................................................................ 222 Respiratory Failure ........................................................................................................................................... 222 Differential Diagnosis of Acute Respiratory Failure (Table)......................................................................... 223 Alveolar-arterial oxygen gradient (Equation) ............................................................................................... 224 Noninvasive Mechanical Ventilation ............................................................................................................ 225 Types of Noninvasive Mechanical Ventilation (Table)............................................................................ 225 Noninvasive Mechanical Ventilation Algorithm (Diagram)...................................................................... 225 Ventilators......................................................................................................................................................... 227 Mechanical Ventilator Variables (Table)...................................................................................................... 227 Ventilator Modes ......................................................................................................................................... 228 Assist-Control (Table) ............................................................................................................................ 228 Pressure-Support (Table) ...................................................................................................................... 228 Synchronous Intermittent Mandatory Ventilation (Table) ....................................................................... 228 Typical Initial Settings for Mechanical Ventilation (Table) ........................................................................... 229 Adjusting the Mechanical Ventilator (Table) ................................................................................................ 229 Ventilator Emergencies ............................................................................................................................... 229 Weaning the Ventilator ................................................................................................................................ 230 Predictive Indices of Extubation (Table)................................................................................................. 231 Sedation ........................................................................................................................................................... 231 Properties of Sedatives Commonly Used in the ICU (Table)....................................................................... 232 Paralysis ........................................................................................................................................................... 232 Properties of Paralytics Commonly Used in the ICU (Table)....................................................................... 233 Acute Respiratory Distress Syndrome .............................................................................................................. 233 General Care of ICU Patients ........................................................................................................................... 234 Blood glucose control .................................................................................................................................. 234 GI prophylaxis ............................................................................................................................................. 234 Nutrition....................................................................................................................................................... 234 DVT prophylaxis .......................................................................................................................................... 234 RHEUMATOLOGY ................................................................................................................................................ 236 Arthrocentesis General Concepts..................................................................................................................... 236 Synovial Fluid Analysis (Table)......................................................................................................................... 236 Acute Monoarthritis Differential Diagnosis ........................................................................................................ 236 Gonococcal Bacterial Arthritis........................................................................................................................... 237 Nongonococcal Bacterial Arthritis..................................................................................................................... 237 Crystal Deposition Arthritides ........................................................................................................................... 238 Gout ............................................................................................................................................................ 238 Pseudogout ................................................................................................................................................. 239 Classification of Vasculitides ............................................................................................................................ 239 Takayasus Arteritis ..................................................................................................................................... 239 Giant Cell (temporal) Arteritis ...................................................................................................................... 240 Polyarteritis Nodosa .................................................................................................................................... 240 Isolated CNS Vasculitis ............................................................................................................................... 240 Churg-Strauss Arteritis ................................................................................................................................ 240 Wegeners Granulomatosis ......................................................................................................................... 240 Microscopic Polyarteritis.............................................................................................................................. 241 Henoch-Schnlein Purpura ......................................................................................................................... 241 Hypersensitivity Vasculitis ........................................................................................................................... 241

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Essential Cryoglobulinemic Vasculitis .........................................................................................................241 Antinuclear Antibody Subtypes (Table).............................................................................................................242 ACR Criteria for Diagnosis of Systemic Lupus Erythematosus (Table).............................................................243 Drugs that cause lupus................................................................................................................................243 Scleroderma Renal Crisis .................................................................................................................................244 TOXICOLOGY .......................................................................................................................................................245 General Approach to Intoxication/Ingestion ......................................................................................................245 Ethanol Intoxication and Withdrawal .................................................................................................................245 Blood Alcohol Concentration and Associated Clinical Signs (Table) ...........................................................246 Ethanol Withdrawal Syndromes (Table) ......................................................................................................247 Opioid Overdose ...............................................................................................................................................249 Properties of Common Opioid Drugs (Table)...............................................................................................249 Cocaine Overdose ............................................................................................................................................250 Benzodiazepine Overdose................................................................................................................................251 Properties of Common Benzodiazepine Drugs (Table) ...............................................................................251 Acetaminophen Overdose ................................................................................................................................251 Rumack-Matthew Nomogram (Diagram) .....................................................................................................253 Salicylate (Aspirin) Overdose............................................................................................................................253 Tricyclic Antidepressants Overdose..................................................................................................................254 Properties of Tricyclic Antidepressants (Table) ...........................................................................................254 Carbon Monoxide Intoxication ..........................................................................................................................255 Digoxin Toxicity.................................................................................................................................................256 MISCELLANEOUS ................................................................................................................................................258 Perioperative Management...............................................................................................................................258 Pain Medication Conversions ...........................................................................................................................258 Steroid Conversions..........................................................................................................................................259 Gastric Tubes....................................................................................................................................................259 Premedication For Contrast Allergy ..................................................................................................................260 Qualifying For Home Oxygen............................................................................................................................260 Vaccinations (Table) .........................................................................................................................................261 ADVANCED CARDIAC LIFE SUPPORT (ACLS) .................................................................................................263 Initial ACLS Assessment...................................................................................................................................263 Ventricular Fibrillation .......................................................................................................................................264 Asystole ............................................................................................................................................................265 Bradycardia.......................................................................................................................................................266 Tachycardia (With Pulses) ................................................................................................................................267 Narrow Complex SVT..................................................................................................................................268 Stable Wide Complex Tachycardia..............................................................................................................269

CONTRIBUTORS C AUTHORS AND EDITORS Neveen El-Farra, M.D. Eve Glazier, M.D. Wylie Hosmer, M.D. Edmund Huang, M.D. Clare Keane, M.D. Jennifer Kious, M.D. Michael Pfeffer, M.D. Stephanie Smooke, M.D. Leo Slavin, M.D. Brian Young, M.D. Steven Le M.D. Nasim Afsar-Manesh M.D. Sunil Reddy M.D. Jennifer Bennit M.D. Wendy Simon M.D. Kevin Breger M.D. Tim Provias M.D. Kuo-Chiang Lian M.D. FACULTY REVIEWERS Eric Buch, M.D. Margrit Carlson, M.D. Christina Charles, M.D. Andrew Drexler, M.D. Sara Hurvitz, M.D. Martha Lewis, M.D. Lenna Martyak, M.D. Mintri Nguyen, M.D. O N T R I B U T O R S

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ACKNOWLEDGEMENTS A C K N O W L E D G E M E N T S

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First, we wish to thank all the generations of UCLA residents who contributed to the three previous editions of this Handbook. Many of you are now fellows and attendings; in this fourth edition may your legacy live on! The following physicians have all been past contributors: Shaun Anand, Arash Bereliani, Lynne Bui, Sue Charette, Mark Edelstein, Rick Fairhurst, Mike Flaningam, Mark Goodarzi, Joel Isackson, Steve Lee, Anuja Mittal-Henkle, Lisa Moore, Ajai Nirula, Tommy Oei, Andy Oh, Jonathan Reitman, Eric Tong, Patsy Tsung, Ruth Wintz, Joe Wu, Brent Drouin, Hannah Hong, Richard Lapin, Rob Lin, Teryl Nuckols, Archana Sadhu, Daphne Stewart, Andrea Sullivan, Rick Hayashi, Lin Jia, Doug Tong, Sara Hurvitz, Lisa Skinner, Henry Niho, Jeannie Chan, Paul Bellamy, Noel Boyle, Margrit Carlson, Gareth Dulai, Gregg Fonarow, Steven Han, Michael Keane, David Klashman, Matthew Leibowitz, Minhtri Nguyen, David Pegues, Michael Rosove, Sammy Saab, Iain Smith, Jan Tillisch, and Andre VanHerle. Thanks to those who were pressed into service (many for a repeat appearance) to review the updated version: Margrit Carlson, Brian Young, Edmund Huang, Christina Charles, Eric Buch, Andrew Drexler, Sara Hurvitz, Martha Lewis, Lenna Martyak, and Minhtri Nguyen. More thank yous to Kathy Oka, Dale Best, Aileen Martinez, and Teresa Roth. Big thank yous to the Big people: Dr. Jan Tillisch, Dr. Alan Fogelman, Dr. Jodi Friedman, and the Department of Medicine for supporting this project. And a very special thank you to Dr. Neveen El-Farra who read/reviewed/edited every word in this bookwithout her genius and dedication this book would be completely useless. Thank you! Eve Glazier, Michael Pfeffer and Jennifer Kious Chief Residents 2007-2008 Wendy Simon, Kevin Breger, Tim Provias, Kuo-Chiang Lian Chief Residents 2008-2009

INTRODUCTION I N T R O D U C T I O N

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This handbook is meant to be a concise guide to help you through floats and call. It contains an evidence-based approach to commonly encountered inpatient clinical problems at UCLA. It is by no means comprehensive or authoritative and is not intended to take the place of your own reading, a thorough review of the literature, and the clinical experience of a practicing physician. The management guidelines here may not be applicable to or appropriate for every patient you encounter. Exercise your clinical judgment and, when in doubt, do not hesitate to refer to your resident, the senior back-up, your chief residents, or your attending with any questions. This handbook, like the field of medicine, is a work in progress. We look to all of you to produce the subsequent editions. Disclaimers aside, we hope you will find the handbook helpful. Take some time to browse through all the new content, the expanded table of contents, and new tables and diagrams. Good luck and have a great year!

GENERAL INFORMATION G E N E R A L I N F O R M A T I O N

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UCLA INSTITUTIONAL LICENSE # AND DEA # FOR PRESCRIPTIONS CA License...................................................................................................................................................... C11739 DEA........................................................................................................................................................... ZZ9994965 Code for Triplicate Exemption .........................................................................................................................11159.2 To write for narcotics without a triplicate on patient with < 6 months life expectancy, must write only one medication per script and use valid license and DEA numbers (the institutional number above will not work) UCLA Tax ID ..............................................................................................................................................956006143 USEFUL INTERNET ADDRESSES UCLA Medicine Housestaff Website ................................................................................ http://medres.med.ucla.edu User ID: docmed Password: docmed2007 UCLA Department of Medicine Website............................................................................... http://www.med.ucla.edu UCLA Medical Center Website........................................................................................ http://www.mednet.ucla.edu PRIMARY DATA SOURCES: PubMed.............................................................................................................http://www.ncbi.nlm.nih.gov/PubMed/ MDConsult ........................................................................................................................http://home.mdconsult.com New England Journal of Medicine ................................................................................................http://www.nejm.org SUMSearch...................................................................................................................http://sumsearch.uthscsa.edu Google Scholar ....................................................................................................................http://scholar.google.com Medline Plus..............................................................................................................................http://medlineplus.gov SYNTHESIZED DATA US Preventive Services Task Force (USPSTF) .............................................. http://www.ahrq.gov/clinic/uspstfix.htm ZYNX Health ...............................................................................................https://www.zynx.com/zynxprd/home.asp Society of General Internal Medicine.............................................................................http://www.sgim.org/tools.cfm Bandolier ..................................................................................................................http://www.jr2.ox.ac.uk/bandolier PIER (Patient Information and Education Resource) .......................................http://pier.acponline.org/index.htm?hp ACP Journal Club........................................................................................................................ http://www.acpjc.org

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MEDICINE W ARD BASICS M E D I C I N E W A R D B A S I C S

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PAGERS From a hospital phone dial 231 to access the automatic pager system From outside dial 1-800-BEEP-231 To signout your pager: Please enter the pager number * + your pager number (i.e. *12345) #, 1, 1, 1 then the covering pager number To cancel your pager signout: * + pager number #, 1, 2 DICTATING From hospital phone, dial #30 to access dictation system From outside dial 1-310-794-2001 Pager number, # Location code, # Work Type, # Patient MRN, # To mark STAT, press * after you hear the beep. To pause, press 1; to resume, press 2. Location Codes 1 = Westwood 2 = NPH 3 = Santa Monica DICTATION CODES Work Type 1 = Discharge, Death or Transfer Summary 11 = Addendum to discharge summary 3 = Inpatient Procedure Note 33 = Outpatient Procedure Note 4 = Inpatient Consultation 44 = Outpatient Consultation 5 = Inpatient H &P 55 = Outpatient H&P 6 = Test Results 7 = Inpatient Progress Note 77 = Outpatient Progress Note 8 = Letter

ADMIT ORDERS (Templates in Forms Portal General Medicine Admission Orders) Admit to (team, R1 name & beeper, R2/3 name & beeper, attending) Diagnosis Condition (stable, guarded, critical) Vitals Activity Allergies Nursing Diet IVF

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Meds Special studies Labs Call HO for: T < 35.0 or > 38.5, RR < 10 or > 30, HR < 60 or > 100, SBP < 100 or > 180, DBP < 50 or > 90, O2 saturation < 92% (adjust according to patients specifics)

ADMIT NOTES (Type or dictate into CDS) Identification/Chief Complaint History of Present Illness Past Medical History/Past Surgical History Allergies Health Related Behaviors Social History Family History Review Of Systems Physical Exam Labs/Studies Assessment & Plan Code Status Ask every patient if they have an advance directive and document their wishes Prophylaxis DVT, delirium, fall, aspiration, constipation, C. difficile, stress ulcer (ICU) PREROUNDS Vitals Medications (check actual medication administration record every day) Nursing notes (in Essentris or talk to overnight nurse) Consult notes in the chart Review all EKGs Examine the patient Write orders for morning labs DAILY QUESTIONS Can I switch IV drugs to oral? Do drug doses need to be adjusted for worsening renal/liver failure? Can I take out the Foley? Chest tube? JP drain? Central line? Can I advance the diet? Is the patient getting out of bed? Is the patient having bowel movements? Does my patient still need a monitor? Is the social worker making a discharge plan? END OF DAY CHECKLIST AM labs ordered (note that not every patient needs AM labs!) Note written Finish tomorrows discharge paperwork Update signout

MEDICINE W ARD BASICS Signout to night float and signout pager

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HOW TO CALL A CONSULT Earlier is better. Try to call consults before noon. Otherwise wait until 1 p.m. as most fellows have noon talks. The decision to call a consultation should be made with your resident and attending Call the page operator (x66766) to find out the fellow on the appropriate consult service Start with I have a patient Id like to discuss with you, and give the patients name and MRN number Give a brief, relevant history and your intended plan, then your question. Always have a specific question (i.e. Does this patient need a pacemaker? Should we start antifungal coverage?). Dont say you just want them on board. In general, try to have the basic workup started. Get old or outside records as soon as possible. On the other hand, dont wait until Friday at 4:55 p.m. to call the consult because you are waiting for the workup. Be sure to provide the consultant with the pager of who to contact with recommendations Read the consult notes! Sign this out to float if you are leaving. If you disagree with a recommendation and are not going to follow it, CALL the consultant and discuss it with them. TRANSFERRING PATIENTS Call chief resident 91010 (R2/3) Call accepting team (R2/3) Call bed control (x56922) if pt will be on different ward (R2/3) Dictate/type transfer note including physical exam, medication list, problem list and plan (R1) Write transfer orders (R1) DISCHARGING PATIENTS The following items are necessary to discharge a patient: Discharge Summary: (R1 writes for the paper chart/CDS, give a copy to R2/3 who will dictate for the electronic record) Date of admission Date of discharge R1, R2/3, attending on discharge Admitting diagnoses (i.e. what the patient had prior to coming to the hospital) Discharge diagnoses (i.e. what the patient was diagnosed with during this hospital stay only) Procedures Consults Brief history of present illness and hospital course Discharge medications Diet/Activity recommendations Follow-up Physician Discharge Sheet Write out prescriptions (narcotics require triplicate forms) All Medi-CAL prescriptions need to be on security paper. Complete list of medications for patient (including which outpatient meds to continue/discontinue) D/C home, D/C IV order Notify patients primary doctor of discharge or schedule a post-discharge appointment with them in IMS clinic with a member of your team

MEDICINE W ARD BASICS If the patient needs a primary care doctor, try to see them yourself, set them up with a member of your team, or verbally communicate with whomever they are intended to establish care with.

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PROCEDURE NOTES Forms can be found on the wards or as a template on Essentris: Place one copy in the chart and the other copy in one of the boxes located in MICU and CCU call rooms, C medicine team office (5W), or charting room (4EMOU). Keep one for your own records (see Appendix for chart to keep track of procedures) Include the following: Date and time Physicians performing procedure Indication for procedure Informed consent Time out was performed IV/PO Meds given/Anesthesia Description of procedure Findings Follow-up CODE TEAM The MICU resident (90090)/intern on-call (90040), CCU resident (90080)/intern on-call (90089), Obs resident (96450), J-call, and Medicine Float pagers are on the Code Team. You will automatically be signed on when you sign on to these virtual pagers. You can add your pager to the Code Team by calling the operator x66766. Codes are to be run by the first person there. If you are the first person there, run the code, with the help of your senior. If you are ever uncomfortable, ask your senior to take over. We cover codes called in RRUCLAMC inpatients, visitors, 1W CHS rehab, 200MP Nuc Med B1 level, 200MP Rad Onc B2 level, and (if after hours) the 200MP 6th floor surgery suite. th We do not cover codes in: 200MP outpatient, CHS outpatient areas, 200MP 6 floor (during daytime), or JSEI/JSEI OR. ***For code blue OUTSIDE RRUCLAMC, only MICU resident and CCU intern should go***. RED GURNEY RUNS When a visitor to the hospital goes down, the MICU resident and CCU intern will respond to evaluate with the assistance of an ER tech/nurse who will bring a gurney. Once stabilized, the visitor is taken to the ER for further evaluation. DECLARING A PATIENT DECEASED You will be informed by nurse that patient has died and needs to be declared. Be prepared to encounter the family at bedside; explain that you need to examine the patient and that they may stay. Examination: Check for pupillary reflexes Observe for spontaneous breathing or movements Auscultate for heart tones Assess for response to pain by pinching finger nail or skin while auscultating (sternal rub can be done as well)

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Note time, offer condolences, and ask family for permission for autopsy. Inform them of benefits of autopsy (will help in the education of housestaff and may identify incidental inherited diseases and thus benefit surviving family). The autopsy will not interfere with an open casket funeral; there is the option of limited autopsy, and costs are covered by the hospital. Call or page attending physician! See checklist in computer under bulletin board for post-mortem information and for information on which deaths are coroners cases. Dictate/Type a Death Note: (R2/3 will need to dictate a complete death note, similar to a discharge summary) Time and date of death Describe exam Mention that the family and attending were informed Give a very brief history and include whether or not the patient was on comfort care protocol per family and medical team (if this is the case)

HOW TO FLOAT (NUTS AND BOLTS) Sign on to the pager at 5 p.m. on weekdays, 12 noon on weekends Stay on pager until 8 a.m. weekdays and weekends Meet teams 7 a.m. next day to give verbal signout in conference room 7134. Provide any notes to team. Sign your name and float pager 91903 on orders Call rooms on B-level of RRUCLAMC, key card gets you in. Get good sign out: The basics (age, location) Code status and fever workup status Attending and threshold to call Problem list Important medications Things to check and their implications (i.e. What do I do about an elevated D-dimer?) Document, Document, Document: See the patient Write a brief SOAP note when called for any significant problem (such as chest pain, dyspnea, fever, abdominal pain, altered mental status, low urine output, falls, etc.) If a patient dies, see declaring a patient deceased above. Always write or dictate a transfer note if patient goes to ICU/CCU and notify primary attending; call bed control to get a unit bed (x56922) Page interns in am to let them know of any unstable patients or pending tests ***Call attending for any major changes in the patients status*** HOW TO FLOAT (GENERAL TIPS) Senior backup is always in the hospital: Page 90090 (ICU) or 90080 (CCU) to reach them or check www.amion.com for his/her pager. Low threshold for calling them, even for simple questions or to talk through a situation. If a patient looks SICK, call senior backup EARLY. Attendings are available 24 hours a day: they should be notified if a patient dies or codes. If there is a situation that they can help with (i.e. an upset family member, a difficult treatment dilemma, code status issues) do not hesitate to call or page them. Resources: this book has good preliminary information on many situations that will arise on float nights. See the Table of Contents for these topics: Chest Pain, Hypotension, Hypertension, Bradycardia, Tachycardia, Transfusions, Transfusion reactions, Low urine output, Headache, Altered mental status, Respiratory failure)

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Sleep Aids: you are not obligated to give a sleep aid if you think the patient is at high risk of becoming confused or altered. If you decide they can have one: Temazepam (Restoril) 15-30 mg Zolpidem (Ambien) 5-10 mg Trazodone (Desyrel) 25-50 mg Diphenhydramine (Benadryl) 25-50 mg (not a first-line choice) Lorazepam (Ativan) IV 0.5-1 mg can be given to patients who are NPO. Be cautious in elderly patients > 65. Would choose trazodone 25-50 mg in the elderly or Ambien. Avoid benzodiazepines and Benadryl. If someone is delirious and agitated do not give sleep aid. Off Monitor: in general, if a patient is on a monitor they likely need to be. It can be difficult to weigh the value of an urgent test against the patient needing a monitor. Remember, if they are off monitor they are only going with escort, not a nurse, and they may sit a while waiting for the scan. You can always accompany them yourself if the test is urgent and the transport nurse is unavailable. Shortness of Breath: Differential: volume overload, aspiration, COPD or asthma, pneumonia, pneumothorax, pulmonary embolus, allergic reaction, acid-base disturbance Go see the patient Can they talk to you? If yes, get a focused history: onset, precipitating factors, history of similar episodes. If no, move on to interventions, call for backup if unsure. Check trend of vital signs, 24 hour total of ins and outs, current vital signs, physical exam (count the respirations yourself, listen for crackles or absent breath sounds) Tests: STAT portable CXR, consider an ABG. Consider CT angiogram if high suspicion for PE. Possible interventions: High flow oxygen, non-rebreather mask, furosemide if you suspect volume overload, albuterol/Atrovent, suctioning, reposition in bed to 90 degrees, intubate if necessary (call senior backup and anesthesia team captain at x70023 to intubate. See respiratory failure in the pulmonary section for more detailed information Uncertainty: you will not know everything! Floats are valuable learning experiences where you will test your limits and gain confidence in your ability to handle a variety of issues, but you should never feel alone, backup is a page away.

OUTPATIENT CLINIC CODES To check clinic schedules: Use the Mainframe Program. Log in with same User ID and Password. Choose option #10, then 1A, then VA. Enter Group name IMS = IMIMH Cardiology = MSCAR Heart transplant Clinic: Physician = HTX (Kobashigawa) Endocrine = MSEND Diabetes = MSDMC GI = MSDDC Private GI = MSPGI Pulmonary = MSPUL Rheumatology = MSRHE Allergy = MSDMC Infectious Disease = MSIFD

MEDICINE W ARD BASICS Nephrology = MSNEP Geriatrics = MSGER Dermatology = DRMOH Womens Health = IMWHF Enter last name of physician who is staffing clinic Type in nx at the bottom to go to the next clinic day

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CARDIOLOGY C A R D I O L O G Y

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EKG TUTORIAL See medres.med.ucla.edu Education EKG tutorial BRADYCARDIA Initial Assessment Is patient symptomatic or hypotensive (SBP<80)? If so, place in Trendelenburg, begin ACLS (Atropine 0.5mg IV, transcutaneous pacing), place pacemaker pads, give fluid bolus, call for back-up. Start Dopamine 5 mcg/kg/min while waiting for cardiology fellow to come in and place a temporary wire. Place on cardiac monitor; check rhythm strip and 12 lead EKG Differential Diagnosis Medications Beta-blockers, calcium channel blockers, digoxin, amiodarone, other antiarrhythmics, morphine Cardiac Sick sinus syndrome, inferior MI, Mobitz type 2 heart block, 3rd degree heart block, Afib with slow ventricular response, increased vagal tone Other Respiratory insufficiency/apnea Hypothyroidism Increased intracranial pressure Normal in athletes Evaluation ABCs, eyeball testdoes patient appear comfortable, uncomfortable, or critical H&P focusing on distinguishing between above causes Chart review/review of medications 12 lead EKG Cardiac enzymes, if indicated by H&P Management ACLS, if appropriateAtropine 0.5mg IV, transcutaneous pacing, consider starting dopamine 5 mcg/kg/min until backup/fellow arrives if hypotensive. Treat underlying cause nd rd If patient is hypotensive, symptomatic, has HR<40, or EKG shows 2 degree AV block Mobitz type II or 3 degree heart block call for ICU/CCU back-up and call Cardiology consult fellow as patient may need urgent temporary transvenous pacer. Discontinue medicationsbut beware of rebound tachycardia. Common Class I indications for pacemaker placement Third degree AV block (typical symptoms include syncope, seizures, dizziness, confusion, limited exercise tolerance, and congestive heart failure) Second degree AV block Mobitz type II with symptomatic bradycardia Symptomatic sinus bradycardia with HR <40 or pauses >3sec Sinus node dysfunction with tachycardia-bradycardia syndrome, episodic sinus arrest, or sinoatrial block Neurocardiogenic syncope with >3sec pause after carotid sinus massage Postoperative cardiac surgery with AV block not expected to resolve Bifascicular block with intermittent complete heart block that is symptomatic Bifascicular block with 2nd degree AV block Mobitz type II

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TACHYCARDIA Initial Assessment Is patient symptomatic or hypotensive (SBP<80)? If so, place pt in Trendelenburg, begin ACLS (synchronized DC cardioversion or defibrillate), give fluid bolus, and call for back-up. Place pt on cardiac monitor; check rhythm strip and 12 lead EKG Evaluation ABCs, eyeball testdoes pt appear comfortable, uncomfortable, or critical Focused H&P looking for evidence of ischemia or congestive heart failure, syncope, altered level of consciousness Chart review/review of medications 12 lead EKG Cardiac enzymes, if indicated by H&P Differential Diagnosis/Management Initiate ACLS, if appropriatesynchronized DC cardioversion or defibrillation Treat underlying cause Narrow complex tachycardia, regular (QRS <120msec, rate >100) Sinus tachycardia Most common (usually rate does not exceed 160 bpm except in young patients) Causes: hypoxia, hypovolemia, myocardial dysfunction, fever, anemia, medications (e.g. albuterol), hyperthyroidism, PE, pain, anxiety, drug or alcohol withdrawal, stimulants Diagnosis: upright P waves in inferior leads (II, III, aVF) followed by QRS Treatment: treat underlying cause AVNRT (atrioventricular nodal re-entrant tachycardia) Cause: dual AV pathways with differing refractory periods; rhythm often initiated by a PAC Diagnosis: rate typically 150-250, inverted P (or pseudo S) in inferior leads (II, III, aVF) on EKG (with short R-P interval) (although P waves may not be visible if buried in QRS) Treatment: If unstable synchronized DC cardioversion If no h/o CVA/TIA/carotid bruit carotid massage; other vagal maneuvers (If patient does not have asthma) (Patient should be warned about symptoms first) Adenosine 6mg IVP, then 12mg IVP, then repeat 12 mg IVP (Make sure patient is on monitor, and record the rhythm). Push the adenosine fast and immediately chase it with a NS flush. Have atropine ready in case patient has a long pause. (rhythm can break with adenosine) -blockerMetoprolol 5mg IV q5min x 3 (push over 2 min -> then flush) Ca-channel blockerDiltiazem 15mg IV, may repeat 15-20mg IV in 5min Radiofrequency ablation AVRT (atrioventricular re-entrant tachycardia) Cause: re-entrant tachycardic circuit with conduction down AV node and back up over bypass tract Diagnosis: retrograde P wave in inferior leads (II, III, aVF) (with long R-P interval) Treatment: as for AVNRT above, and Procainamide (only in the setting of pre-excitation) (procainamide is really best used for Afib with pre-excitation. WPW patients show no pre-excitation during AVRT, since all ventricular activation is via the AV node.) Atrial tachycardia Cause: enhanced automaticity of atrial tissue or ectopic atrial pacemakers Diagnosis: P wave precedes each QRS (usually with abnormal P wave axis, since atrial activation does not start at sinus node) Treatment:

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Beta-blocker Ca-channel blocker Class III antiarrhythmics RF ablation Atrial flutter with regular block Causes: see Afib below Diagnosis: flutter waves in inferior leads, ventricular rate is some division of 300 (think of flutter in HR=150, 100, 75); adenosine may help to reveal flutter waves Treatment: Rate control: Digoxin Beta-blocker Ca-channel blocker Cardioversion: Synchronized DC cardioversion (50J, 100J, 200J, 300J, 360J) Pharmacologic: Ibutilide (administered by EP, although Ibutilide is not often given for flutter and is administered as a one-time dose) Anticoagulation: IV Heparin or enoxaparin, then Coumadin (see Afib below) Long term management: Class IC or III drugsrequires very careful patient selection Amiodarone and dofetilide are only antiarrhythmic shown not to increase mortality in patients with structural heart disease Radiofrequency ablation (usually treatment of choice for flutter, since low risk and high effectiveness) Narrow complex tachycardia, irregular (QRS<120 msec, rate >100) Atrial fibrillation Cause (PIRATES): Pulmonary disease Idiopathic (common cause)/Ischemia (rarely causes Afib acutely) Rheumatic heart disease (valvular disease) Atrial myxoma (very rare cause of Afib) Thyrotoxicosis Ethanol Sepsis (uncommon cause of Afib) Hypertension (#1 cause)/CHF Diagnosis: Irregular ventricular rate in the absence of P waves or well-defined flutter waves in all leads Check chemistry panel, thyroid function tests, cardiac enzymes in patients with known heart disease, echo to help determine cause and risk stratify Treatment: Rate control: Digoxin: load 0.5 mg IV x 1, then 0.25mg IV q6h x 2, then 0.125mg PO/IV qd; check level; slow onset of action; adjust dose in renal failure, with amiodarone, etc. Beta-blocker: Metoprolol 5mg IV q5min x3 (contraindicated in COPD and low EF) Ca-channel blockers: Diltiazem 15mg IV, may repeat 15-20mg IV in 5min (can also be given as a continuous infusion until rate control is achieved)

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Anticoagulation: Any pt with Afib>48hours (or unknown) duration should be anticoagulated if no definitive contraindication (active hemorrhage, recent neurosurgery, recent hemorrhagic CVA, etc.) to prevent risk of thromboembolization Start with Heparin drip (see protocol under Hematology), then Coumadin Pt must be therapeutic (INR 2-3) for 3 weeks prior to attempt at cardioversion and must remain on anticoagulation for 1 month subsequent to successful cardioversion Alternatively get TEE to r/o atrial appendage clot and proceed with earlier cardioversion, still need to anticoagulate for 4 or more weeks post cardioversion Risk factors for thromboembolism: CHADS2 score (0-1 use ASA 325; if > 1 use Coumadin): C = CHF (1 pt) EF < 45%, (1 pt) valvular heart disease H = HTN (1 pt) A = Age > 75 (1 pt) D = Diabetes (1 pt) S = Stroke/TIA in past (2 pt) Cardioversion: Synchronized DC (100J, 200J, 300J, 360J) OR pharmacologic: Amiodarone 150 mg IV over 10min, then 1 mg/min x 6hrs, then 0.5 mg/min x 18 hrs to complete the load. Procainamide: 1gm IV over 1 hour, then Procan SR 750mg PO QID; check for QT prolongation, QRS prolongation, hypotension; follow procainamide and NAPA (toxic metabolite) levels (total level of 10-20 is therapeutic); be sure to give AV nodal blocking agent (e.g. Digoxin) first Ibutiliderisk of torsades; use with guidance of Cardiology attending or fellow only Treat underlying cause: Rarely possible (e.g. thyrotoxicosis) Maintenance of sinus rhythm: Complex problem! Choice of antiarrhythmic is dependent on pts other medical problems (i.e. amiodarone is safest drug in patients with ischemic disease and/or low EF). Involve cardiology! Some commonly used antiarrhythmics: Amiodarone Sotalol Propafenone (reserved for lone Afib, no structural heart disease) Flecainide (reserved for lone Afib, no structural heart disease) Dofetilide Atrial flutter with variable block (see Aflutter/Afib above) Multifocal atrial tachycardia Causes: multiple ectopic pacemakers; often associated w/pulmonary disease, hypomagnesemia and hypokalemia Diagnosis: three distinct P wave morphologies with three different PR intervals Treatment: treat underlying cause (K > 4, Mg > 2, digoxin not very effective, some data for ibutilide (EP-guidance) Frequent premature atrial complexes (PACs) Wide complex tachycardia, regular (QRS >120msec, rate >100) Ventricular tachycardia (monomorphic): assume VT in all patients with heart disease!

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See ACLS protocol. Synchronized shock for perfusing VT, and defibrillation for VF; Amiodarone (give 300 mg IV x 1 if in a code, if pt is not hemodynamically unstable 300 mg IV over 10 min followed by (similar dosing to Afib) for stable patients Check electrolytes Ischemic disease predisposes to VT EKG findings that favor VT: Very wide QRS (>140msec) Abnormal axis AV dissociation Fusion beats Capture beats SVT with aberrancy or over bypass tract This is diagnosis of exclusion Treat as SVT (AVNRT vs. AVRT), if appears as left bundle or right bundle morphology Hyperkalemia (see Hyperkalemia give calcium, insulin, D50W, etc.) Wide complex tachycardia, irregular (QRS >120msec, rate >100) VT (polymorphic): see ACLS protocol and defibrillate Torsades de pointes Causes: Medications: antiarrhythmic drugs that prolong QT, TCAs, phenothiazine, H1 blockers (astemizole, terfenadine), pentamidine, erythromycin, antifungal agents Electrolyte abnormalities: hypokalemia, hypomagnesemia Subarachnoid hemorrhage Congenital long QT syndrome Diagnosis: Twisting QRS complex Prior EKGs may show long QT (QTc = QT/RR) (>450) Treatment: Magnesium sulfate 2gm IV over 1min Isoproterenol infusion or temporary pacing to increase heart rate (involve Cardiology) Treat underlying causestop precipitating medications, etc. Atrial fibrillation with aberrancy or over accessory pathway This is a diagnosis of exclusion Treat as VT until proven otherwise

HYPERTENSION Do you believe the BP? Measure yourself manually with correct cuff size. Differential Diagnosis Alcohol withdrawal Drug overdose (cocaine, amphetamines) Drug withdrawal (alcohol, cocaine, amphetamines, narcotics, anti-hypertensive medications) Drug interactions (MAO inhibitors + tricyclics/Demerol/antihistamine/foods) Increased intracranial pressure (Cushings reflex) Renal failure and renal artery stenosis Eclampsia Coarctation of the aorta

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Endocrine (thyrotoxicosis, Cushings syndrome, pheochromocytoma) Pain or Anxiety Hypertensive Emergency Exists when elevated BP (usually DBP>120) is associated with end-organ damage Signs/Symptoms: CNS: headache, mental status changes, seizure, stroke, irritability Eyes: blurred vision, papilledema, exudates, flame hemorrhages Cardiac: chest pain, EKG strain or ischemic changes, pulmonary edema Vascular: aortic dissection Renal: low urine output, edema, hematuria, azotemia Management: Hypertensive emergencies require admission to ICU with arterial line and reduction of BP, usually with IV medications, to reduce permanent organ dysfunction and death IV Nipride 0.2-5 mcg/kg/min 1st line in most patients Arteriolar and venous dilation Toxicity with thiocyanate and cyanide metabolite must be considered with several days of therapy and with renal and hepatic insufficiency IV Nitroglycerin 10-400mcg/min First choice agent for patients with myocardial ischemia Venous dilation IV Labetalol (1, 1, 2 antagonist) 20mg IV bolus, then 2mg/min First choice agent for patients with myocardial ischemia or acute aortic dissection Most potent adrenergic blocker. Favorable response in hypertension associated with pregnancy. Do not lower BP too abruptly as sudden drop in BP may lead to cerebral and other organ hypoperfusion; goal is 25% reduction in mean arterial pressure or to reduce DBP to no lower than 100-110mmHg in first 12-24 hrs. Hypertensive Urgency Exists when BP>220/120 without evidence of end-organ damage Management (can usually be treated with short acting oral medications): Clonidine: 0.2mg orally, followed by 0.1mg q hour to total of 0.8mg. Watch for sedation, bradycardia with AV nodal blockers. Onset in 30-60 minutes. Rebound hypertension if abruptly stopped. Captopril 12.5-25mg orally works in 15-30 minutes with variable episodes of excessive response. Metoprolol 12.5-100mg PO BID (ok to start titrating 25 mg p.o. q6hrs x 48 hrs -> then convert to BID). Try to avoid IV MTP as it lasts a short time. (2.5 mg PO MTP = 1 mg IV MTP) Topical Nitropaste 1-2 inches to chest wall q6hr; wipe off for BP < (your parameter)

HYPOTENSION Do you believe the BP? Re-check it yourself manually with correct cuff size. If not audible, palpate radial pulse (present w/ SBP > 80) or carotid/femoral pulse (present w/ SBP > 60). If pulse not found, ask for assistance and call CODE BLUE! Continue assessment of ABCs and start CPR. Is the hypotension relative? Check patients baseline BP? BP 100/50 is abnormal in pt whose usual BP is 160/80 BP 80/40 may be normal & represent a physiologic state like CHF or liver disease

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Causes (see differential of shock in Pulmonary/Critical Care section) Hypovolemia: hemorrhage (internal or external), vascular dissection, GI losses, over-diuresis, post-dialysis, third spacing Cardiogenic: MI, valvular dysfunction, arrhythmia Obstructive: PE, tamponade, tension pneumothorax, atrial myxoma Distributive: sepsis, anaphylaxis, medications, neurogenic, adrenal insufficiency Evaluation (do a focused history, PE, and chart review) Any signs or symptoms of hypoperfusion or shock? (i.e. altered mental status, cool, clammy skin, diaphoresis, chest pain, decreased urine output, decreased peripheral pulses) If so, call for back up and begin initial management listed below. Hypovolemia: volume status (mucous membranes, low JVP, skin turgor) Cardiac ischemia: chest pain, SOB, history of CAD, EKG Arrhythmia: pulse rate & rhythm, rhythm strip Tamponade: pulsus paradoxus, distant heart sounds, JVD, electrical alternans on EKG Pneumothorax: tracheal deviation, JVD, unequal breath sounds, hyperresonance Pulmonary Embolism: dyspnea, hypoxia, JVD, loud P2, RV strain/S1Q3T3 pattern on EKG (sinus tachycardia occurs in 80% of the time) Hemorrhage: GI, retroperitoneum, thigh, abdomen, pancreas, adrenal, hip or pelvic fracture Anaphylaxis: stridor, wheezing, urticaria, flushed skin, pruritus, angioedema Sepsis: fever or hypothermia, leukocytosis or leukopenia Adrenal insufficiency: history of steroid use, hypopituitarism, adrenal hemorrhage/infection/trauma Work-up Determine likely cause(s) from your evaluation. Review medication list (check for anti-hypertensives, diuretics, etc.) Send indicated laboratory studies: Stat CBC and chemistry panel. Consider PT/PTT, UA, blood & urine cultures, CK, CK-MB, troponin, type & cross, BNP, lactate EKG & CXR Initial Management Evaluate ABCs & confirm IV, O2, monitor in place Place patient in Trendelenburg position Stop anti-hypertensives. Wipe off nitropaste, take off the clonidine patch Begin fluid resuscitation with 1L NS bolus if no clinical evidence of CHF. Continue with boluses and vigorous IV hydration as needed to replete intravascular volume depletion and maintain adequate BP. Remember only 1/10 of the bolus stays in the vessel, edema is only cosmetic. If the patient has adequate cardiovascular reserve and renal function one can continue giving fluids until O2 requirement begins to increase. If exam or CXR suggests pulmonary edema/CHF or if volume status unclear, consider Swan-Ganz catheter to evaluate patients hemodynamics (i.e. PCWP, SVR)see table of hemodynamic parameters associated with specific shock states. If hypotension persists after adequate fluid resuscitation, pressors may need to be started and you should consult your resident. Norepinephrine (Levophed) is typically initiated first if appears sepsis/hypovolemia. Other pressors include: dopamine, dobutamine, vasopressin, Phenylephrine (Neo-Synephrine), epinephrine. See the Vasopressor & Vasodilator chart below for guidance on dosing. Specific Management Cardiac ischemia: see acute MI protocol. Tamponade: call CCU fellow for emergent echo and pericardiocentesis

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Pneumothorax: dont wait for CXR; place 14 or 16 gauge needle into second intercostal space at midclavicular line ASAP. Call pulmonary fellow for chest tube placement. Pulmonary Embolism: start thrombolytics/heparin. Dose: tPA: no loading dose, start 100 mg infuse over 2 hrs (ok to give w/ heparin), unless contraindications to tPA are present. Attain an echo to assess for RV function/strain. Please consult pulmonary fellow or attending prior to administration. Bleeding: large bore IV, NS, blood product repletion, reverse any coagulopathy, Anaphylaxis: epinephrine 0.1 mg (1cc of 1:10,000) slow IVP or 0.3 mg (0.3cc of 1:1,000) SQ Sepsis: start broad spectrum antibiotics emergently (always double gram negative, and dont be afraid to give aminoglycosides) and pressors (Levophed > dopamine > vasopressin > Neo-Synephrine) as needed Adrenal insufficiency: hydrocortisone 50mg IV q6hrs, after attaining the cosyntropin stim test; see Adrenal Testing in Endocrinology section.

CARDIOLOGY VASOPRESSORS AND VASODILATORS (ADAPTED FROM PRESSOR CARD, CCU) -1 -2 Inotropy Vasoconstriction Vasodilation Chronotropy + +++ ++++ >10 mcg/kg/min ++++ ++++ 0 ++++ ++++ +++ 5-10mcg/kg/min +++ 0 ++++ chronotropy ++++ ++ ++ ++ 0 0 ++++

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Drug Dobutamine (500mg/250 D5W) Epinephrine (2mg/250 D5W) Dopamine (400mg/250 D5W) Norepinephrine (4mg/250D5W) Phenylephrine (50mg/250 D5W) Isoproterenol (2mg/250 D5W) Milrinone* (20mg/100 D5W)

Drip 2-20 mcg/kg/min 0.01-0.1mcg/kg/min 1-200mcg/min 2-20mcg/kg/min 2mcg/kg/min=renal dose 0.5-70mcg/min 40-200mcg/min 2-10mcg/min Load 50mcg/kg then maintenance doses: Min: 0.375mcg/kg/min Std: 0.5mcg/kg/min Max: 0.75mcg/kg/min 20-300mcg/min 10-240mcg/min Initial 2mcg/kg bolus then 0.01mcg/kg/min, may increase by 0.005mcg/kg/min in 3 hour intervals (preceded by 1mcg/kg boluses) up to max of 0.03mcg/kg/min

0 Nitroprusside (100mg/250 D5W) Nitroglycerin (100mg/250 D5W) Nesiritide (1.5mg/250 D5W)

++/+++

0 0

0 0

++++ ++++

++++

*Vasodilation via phosphodiesterase (PDE) inhibition, not via -2 receptor Vasodilation via NO pathway, not via -2 receptor Vasodilation via binding to guanylate cyclase receptor on VSMC activating cGMP, not via -2 receptor

CARDIOLOGY VASOPRESSORS AND VASODILATORS (ADAPTED FROM PRESSOR CARD, CCU) BP Effects Disadvantages When To Use No change since Not for use as 1st line in low output cardiac failure and 2 decreases single agent in often needs support from concurrent SVR; may even hypotension. pressor such as dopamine lower BP. Tachycardia. Increases BP at all dosing range Tachyarrhythmias (Atrial and Ventricular) Coronary ischemia, ischemic limb, renal, and bowel Tachyarrhythmias (AF, SVT, and Ventricular) Ischemic limb necrosis Norepinephrine (4mg/250D5W) Phenylephrine (50mg/250 D5W) Isoproterenol (2mg/250 D5W) Milrinone* (20mg/100 D5W) Nitroprusside (100mg/250 D5W) Nitroglycerin (100mg/250 D5W) Nesiritide (1.5mg/250 D5W) Increases BP at all dosing ranges Increases BP at all dosing ranges Bowel / renal / limb hypoperfusion Reflex bradycardia, peripheral hypoperfusion Hypotension, thrombocytopenia Considered 1st line alternative in septic shock 1st line in distributive shock other than anaphylaxis Incredibly potent generally used as the LAST RESORT vasopressor for any type of shock

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Drug Dobutamine (500mg/250 D5W)

Epinephrine (2mg/250 D5W)

Dopamine (400mg/250 D5W)

Increases BP at all dosing range

1st line in cardiogenic shock and distributive shock; also used concurrently in low output cardiac failure with dobutamine

CO + SVR tends to drop blood pressure

2nd line agent in cardiogenic shock from low-output state

No change since 2 decreases SVR; may even lower BP.

Not for use as single agent in hypotension. Tachycardia.

1st line in low output cardiac failure and often needs support from concurrent pressor such as dopamine

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CHEST PAIN Differential Diagnosis Life threatening Causes: MI: consider in all patients, especially the elderly, those with cardiac risk factors; pain is often pressure like, associated with SOB, diaphoresis, nausea; may radiate to jaw/arm Aortic dissection: consider in patients with HTN, smoking; often tearing pain radiating to back, unequal pulses Pneumothorax: consider in patients with COPD, trauma, on mechanical ventilation; look for decreased breath sounds, hyperresonance, deviation of trachea away from side with pneumothorax, hypoxia not responding to 100% oxygenation PE: consider in all hospitalized patients; pain may be pleuritic; pt is often dyspneic, hypoxic, may have hemoptysis; A-a gradient may be increased Other Causes: Pericarditis Pneumonia/Pleurisy Stable angina GERD PUD Esophageal spasm Esophagitis (candida, herpes) Varicella zoster (shingles) Costochondritis Anxiety (diagnosis of exclusion!) Evaluation Check vital signs immediately, including O2 sat and BP in both arms Focused H&P to distinguish between the life-threatening causes Check EKG, compare to previous Consider ABG, CXR, other tests as indicated by H&P Risk Stratification TIMI Score can be used to stratify chest pain patients One point for each of the following: Age over 65 3 or more risk factors for CAD [Diabetes, cigarette smoking, HTN (BP 140/90 mm Hg or on antihypertensive medication), dyslipidemia, Family history of premature CAD (CAD in male firstdegree relative 55 or younger, CAD in female first-degree relative 65 or younger, Age (men 45 years; women 55 years)] Established CAD (Angiographic stenosis of 50%) 2 or more angina episodes in past 24 hours ASA use in the last 7 days Elevated cardiac enzymes ST depression 0.5 mm TIMI Scale 0-2 = low risk 3-4 = intermediate risk 5-7 = high risk

CARDIOLOGY GRACE (Global Registry of Acute Coronary Events) http://www.outcomes-umassmed.org/GRACE/acs_risk.cfm Variables at admission to determine risk: Age Heart rate SBP Creatinine CHF Class Cardiac Arrest? ST-deviation (elevation or depression) Elevated cardiac enzymes

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CARDIOLOGY Chest Pain Algorithm

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Management If suspect angina/MI: give ASA, Metoprolol, sublingual NTG or nitropaste, Heparin and see acute MI below If suspect aortic dissection: begin IV labetalol, transfer to ICU, arrange for emergent CT or TEE and call vascular surgery

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If suspect pneumothorax: call surgery or pulmonary for emergent chest tube placement; if suspect tension pneumothorax, do NOT wait for CXR place needle or Angiocath into 2nd intercostal space at midclavicular line on side of pneumothorax If suspect pulmonary embolism: see Pulmonary/Critical Care section

ACUTE MYOCARDIAL INFARCTION Adapted from Fonarow, GC. UCLA Clinical Practice Guideline for Acute Myocardial Infarction,1994 and UCLA Acute Myocardial Infarction Program: The CLOT Team Protocol-97/98. Please refer to these for further details at www.med.ucla.edu/champ. Definition Acute ST elevation MI requires two of the following: Chest pain or chest pain-equivalent (indigestion, SOB, dizziness, etc.) EKG with 1mm ST elevation in 2 contiguous leads Left bundle branch block, not known to be old Patients with sustained symptoms in absence of diagnostic EKG should have repeat EKG in 30mins Patients who have symptoms associated with an EKG showing ST depression unrelieved within 30 minutes of initiating medical therapy should be considered to have refractory unstable angina. As the CCU resident, call CCU fellow (#94228) immediately if called for suspected AMI patient (meeting above criteria); perform a brief evaluation of all chest pain/rule out MI patients and review EKG within 10 minutes of being informed of admission; call CCU fellow if any question on EKG. Assessment Rapid assessment is key! Patients who are revascularization candidates should receive an EKG within 10 minutes of arrival, then either: Direct catheterization and angioplasty (within 90 minutes of arrival), OR Thrombolytics within 30 minutes of arrival in ER Focused H&P: Current symptoms: onset, duration, and quality; exacerbating/alleviating factors; associated symptoms. Prior ischemic disease? CHF? Arrhythmia? Other cardiac disease? Cardiac risk factors: Age, HTN, DM, PVD, CVD, hyperlipidemia, family history of premature CAD, smoking Other medical problems: renal failure, bleeding disorders, GI bleeds Assess vital signslook for signs of cardiogenic shock or CHF; BP in both arms, JVP, murmurs (MR, VSD, etc) Diagnostic tests: EKG: (with rapid interpretation) call CCU fellow with any questions; repeat EKG in 30mins, in 6 hrs, or if any recurrent symptoms, then QD x 2d and on day prior to discharge; in reperfusion patients, check at end of therapy and repeat in 4-6hrs, then as above Labs: CBC with platelets, Chem 7, PT/PTT, nonfasting lipid panel; others as indicated (ABG for respiratory insufficiency, hypoxia, etc.) CXR Cardiac enzymes: STAT troponin, CK, CK-MB immediately; repeat troponin, CK, CK-MB in 6hrs. If first trop (-) but symptoms/EKG worrisome, can get cardiac enzymes in 3 hrs. Echocardiography: indicated acutely if you suspect pericarditis, aortic dissection (TEE), tamponade, acute MR; also useful to assess LV dysfunction, size, location and severity of regional wall motion abnormalities, valvular abnormalities Acute coronary angiography: for urgent reperfusion by angioplasty or CABG, or localization of lesions for further management

CARDIOLOGY Right heart catheterization: for complicated MIhypotension, oliguria, CHF, cardiogenic shock. Initial Therapy (Use in ST elevation AMI, non-ST elevation AMI, and unstable angina) ASA: 325mg chewed immediately Contraindications: Active hemorrhage Severe aspirin allergy Note that heme positive stool, non-melenic stool, peptic ulcer disease are NOT contraindications Clopidogrel: 600mg orally (eight 75mg tablets) No dose adjustment is required in elderly or renal insufficiency Contraindications: Severe thrombocytopenia (platelets < 20,000) Active pathological hemorrhage History of intracranial hemorrhage or hemorrhagic stroke Severe uncontrolled hypertension Known hypersensitivity to drug IV Heparin or Low Molecular Weight Heparin: Unfractionated Heparin 71U/kg IV bolus followed by continuous infusion 14U/kg/hr with goal PTT 1.8-2.5x control (see Heparin protocol). Alternatively Enoxaparin 1mg/kg SQ q12hrs. Use in all patients regardless of treatment plan (cath vs. thrombolytics vs. medical management). Studies have shown Lovenox and Arixtra to be superior to heparin gtt, however, most interventional cardiologists at UCLA prefer heparin gtt, therefore in majority of the cases heparin gtt is started Contraindications: Hemorrhage Pericarditis Aortic dissection Beta-blockade: Metoprolol 5mg IV q2-5mins x 3, followed by 25 mg p.o. q6hrs x 48hrs 50mg PO BID begin 30-60mins after IV infusion. Contraindications: Cardiogenic shock Hypotension (SBP < 80 mmHg) Decompensated heart failure (crackles > 1/3 the way up from the bases) Symptomatic bradycardia nd rd 2 or 3 heart block without a pacemaker Active wheezing Direct Angioplasty: Preferred reperfusion therapy in patients presenting <24hrs after onset of symptoms Indications: Need for rapid, successful (95%) reperfusion (symptoms <1-2 hrs with large infarct) Cardiogenic shock with single vessel disease Glycoprotein IIb/IIIa (abciximab, eptifibatide, or tirofiban) are decided upon in the cath lab Thrombolytic therapy: Commonly used as 1st line reperfusion at other institutions Indications: Symptoms <12hrs, EKG with ST elevation in 2 contiguous leads, or LBBB, not known to be old Symptoms >6hrs but <12hrs with Q wave development Contraindications:

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CARDIOLOGY

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Absolute: Cardiogenic shock, active bleeding, recent surgery (<1wk), h/o CNS hemorrhage, tumor, aortic dissection, acute pericarditis Relative: prior MI with LV dysfunction, moderate-severe CHF, remote GI bleeding, bleeding diathesis, uncontrolled hypertension in elderly, pregnancy Dosing: (do NOT initiate without discussing w/CCU attending) Tissue plasminogen activator: front-loaded, weight adjusted regimen Acute CABG: Indicated in cardiogenic shock with left main or multivessel disease Intra-aortic balloon pump: May be necessary, in setting of cardiogenic shock, as bridge to CABG/other reperfusion or postrevascularization Nitroglycerin: Indicated for symptom control of ischemia and to prevent vasospasm after direct angioplasty. Sublingual NTG (400mcg) q5 min PRN chest pain, repeat PRN up to 3 doses and topical Nitropaste (1-2 inches to chest wall) If pain unrelieved by above, or pain recurs, begin IV NTG drip (20-200mcg/min) Contraindications: Use of sildenafil/tadalafil/vardenafil Hypotension Severe anemia Cerebral hemorrhage Increased intracranial pressure Oxygen: Indicated for treatment of hypoxia Analgesia: Consider morphine (venodilation decrease PCWP) in patients whose symptoms are not relieved with nitroglycerin and beta-blockers while you prepare for reperfusion Sub-Acute Therapy Monitoring: cardiac monitoring for arrhythmias and silent ischemia for 48-72hrs in uncomplicated MI ASA: 81-325mg PO QD should be continued long term in all patients without contraindications; clopidogrel 75mg PO QD or warfarin to INR 2-3.5 can be used in patients with contraindications to ASA. Clopidogrel: 75mg PO QD should be continued for at least 6mos or indefinitely based on physician discretion; patients undergoing stenting for acute coronary syndrome should receive therapy for at least 1 month (Bare-metal stents), and 1 year or longer (Drug-eluting stent). Heparin or Low Molecular Weight Heparin: continue for 48hrs or until revascularization is performed; indications beyond 48hrs include Afib or LV thrombus; consider long-term (3mos) SQ heparin for large anterior MI or anticoagulation with warfarin. If no intervention, ok to stop heparin once troponin trends down or 48hrs. -blockade: continue Metoprolol 50-100mg PO BID long-term in all patients without contraindications. The benefit of -blockers occurs once the HR reaches 55-60, make sure you titrate up the -blocker aggressively. ACE-inhibition: long term use in all patients; begin within 12-24 hrs of AMI onset; start at low dose and titrate to target doses HMGCo-A Reductase Inhibitors (statins): indicated in all patients with atherosclerosis; check nonfasting lipid panel on admit (within 6-12 hours of onset of AMI; acute phase reaction beginning at 12-24 hours will lower LDL levels by 25-50% for up to 6wks) and start statin; aim for dose that will achieve LDL<70 see CHAMP card; if baseline LDL is pending or not known, empiric doses may be used: pravastatin 40mg PO

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QHS, simvastatin 40mg PO QHS, or atorvastatin 80 mg PO QHS (anti-inflammatory affect). Baseline LFTs should be checked upon admission and at 6 weeks to screen for statin-induced hepatitis. GOAL LIPID LEVELS BY CAD RISK Risk Factor(s) LDL goal (mg/dl) No DM or CAD, but 0-1 risk factor(s) <160 No DM or CAD, but 2 or more risk factors < 130 DM and/or CAD, PVD < 70 Age (male>45yo, female>55yo or premature menopause without HRT), Tobacco, HTN, HDL<35 (subtract one risk factor if HDL>60), family history of premature CAD (male<55yo, female<65yo) Warfarin: indicated for Afib, LV thrombus; consider in pts unable to take ASA post-MI Antiarrhythmics: only amiodarone is safe post-MI; all others substantially increase risk of sudden death and overall mortality Exercise: begin ambulation by day 2-3; give instructions for minimum of 30-60 mins of moderate intensity activity 5-7 times per week aerobic exercise program Smoking Cessation: give patients written information re outpatient programs, nicotine replacement therapy and bupropion or varenicline. Diet: patient and family should receive counseling about National Cholesterol Education Program Step 2 Diet Follow-up: set up appointment with cardiologist in 2-6 weeks. Risk Assessment Inpatient or outpatient stress or modified stress test: risk stratify if ruled out for MI or in patients with uncomplicated MI not undergoing direct catheterization where information about residual ischemia would alter therapy or follow-up (Inpatient Echo lab x66701) Electrophysiology study: consider if cardiac monitoring or 24 Holter demonstrate NSVT > 24hrs after MI onset in patients with LVEF< 35%; if pt is inducible, ICD placement

EKG DIAGNOSIS IN ISCHEMIA, INFARCTION AND INJURY Adapted from Dr. Henry Hondas handout, November 6, 2000. In patients with ischemic chest pain symptoms, sensitivity of EKG for diagnosis of all MIs is ~50% with a specificity of ~90% ROUGH ANGIOGRAPHIC CORRELATION OF EKG DIAGNOSIS OF MI Location Leads Culprit Vessel Septal V1-2(3) LAD (if +I +aVL, prox to D1) Anterior V(2)3-4 LAD (distal to S1) Anterolateral I, aVL, V3-6 LCx Lateral V5-6 +/- I, aVL LAD High lateral I, avL OM or MR Inferior II, III, avF RCA (90%) or LCx (esp if +lat) Posterior V1-2 (large R) PDA RV V4R RV branches from RCA Diagnosis of MI in presence of bundle branch block: No change in criteria in setting of RBBB, RBBB+LASH and RBBB+LPHB In LBBB, normally ST-T wave changes are in opposite direction of QRS

CARDIOLOGY Acute MI: 1mm concordant ST elevation, or 1mm ST depression in V1-3 > 5mm discordant ST elevation Q waves in I, aVL, V5-6 suggestive of Q wave infarction

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CONGESTIVE HEART FAILURE Adapted from Fonarow, GC. UCLA Heart Failure Clinical Practice Guideline and Summary, 1996, 1998, 2000. Definition Congestive heart failure is inadequate blood supply to maintain normal function. Heart failure may be due to systolic dysfunction (LVEF<50%) or due to isolated diastolic dysfunction (LVEF>50%). Goals of treatment for heart failure due to systolic dysfunction should be diuresis, afterload reduction and inotropy. Goals of treatment for diastolic dysfunction should be improved ventricular filling with rate control. Etiology Coronary artery disease Hypertension Idiopathic dilated cardiomyopathy Valvular heart disease Drugs (i.e. alcohol, cocaine, methamphetamine) Diastolic dysfunction Less common: congenital, infiltrative cardiomyopathy (amyloid, sarcoid), hemochromatosis, thyroid disease, pheochromocytoma, chronic renal disease, HIV and viral cardiomyopathy Factors Contributing to CHF Exacerbation Ischemia Arrhythmia Cardiovascular stress (infection, anemia, pregnancy, stress, hyperthyroidism) Pulmonary embolism Medical noncompliance Dietary indiscretion Diagnosis History: Focus on distinguishing between possible reasons for exacerbation and for symptoms of volume excess (decreased exercise tolerance, SOB, DOE, PND, weight gain, edema, RUQ tenderness) and/or low cardiac output (fatigue, malaise, decreased appetite) Physical: Look for signs of left and/or right sided failure, cardiogenic shock, and hypoperfusion Left sided signs: rales, tachypnea, S3 Right sided signs: elevated JVP, hepatojugular reflux, ascites, peripheral edema, enlarged liver Low cardiac output signs: cachexia, muscle loss, cool extremities, tachycardia, S3 Tests: Labs: Chem 7, CBC, TSH, FT4, FT3, LFTs, Lipid panel, Urinalysis, trop, CK, CK-MB x 2 B-type natriuretic peptide (BNP) Neurohormone secreted by cardiac ventricles as a response to ventricular volume expansion and pressure overload

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BNP levels <100 pg/ml essentially excludes heart failure as a cause of a patients symptoms or physical exam BNP that is elevated (>100 pg/ml) suggests possible CHF BNP levels are NOT influenced by HTN, diabetes, mild renal insufficiency, or COPD Dialysis patients may have increased BNP levels reflecting increased ventricular filling pressures 12 lead EKG, CXR Echo or cath report describing ejection fraction, systolic vs. diastolic dysfunction Hemodynamic monitoring with Swan-Ganz catheter indications: Hypoperfusion: narrow pulse pressure, altered mental status, declining renal function despite adequate volume status Congestion in presence of angina, baseline renal insufficiency, or hemodynamic intolerance of ACE inhibitors Persistent congestion despite salt and fluid restriction, high dose loop diuretics and metolazone Management Antagonism of Neurohormonal Activation: ACE-inhibitor: first line therapy for afterload reduction in all pts with reduced EF (because heart failure is characterized by systemic vasoconstriction) Target doses: Captopril 50mg PO TID, Enalapril 10mg PO BID, Benazepril 40mg PO QD, Lisinopril 40 mg p.o. daily. Beta-blocker: indicated in all classes of heart failure once clinically stable; start at low doseCarvedilol 3.125mg PO BID, titrate up to target 25mg PO BID, Toprol-XL 12.5 QDAY and titrate up. Carvedilol was superior to MTP BID in pt with EF < 40%. Spironolactone: aldosterone antagonism; start at 12.5 mg or less, goal 25mg PO QD; adjust loop diuretic and potassium supplementation; must check chemistry panel within 7 days; closely monitor K, BUN, Cr. Contraindications: Male Cr > 2.5, Female Cr > 2.0. Only benefit patients with Class III-IV HF (EF < 40%), ischemic etiology Volume Excess: for diuresis in acute CHF with adequate BP, consider the mnemonic below: Lasix: add PRN metolazone Morphine: for comfort and vasodilation Nitrates: for preload reduction Oxygen Position: head up will improve oxygenation Pee: what the patient should do following the above Vasodilators: Add hydralazine up to 100mg p.o. QID, Isordil up to 80mg TID if patients BP remains high despite maximum dose of ACE-I. Also if pt is intolerant to ACEI/ARB due rise in Cr, regimen provides good afterload reduction. Inotropes: necessary in patient with evidence of systemic hypoperfusion (that has not responded to afterload reduction). Prior to starting, please call the CCU fellow. (Usually requires central access) Other: Maintain strict I/Os, daily weights, 2g Na diet, 2L fluid restriction, frequent electrolyte checks

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ACE Protocol UCLAs heart failure guideline for hemodynamic optimization of patients with NYHA Class III or IV symptoms. Refer to ACE protocol guidelines for details; brief review follows. CCU fellow to place Swan-Ganz catheter to determine patients filling pressure, cardiac index, and SVR; patient should be admitted to COU or CCU, depending on acuity Goals: RA < 7mmHg, PCWP < 15mmHg, SVR < 1200, and SBP 80mmHg. Optimal filling pressure (PCWP) is the lowest one that can be maintained without a fall in cardiac index and/or blood pressure If elevated filling pressures (PCWP > 20 and/or RA > 10), diurese with IV Lasix until PCWP is as low as possible while maintaining SBP 80. Follow K and Mg. If elevated SVR > 1300, begin afterload reduction with nitroprusside 20mcg/min, titrate to max 300mcg/min to keep SVR < 1200, RA < 7, PCWP < 15, while maintaining SBP 80. When optimal hemodynamics have been achieved and maintained for 2-6hrs, add oral captopril at 6.25mg PO, doubling dose q2hr to target 50mg PO q6hr while weaning off nitroprusside. For additional vasodilation, add Isordil when captopril has been titrated up to 25mg (especially in patients with CAD). If patient has low cardiac index (< 1.2), consider inotropic agent such as dobutamine (if BP can tolerate, because dobutamine can decrease the BP), ok to start with dopamine to increase BP, then add dobutamine to increase CI. Check patients Swan tracings, Is/Os, and electrolytes several times per day and adjust medications accordingly; keep K 4, Mg 2 D/C Swan after 4-8 hours of optimal hemodynamics (by two sets of readings) on final oral regimen.

CARDIOLOGY PULMONARY ARTERY (SWAN-GANZ) CATHETER TRACING Normal Values for Hemodynamic Monitoring Central venous pressure (CVP)/Right atrial pressure (RA): 1-7 mmHg Right ventricular (RV) systolic pressure: 15-25 mmHg Right ventricular (RV) diastolic pressure: 0-8 mmHg Pulmonary artery (PA) systolic pressure: 15-25 mmHg Pulmonary artery (PA) diastolic pressure: 8-15 mmHg Pulmonary capillary wedge pressure (PCWP)/Left atrial (LA) pressure: 6-12 mmHg Cardiac output (CO): 3.5-5.5 L/min Systemic vascular resistance (SVR): 900-1200 dyne/sec/cm2 Calculated Hemodynamic Variables CO = HR SV Cardiac index (CI) = CO body surface area (BSA) Mean arterial pressure (MAP) = (SBP + DBP 2) 3 SVR = (MAP-CVP) CO 80 Trans-pulmonary gradient = Mean pulmonary artery pressure (MPAP) - PCWP If transpulmonary gradient > 15 (intrinsic pulmonary vascular disease, patient needs lung/heart transplant)

57

EARLY PACEMAKER COMPLICATIONS Pneumothorax (check CXR) Hematoma formation (especially if patient on anticoagulation) Lead perforation of RA or RV (suspect if hemodynamically unstable) Lead dislodgment or pacemaker failure (suspect if failure to sense or capture) CHRONIC VALVULAR DISEASE Chronic Aortic Stenosis Clinical signs: systolic murmur heard best at RUSB, crescendo-decrescendo, transmitted to carotids, A2 decreased; paradoxical splitting of S2; narrow pulse pressure; pulses parvus et tardus.

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Mean gradient and valve area (normal is 3-4 cm ) Mild: < 25 mmHg, > 1.5 cm2 2 Moderate: 25-50 mmHg, 1.0-1.5 cm Severe: > 50 mmHg, < 1.0 cm2 Critical: > 80 mmHg, < 0.7 cm2 AV replacement should be considered in symptomatic patients. Patients should NOT be treated on the basis of a determination of valve area alone. Clinical symptoms predict survival: mnemonic Aortic Stenosis Failure or ASF 5,3,2 Rule. In the setting of the following symptoms, without AVR, 50% survival rates are as follows: Angina 5 years Syncope 3 years Failure < 2 years Chronic Aortic Regurgitation Clinical signs: diastolic blowing murmur heard best at LUSB; wide pulse pressure, Quinckes sign (capillary pulsations at fingertips), De Mussets sign (bobbing head), Mllers sign (pulsing uvula), Corrigans pulse (water hammer). Indications for operation: NYHA functional class III or IV Severe LV dilatation: LV end diastolic dimension > 75mm, LV end systolic dimension >55mm Mild to moderate LV dysfunction with EF < 50% Concomitant angina and severe AR Progressive LV dilatation, declining LVEF or exercise tolerance Chronic Mitral Stenosis Clinical signs: low rumbling diastolic murmur heard best at apex; opening snap may be heard. Mean gradient and valve area Mild: < 5 mmHg, > 1.5 cm2 Moderate: 5-10 mmHg, 1-1.5 cm2 2 Severe: > 10 mmHg, < 1 cm Indication for MV repair or balloon valvuloplasty: NYHA class III-IV symptoms, moderate or severe MS (MVA < 1.5 cm2), and valve morphology favorable for repair. Chronic Mitral Regurgitation Clinical signs: loud, holosystolic, high-pitched, heard best at apex and transmitted to axilla, soft S1. Surgical indications: NHYA class III or IV, LV end-systolic dimension > 45mm, LV end-systolic volume index > 50ml/m2, LVEF < 60 and progressive declining. Mitral valve REPAIR should be preferred over mitral valve REPLACEMENT whenever possible. However, mitral valve repair is LESS favorable in cases that are a) rheumatic, b) ischemic, c) infective, d) anterior or bileaflet prolapse, and e) significant calcification present.

SYNCOPE Major Causes of Syncope Neurologic: vertebrobasilar TIA, subclavian steal syndrome, normal pressure hydrocephalus, seizure disorder Metabolic: hypoxia, hypoglycemia, hyperventilation Psychiatric: panic disorder, hysteria Mechanical cardiac disease: aortic stenosis, mitral stenosis, pulmonary stenosis, global ischemia, aortic dissection, obstructive cardiomyopathy, left atrial myxoma, prosthetic valve dysfunction, pulmonary embolus, pulmonary hypertension (careful cardiac auscultation and obtain ECHO)

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Cardiac arrhythmias: Bradyarrhythmia Sinus node dysfunction AV conduction disease Tachyarrhythmia Supraventricular arrhythmia Ventricular arrhythmia (MOST important one to exclude risk of sudden cardiac death in patients with history of cardiac disease) Vasodepressor syncope (most common) AKA vasovagal syncope, cardioneurogenic syncope, and reflex syncope Mechanism: Stimulation of medullary vasodepressor region of brainstem via afferent pathways from: Gastrointestinal & genitourinary mechanoreceptors: micturition, postprandial, defecation, peptic ulcer Cerebral cortex: panic, fright, pain, noxious stimuli Cranial nerve: glossopharyngeal neuralgia, oculovagal Cardiopulmonary baroreceptor: carotid sinus, tussive Cardiac C fibers: Valsalva, upright tilt, jacuzzi, weight lifting, trumpet playing, post-exercise, volume depletion, pacemaker syndrome, supraventricular tachycardia. Brainstem vasodepressor region generates efferent signals that cause increase vagal tone via vagus nerve (bradycardia) and vasodilation via unclear pathway (decrease cardiac filling and blood pressure). Both bradycardia and vasodilation lead to syncope. Diagnosis: tilt table testing Treatment: -blocker and avoidance of precipitating factors. Hypersympathetic tone is necessary to engage cardiac C fiber and therefore beta-blocker can inhibit this step in the beginning, however the benefit is marginal.

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PREOPERATIVE CLEARANCE FOR NONCARDIAC SURGERY Adapted from Eagle, K. Guidelines for Perioperative Cardiovascular Evaluation for Noncardiac Surgery. Circulation. 2002;105:1257-1267. What are the cardiac complications of noncardiac surgery? Death, MI, CHF, arrhythmia Step1: What is the urgency of surgery? If emergent, patient must go to OR regardless of cardiac risk. Perioperative optimization with beta blockers may be indicated Step 2: Has patient been revascularized in past 5 years? If patient has had PTCA or CABG in past 5 years and no change in symptoms, no further evaluation is necessary. Step 3: Has patient had coronary evaluation in past 2 years? If yes with favorable prognosis and no new symptoms, and intermediate or low risk procedure, no further evaluation is necessary. Step 4: Does patient have unstable heart disease? Step 5: Does patient have intermediate predictors of coronary risk? Consider functional capacity (see below) Clinical Features for Risk Stratification

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Functional capacity: MET = metabolic equivalent of O2 1 MET: ADLs, walk around block 4 METs: climb flight of stairs with load Risk class: High (worst prognosis): < 4 METs Intermediate: 4-6 METs Low: > 6 METs Predictors of Risk: Major (consider angiography or delay elective surgery): Recent MI (< 1 month) Unstable angina or severe angina (class III or IV) Decompensated CHF Significant arrhythmia (high degree AV block, symptomatic VT, SVT with uncontrolled ventricular rate) Severe Valvular disease especially obstructive lesions (AS, MS, HOCM and LVH ) as one cannot compensate with increase cardiac output Intermediate: Mild angina Previous MI or pathologic Q waves on EKG Compensated or previous CHF DM Renal Insufficiency Minor: Advanced age Abnormal EKG (LVH, LBBB, ST-T wave changes) Rhythm other than sinus Low functional capacity History of CVA Uncontrolled HTN Risk by type of surgery: High risk (>5% risk MI or death): Emergency procedures, particularly in the elderly Vascular (AAA, PVD) Prolonged procedures with large fluid shifts/blood loss (Whipple) Intermediate risk (<5% risk MI or death): CEA Head and neck Intraperitoneal/Intrathoracic Orthopedic Prostate Low risk (<1% risk MI or death): Cataract Breast Endoscopy Decision-Making If minor or intermediate predictors with moderate to excellent functional capacity and: Intermediate or low risk procedureOR without further testing

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High risk procedurepursue noninvasive testing If operation is not urgent and pt is felt to have significant risk as defined above, then it is prudent to first perform further cardiac testing (treadmill, angiography, etc.) Most hospitalized patients requiring surgery are in an urgent situation For example, delay in surgical repair of a hip fracture affects functional recovery and is optimally done within 48 hours of admission. Therefore, medically optimizing risk is preferred over further cardiac evaluation. Stress Testing Treadmill (85% sensitive): do not use if LBBB, WPW, paced rhythm, or other EKG abnormalities that will make it uninterpretable-use imaging (i.e. stress echocardiogram or adenosine Myoview in these cases) Positive stress test: > 1 mm ST depression horizontal or downsloping 2 boxes beyond J point in 2 consecutive leads > 2 mm ST depression rapidly upsloping 2 boxes beyond J point in 2 consecutive leads Any ST elevation necessitates urgent cardiac cath Hypotension or typical angina at low workload Contraindications to stress testing: Absolute: aortic dissection, critical AS Relative: left main disease, moderate AS Minimizing perioperative risk Perioperative beta-blockade: decreased mortality in patients receiving atenolol or bisoprolol before and after surgery during perioperative period-goal HR<60 Restart aspirin early postoperatively (or continue throughout perioperative period if bleeding risk is acceptable) Antibiotic prophylaxis if indicated (see Infectious Disease section) Minimizing long term risk: ensure initiation, reinitiation or continuation of CHAMP medications (ASA, beta blocker, ACE-I, statin) postoperatively in all patients with established CAD, CVD, PVD and/or diabetes unless contraindicated or intolerance exists.

CARDIOLOGY Revised Goldman Cardiac Risk Index (RCRI) Stratification Adapted from Auerbach A, Goldman L. Assessing and reducing cardiac risk of noncardiac surgery. Circulation. 2006;13:1361-1376.

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REVISED GOLDMAN CARDIAC RISK INDEX (RCRI) Patient is at risk if he or she has any one of the following: 1. High-risk surgical procedure: thoracic, abdominal, pelvic vascular (i.e. aorta, renal, mesenteric) 2. Ischemic heart disease: history of myocardial infarction, history of or current angina, use of sublingual nitroglycerin, positive exercise test, Q waves on ECG, patients who have undergone PTCA or CABG and who have chest pain presumed to be of ischemic origin 3. Heart failure: left ventricular failure by physical examination, history of paroxysmal nocturnal dyspnea, history of pulmonary edema, S3 or bilateral rales on physical examination, pulmonary edema on chest x-ray 4. Cerebrovascular disease: history of transient ischemic attack or history of cerebrovascular accident 5. Insulin-dependent diabetes mellitus 6. Chronic renal insufficiency with baseline creatinine 2.0 mg/dl

CARDIOLOGY DOSING OF COMMON CARDIOVASCULAR DRUGS Dose 6 mg rapid IV, may repeat with 12 mg rapid IV, 12 mg may be repeated once Arrest: 1 mg IV, may repeat q 3-5 min, max 0.04 mg/kg Bradycardia: 0.5 mg IV, may repeat q 3-5 min, max 0.04 mg/kg Bretylium Arrest: 5 mg/kg IV, Repeat in 5 min 10 mg/kg to total of 30 mg/kg Stable: 5-10 mg/kg over 10 min, may repeat in 10-30 min, max 30 mg/kg per 24h Diltiazem 0.25 mg/kg IV, may repeat in 5 min 0.35 mg/kg. Maintenance drip 5-15 mg/h Dobutamine 2-20 mcg/min IV (250 mg in 250 ml D5W or NS) Dopamine 2-20 mcg/kg/min IV (400 mg in 250 ml D5W or NS) Epinephrine* Arrest: 1 mg IV (10 cc 1:10,000) q3-5 min. May increase doses Bradycardia: 2-10 mcg/min (1mg in 500 ml NS) Anaphylaxis: 0.1 mg (I cc of 1:10,000) slow IV OR 0.3 mg (0.3 cc of 1:1,000) SQ Furosemide 0.5-1 mg/kg IV Isoproterenol 2-10 mcg/min titrate to heart rate; use with caution Lidocaine* Arrest: 1.5 mg/kg q 3-5 min, max 3 mg/kg Drip: 2-4 mg/min Magnesium Sulfate 1-2 g IV Morphine Sulfate 1-3 mg slow IV, may repeat to desired response Naloxone* 0.8-4 mg IV Nitroglycerin Sublingual: 0.4 mg SL, may repeat q 3-5 min Drip: 10-20 mcg/min (50 mg in 250 ml D5W), titrate to response, watch BP Nitroprusside 0.1-5 mcg/kg/min (50mg in 250 ml D5W), titrate to BP Norepinephrine 0.5-30 mcg/min IV, (4mg in 500cc D5W), titrate to BP Procainamide Arrest: 20-30 mg/min IV, max 17 mg/kg, watch QT interval Sodium Bicarbonate 1 mEq/Kg IV Verapamil 2.5-5 mg IV, may repeat 15-30 min 5-10 mg IV *Denotes medications that may be given by endotracheal tube. Dose should be 2-2.5 x IV dose Drug Adenosine Atropine*

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Months after transplant 0-1 2-3 >3 >6

GOAL IMMUNOSUPPRESSION LEVELS Tacrolimus 10-15 8-12 5-10 5-10

Cyclosporine 250-350 200-300 150-250 100-200

Cardiac transplant medications Tacrolimus=Prograf=FK506 Cellcept=Mycophenolate mofitil=MMF Rapamune=Sirolimus Cyclosporine=CSA (note, different brands of cyclosporine have different bioavailabilities; therefore use the same brand the patient gets as an outpatient.

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Cylex test=immune cell function (measures how much ATP a patients WBCs are using as a surrogate marker of level of immune function. Very immunosuppressed: <225 (i.e. patient at risk of infection) Goal immunosuppression: 270-300 depending on type of organ transplant. Poor immunosuppression: >525 (i.e. patient at risk of rejection)

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Visit http://www.endocrinology.med.ucla.edu/EndoSyst.htm for detailed endocrinology references. DIABETES MELLITUS Diagnosis of Diabetes Mellitus Symptoms of DM (polyuria, polydipsia, unexplained weight loss with glucosuria and ketonuria) plus a random plasma glucose > 200 mg/dL. (Whole blood values are lower by 10-15 mg/dL). Of note, symptoms are most commonly absent. Fasting plasma glucose > 126 mg/dL. Fasting value determined in the morning after absence of caloric intake at least 8 hours. OGTT (oral glucose tolerance test): Plasma glucose > 200 mg/dL at 2 hours during a 75g OGTT. The diagnosis of diabetes must be confirmed on a subsequent day by using any one of the three criteria above. Insulin Therapy Subcutaneous Standard IV insulin bolus Regular (Humulin/Novolin R) NPH (Humulin/Novolin N) Analogues Insulin lispro (Humalog) Insulin aspart (NovoLog) Insulin detemir (Levemir) Insulin glargine (Lantus) TYPES OF INSULIN Onset Immediate 30 min 1 hr 2 4 hr 5 15 min 5 15 min 3 4 hr 2 4 hr Peak Duration 2 3 hr 6 8 hr 12 16 hr 4 6 hr 4 6 hr 6 24 hr (dose dependent) 18 24 hr

20 30 min 2 4 hr 4 10 hr 1 -2 hr 30 90 min 6 8 hr None

Insulin sliding scale (check BG qAC and q.h.s. or q6hr if patient NPO) Remember to add long-acting insulin for more optimal BG control This may also be used to supplement standing pre-meal coverage used as an outpatient Blood Glucose 0-70 71-150 151-200 201-250 251-300 301-350 351-400 > 400 INSULIN SLIDING SCALE Regular Insulin SQ D50 amp IV, or orange juice, call HO No coverage 2 units 4 units 6 units 8 units 10 units 12 units, call HO

Basic mixed/split insulin regimen Step 1: Calculate the total insulin requirement in 24 hours = weight (kg) 0.5 A good start is 30 units, it is conservative to avoid hypoglycemia

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Step 2: Divide the total insulin requirement by 3: 2/3 of total requirement in AM, 1/3 in PM (need more insulin in AM since eating) Step 3: Divide the AM and PM doses by 3: 2/3 of the dose is NPH, 1/3 of the dose is regular (or Humalog or NovoLog) Doses of short-acting insulin can be further divided to provide pre-meal coverage May also estimate total daily insulin dose based on previous insulin sliding scale requirements Guidelines to starting insulin glargine (Lantus) Multiple methods are utilized to convert to long-acting insulin after insulin requirements stabilize Recommend giving 0.5-0.6 units/kg with 50% of dose as Lantus and 50% as nutritional dose divided qAC. Then titrate dose as needed. Guidelines to starting insulin drip (See Insulin Protocol Form) Inhaled insulin (Exubera) May be used for pre-prandial but not basal coverage. The onset of action is approximately 10-20 minutes. The duration of action is between that of the rapidly acting insulin analogues and that of regular human insulin. Dispensed in two doses: 1 mg = 3 units and 3 mg = 8 units Inhaled insulin should not be used in smokers or patients with underlying lung disease (including those with an FEV1 < 70%). Spirometry should be completed prior to initiation of medication and repeated at 6 months. The drug should be discontinued if FEV1 decreases by > 20% or > 500 ml from baseline. Perioperative insulin management Maintain BG 100-180 mg/dL to prevent dehydration/ketosis, promote wound healing, optimize leukocyte function, avoid hypoglycemia. Start 5 gm/hr glucose infusion (i.e. D5 NS + 20 mEq KCl @ 100 mL/h). Can start IV insulin (1 unit/h) and adjust for goal or, if surgery is minor and patients glucose is wellcontrolled, give 50% of usual SC insulin (if NPH) in the AM of surgery and supplement with regular insulin q4-6 hr to achieve goal. Diabetic Ketoacidosis (DKA) Pathogenesis: absolute/relative insulinopenia plus counter-regulatory hormones Diagnosis: hyperglycemia (>250), ketogenesis (+ serum and urine ketones), acidosis (pH < 7.3 or bicarbonate < 15). Of note, if the patient is severely dehydrated, ketones may be negative secondary to a shift to -hydroxybutyrate. Symptoms: polyuria, polydipsia, N/V, abdominal pain, tachypnea, obtundation, coma Physical Exam: profound dehydration, acetone breath, Kussmaul breathing Precipitants: infection, acute illness, MI, trauma, not taking insulin, pregnancy Labs: CBC, chemistry panel, glucose, serum/urine ketones, lactate, RUA, ABG, CXR, EKG, blood cultures, calculate anion gap Treatment Guidelines: st IV fluids: 1L normal saline in 1 hour, then assess volume status. May switch to NS when intravascular volume repleted, add dextrose to fluids when glucose < 250, need to replete 5-8 liters on average, watch fluid status closely. Insulin: give fluids in 1st hour, then give 0.1 units/kg bolus followed by 0.1 units/kg/hour, titrate to decrease glucose by 100 mg/dL/hour. Do not start insulin if the potassium is < 3.3! Potassium: usual deficit 3-5 mg/kg, add to fluids as 20 mEq/L until deficit repleted, following K levels closely, do not replete until serum K < 5.5, be careful if patient anuric.

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Potassium typically decreases rapidly with insulin, be careful! K 4-5, add 20 mEq/L to IVF; K 3-4, add 30-40 mEq/L to IVF. Adding K to NS yields a hypertonic solution, which will not help the patients hyperosmolality. If hemodynamically stable, add potassium (especially when using 30-40 mEq/L) to NS. Phosphorus: Replete if < 1, usual deficit is 1mmol/kg. Bicarbonate: only give if pH <7.0, if 6.9-7.0 give 44 mmol (1 amp). If <6.9, give 88 mmol (2 amps), dont give until potassium repletion has been initiated Look for and treat potential precipitants (i.e. infection, MI) Monitoring: hourly blood glucose for first several hours, then q2-4hrs, electrolytes (including Mg and Phos) q2hr until K/bicarb normalizing, then q4-6hrs, follow volume status closely, follow gap/pH/bicarb as index of treatment rather than ketones Hyperosmolar Nonketotic Coma (HONC) Pathogenesis: decreased insulin, increased stress hormones, usually precipitating event Characteristics: hyperglycemia, water deficit, hyperosmolarity, mental status changes Diagnosis: serum glucose > 600-800, Osm > 350, mental status changes, absent to low ketones, no acidosis Symptoms: polyuria, polydipsia, fatigue, weakness, lethargy, drowsiness, anorexia, mental status changes, seizures, aphasia, hemiplegia Precipitants: infection, CVA, pneumonia, MI, acute pancreatitis, drugs (phenytoin, diuretics, steroids, immunosuppressants) Physical Exam: orthostasis, tachycardia, tachypnea (shallow), fever, dry skin, myoclonus, hyperreflexia, positive Babinski sign, altered mental status/coma, sensory deficits, volume contraction, no Kussmaul breathing Labs: CBC, chemistry panel, glucose, serum/urine ketones, RUA, ABG, CXR, EKG, blood cultures Treatment: IV fluids: start with rapid repletion NS 2-3 liters, replete 1/2 estimated deficit within 6 hours (usual total deficit is 10 L), then change to NS. Given the large amount of fluid administered, very careful monitoring of fluid status is imperative. Insulin: titrate to decrease glucose 100 mg/dL/hour, use regimen described above for DKA, only give insulin after fluid deficit is starting to be repleted and potassium level normalized. Consider antibiotics if infection suspected

ENDOCRINOLOGY NON-INSULIN DIABETIC MEDICATIONS Hypoglycemia? Insulin secretagogue, Yes improves -cell function Mechanism of Action

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Class/Name Sulfonylureas [tolbutamide, chlorpropamide, tolazamide, acetohexamide, glipizide (Glucotrol), glyburide, glimepiride] Meglitinides [repaglinide (Prandin), nateglinide (Starlix)] Biguanides [metformin (Glucophage)] -Glucosidase Inhibitors [acarbose , miglitol (Glyset)] Thiazolidinediones [rosiglitazone (Avandia), pioglitazone (Actos)]

Caution Weight gain, hypoglycemia, caution if hepatic or renal dysfunction (may prolong duration)

Also insulin secretagogue, but fast onset and short duration of action Insulin sensitizer, decrease hepatic glucose output and increase peripheral glucose uptake and usage Inhibit GI tract enzymes which digest oligosaccharides, thus delaying glucose absorption Bind to nuclear receptorsperoxisome proliferator activated receptorsenhance expression of proteins that enhance cellular insulin action Main mechanism of action is the stimulation of glucosedependent insulin release from the pancreatic islet cells. Also reduces the secretion of glucagons. Function as incretin enhancers, inhibiting DPPIV, an enzyme that breaks down GLP-1.

Yes No

As above, must take before meal Lactic acidosis (esp. if renal, hepatic or cardiac dysfunction), Hold doses prior to IV contrast, GI disturbances common Flatulence, diarrhea. Warn patients they cant treat hypoglycemia via usual mechanisms Idiosyncratic hepatic failure, LDL levels, weight gain, fluid retention (caution in CHF)

No

No

GLP-1 Mimetics [exenatide (Byetta)]

No*

May slow gastric emptying and cause nausea. *Mild to moderate hypoglycemia may occur when given with sulfonylureas. *Hypoglycemia may occur when used with other agents

DPP IV Inhibitors [vildagliptin (Galvus), sitagliptin (Januvia)]

No*

ADRENAL INSUFFICIENCY Primary (Addisons Disease) Destruction of the adrenal cortex resulting in deficiency of cortisol and aldosterone. Etiology: Adrenal destruction Autoimmune adrenalitis Autoimmune polyglandular syndromes Tuberculosis

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Metastatic disease Infiltration from amyloidosis, hemochromatosis, etc. Infection (histoplasmosis, crypto, cocci, blastomycosis; not candida) Adrenal hemorrhage (Waterhouse-Friderichsen) Dysgenesis/hypoplasia Impaired steroidogenesis Accelerated cortisol metabolism (i.e. thyrotoxicosis) Drugs (phenytoin, barbiturates, and rifampin accelerate cortisol metabolism; ketoconazole, etomidate, and metyrapone impair steroidogenesis). Secondary Pituitary or hypothalamic disorder resulting in deficiency of cortisol without aldosterone deficiency. Etiology: Malignancy Pituitary surgery or irradiation Head trauma Lymphocytic hypophysitis Sarcoidosis Amyloidosis Histiocytosis X Empty sella syndrome Infections (TB, fungi, nocardia, actinomycosis) Drugs (Megace, progesterone, valproic acid, etc.) Also consider long-term glucocorticoid therapy if a patient has been on 7.5 mg daily of prednisone (or equivalent) for > 2-3 weeks (HPA axis may be suppressed for 8-12 months) Functional/Relative Adrenal Insufficiency Consider during sepsis or critical illness. High levels of inflammatory cytokines may inhibit cortisol synthesis and/or induce systemic or tissue-specific corticosteroid resistance. Clinical Manifestations Acute adrenal insufficiency can be lethal. Suspect in the setting of unexplained, pressor-resistant hypotension, abdominal pain, vomiting, high fever, confusion. Hyponatremia and hyperkalemia may or may not be present. Remember, in primary adrenal insufficiency, aldosterone deficiency causes both renal Na loss and impaired K excretion as well as H+ accumulation; in secondary deficiency, aldosterone is preserved. Therefore, hyponatremia is related to SIADH because cortisol deficiency causes ADH. Patients often have non-specific symptoms.

ADRENAL FUNCTION TESTING When is testing indicated? Signs and symptoms of adrenal dysfunction may be non-specific, therefore testing may be done based on the clinicians level of suspicion. Normal range of cortisol is 6-24 mcg/dl. In an ICU patient, normal values may be 25 mcg/dl. In some studies, baseline and post-ACTH serum cortisol < 23.7 mcg/dL predict responsiveness to exogenous steroids in septic shock. AM cortisol: Drawn before 9 am; a value 3 mcg/dl indicates adrenal insufficiency, and concentrations 18-20 mcg/dl rule it out. Intermediate values necessitate dynamic testing. ACTH measurement: helpful in primary adrenal insufficiency where ACTH > 100 pg/ml, even if the plasma cortisol is in the normal range. Normal ACTH values rule out primary but not mild secondary adrenal insufficiency

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Cosyntropin stimulation test: This test evaluates for both primary and secondary adrenal insufficiency. In recent onset or mild secondary insufficiency, results may be normal given the supraphysiologic dose used in this test. Measure baseline cortisol 250 mcg of cosyntropin (Cortrosyn) is given IV (inject and flush in) or IM, and plasma cortisol is measured 30-60 minutes later. Of note, new tests are in-process using lower doses of cosyntropin (i.e. 1 mcg) to improve sensitivity of testing. Adrenal insufficiency is ruled out if basal or post-stimulation cortisol is 18-20 mcg/dl (using higher cutoff minimizes underdiagnoses). Some also consider a rise 9 mcg/dl or doubling of baseline as normal. Metyrapone test: Metyrapone inhibits the conversion of 11-deoxycortisol (compound S) to cortisol (by 11-hydroxylase); the resultant drop in cortisol should stimulate the HPA axis. Metyrapone 3 gm (or 30 mg/kg) is given at midnight (with a snack, to minimize nausea) At 8 am the next day, cortisol, 11-deoxycortisol & ACTH are measured Normally, 11-deoxycortisol rises to 7 mcg/dl (simultaneous cortisol < 5-8 mcg/dl to insure adequate 11hydroxylase inhibition) and ACTH rises > 150 pg/ml. Note that phenobarbital and phenytoin increase metyrapone metabolic clearance. Screening for Cushings syndrome (adrenal hyperfunction): Best test is 24 hour urinary free cortisol; normally UFC is < 90 mcg/day. May also use overnight dexamethasone suppression test: 1 mg dexamethasone given at 11pm-12mid 8 am cortisol measured next day, normally will be < 5 mcg/dl. A value > 10 mcg/dl suggests Cushings syndrome. The above tests do not distinguish between causes of Cushings syndrome.

ADRENAL REPLACEMENT THERAPY Physiologic Replacement Hydrocortisone 30 mg (20 mg qAM, 10 mg qPM) OR Cortisone 37.5 mg (25 mg qAM, 12.5 mg qPM) OR prednisone 7.5 mg (5 mg qAM, 2.5 mg qPM) For primary adrenal insufficiency, add fludrocortisone in a single daily dose (0.05-0.2 mg with adjustments for BP, serum potassium, peripheral edema, and plasma renin activity). Emergency Therapy Immediate high-dose IV hydrocortisone 100 mg bolus followed by infusion of 100-200 mg over the next 24 hours or intermittent IV dosing at 100 mg q6-8 hours. This provides adequate mineralocorticoid action, so fludrocortisone should not be added until the patient is tapered to oral glucocorticoids or the cumulative dose of hydrocortisone is < 100 mg/day. Stress dose steroids is poorly defined but typically means at least 200-300 mg of hydrocortisone per day. If you are concerned about altering the outcome of cosyntropin stimulation testing, Decadron may be used. But, remember, Decadron does not provide the same mineralocorticoid effects as hydrocortisone. Other Considerations Regarding Corticosteroids in Shock Shock patients with cortisol increment 9 mcg/dl, after cosyntropin stimulation testing, had increased mortality in some but not all studies. Therefore, the benefit of corticosteroids in shock may be independent of adrenal insufficiency.

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It is recommended (Grade 1B) that IV corticosteroids be initiated in patients with septic shock immediately following completion of a high-dose ACTH stimulation test. Initiation of corticosteroids should not be delayed until test results are known. Consider discontinuation of corticosteroids in patients who have a maximum serum cortisol increase 9 mcg/dl following ACTH stimulation and no hemodynamic response to corticosteroid therapy. Response is typically defined as vasopressor withdrawal within 48 hours of starting corticosteroids (Grade 2B). Consider continuing corticosteroids at full doses for 7 days, regardless of the clinical response, if the maximum increase of serum cortisol is 9 mcg/dl after ACTH stimulation (Grade 2B).

ADRENAL INCIDENTALOMA Differential Diagnosis Cushings Syndrome Hyperaldosteronism Pheochromocytoma Adrenal adenoma or carcinoma Metastatic carcinoma Adrenal cyst Work-up 1 mg dexamethasone suppression test and measurement of plasma free metanephrine. If the patient is hypertensive, measure K and aldosterone/plasma renin activity ratio. Of note, a homogeneous mass with low attenuation value (< 10 HU) on CT is likely a benign adenoma. Management Surgery should be considered in all patients with functional adrenal cortical tumors that are clinically apparent. Data are insufficient to indicate the superiority of a surgical vs. non-surgical approach to manage patients with subclinical hyperfunctioning adrenal cortical adenomas. All patients with biochemical evidence of pheochromocytoma should undergo surgery. Masses < 4 cm are generally monitored. Masses between 4-6 cm need close follow-up. Masses > 6 cm require surgical removal. Masses that are stable on two imaging studies done at least 6 months apart and do not exhibit hormonal hypersecretion over 4 years may be followed on an as needed basis. PHEOCHROMOCYTOMA Rare tumors arising from chromaffin tissue. 90% occur in the adrenal medulla and the remainder are abdominal or thoracic. 10% are bilateral, 10% malignant. Clinical Signs and Symptoms - have sustained hypertension, though we commonly think of these patients as having paroxysmal symptoms. Hypertension is often refractory to routine management. Diagnosis Screen with 24 hour urine for metanephrines, VMA, and catecholamines. This test is very sensitive and specific if it is collected while the patient is symptomatic, resting, or off medications. Also consider testing for fractionated plasma free metanephrines as its sensitivity is 96-100%. If testing is inconclusive and clinical suspicion is high, check resting serum catecholamines. This test is finicky but, in general, > 1000 pg/ml is suggestive and > 2000 is diagnostic. Note that clonidine will decrease serum norepinephrine into normal range in essential hypertension, but not with pheochromocytoma.

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Localization Begin with a CT or MRI of the adrenal glands. If not apparent, scan more broadly. Metaiodobenzylguanidine (MIBG) scintigraphy may also be used. This test employs a norepinephrine analogue that concentrates in the adrenal glands and pheochromocytomas. Treatment Management is surgical with preoperative administration of phenoxybenzamine (alpha blockade) to control blood pressure. May also use propranolol as needed to control tachycardia.

THYROTOXICOSIS Symptoms: weight loss, heat intolerance, weakness/fatigue, palpitations, dyspnea, nervousness, hoarseness, hair loss, sandy sensation in eyes (Graves only), hyper-defecation, oligomenorrhea, anovulation. Physical Exam: hyperhidrosis, flushing, pelvic girdle/shoulder muscle weakness, tachycardia, atrial fibrillation (especially in elderly), possible thyromegaly (depending on etiology), tremor, hyperreflexia, alopecia, fine/silky hair, smooth skin, moist palms, proptosis & pretibial myxedema (only in Graves). Labs: free T4, T3 by dialysis, TSH, radioactive iodine uptake scan, consider anti-thyroid peroxidase (TPO) and anti-thyroglobulin (Tg) antibodies, ESR, thyroglobulin level Differential Diagnosis: Graves disease, subacute thyroiditis, toxic adenoma, toxic multinodular goiter, iatrogenic, surreptitious Treatment: Antithyroid drugs: propylthiouracil (100-200 mg p.o. q8hrs), methimazole (20 mg p.o. q12hrs) Iodine and iodine-containing compounds (use with above) Radioactive iodine Surgery THYROID STORM Cause: extreme thyrotoxicosis, usually with precipitating factor Characteristics: fever (T > 106F), mental status changes, tachycardia, arrhythmia, diaphoresis, CHF, agitation, delirium, psychosis, nausea/vomiting, diarrhea, jaundice, coma and hypotension late in course Diagnosis: clinical. Initiate treatment while awaiting thyroid function tests given the high associated morbidly and lag-time on the results of the testing. Precipitants: thyroid surgery, withdrawal of antithyroid medication, radio-iodine therapy, vigorous thyroid palpation, iodinated contrast dyes, infection, CVA, PE, labor, toxemia of pregnancy, DKA, stress, trauma Treatment: ICU admission Propylthiouracil (PTU): loading dose 600-1000 mg (can give PO or PR), followed by 200-1500 mg daily given as 200-250 mg q4hr Iodine: given as Lugol's solution (1 drop q6hrs) OR SSKI = potassium iodide (5 drops q6hrs) OR Telepaque 1-3 g/day (must give at least 1 hour after PTU) -blocker: give as propranolol 40-80 mg p.o. q 4-6 hours or 0.5 mg-1 mg IV OR esmolol 250-500 g/kg then 50-100 g/kg/min Hydrocortisone: 300 mg IV then 100 mg q8hrs with rapid taper as patient improves Tylenol: as antipyretic (do NOT give ASA) Intravenous fluids (may need to give up to 3-5 L/day) Panculture

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MYXEDEMA COMA Cause: inability to compensate for severe hypothyroidism Characteristics: altered mental status, thermoregulatory deficiency, precipitating event th Epidemiology: usually in 6 decade, 80% in women, 90% in wintertime Symptoms: altered mental status (including lethargy, psychosis, confusion, coma), dry/thick skin, bradycardia, bradykinesia, constipation, bladder distention, hypoglycemia, pitting edema, periorbital edema, generalized edema, hypothermia, muscle weakness, hypoventilation, hypotension, pleural/pericardial effusion, abdominal distention, frontal/occipital headache, ataxia, nystagmus, muscle spasms, seizures, decreased DTR Precipitants: UTI, pneumonia, flu, cold exposure, narcotics, sedatives, hospitalization, surgery, trauma, CVA, hypoglycemia, CO2 narcosis, drug overdose, diuretics Diagnosis: clinical, based on above, can send thyroid studies but treat first as mortality high Labs: T4, TSH, free T4, free T4 index, cortisol, CBC (r/o anemia), glucose (r/o hypoglycemia), chemistry series (r/o hyponatremia), blood/sputum/urine cultures, consider ABG (r/o CO2 retention) Treatment: ICU admission, cardiac monitoring, low threshold for intubation, NO heating blankets 300-800 mcg IV T4 or PO followed by daily doses 100 mcg Hydrocortisone 100 mg IV q8hrs must be given with thyroid hormone until coexisting adrenal insufficiency has been ruled out, as thyroid hormone cortisol metabolism and can precipitate adrenal crisis. Empiric antibiotics Intravenous fluids as indicated NON-THYROIDAL ILLNESS SYNDROME Definition: patterns of abnormalities in thyroid function tests observed in patients with severe illness (i.e. sepsis, trauma, malignancy, myocardial infarction), and those fasting or undergoing surgery. These lab abnormalities (i.e. T3, T4) often revert to normal if the patient recovers. Clinical features may take 2-3 weeks to develop and lab values are often suspect. Lab findings: TSH: normal or reduced (yet, these are inappropriately low for the observed T4). This may be because low TSH is the proximate cause of this disorder (therefore the pituitary or hypothalamic function is impaired in these patientssupported by the fact that testosterone, FSH and LH also drop in serious illness). Free T3: reduced Free T4: variable Given the elevated mortality risk, is thyroid replacement beneficial? The dogma in endocrinology has been that the decrease in thyroid hormone is a beneficial physiologic response and that it is difficult to advocate or even defend the treatment of NTI patients. But, there is also no definitive proof that treatment is disadvantageous. Treatment (if administered): Given the high mortality rate in patients with T4 < 4 g/dL and an absence of contraindications to replacement therapy, treatment may be initiated. The evidence is more uncertain in patients with cardiac decompensation or arrhythmias. T3 and T4 should be given together (50 g/day with 75 g/day over the first 3-4 days). Follow levels every 48 hours and adjust as needed to keep total T3 at low normal level (70-100 ng/dL). As patients recover, the ratio of T3:T4 replacement should shift toward increased T4 replacement. Further prospective studies are needed to determine the impact of thyroid replacement on mortality of critically ill patients.

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THYROID FUNCTION TESTS TBG: estrogen (supplements, OCP, pregnancy), Tamoxifen, Clofibrate, narcotics, hepatitis, biliary cirrhosis. TBG: androgens, glucocorticoids, nephrotic syndrome. Block peripheral conversion of T4T3: propranolol, glucocorticoids, propylthiouracil (PTU), methimazole. Block synthesis of new T4 and T3: lithium, iodine, PTU, methimazole, amiodarone. TSH (thyrotropin): Normal range 0.3-4.7 mIU/L Best marker of thyroid hypo- or hyperfunction, except in cases of pituitary disease. Total Thyroxine (T4): Normal range 5-11 g/dL Measures bound plus free T4. Since the majority (99.95%) of T4 is protein-bound, total T4 is affected by TBG concentrations and drugs/diseases affecting binding of T4 to TBG or TBG affinity for T4. In particular, elevated estrogens (OCP, pregnancy, etc.) lead to higher levels of TBG. Triiodothyronine (T3) Resin Uptake: Normal range 25-35% Measures unoccupied protein-binding sites for T4 or T3. Thyroid hormone binding ratio (THBR, normal range 0.8-1.15) is ratio of T3 resin uptake in patients serum to control serum. THBR is helpful in distinguishing hypothyroidism (THBR low) from non-thyroidal illness syndrome (THBR normal or high). UCLA lab now reports 1/THBR. Free T4 Index: Normal range 5-11 Total T4 multiplied by THBR (or divided by 1/THBR). Total T3: Normal range 75-175 ng/dL Measurement not indicated if hypothyroidism is suspected (will be normal in 20-30% of hypothyroid patients). In hyperthyroidism, T3 may increase disproportionately to T4 through augmented peripheral conversion as well as increased thyroidal secretion. Free T3 index: Normal range 75-175 Total T3 multiplied by THBR Free T4 by equilibrium dialysis: Normal range 0.7-2.2 ng/dL Most precise method since it measures free fraction directly. Heparin causes elevation of FT4 by dialysis. Free T3 by dialysis: Normal range 210-440 pg/dL Thyroglobulin Level: used in the management (not diagnosis) of thyroid cancer Reverse T3: Normal range 10-24 ng/dL Elevated in hyperthyroidism, low in hypothyroidism, and often elevated in non-thyroidal illness syndrome as well as with amiodarone use. In thyrotoxicosis, a ratio of total T3/T4 (ng/g) > 20 suggests Graves disease or toxic multinodular goiter; T3/T4 < 15 suggests thyroiditis (subacute, silent), iodine-induced, or exogenous thyrotoxicosis. Radioactive iodine uptake (RAIU):

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Patient should be on low iodine diet for 10 days before RAIU and scan. Use either 123I (short half-life, less radiation) or 131I. 24-hour uptake is normally 10-35%. Uptake correlates with level of thyroid hyperfunction or destruction. Particularly useful in differentiating Graves disease from thyroiditis. Thyroid ultrasound is useful to characterize presence of nodules and size of gland. Thyroid hormones influence on metabolism reflected in other lab tests: in hypothyroidism, cholesterol and CPK are elevated; in hyperthyroidism, they are decreased.

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ACUTE GI BLEED Classification Upper (above ligament of Treitz) Lower (below ligament) History Prior bleeds, diverticular disease, prior GI or aortic surgery, trauma, coagulopathy, medications (ASA, NSAIDs, anticoagulants, steroids, antiplatelet medications), liver disease, alcohol abuse, renal insufficiency, poor cardiac output, hypertension, hypotension, recreational drugs (cocaine, amphetamines), rectal foreign objects (sexual activity or used to disimpact), history of STDs Etiology Upper GI Bleeds (UGIB): Peptic ulcer disease (H. pylori or NSAIDs) Portal hypertensive gastropathy Varices Mallory-Weiss tear Erosive esophagitis (especially alcoholics) Vascular malformations Dieulafoys lesion (an abnormally large submucosal artery located in the proximal stomach) Neoplasm Note that gastritis is not a cause of bleeding (possibly occult blood loss but not acute bleeding) Lower GI Bleeds (LGIB): Diverticular disease Hemorrhoids Solitary rectal ulcer syndrome Ischemic colitis Infectious colitis Inflammatory bowel disease (IBD) Angiodysplasia Neoplastic disease NSAID ulcerations CMV ulcerations (immunosuppressed) Portal hypertensive colopathy and rectal varices (cirrhosis) Clinical Signs and Symptoms Suggestive of UGIB: nausea, vomiting, hematemesis, melena, epigastric pain, liver disease, EtOH abuse, NSAID use, peptic ulcer disease, syncope Suggestive of LGIB: hematochezia (BRBPR), diarrhea, diverticulosis, colon cancer Physical Exam Vital Signs: Tachycardia (at10 % volume loss) Orthostatics (at 20% volume loss) Hypotension (at 30% volume loss) Pallor, stigmata of liver disease, localized abdominal tenderness Rectal: Stool may appear bright red, maroon, black and tarry, or brown Look for evidence of hemorrhoids or fissures

GASTROENTEROLOGY No guaiac necessary if concern of acute bleed. Guaiac should be used for colon cancer screening and workup of iron deficient anemia of unclear etiology not for acute hemoglobin drops. 1 cc of blood loss will result in a positive guaiac; 50 cc of blood loss results in melena. Therefore if recent bleeding you will find it without a guaiac.

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Labs CBC, chemistry panel, coags, type and cross, liver function tests Consider that the patient initially may have a normal Hgb value due to hemoconcentration BUN disproportionately elevated from Cr suggests an upper GI source Management Access: 2 large bore IVs (14-18 gauge) Volume resuscitation with NS ICU management if orthostatic NG tube placement and lavage: Note the volume of NS needed to clear the lavage fluid of bright red blood. If you are unable to clear the lavage fluid of bright red blood, this implies a 40% mortality without intervention! Clear nonbilious lavage = 15% chance of bleeding beyond pylorus. Clear bilious = 5% chance of active bleeding Transfusion: keep Hgb > 9 (> 10 if cardiac disease) Serial Hgb q4hrs (anticipate a slight decline in values from hemodilution) Correct any coagulopathies (FFP if INR > 1.5; keep platelets > 50) Intubate patients at high risk for aspiration (i.e. active bleeding + AMS) especially cirrhotics Stop all anticoagulants and anti-platelet agents NPO except medications Do not give the patient sucralfate or antacids until after EGD, as they will interfere with the endoscopy Acid suppression: IV PPI drip if suspect PUD x 72 hours (pantoprazole 80 mg IV 1 then drip at 8 mg/hr 72 hours) PPI IV/PO b.i.d. in other UGI bleeds (pantoprazole 40 mg IV/PO b.i.d.) Octreotide: If strong suspicion for an ongoing variceal bleed/advanced liver disease Dose at 50 g IV bolus followed by 50 g/hr drip. GI consult urgently if there is evidence of active bleeding and hemodynamic instability. Reglan 10mg IV q6hrs until endoscopy in setting of UGI bleed st Colonoscopy prep: 1 choice for initial evaluation of LGIB For colon prep in setting of LGIB, GoLYTELY 800 cc/hour via NG tube. Start with 6 L but give as many liters until clear. Reglan 10mg IV 30min prior to and 2 hours after starting the prep. Do not do PO prep when trying to clear bleeding. Strict aspiration precautions. Radionuclide imaging: detects bleeding at 0.1 to 0.5 ml/min Angiography: For faster bleeds 1.0 to 1.5 ml /min A positive angiogram is associated with high likelihood of requiring surgical intervention Comments: First consideration is ABCs. Secure airway (intubate if necessary). Achieve hemodynamic stability. Resuscitation is the most important treatment Endoscopy/Colonoscopy after blood and fluid resuscitation, ICU stabilization, and correction of coagulopathy and administration of IV PPI or octreotide gtt if indicated.

GASTROENTEROLOGY Admit patients with multiple comorbidities, orthostatic vitals that cannot be corrected quickly with IV fluids, and advanced age to ICU as they have a higher mortality rate. Approximately 70-80% of all GI bleeds stop spontaneously. Pepto-Bismol, iron, and spinach can turn stools black!

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NASOGASTRIC LAVAGE Get NG tube, chucks, 30 cc cath tip syringe, cup of water, straw, Surgilube, tape strips and normal saline. Sit the patient up as straight as possible. Determine the length of tube that is needed. Measure from the patients naveleartip of nose. Lubricate distal end of the tube. Put the NG tube straight posteriorly into patient's nose. Ask the patient to swallow (sip the water) as you slowly push the NG tube. Gagging or vomiting suggests going down the esophagus. Coughing suggests going down the tracheapull back. Push until you reach predetermined line. Push 30 cc of air from syringe through tube and listen to the area over the stomach with your stethoscope for gurgling. Tape the NG tube to the patients nose. Try sucking back with the syringe. If there is no fluid returned or if there is a question about proper placement, consider CXR to verify proper placement. Lavage stomach with normal saline. Note the presence of blood or coffee grounds. If present, lavage until clear and take note how much fluid required to clear the blood. Note if bile-tinged fluid is detected (indicates you are sampling contents of early duodenum as well) If the coffee grounds clear or if the lavage was completely clear, the NG tube can usually be pulled out. NG tube should be left in place if any suspicion of LGI bleeding in order to prep the patient. If NG tube is to be left in place, check a CXR to confirm proper placement. ABDOMINAL PAIN Initial Considerations Rule out the presence of the surgical abdomen as this can kill the patient quickly. Make sure that the patient is hemodynamically stable. History Timing: acute versus chronic, gradual versus sudden Location: localized versus referred pain Quality: sharp, dull, tearing, burning, boring; has the quality changed over time? Prior episodes of similar pain, relationship to menstrual cycles Associated symptoms such as nausea, vomiting, fever, diarrhea, etc. Previous intra-abdominal procedures (appendectomy, cholecystectomy, laparoscopies) Last bowel movement - time and quality (soft, hard) Exacerbating or relieving factors (such as food, BMs, deep breath, positional etc.) Presence fresh blood (hematochezia) vs old blood (melena) Differential by location of pain: RUQ: hepatitis, hepatic abscess, perihepatitis, cholecystitis, cholangitis, choledocholithiasis, intestinal obstruction. RLQ: appendicitis, ovarian torsion or ruptured cyst or CA, Crohns disease of terminal ileum. LUQ: splenic rupture, PUD, infarct or abscess, intestinal obstruction. LLQ: diverticulitis, ischemic colitis, ovarian etiologies, Ulcerative Colitis. Epigastrium: MI, pericarditis, aortic dissection, AAA, pneumonia, pleurisy, subphrenic abscess, GERD, PUD, pancreatitis, pyelonephritis, renal colic.

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Hypogastrium: renal colic, psoas abscess, intestinal infection or obstruction, IBD, ovarian causes, ectopic pregnancy, salpingitis, endometriosis, cystitis, distended bladder. Generalized: appendicitis, intestinal obstruction or infection, IBD, peritonitis, DKA, sickle cell crisis, acute intermittent porphyria, acute adrenocortical insufficiency. Physical Exam Focus on any signs of an MI as angina may present as epigastric pain Check for localized tenderness, rebound, guarding, bowel sounds Stool guaiac Any woman who complains of lower abdominal/pelvic pain should get a pelvic examination Murphy sign: pain on palpation of the right subcostal area during inspirationcholecystitis Psoas or obturator sign: passive extension of the thigh with knees extended appendicitis Rectal exam (unless contraindicated by neutropenia) Carnett test: used to distinguish intraabdominal pain from abdominal wall pain Press in the location of the pain and have patient do a sit-up. If the pain worsens with the situpabdominal wall pain. Pain out of proportion to abdominal exam suggestive of mesenteric ischemia Immunosuppressed may have benign exam despite surgical abdomen Labs CBC, chemistry panel, liver function tests, amylase and lipase, lactate, coags Clot for type and cross (if surgical abdomen or blood in stool) Urinalysis and urine pregnancy test In a patient with ascites, a paracentesis must be done to rule out SBP Radiology Abdominal series: rule out the presence of free air under the diaphragm, obstruction, volvulus, sentinel loop, toxic megacolon (> 7 cm in midtransverse colon diameter), pleural effusion (pleurisy, pancreatitis if effusion is left-sided), etc. Ultrasound: to investigate hepatobiliary pathology if RUQ pain CT abdomen/pelvis: to rule out diverticular disease, appendicitis, colitis Other studies will depend on the patients specific situation Treatment If there is potential for a surgical abdomen, request a surgical consultation. Keep NPO. Consider IV hydration. Type and cross for PRBC. Watch for septic/hypovolemic shock. Hang appropriate antibiotics early if theres suspicion for ascending cholangitis, diverticulitis, sepsis, etc. Try a GI cocktail (30 cc of Mylanta or Maalox + 10 cc of viscous lidocaine 10 cc of Donnatal) if dyspepsia is a possibility

ACUTE PANCREATITIS Goal Rest the pancreas and support as necessary. Etiologies Alcohol Gallstones Blunt trauma Hypertriglyceridemia Hypercalcemia Medications: pentamidine, azathioprine, 6-mercaptopurine, thiazide diuretics, sulfonamides, valproic acid, estrogens, tetracyclines

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Infections: mumps, CMV, HIV, E. coli Scorpion sting Mechanical: post-ERCP, sphincter of Oddi dysfunction, pancreatic divisum, malignancy, perforated peptic ulcer Miscellaneous: cystic fibrosis, genetic mutations Clinical Signs and Symptoms Constant, epigastric tenderness radiation to back, nausea/vomiting, relief with bending forward Physical Exam Hypovolemia, abdominal tenderness, guarding, decreased bowel sounds, signs of retroperitoneal hemorrhage (Cullens and Turners signs) Diagnosis Labs: amylase, lipase, liver function tests, calcium, chemistry panel, C-reactive protein Amylase is a sensitive diagnostic method if patient presents within hours of the onset of pain. Returns to normal faster than lipase. Nonpancreatic sources of amylase include salivary glands, lung CA, ovaries, fallopian tubes. Amylase levels tend not to be as high in alcoholic pancreatitis as in nonalcoholic forms. Lipase is a more sensitive and specific test. It is made only in the pancreas and stomach. Nonpancreatic elevation may be seen if the bowels are inflamed and the lipase is reabsorbed after being properly secreted from the pancreas. Note that renal insufficiency and inflammation/perforation of small bowel can lead to elevated amylase/lipase levels without active pancreatitis. Increase in ALT to 3 the baseline points more to gallstone-induced pancreatitis. Degree of amylase and lipase elevation does not correlate with severity. Imaging: Ultrasound is the most sensitive way of evaluating the biliary tract in acute pancreatitis Contrast-enhanced CT (p.o. and IV) with pancreatic protocol is used to diagnose as well as to determine potential complications. Indicated for those patients who are clinically deteriorating or have severe pancreatitis (necrosis may not be apparent for first 2-3 days) MRCP can also be used to exclude choledocholithiasis Management IV hydration NPO until symptomatically improved (pain-free, hungry) Repletion of electrolytes NGT to suction only if protracted nausea and vomiting to prevent aspiration not to help pancreas as previously believed Treat infections if clinically suspected Pain control: meperidine (morphine in theory causes spasm of sphincter of Oddi; no evidence in humans and most feel clinically safe) Patients with gallstone-induced pancreatitis who develop cholangitis require urgent ERCP Complications Acute fluid collection, pseudocyst, necrosis, Infection, abscesses, ARDS, renal failure, sepsis Prognosis Outcomes depend on whether disease is interstitial versus necrotizing Interstitial mortality rate < 1% Necrotizing (defined as necrosis of 30% of the gland seen on CT) mortality rate 10-30% mortality risk with a 70% complication risk

GASTROENTEROLOGY Scoring systems: Ranson, Glasgow, Apache II (none are completely accurate) RANSONS CRITERIA FOR ACUTE PANCREATITIS Non-gallstone Gallstone On Admission Age > 55 years Age > 70 years WBC > 16,000/mm3 WBC > 18,000/mm3 Glucose > 200 mg/dl Glucose > 220 mg/dl LDH > 350 IU/L LDH > 400 IU/L AST > 250 IU/L AST > 250 IU/L Within 48 Hours Hematocrit > 10% Hematocrit > 10% BUN > 5 mg/dl BUN > 2 mg/dl Serum calcium < 8 mg/dl Serum calcium < 8 mg/dl Base deficit > 4 mEq/L Base deficit > 5 mEq/L Fluid deficit > 6 L Fluid deficit > 4 L PO2 < 60 mmHg Mortality Risk < 3 risk factors 1% mortality 4 risk factors 15% mortality 5-6 risk factors 40% mortality >7 risk factors 100% mortality SMALL BOWEL OBSTRUCTION Consider the possibility that the patient is having strangulation of the bowels vs a simple mechanical obstruction. History Symptoms: crampy abdominal pain, decreased or absent flatus and stool, nausea and vomiting. Prior episodes, intra-abdominal surgeries, adhesions and hernias History of Crohn's disease? If positive, ask about recent meals. Impaction of undigested foods can often cause obstruction in a strictured area. Previous radiation exposure? History of ovarian cancer Physical Evidence of hypovolemia? Abdominal distention: the lower the obstruction, the greater the degree of distention. High pitched tinkling bowel sound Hernias and surgical scars? Labs CBC and a chemistry panel. The presence of marked leukocytosis suggests strangulation or ischemia. Radiology Abdominal series to rule out the presence of free air under the diaphragm, air-fluid levels, and possible volvulus. Consider getting a CT scan with contrast to attempt to localize the site of transition. Look for evidence of strangulation!

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GASTROENTEROLOGY Treatment Correct the hypovolemia and electrolyte abnormalities Make the patient NPO Insert an NG tube and place on intermittent suction for decompression and symptom relief Surgery consult

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ACUTE NAUSEA General Medications (see table of Antiemetic Agents for Chemotherapy Patients in Hem/Onc section) Prochlorperazine (Compazine) 5-10 mg PO/IV/IM t.i.d. Selectively antagonizes dopamine D2 receptors Side effects include urinary retention, hypotension, spastic torticollis, dystonia (treat with Benadryl), cytopenias, and QT prolongation Metoclopramide (Reglan) 10 mg PO/IV q6hrs Antagonizes central and peripheral dopamine receptors Side effects include extrapyramidal symptoms, urinary frequency, cytopenias, SVT, HTN, sedation. Promethazine (Phenergan) 12.5-25 mg PO/IM/PR q6hrs (antihistaminewill also produce sedation) Antagonizes central and peripheral H1 receptors (non-selective antihistamine) Side effects include sedation, cytopenias, urinary retention. Lorazepam (Ativan) 0.5-2 mg IV/PO q4-6hrs Benzodiazepine Side effects include delirium in the elderly, sedation, hypotension. Droperidol (Inapsine) 0.625-2.5 mg IV/SQ Antagonizes dopamine and -adrenergic receptors Side effects include sedation, delirium in the elderly, and prolonged QT interval Chemotherapy-induced: consider using serotonin antagonists, such as ondansetron or granisetron (will need Heme/Onc consult approval). Fluid hydration If the patient cannot tolerate orals, consider making patient NPO and starting IV hydration. Radiology If an obstruction is a possible etiology, order an abdominal series x-ray. If there is evidence of an obstruction or ileus, place an NG Tube to help decompress the abdomen. Resolution As the symptoms resolve, slowly advance the diet from clears to pureed to soft mechanical to regular. Always ensure that the patient is adequately hydrated and that electrolytes are repleted. CONSTIPATION General Concepts Make sure there is no impaction or obstruction Do rectal exam and KUB before starting medical therapy Do not give agents with magnesium to renal failure patients Make sure to start bowel regimen for patients on narcotics or who are bed-bound ALWAYS MOVE FROM BELOW FIRST! Treatment Diet: increase both total fiber and water intake. Psyllium 1 tsp daily-t.i.d. is a common 1st choice. If the patient is bed-bound and/or not drinking sufficient water, fiber can make the constipation worse. Laxatives: separated into 4 groups according to their mechanism of action Emollients (stool softeners): mineral oil and docusate salts (Colace).

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Note: Mineral oil causes lipoid pneumonia if aspirated and decreases the absorption of fat-soluble vitamins if given with meals. Hyperosmolar agents: polyethylene glycol (MiraLax), lactulose, sorbitol, and glycerol. Both lactulose and sorbitol are very effective and are highly recommended for use in chronic constipation if fiber and fluid supplementation do not work alone. Saline Laxatives: Magnesium sulfate, phosphate, and citrate Should not be used in patients with renal insufficiency because of magnesium toxicity. This is usually not a good long-term option in the elderly Stimulant Laxatives: castor oil, senna (Senokot), bisacodyl (Dulcolax) Not recommended for long-term use. Dulcolax is a gastric irritant. Tablets are enteric coated and should not be broken or chewed. Prokinetic: misoprostol increases gut motility (sometimes used in patients on opiates) Enemas: can be used episodically for "salvage" therapy if an alternative bowel program has not produced a BM. Don't use Fleet's enemas in patients with renal insufficiency because of retention of phosphateuse tap water enemas instead. Suppositories: Both glycerin and bisacodyl (Dulcolax) can be used. However, they can be associated with cramping. They can also be used for "salvage" therapy.

ACUTE DIARRHEA History Acute diarrhea usually has an infectious etiology (viral, bacterial, parasitic), but the pace of certain infections tends to vary among the different organisms. Food exposure: diarrhea may occur between 12 hours and 10 days after ingestion of the offending meal. Appearance of the stool: blood (inflammatory or invasive ulceration), mucus (IBS), or oil (malabsorption). Volume: small (left colon or rectum), large (small bowel or proximal colon). Urgency and tenesmus: inflammation of the colon. Nocturnal diarrhea: suggests infectious or inflammatory etiology, not IBS. Medications: antibiotics, alcohol, illicit drugs, laxatives, magnesium-containing antacids, digoxin, quinidine, colchicine. Diet: caffeine intake, dietary foods with poorly absorbed sugars (sorbitol or mannitol), fiber, dairy products, gluten Social history: travel, sexual preference, occupation, living situation History of gastrectomy, vagotomy, intestinal resection (short gut syndrome). Risk factors for intestinal ischemia: hypertension, DM, chronic a-fib related emboli, hypercholesterolemia, etc. Post-obstructive diarrhea. Immunocompromised hosts: in addition to more common pathogens, consider CMV, MAI, Cryptosporidium, Cyclospora, Isospora, Entamoeba histolytica, etc. Physical Exam Check for fever, hypovolemia, surgical abdomen. Evaluation Most episodes are self-resolving with OTC medications and dietary modifications. Medical attention and treatment is indicated only for patients with moderate or severe illness: Severe diarrhea with dehydration Dysentery (passage of bloody or mucoid stools) Temperature > 38.5C Passage of > 6 unformed stools per day.

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Duration of diarrhea of 48 hours or longer. Diarrhea with severe abdominal pain in a patient > 50 years old (consider mesenteric ischemia and intraabdominal abscess) In patients with the red flag symptoms, consider sending: Stools for markers of inflammation (leukocytes, guaiac) Bacterial cultures Assays for E. coli O157:H7 (in patients with hemolysis, uremia, or exposure to undercooked meat or raw vegetables) Ovocytes and Parasites (O&P) (in patients who have traveled recently) C. difficile toxin (in patients with recent institutionalization and/or antibiotic or chemotherapy exposure) Note that every lab is different in the panel they run when you ask for stool culture. Depending on the history, you may want to specify organisms like Campylobacter, microsporidia, Isospora, and cryptosporidia. Also consider Giardia antigen. Send 3 fresh samples for the cultures and toxin assays. Management Treat hypovolemia and electrolyte abnormalities. IV therapy can be used for severe illness, but oral rehydration fluids that contain K, Na, and glucose can be used for milder cases. Withhold milk and other dairy products for 24-48 hours and initiate refeeding with cereals, starches, soups, and broth. Don't treat potentially infectious causes of diarrhea with antimotility agents (i.e. opioids, Imodium, Lomotil), until stool studies come back negative. Consider stopping any new medications. Treat non-specifically with bulking agents such as Kaopectate, but do not stop bowel motility. Once the specific diagnosis is made for the cause of the diarrhea, treat with the appropriate medication. If an infectious etiology is ruled out, consider using Imodium or Lomotil. Consider using cholestyramine in post-cholecystectomy patients. Many physicians advise avoidance of lactose-containing foods during and immediately following a diarrheal illness. Consider octreotide in patients with dumping syndrome and chemotherapy-induced diarrhea if other treatments have failed. The initial dose is 50-100 g SC q8hrs. The dose should be escalated gradually every 48 hours until symptoms are under control or a maximum dose of 500 g q8hrs has been reached.

HELICOBACTER PYLORI Diagnosis Recommendations for testing: Presence of active peptic ulcer disease or a history of a documented peptic ulcer or gastric MALT lymphoma Non-endoscopic studies are preferred for initial diagnosis Commonly used tests: H. pylori antibody titer by ELISA is 90% sensitive, but cannot distinguish current from past infection. The antibody test can remain positive after eradication, so dont order to confirm successful treatment! Urea breath test (discontinue PPI, antibiotics, and bismuth at least 1 week prior to the test) Sensitivity 88-95% Specificity 95-100% H. pylori stool antigen Sensitivity 94%

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Specificity 86-92% Invasive test options: histology (from biopsy), culture. Treatment Controversial but most recent consensus recommends treatment for those patients with documented PUD irrespective of symptom severity, confounding factors, whether the episode is the initial or recurrent or whether ulcer is active or in remission. Combination regimen: PPI + clarithromycin + amoxicillin 1-2 weeks May substitute amoxicillin with metronidazole if penicillin allergic (500 mg p.o. b.i.d.) Perform post-treatment confirmation test (urea breath test) only if patient has severe symptomatic ulcer, complicated ulcer (bleeding, perforation), or recurrent symptoms. Wait at least 4 weeks post-treatment before repeating the test. Patients with ongoing symptoms or active ulcer should stay on PPI for 2-4 weeks after triple therapy has completed. REGIMENS FOR TREATMENT OF H. PYLORI INFECTION Regimen Dosing Eradication Rate Lansoprazole 30 mg b.i.d. 86-92% LAC (Prevpac) 10-14 days Amoxicillin 1 gm b.i.d. Clarithromycin 500 mg b.i.d. Bismuth subsalicylate 524 mg q.i.d. 77-82% BMT 2 weeks Metronidazole 250 mg q.i.d. Tetracycline 500 mg q.i.d.

ABDOMINAL RADIOGRAPHY Abdominal Series Systematically look at the different parts: Bones Bowel Gas Pattern Soft tissues: psoas, liver edge, occasionally the spleen, may see the kidneys check for extraluminal gas (i.e. free air under the diaphragm). other soft tissue masses Significant findings/possible diagnoses: SBO: see multiple air-fluid levels Gallstone ileus: see air in the biliary tree Hernia: see bowel extending beyond inguinal line String of pearls: bowels filled with fluid; high degree of obstruction; very little air Gasless abdomen: either esophageal obstruction and nothing going through or marked obstruction because the loops are filled with fluid. Colitis: often do not see haustra. In long-standing UC, see a "lead pipe" (no haustra) image of the sigmoid/descending colon. Obstruction versus ileus: clues suggestive of obstruction include asymmetric dilation of bowel, no air in the cecum/rectum, a definite point of transition, alternating levels of air-fluid. RUQ Ultrasound In general, this test is the most sensitive in investigating hepatobiliary pathology. Abdominal CT Order this test when you are looking for masses.

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ASCITES Adapted in part from Jaffe DL, Chung RT, Friedman LS. Management of portal hypertension and its complications. Med Clin North Am. 1996;80:1021-1034. Pathophysiology Stimulation of rennin-angiotensin-aldosterone systemrenal Na and water retention Pressure in hepatic sinusoids and splanchnic vessels Clinical Signs and Symptoms Medium/large volume ascites can be detected on physical exam generally by a distended abdomen, shifting dullness or a fluid wave Workup New onset: needs diagnostic paracentesis to determine cause (even if admitted for other reason) If you suspect ascites but none is apparent on physical exam, get an abdominal ultrasound to detect fluid and mark ascites for paracentesis Looking for infected ascites is part of the workup in a patient with cirrhosis and fever/leukocytosis/altered mental status. Send ascitic fluid for: Cell count and differential Albumin (also send serum albumin) Protein <1g/dL increases risk of SBP Bacterial culture Others: LDH, glucose, amylase, cytology, AFB Etiologies Classification by serum ascites albumin gradient >95% accuracy SAAG = Serum Albumin Ascites Albumin ETIOLOGY OF ASCITES BASED ON SAAG High Gradient 1.1 g/dl Low Gradient < 1.1 g/dl Cirrhosis Nephrotic syndrome Alcoholic hepatitis Peritoneal carcinomatosis Cardiac ascites Pancreatic ascites Fulminant hepatic failure Tuberculous peritonitis Budd-Chiari syndrome Biliary ascites Massive hepatic metastases Collagen vascular disease serositis Veno-occlusive disease Portal vein thrombosis Myxedema Fatty liver of pregnancy Treatment Initial: Dietary salt restriction Spironolactone 100 mg daily + furosemide 40mg daily In this proportion as long as renal function is preserved

HEPATOLOGY Fluid restriction only if hyponatremic (Na < 120-125 mEq/L) Refractory ascites: Serial large-volume paracentesis or transjugular intrahepatic portosystemic shunt (TIPS)

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PARACENTESIS Indications for Diagnostic Paracentesis New onset ascites Patients with ascites and fever, leukocytosis or other signs/symptoms of infection Patients with cirrhosis who have ascites at the time of hospitalization Patients with cirrhosis and ascites who have worsening of their clinical condition or deterioration in laboratory parameters (i.e. acidosis, azotemia) Indications for Therapeutic Paracentesis Tense ascites Respiratory distress Procedure Paracentesis can be performed via the RLQ, LLQ or the midline approach. Make sure the bladder is empty if doing the midline approach. Make sure to percuss the area before doing the procedure. If minimal ascites present, have radiology do an ultrasound and mark the fluid or do an ultrasound guided paracentesis. Alternative to thoracentesis tray (we do not have paracentesis trays): 1% lidocaine 18 gauge needle 2, 25 gauge needle 1, 5 cc syringe 1, 30 cc syringe 2 Chlorhexidine prep sponges 3 (or Betadine swabs) 4x4 gauze Culture bottles Lavender and red top tubes Vacuum bottles Male-male tubing for therapeutic tap (some people prefer using an Angiocath instead of a regular needle when doing a large volume tap) Get help from your resident if you are not comfortable with the procedure (This rule applies to ALL procedures!) Explain the procedure including risks to the patient and get informed consent. Make sure the unit secretary makes the correct lab requisition for the tests. Dont leave the patient unattended while doing a large volume tap (i.e. while the needle or Angiocath is still in the peritoneal cavity) Make sure to follow-up on the ascitic fluid lab results, especially the cell count as you may need to start antibiotics (see SBP section) SPONTANEOUS BACTERIAL PERITONITIS (SBP) Adapted in part from Guarner C, Soriano G. Spontaneous Bacterial Peritonitis. Seminars in Liver Disease. 1997;17:203-217. Definition Bacterial infection of ascitic fluid: PMN count 250 cells/mm3 OR ascitic fluid WBC 500 cells/mm3 with a positive fluid culture Culture-negative neutrocytic ascites: PMN count 250 cells/mm3 with a negative fluid culture (subtract 1 PMH for every 250 RBCs) One should rule out previous treatment with antibiotics, TB, pancreatitis, etc.

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Pathogens Common organisms are E. coli , Klebsiella pneumoniae, Enterobacteriaceae, Streptococcus pneumoniae, and Enterococcus. Cirrhotic patients can also get secondary bacterial peritonitis, which usually requires surgical intervention. One should suspect secondary peritonitis with perforation if the ascitic fluid meets 2 or more of the following: Total WBC >10,000 Total protein > 1 g/dl Glucose < 50 mg/dl LDH > 225 milliunits/ml (or higher than upper normal for serum) Multiple organisms cultured Failure to improve after 48 hours of standard therapy Risk Factors Severe liver disease GI hemorrhage Prior SBP Ascitic fluid protein 1 g/dl Clinical Signs and Symptoms Fever, abdominal pain, hepatic encephalopathy, vomiting, diarrhea Diagnosis Abdominal paracentesis Send fluid for cell count and differential and send fluid directly in the culture bottles Treatment Start antibiotic therapy as soon as the diagnosis of SBP is made based on fluid PMN count OR earlier if clinically indicated Third generation cephalosporin (ceftriaxone OR cefotaxime) HIGH dose 2gm/day. IV albumin 1.5 g/kg on admission and 1 g/kg 48 hours later has been shown in one study to improve the probability of survival by preventing hepatorenal syndrome (which occurs in up to 30% of patients with SBP). This study was open-labeled trial with a total of 126 patients, and the dose of albumin used is empirical, and a lower dose may be just as efficacious. (NEJM 1999;341:403-409 and NEJM 2004;350:1646-1654) Consider IV albumin in patients with a serum creatinine > 1 mg/dl OR a total bilirubin > 4 mg/dl. (Diagnosis, prevention, and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007;preprint) Prevention Long term prophylaxis indicated for patient with prior SBP episode with 1st line Cipro 750mg PO weekly or 2nd line TMP/SMX DS 5x week. In patients with cirrhosis who are hospitalized with GI bleeding, initiate IV antibiotics with transition to norfloxacin 400 mg qday or TMP/SMX DS for 7 days once patients are stable and tolerating orals. In patients with cirrhosis hospitalized for other reasons and whose ascitic total protein is <1, start norfloxacin or TMP/SMX just during hospitalization

HEPATIC ENCEPHALOPATHY Adapted in part from Jaffe DL, Chung RT, Friedman LS. Management of portal hypertension and its complications. Med Clin North Am. 1996;80:1021-1034. Consider the diagnosis in any patient with clinical or laboratory evidence of liver disease and altered mental status. Can present as insomnia, seizures, delirium and coma and occurs in patients with cirrhosis, portal hypertension, and portosystemic collaterals.

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Usually patients have asterixis on physical exam (also seen in other conditions) and have an elevated serum ammonia level. Precipitating factors GI bleeding, infection, increased dietary protein intake, azotemia, constipation, sedative/analgesics/tranquilizers, volume depletion, hypoglycemia. Treatment Correcting the precipitating cause Lactulose (start with 30 cc t.i.d. and titrate to 3-4 soft bowel movements per day) Can be used as second-line agents: rifaximin (a nonabsorbable derivative of rifampin) to decrease the colonic concentration of ammoniagenic bacteria Of note, rifaximin may be as effective and better tolerated than lactulose, though it is not FDAapproved for hepatic encephalopathy Dietary protein restriction (0.8g/kg/day) but no definitive data.

ABNORMAL LIVER FUNCTION TESTS Adapted in part from MKSAP 14 and The Washington Manual Liver Tests Aminotransferases (AST, ALT): ALT (SGPT) is more specific for the liver AST (SGOT) can be derived from the liver, heart or skeletal muscle High levels of AST and ALT (about 10 normal) usually indicate acute hepatocellular injury In alcoholic liver disease, AST and ALT are generally modestly elevated (about 5-6 normal) and the AST/ALT ratio is around 2 Alkaline phosphatase: derived from liver, intestine, bone, kidney, and placenta. GGPT, 5-nucleotidase are more liver specific enzymes Alkaline phosphatase is increased in biliary obstruction, cholestasis, and space occupying lesions Albumin and prothrombin time: markers of synthetic function Bilirubin: marker of clearance Patterns of Liver Injury Hepatocellular: aminotransferases + alkaline phosphatase bilirubin Viral, autoimmune, or drug-induced hepatitis, ischemic, toxic, hereditary, nonalcoholic steatohepatitis (NASH) Cholestasis: alkaline phosphatase + bilirubin aminotransferases Hepatocellular dysfunction: Biliary epithelial damage from hepatitis, cirrhosis Intrahepatic cholestasis from medications, sepsis, primary biliary cirrhosis, CHF Biliary obstruction Isolated Hyperbilirubinemia: Conjugated: impaired excretion (hepatocellular injury, Dubin-Johnson) Unconjugated: overproduction (hemolysis) or impaired conjugation (Gilberts, Crigler-Najjar) Infiltrative: alkaline phosphatase bilirubin or aminotransferases Malignancy, granulomas, abscess Mnemonic for Differential Diagnosis for Abnormal LFTs Autoimmune hepatitis/Hepatitis A Hepatitis B Hepatitis C Drugs/Medications: acetaminophen, NSAIDs, antibiotics, statins, anti-epileptics, anti-TB.

HEPATOLOGY EtOH Fatty Liver/Nonalcoholic steatohepatitis Granulomatous Hemochromatosis/Wilsons/1-antitrypsin deficiency Hepatitis A Fecal/oral Blood HEPATITIS SEROLOGIES Hepatitis B Hepatitis C Blood Blood Sexual Sexual (rare) Perinatal Perinatal (rare) 1-6 2 weeks-6 months months HBsAg Tests may be negative Anti-HBc IgM Anti-HCV Ab HCV RNA HBsAg Anti-HBc total Anti-HCV Ab HCV RNA RIBA II Anti-HCV Ab RIBA II N/A Hepatitis D* Blood Sexual Perinatal 3 weeks3 months Anti-HDV IgM HDAg Hep B markers HDAg anti-HDV total Hep B markers Anti-HDV total N/A Hepatitis E Fecal/oral

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Transmission

Incubation Acute Infection

2-6 weeks Anti-HAV IgM

3-6 weeks Anti-HepE IgM

Chronic Infection

N/A

N/A

Recovered

Anti-HAV Ab

Vaccinated

Anti-HAV Ab

Anti-HBs Ab Anti-HBc total AntiHBsAb

Anti-HepE Ab N/A

*Hepatitis B infection needed for Hepatitis D Adapted from MKSAP 14 and The Washington Manual

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Portions of this section adapted from Handbook for Housestaff/Fellows on J/SO Services GUIDELINES FOR DVT/PE PROPHYLAXIS Assess for any contraindications to prophylaxis: if contraindications, consider sequential compression devices (SCDs). Relative contraindications: history of cerebral hemorrhage, GI/GU hemorrhage or stroke within last 6 months, thrombocytopenia, coagulopathy (PT > 18 sec), active intracranial lesions/devices, proliferative retinopathy, vascular access/biopsy sites that are inaccessible to hemostatic control. Absolute contraindications: active hemorrhage, history of heparin-induced thrombocytopenia, pregnancy (heparin okay, warfarin not okay), severe trauma (head, spinal cord, extremity) within last 4 weeks, or epidural/indwelling spinal catheter. Cautions: Avoid LMWH in patients with renal insufficiency (defined as Cr > 2.0 or CrCl < 30 ml/min) and if obese (weight > 120 kg). Accurate dosing has not been established in these groups of patients. Evaluate patient for risk factors One point for: Age 41-60 Prior history post-op DVT Family history of DVT/PE, Leg swelling/ulcer/stasis/varicose veins MI/CHF stroke with paralysis IBD central line bed immobilization > 12 hours general anesthesia > 2 hours. Two points for: age 61-70 prior history of idiopathic or unprovoked DVT major surgery malignancy multiple trauma spinal cord injury with paralysis. Three points for: age > 70 prior history of PE inherited thrombophilia acquired thrombophilia. Prophylaxis regimens: determined by risk factor score. Low risk (zero risk factors): Early ambulation Moderate risk (1-2 risk factors): LDUH q8 hours, LMWH, Arixtra, or SCDs High risk (3-4 risk factors): LDUH q8 hours, LWMH, Arixtra, or SCDs Very high risk (> 4 risk factors): LMWH, warfarin, or IV heparin drip

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Dosing: LDUH = low dose unfractionated heparin 5000 U SQ q8-12h. LMWH = low-molecular weight heparin Medical conditions: enoxaparin 40 mg SQ qd or Arixtra 2.5 mg SC QD General surgery: enoxaparin 40 mg SQ qd or Arixtra, 1st dose 2 hours pre-op. Gynecologic surgery: enoxaparin 40 mg SQ qd or Arixtra Extensive urologic surgery: enoxaparin 30 mg SQ bid. Major orthopedic surgery: enoxaparin 30 mg SQ bid; start early (12-24 hours post-op) and continue for 2 weeks (even as an outpatient if the appropriate resources are available). Warfarin = titrate dose to achieve INR 2-3. IV heparin drip = see Forms Portal for protocol. Titrate dose to target PTT of high normal (~ 35 seconds). SCDs = sequential compression devices.

References: Geerts WH, Heit JA, Clagett GP, et al. Prevention of venous thromboembolism. Chest 2001; 119:132S-175S and the UCSF Housestaff Handbook ANEMIA General Definition Adult males Hgb < 13.5, adult females Hgb < 12 mg/dl. Signs and Symptoms Acute anemia: pallor, visual impairment, tachycardia, syncope, hypotension Treat urgently with volume and RBC repletion! Chronic anemia: patient has time to compensate for hypovolemia with increased plasma volume, generally will not experience symptoms until Hgb < 7 mg/dl. Symptoms are due to tissue hypoxiafatigue, headache, dyspnea, light-headedness, angina. Etiologies Decreased RBC production: reticulocyte count. Nutritional deficiency of iron, folate, B12, pernicious sprue BM disease, aplastic anemia, myelodysplastic syndromes, tumor infiltration. BM suppression, drugs, chemo, XRT. Increased RBC destruction or blood loss: reticulocyte count, may be normal in setting of acute blood loss since marrow hasnt had time to respond. Laboratory Workup Complete Blood Count (CBC): Red Blood Cell (RBC) Count Hemoglobin Hematocrit (calculated based on the RBC count and volume) Red Blood Cell Indices Mean Cell Volume: based on volume distribution, detects macrocytosis (>100) or microcytosis (<80) Remember that reticulocytes are larger than mature RBCs and will raise the MCV if there is a significant reticulocytosis Microcytosis: iron deficiency, lead poisoning, thalassemia Macrocytosis: B12 deficiency, folate deficiency, hypothyroidism, liver disease, alcoholism, HIV drugs, chemotherapy, MDS Mean Cell Hemoglobin: hemoglobin divided by RBC count, sensitive to defects in hemoglobin production, reflected by hypochromia.

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Mean Cell Hemoglobin Concentration: hemoglobin divided by hematocrit Red Cell Distribution Width: index of distribution of RBC volumes White Blood Cell Count Cell Differential Leukopenia: infection, leukemia, aplastic anemia, B12/folate deficiency, drugs, Feltys syndrome Leukocytosis: infection, chronic or acute leukemia, steroids, inflammation Nuclear segmentation of neutrophils (>5 lobes characteristic of B12 or folate deficiency) Platelet Count Thrombocytosis often seen with bleeding and iron deficiency Thrombocytopenia may been seen with B12 or folate deficiency Peripheral Smear: Evaluate portion where RBCs are nearly touching one another. Cell size Microcytic cells suggest cytoplasmic defect (later in cell maturation) Macrocytic cells suggest nuclear defect (early in cell maturation) Hemoglobin content Anisocytosis: correlates with RDW Poikilocytosis: suggestive of defect in RBC precursor formation, fragmentation, or hemolysis Polychromasia: presence of polychromatic macrocytes (slightly larger cells, gray-blue in color), or marrow reticulocytes in circulation in response to increased levels of erythropoietin Reticulocyte Count: Reflects rate of marrow production of RBCs. Normal = 1-2% of total RBCs, given the 120-day life span for RBCs, about 1% of circulating cells are reticulocytes to replace RBCs that will be removed from the circulation. Normal reticulocyte response: when hematocrit falls below 30, reticulocytes 2-3 normal. Absolute reticulocyte count = (% reticulocytes 100) RBC count To adjust for the correct reticulocyte response to the level of anemia, use the reticulocyte index:
Reticulocyte Count ( % ) Hematocrit Reticulocyte Index = Maturation Correction 45

Hematocrit (%) 41-50 30-40 20-29 10-19

Maturation Correction 1.0 1.5 2.0 2.5

3 factors determine degree of reticulocyte response: Appropriate response erythropoietin stimulus Normal erythroid marrow Sufficient iron supply Iron Supply Studies: Serum iron: normal = 50-150 g/dl Total iron binding capacity: normal = 300-360 g/dl Serum ferritin: evaluates body iron stores

HEMATOLOGY/ONCOLOGY < 30 g/L indicates iron deficiency Also an acute phase reactantmay be elevated secondary to inflammation Iron saturation ratio: serum iron TIBC (basal state 30-50% of circulating transferring is saturated with iron) <15% indicates iron deficiency Soluble transferrin receptor: helpful to differentiate anemia of chronic disease (normal level) from iron deficiency (high) Anemia Algorithm: Results are most reliable when labs drawn prior to administering transfusion! Physical exam: Document stool guaiac, UA, pelvic exam. Examine skin for ecchymoses, lacerations, and jaundice. Look for hepatosplenomegaly and lymphadenopathy. Decreased Production: (Reticulocyte Index < 2%) Cause Iron Deficiency MICROCYTIC ANEMIA (MCV < 80 FL) Evaluation MCV may be normal early Anisopoikilocytosis Fe, TIBC, Ferritin, Transferrin sat < 16% Increased soluble transferrin r/o GIB Normal iron studies Very low, MCV often < 65 Hgb electrophoresis Splenomegaly & bony abnormalities Mild anemia (may be normocytic) Fe, TIBC, Ferritin Transferrin saturation generally normal to slightly low Normal soluble transferrin Abnormal erythrocyte iron metabolism May be hereditary or secondary to drugs, malignancy RDW, Fe, basophilic stippling, Ferritin Treatment Iron Replacement Consider IV iron for severe disease

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Thalassemia

Anemia Chronic Disease

Transfusion support Iron chelation

Address underlying disease

Sideroblastic

Treat underlying condition or stop any offending medication

Cause Aplastic Anemia Myelodysplastic

NORMOCYTIC ANEMIA (MCV 80-100 FL) Evaluation Treatment Usually pancytopenia Immunosuppression Idiopathic, drug, viral Bone marrow transplantation Bone marrow biopsy Epoetin, G-CSF Morphologic abnormalities in all cell lines Bone marrow transplantation Often macrocytic Epoetin, G-CSF Peripheral smear Bone marrow biopsy

HEMATOLOGY/ONCOLOGY Chronic Renal Disease Erythropoietin level Burr cells due to uremia r/o associated iron deficiency Epoetin

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Cause Folate Deficiency

B 12 Deficiency

MACROCYTIC ANEMIA (MCV > 100 FL) Evaluation Pancytopenia possible Hypersegmented neutrophils Folate Homocysteine Normal methylmalonic acid B12 Neurologic changes Methylmalonic acid Homocysteine Anti-intrinsic factor antibodies (pernicious anemia) Bone marrow biopsy Ethanol, liver disease, hypothyroidism

Treatment Folate replacement

IM B12

Iron Deficiency Anemia Most common causes: GI blood loss (ETOH, NSAIDS, liver disease, uremia, occult malignancy) Menstrual blood loss Decreased iron absorption (celiac disease, post-gastrectomy) Increased iron requirements (lactation, pregnancy) Physical findings (rare): splenomegaly, koilonychia (spoon nail), Plummer-Vinson syndrome (glossitis, dysphagia, esophageal webs) Lab results: when Hct < 30: hypochromia, anisocytosis, microcytosis, increased platelet count Peripheral smear shows pencil cells, occasional target cells Serum iron < 50 g/dl. May have depleted BM iron stores with serum iron 60-150 g/dl. Total iron binding capacity > 420 g/dl May be < 400 with mild iron deficiency anemia. Soluble transferrin receptor (can also use soluble transferrin-ferritin index for more accurate diagnosis) Ferritin: Usually < 20 even in patients with normal serum iron levels Acute phase reactant (can divide value by 3 to get an approximate baseline ferritin in patients with inflammation) If ferritin > 200 unlikely to have iron deficiency even with concomitant inflammation Iron Therapy: Adequate repletion will lead to reticulocyte peak in 5-10 days, with Hgb rising over 3 weeks. Oral replacement Ferrous sulfate 325 mg t.i.d. (give between meals to maximize absorption) Contains approximately 65 mg of elemental iron per 325 mg tablet (for a total dose of 195 mg per day with t.i.d. dosing) Side effects: constipation, cramping, nausea, dark stools

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Manage by introducing pills with meals, then between meals, increasing frequency of dose gradually. (Alternate) Ferrous gluconate 325 mg q.i.d. (contains 36 mg elemental iron per tablet) Do not give within 2 hours of antacids or antibiotics Concomitant vitamin C 500 mg improves absorption Consider stopping therapy when HgB normalizes to allow identification for future blood loss Parenteral replacement: Useful when in setting of malabsorption/IBD, very high iron requirements, or intolerance to oral preparations. Formula to calculate amount required to restore iron stores:
Hgb ( g dl) Iron ( mg) = 0.3 weight ( lb ) 100 100 14.8

Most patients require 1000-2000 mg iron Iron dextran: easiest route is IVPB diluted in NS, infused at 6 mg/min. Ferric gluconate complex and iron sucrose demonstrated to have decreased incidence of anaphylactic reactions compared to iron dextran. Ferric gluconate 125mg = 12.5mg/min if diluted in 100ml NS. Infuse over 30-60min. Side effects: anaphylaxis (rare), arthralgia, myalgia, fever, pruritus may be seen within 3 days of therapy. For hemodialysis patients: 100 mg iron dextran IV with hemodialysis x 10 doses. When transferrin saturation exceeds 20%, start maintenance therapy at 50-100 mg weekly. In case of poor response, consider: non-compliance, poor absorption, ongoing blood loss, incorrect diagnosis. Thalassemia Inherited disorders of underproduction of either or chains of the Hgb molecule. Anemia secondary to hypoproliferation, ineffective erythropoiesis, and hemolysis. Diagnosis: hemoglobin electrophoresis Beta-thal major Hb <4 Beta-thal minor MCV <75, Hb >10 Alpha-thal, 4 forms. Treatment: Primarily transfusion support with iron chelation. Stem cell transplantation in some situations. Myelodysplastic Syndrome Clonal disorder of stem cells, diagnosed by morphologic findings on smear and bone marrow biopsy. Causes: idiopathic, radiation, chemotherapy, or toxin exposure Classification: based on peripheral blood findings and bone marrow biopsy. May have associated neutropenia, thrombocytopenia. Progression to marrow failure, or acute leukemia common. Diagnosis: bone marrow biopsy (hypercellular marrow) Treatment: transfusion, epoetin, chemotherapy, BMT Sideroblastic Anemia Acquired or hereditary disorder characterized by abnormal iron metabolism by RBC caused by genetics, drugs, lead toxicity, malignancy, chronic inflammation, or infection Megaloblastic Anemia: Characterized by abnormal DNA synthesis Causes:

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Folic acid: decreased intake (alcoholism), malabsorption, increased use (hemolytic anemia, pregnancy), drugs inducing abnormal metabolism (alcohol, trimethoprim, pyrimethamine, methotrexate, OCPs, anticonvulsants) Vitamin B12: pernicious anemia, gastrectomy, pancreatic insufficiency, intestinal bacterial overgrowth, ileitis, ileal resection, intestinal parasites Diagnosis: macrocytosis, leukopenia, thrombocytopenia, LDH, total bilirubin (due to hemolysis) Peripheral smear: anisocytosis, poikilocytosis, macro-ovalocytes, hypersegmented neutrophils. Measure both B12 and folate Serum methylmalonic acid (MMA) and homocysteine (HC) when levels are equivocal. MMA and HC elevated in B12 deficiency. Only HC elevated in folate deficiency. Bone marrow biopsy to exclude MDS or malignancy Look for pernicious anemia: Schilling test (rarely done), anti-intrinsic factor ab, anti-parietal cell ab. Treatment: Folic acid 1 mg daily. Give 5 mg daily in malabsorption. Cyanocobalamin 1 mg IM daily 7 days, then weekly 1-2 months, then maintenance therapy with 1 mg IM monthly. Erythropoietin Deficiency Seen with chronic renal failure, usually with CrCl < 30. May check erythropoietin blood levels as renal function worsens to plan treatment. Lab tests: Hct usually 20-30, normal MCV, normochromic RBCs on smear Treatment: typical epoetin dose = 50-100 units/kg to goal Hgb 11-12. Recent RCT demonstrated worse outcomes with Hgb > 13. Decreased response to treatment seen with: concurrent iron deficiency, chronic inflammatory conditions, chronic bleeding, aluminum intoxication. Anemia of Chronic Disease Labs: no specific diagnostic lab test exists! Generally mild anemia. May be normocytic or microcytic anemia. Ferritin normal to elevated, iron and TIBC generally decreased. Soluble transferrin receptor generally normal as compared to increased in iron deficiency Common systemic associations: connective tissue diseases, malignancy, uremia, endocrine failure (thyrotoxicosis, myxedema), chronic liver disease No benefit to iron supplementation. Treat underlying disorder. Epoetin can decrease need for transfusion but no mortality benefit.

HEMATOLOGY/ONCOLOGY Increased Destruction or Loss: (Reticulocyte Index > 2%) HEMOLYTIC ANEMIA Evaluation Membrane (Spherocytosis) Enzyme (G6PD deficiency) Hemoglobin (Sickle cell) Warm: IgG that bind Rh (idiopathic, SLE, malignancy, drug) Cold: IgM (mycoplasma, EBV, idiopathic, lymphoma) RBC Clumping Auto-antibodies Haptens Immune complex DIC, TTP, HUS Schistocytes

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Cause Intrinsic RBC Defects

Auto-immune hemolytic anemia

Treatment Disease specific Spherocytosissplenectomy Sickle cellhydroxyurea Steroids, splenectomy Avoid the cold Plasmapheresis.

Drug induced hemolytic anemia

Microangiopathic hemolytic anemia

Treat primary process

Hemolytic Anemia Intravascular: fever, chills, tachycardia Extravascular: splenomegaly, jaundice Causes: Hypersplenism: myeloproliferative disorders, lymphoma, splenic storage diseases (Gauchers), congestive splenomegaly (splenic vein thrombosis, cirrhosis) Immune-mediated: lymphoma, SLE, drugs (PCN, Aldomet, quinidine), mycoplasma infections (cold AIHA) Microangiopathic hemolytic anemia: DIC, TTP, HUS, severe hypertension, vasculitis Intravascular prostheses: especially prosthetic aortic valve RBC disorders (chronic hemolysis): sickle cell anemia, thalassemia, sideroblastic anemia, hereditary spherocytosis, G6PD deficiency Diagnosis: Reticulocyte count and reticulocyte index > 2% Peripheral smear: Spherocytes: autoimmune hemolytic anemia, hereditary spherocytosis Target cells: thalassemias, liver disease Schistocytes: microangiopathic conditions, intravascular prostheses Sickled cells Agglutinated cells: presence of IgM antibody, multiple myeloma LDH (but may be normal) Haptoglobin (may be absent) Unconjugated bilirubin RUA: positive hemosiderin or hemoglobin in severe hemolysis Also consider ordering: G6PD level (think of this in men, especially blacks)

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Many drugs cause hemolysis if G6PD deficient: sulfa, dapsone, nitrofurantoin, vitamin K, doxorubicin, methylene blue. Note that the G6PD level may be normal after acute hemolysis Direct Coombs test: indicates presence of IgG or C3 on red blood cell surfaces, usually differentiates between immune and non-immune causes of hemolysis. Acid Hemolysis (Hams Test) or Sucrose Hemolysis: to evaluate for possible PNH. More commonly use evaluation of GPI membrane protein deficiency to make PNH diagnosis.

PANCYTOPENIA Definition Anemia, thrombocytopenia, and leukopenia due to injury or destruction of pluripotential marrow stem cell. Diagnosis CBC: all 3 cell lines of CBC below normal Hemolysis parameters: negative Iron studies: serum iron, normal serum transferrin, iron saturation index Bone marrow: dry tap (hypocellular or aplastic bone marrow with marrow elements replaced by fat) Differential Diagnosis Marrow hypoplasia (aplastic anemia): idiopathic, chemotherapeutic agents, ionizing irradiation, drugs (chloramphenicol), immune mediated, hepatitis or other viral infections, SLE, diffuse eosinophilic fasciitis, transfusion associated GVHD, pregnancy Pancytopenia with normal or increased marrow cellularity: hypersplenism, vitamin B12 or folate deficiency, AIDS Paroxysmal nocturnal hemoglobinuria Bone marrow replacement: metastatic tumor, leukemia, multiple myeloma, amyloidosis, myelofibrosis, granuloma Myelodysplastic syndromes SICKLE CELL ANEMIA Types Sickle cell anemia (homozygous HbSS) Sickle cell--thalassemia (HbS-thal): milder than HbSS Sickle cell-hemoglobin C (HbSC): milder than HbSS, HbC causes target cells Sickle cell trait (heterozygous HbAS): no accompanying anemia Have impaired ability to concentrate urine. May develop symptoms under conditions of severe hypoxia. Clinical Signs Chronic hemolytic anemia, vasoocclusive ischemic tissue injury, increased susceptibility to infections, especially in tissues susceptible to infarcts (bone, kidney, lung), functional asplenism Characteristic Lab Findings Hgb = 5-10 mg/dl, reticulocyte count, chronic neutrophilia, thrombocytosis, Howell-Jolly bodies on smear Acute Vasoocclusive Complications Painful crises: sickled cells occlude arterioles and cause tissue infarction. Characterized by severe pain, typically of back, limbs, ribs, lasting 5-7 days. Pattern of pain in a given patient usually consistent from crisis to crisis. If new pain consider alternative diagnosis. Precipitated by infection, fever, dehydration, or exposure to low oxygen tension (high altitude travel). Management consists of oral hydration with 3-4 liters fluid per day. Oral or IV analgesia (start with 2-5 mg morphine every 3-4 hours). Supplemental O2 if hypoxia present. Acute chest syndrome: fever, chest pain, pulmonary infiltrates, leukocytosis, hypoxia.

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Treat with broad spectrum antibiotics (3 generation cephalosporin plus azithromycin to cover atypicals), analgesia, O2 support. Consider exchange transfusion for more severe disease. Generally vasoocclusive disease but complicated by infection, embolism, thrombosis. Splenic sequestration crisis: usually occurs in those with an intact spleen (children, adults with HbSC or HbS--thal) though it may occur in adults with splenomegaly. Sudden massive pooling of bloodhypovolemic shock. Priapism: painful erection. Treat with hydration, analgesia. If lasts > 24 hours, should consider transfusion and surgical intervention. Other Complications Aplastic crisis: sudden decrease in Hgb and reticulocyte count. Usually a complication of infection with parvovirus B19. Treat with RBC transfusion. Most recover by 10-14 days. Cholelithiasis: secondary to chronic hemolysis Chronic Organ Damage Osteonecrosis: affects femoral, humeral heads. Treat with analgesia, local heat, non-weight bearing activity, arthroplasty. Stroke: treat with transfusion to reduce HbS concentrations. Leg ulcers: treat with rest, leg elevation, wet to dry dressing changes, split thickness skin grafts. Renal tubular defects: inability to concentrate urine, hematuria. Pulmonary infarction: pulmonary hypertension, CHF Vision defects: caused by retinal vessel obstruction with hemorrhage, scarring, retinal detachment, blindness. Prevention and Health Maintenance Avoid dehydration, hypoxia, intense exercise, high altitude. Folic acid 1 mg p.o. daily Vaccinations: Hepatitis B, influenza, Pneumovax Ophthalmic exams annually (high incidence of proliferative retinopathy) Transfuse to Hgb = 10 mg/dl prior to elective surgery. No evidence for exchange transfusion. Hydroxyurea (15-35 mg/kg p.o. daily): levels of fetal hemoglobin and pain crises by 50-70%. Other therapies: Small trials only of prophylactic anticoagulation. No data to support widespread use at this time. Conflicting data on epoetin. Can be considered if no response to hydroxyurea. Early trials on use of stem cell transplant.

BLEEDING DISORDERS CHARACTERISTIC BLEEDING PATTERNS Mucous Skin Others membranes Petechiae, Common Rare purpura (oral, nasal, GI, GU) Ecchymoses Rare Joint, muscle, retroperitoneum

General Plateletvascular Coagulation factor deficiency Initial Evaluation Superficial surfaces Deep tissues

Onset of bleeding Spontaneous or immediately after trauma Delayed after surgery or trauma

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Platelet count: normal or low, verify thrombocytopenia with peripheral smear to rule out clumping (seen in paraproteinemias) PT: measures tissue factor, VII, II (prothrombin), X, V, fibrinogen if 1 or more factors < 30-50% of normal or in early vitamin K deficiency. PTT: measures factors XII, XI, IX, VIII, V, X, fibrinogen. if 1 or more factors < 30-50% of normal or if inhibitor exists Disseminated intravascular coagulopathy (DIC) screen: fibrinogen and D-dimer Other Studies (after youve ordered a Hematology consult!) Mixing studies: mixes test plasma with normal plasma to restore deficient factors to 50% of normal level. If an inhibitor is present, PT or PTT will not correct after mixing (1 hour). Inhibitors generally are antibodies which occur in post-partum women, autoimmune disorders (especially SLE), or patients taking drugs such as penicillin or streptomycin. Can be acquired in hemophilia patients, rendering them less responsive to factor replacement. Can lead to bleeding. Most useful in workup of isolated elevation of PTT which suggests presence of lupus anticoagulant. DRVVT: confirms presence of lupus anticoagulant. von Willebrands disease screen: order in setting of normal platelet count and prolonged bleeding time. vWF antigen: measures circulating vWF protein vWF activity: measures ability of vWF to agglutinate platelets Factor VIII activity: vWF stabilizes factor VIII in plasma Bleeding time: prolonged by qualitative platelet dysfunction (very non-specific!) Thrombin time: tests fibrinogen conversion to fibrin by thrombin. Prolonged by fibrinogen deficiency, heparin, fibrin degradation products, paraproteinemia. Etiology/Treatment von Willebrands disease: most common inherited disorder. Type I: quantitative deficiency Type II: qualitative deficiency Type III (rare): severe deficiency. Treat with DDAVP (contraindicated in Type IIb), cryoprecipitate, factor VIII concentrate, recombinant vWF Hemophilia: X-linked disorder with factor VIII (hemophilia A) or factor IX (hemophilia B) deficiency. 30% of cases without prior family history (i.e. spontaneous mutation). PTT normalizes with mixing study. Treat with factor VIII (50 units/kg load, then 25 units/kg q12hrs until bleeding controlled) or factor IX (100 units/kg load then 50 units/kg q24hrs) concentrates, DDAVP for mild. Recombinant factor VIIa used for hemophilia A/B patients with inhibitors to factor replacement. Vitamin K deficiency: secondary to malnutrition, malabsorption, warfarin, antibiotics

THROMBOCYTOPENIA Definition: platelet count < 150K If platelets = 50-100K, patients may have prolonged bleeding following severe trauma If platelets = 20-50K, bleeding occurs with minor trauma If platelets < 20K, patients at risk for spontaneous bleeding > 50% drop occurs < 1% of the time as normal variant Initial Workup CBC Peripheral smear: clumping, RBC fragmentation

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Coagulation panel: PTT suggests lupus anticoagulant Fibrinogen and D-dimer suggests concomitant DIC Evaluate for splenomegaly Causes Impaired marrow production: Marrow aplasia or infiltration: tumor, storage diseases, infection, fibrosis (will see associated anemia, leukopenia) Suppression of megakaryocyte differentiation: CMV, HIV Drug induced marrow suppression: chemotherapy, radiation, ETOH, thiazide diuretics. Should see rebound thrombocytosis after withdrawal of offending agent Ineffective thrombopoiesis: B12 or folate deficiency Congenital thrombocytopenia: Wiskott-Aldrich syndrome Increased platelet destruction: due to consumption or immune-mediated clearance Antibody mediated Idiopathic thrombocytopenic purpura (ITP): production of anti-platelet IgG antibodies with clearance by the reticuloendothelial system. Diagnosis: isolated low platelet count with mucocutaneous bleeding. Diagnosis of exclusion. Need to r/o secondary conditions (SLE, HIV) Bone marrow biopsy: megakaryocytes (only needed for adults > 60 years or patients with associated cytopenias) Positive anti-platelet antibodies (not very sensitive or specific, not commonly needed) Treatment: No therapy for asymptomatic patients with platelets 30,000-50,000 For mild symptoms: prednisone 1-2 mg/kg/day with slow taper over 3-6 months. For life threatening hemorrhage: high dose steroids, IVIG 1 gm/kg/day 2 days, platelet transfusion. For steroid refractory patients: splenectomy (effective in 80-90%) Immunotherapy (AZA, Cytoxan) or Rituxan if no response to splenectomy. Platelet transfusion minimally effective unless preceded by other therapy. New evidence for role of an experimental thrombopoietin drug. Infections: HIV, CMV, EBV Drug induced (hapten mediated): chemotherapy, thiazides, alcohol, sulfa, ranitidine/cimetidine (rare), procainamide, furosemide, quinidine, Tegretol, Dilantin, valproic acid, methyldopa, ASA, gold salts, heparin Heparin-induced thrombocytopenia (HIT): immune mediated thrombocytopenia secondary to heparin therapy (HIT I/II terminology no longer used). Diagnosis suggested by gradual drop in platelet count > 50% from baseline usually within 5-10 days of starting heparin therapy (including heparin flushes). May occur more quickly if past heparin exposure. 17-30% mortality if untreated. Incidence: 1%-5% depending on clinical scenario (higher incidence post orthopedic surgery) Diagnosis: clinical scenario. Order heparin associated anti-platelet antibody (UCLAs ELISA test is > 90% sensitive). Complications: development of thrombocytopenia may be accompanied by heparin associated thrombosis, which occurs in 35-75% of patients if treated with withdrawal therapy alone. May cause life threatening arterial thrombosis and limb ischemia.

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IgG binding to heparin on platelet surfaces leading to platelet activation. Treatment: dont delay therapy while waiting for antibody results! Stop all heparin products Watch for IV hep lock and flushes No LMWH (lower risk of developing HIT but almost 100% cross-reactivity). Need to use alternative anti-coagulant. Direct thrombin inhibitors: Lepirudin (0.4 mg/kg bolus, 0.15 mg/kg/hr) OR argatroban (2 g/kg/min) Goal aPTT 1.5-2.5 normal. Avoid lepirudin if Cr > 1.5-2. Also, may need to avoid if history of past use as many patients develop anti-lepirudin antibodies. argatroban dose for hepatic dysfunction. Avoid platelet transfusions Fondaparinux (not currently approved). No evidence of cross-reactivity. Warfarin: Stop/reverse in acute setting. Start when platelets > 150. Note that an INR of 4.0 with argatroban is likely a true INR of 2.3-3.7 Thrombotic Thrombocytopenic Purpura (TTP) Definition: Consumptive thrombocytopenia and microangiopathic hemolytic anemia (MAHA). May also see fever, renal dysfunction, and fluctuating neurologic deficits. Initial symptoms can be nonspecific (abdominal pain, nausea, vomiting) as microthrombi occur in multiple organ systems. Etiology: deficiency of ADAMTS-13 (level can be measured but takes too long be clinically useful in acute setting) leads to abnormally large vWF multimers that cause platelet aggregation. Severe deficiency has increased risk of recurrence. Can also be seen within the context of HUS, pregnancy (HELLP, pre-eclampsia), auto-immune disorders, drug toxicity (quinine, chemotherapy) Diagnosis: anemia, haptoglobin, LDH, indirect bilirubin, prominent RBC fragmentation on smear. Given the effectiveness of plasma exchange, you should have a low threshold to treat when MAHA and thrombocytopenia are present. Dont wait for fever, renal dysfunction, or neurologic changes! Treatment: Plasma exchange: good RCT mortality data. May be effective by increasing ADAMTS-13 level. Should be continued until platelet counts normalize. Plasma exchange not effective for HUS. Steroids: no real clinical trials. Theoretical benefit to decrease level of anti-ADAMTS-13 ab. Platelet transfusions: may worsen end organ ischemia so only transfuse in case of hemorrhage. Others Sepsis (DIC), intravascular prostheses, malignant hypertension, acute renal transplant rejection Splenic Sequestration: portal hypertension, myeloproliferative disorders, storage diseases Dilutional: occurs following massive transfusion of packed RBCs.

DISSEMINATED INTRAVASCULAR COAGULOPATHY (DIC) Pathophysiology Entry into circulation of procoagulant substances (i.e. tissue factor, gram negative endotoxin) triggers activation of coagulation cascade and platelets. Disseminated deposition of fibrin-platelet thrombi in microvasculature. Increased fibrin formation stimulates compensatory fibrinolysis by plasmin, resulting in hemorrhage (acute), while chronic DIC results in thrombotic events.

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Etiologies Infection (40%) (especially gram negative sepsis) Trauma/shock (via liberation of tissue factor) Common in traumatic brain injury since the brain is a rich source of tissue factor Malignancy (10-15%) (especially pancreatic cancer, mucinous adenocarcinoma, acute promyelocytic leukemia) Liver failure Obstetric complications (eclampsia, amniotic fluid embolism) Pancreatitis Envenomation (especially snake venom) Heat stroke Rhabdomyolysis Transfusion reaction Diagnosis Prolonged PT, thrombocytopenia (< 100k or sharp decline), D-dimer (not specific until > 2000-4000), RBC fragmentation on smear, fibrinogen < 100 (low fibrinogen correlates most directly with risk of hemorrhage). Differential Diagnosis Severe liver disease with hyperfibrinolysis TTP/HUS Treatment Mortality is 40-80%. Goal is to identify and treat the underlying cause. Supportive measures are only temporizing! No treatment is necessary if DIC is mild and asymptomatic. For active bleeding: Replace depleted coagulation factors with FFP to correct PT/PTT to 1.5 normal (will need to transfuse every 8-12 hours due to short half lives of some components) Transfuse platelets to goal of 50-100K Transfuse cryoprecipitate to keep fibrinogen > 100 mg/dl Hemodynamic support Heparin: no RCT data. Use indicated for prominent thrombosis or acrocyanosis of limbs. No bolus, goal aPTT= 45. Anti-Thrombin III: no clear mortality benefit in RCT. Increased bleeding rates.

HYPERCOAGULABLE STATES Venous thromboembolism generally is precipitated by an acquired prothrombotic hypercoagulable state combined with a hypercoagulable phenotype. No clear data on who should be screened. Consider screening for inherited disorders in patients with recurrent thromboses. Consider for lifelong, prophylactic anticoagulation. Arterial thrombosis may occur with hyperhomocysteinemia, PNH, oral contraceptives, HIT, vasculitis, myeloproliferative disorders, or antiphospholipid syndrome. Etiologies Acquired: Post-operative periods (immobilization, tissue factor release) Cancer Estrogens (especially OCPs), pregnancy, HRT Myeloproliferative disorders Ulcerative colitis Heparin-induced thrombocytopenia (HIT)

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Antiphospholipid syndrome (SLE) Hyperhomocysteinemia Nephrotic syndrome (the more proteinuria, the greater the risk) Central venous catheters Hereditary: Factor V Leiden mutation 40-50% inherited disorders Relative risk (RR) of DVT 2-7 with the risk of PE lower than other inherited disorders Homozygous with significant increased risk (RR = 80) Prothrombin Gene 20210A mutation (RR = 2.8) Antithrombin III deficiency (RR = 20) Protein C deficiency (RR = 7.1) Protein S deficiency (RR = 8.5) Dysfibrinogenemia Elevated factor VIII Hereditary hyperhomocysteinemia due to deficiency of cystathionine -synthase or thermolabile variant of methylenetetrahydrofolate reductase Workup Activated Protein C Resistance (APCR), may be performed during anticoagulation Factor V Leiden PCR Prothrombin Gene 20210A mutation Protein C level (falsely low in patients taking warfarin or in acute thrombosis) Protein S level (falsely low in patients taking warfarin) Antithrombin III (ATIII) level (falsely low in patients on heparin or in acute thrombosis) Homocysteine level (if high, rule out folate and B12 deficiencies) Anti-cardiolipin antibody, Dilute Russel Viper Venom Time (DRVVT) ( with lupus anticoagulant) PT/PTT Factor VIII Thrombin time Characteristic Types of Thrombosis Migratory, superficial thrombophlebitis: non-bacterial thrombotic endocarditis, malignancy Hepatic or portal vein thrombosis: myeloproliferative disorder, paroxysmal nocturnal hemoglobinuria Warfarin induced skin necrosis: protein C deficiency Recurrent, spontaneous abortions: antiphospholipid antibody syndrome

ANTICOAGULATION Acute Thromboembolism Document stool guaiac: if patient is at low risk for GI bleeding, do not delay anticoagulation while waiting for result. Prior to initiating anticoagulation, consider increased risk of bleeding in the following conditions: Surgery, trauma, or embolic stroke within preceding 14 days Recent or active peptic ulcer disease, GI or GU bleeding Platelet count < 50-100K Age > 70 Hepatic failure Uremia

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Bleeding diathesis Brain metastases Treatment Once decision is made to anticoagulate, start heparin and warfarin at the same time. Low Molecular Weight Heparin (LMWH): enoxaparin (Lovenox), tinzaparin, dalteparin Almost every patient with acute venous thromboembolism may be treated with LMWH. May want to consider an alternative anticoagulant for CrCl < 30 or for obese patients Use unfractionated heparin if you must be able to turn off anticoagulation quickly. Mechanism of action: preferential inhibition of factor Xa Compared to unfractionated heparin, LMWH has bioavailability (> 90% after SQ injection), prolonged half life, predictable clearance, and an ability to inhibit platelet bound factor Xa. LMWH cross-reacts with heparin, so it is not a safe alternative in the setting of HIT. Laboratory monitoring: can use factor Xa levels to monitor. Target factor Xa level (drawn at midpoint between injections) is 0.4-1.0 units/ml. Clinical Uses: DVT prophylaxis Enoxaparin 30 mg SQ b.i.d. or 40 mg SQ daily (should be first line therapy as reduced risk of HIT) Post-operatively: Hip replacement: for extended prophylaxis, enoxaparin 40 mg SQ daily x 3 weeks Knee replacement: enoxaparin 40 mg SQ daily for 7-10 days General surgery: enoxaparin 40 mg SQ daily for 7-10 days DVT with or without PE Enoxaparin 1 mg/kg SQ q12hrs or enoxaparin 1.5 mg/kg SQ daily as a bridge to warfarin Unstable angina and NSTEMI Enoxaparin 1 mg/kg SQ q12hrs plus aspirin 325 mg daily Concerns about bleeding associated with percutaneous coronary intervention. ACC/AHA guidelines: probably safe for patients to undergo PCI. Check with cardiology fellow if patient likely to undergo PCI. Note that LMWHs are dosed in units (1 mg enoxaparin = 100 units LMWH) Unfractionated Heparin: indicated for use in acute DVT, PE, MI, and unstable angina. See Heparin Protocol (see UCLA Forms Portal) for full details Initiating the infusion Bolus 71 units/kg for DVT, PE, AFib, UA, mechanical valves Initial infusion rate of 18 units/kg/hr for DVT/PE OR 14 units/kg/hr for UA, AFib, mechanical valves Adjusting the infusion Goal PTT 55-80 Check PTT 6 hours after start of infusion and after 6 hours after any change in the infusion rate PTT < 35: rebolus 71 units/kg and rate by 4 units/kg/hr PTT 35-44.9: rebolus 40 units/kg and rate by 2 units/kg/hr PTT 45-54.9: rate by 1.5 units/kg/hr PTT 80.1-95: hold infusion for 1 hour then rate by 2 units/kg/hr PTT > 95: hold infusion for 2 hours then rate by 3 units/kg/hr Warfarin: Day INITIATING WARFARIN DOSING (IN MILLIGRAMS) Initial dose INR < 1.5 INR INR INR INR > 3.0

HEMATOLOGY/ONCOLOGY 1.5-1.9 2.5 2.5-5 5-7.5 7.5-10 5-10 2.0-2.5 1-2.5 0-2.5 0-5 0-5 0-7.5 2.5-3.0 None None None 0-5 0-7.5

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1 2 3 4 5 6

5 -

5 5-10 10 10 7.5-12.5

None None None None None

***Use above table cautiously as there is no way to predict how a patient will react to coumadin***. Many indications for anti-coagulation do not require urgent coumadininzation. Consider using lower than 5mg increments. In patients with higher body weights, no nutritional deficiencies, who are eating, and not on antibiotics, and have normal liver function, may start with initial dose of 7.5-10 mg. Conditions such as CHF, liver disease, vitamin K deficiency, changes in diet, and many drugs (i.e. Bactrim, ciprofloxacin, phenytoin) can influence warfarin response. st 1 month of treatment requires close PT monitoring until dosing is clarified. Goal INR: INR 2.5-3.5 for mechanical prosthetic valves INR 2-3 for Afib, DVT, PE, hypercoagulable states Reversing warfarin: necessary for active bleeding with therapeutic INR, or prior to interventional procedure that carries risk for bleeding. Vitamin K 1-10 mg IV (takes 6 hours for effect, lasts > 36 hours) plus 4-6 units FFP. Give infusion over one hour to decrease possibility of anaphylactic reaction. FFP should be given immediately prior to procedure since effect lasts only 2-4 hours. For INR > 4 give FFP every 6 hours and follow PT/PTT every 6 hours. May need vitamin K daily x 3 days for complete reversal. For INR 5-9 without bleeding: hold warfarin and monitor INR. For patients at higher risk of bleeding, give 1-2.5 mg oral vitamin K. Oral or IV route preferred for vitamin K. SQ replacement no better than placebo in large metaanalysis and has unpredictable absorption. Alternative anticoagulants: Fondaparinux: factor Xa inhibitor Approved for DVT prophylaxis in hip replacement (2.5 mg SQ daily) and treatment of PE/DVT. No reported crossreactivity with HIT antibody but not FDA approved for patients with diagnosed HIT. Performed as well as unfractionated and LMWH in RCT trials without increased bleeding complications. Also comparable for treatment of ACS. Argatroban: direct thrombin inhibitor Primarily used for patients with HIT (see HIT section for dosing information)

TRANSFUSION PRACTICES Consent Always consent the patient or family member for transfusion of blood products on admission, unless emergent. Risk of transmitting infectious agents through blood transfusion: HIV: 1 in 2,100,000 HTLV-I/II: 1 in 2,000,000 HBV: 1 in 200,000

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HCV: 1 in 1,900,000 Blood Ordering Options Type and crossmatch: When a patient is likely to require a transfusion, order type and crossmatch for the number of units you expect to transfuse. Verifies ABO-Rh status of donor and recipient, screens for unexpected antibodies to common RBC antigens, mixes donor RBCs and recipient serum to exclude immediate hemolysis (indirect Coombs test). Type and screen: Order when there is a possibility a patient will require blood, but too low likelihood to justify setting aside cross-matched units. Tests ABO, Rh, and routine antibodies. Hold clot: Specimen is stored for 3 days. No serological testing performed. Type O, Rh negative: Available for immediate transfusion when patients blood type is not known. Use only in emergency. Type specific, uncrossmatched: Available within 5 minutes after receiving patients blood sample. Preserves valuable O negative blood. Leukocyte filtered/reduced: WBCs are the chief cause of alloimmunization to HLA antigens, which leads to future febrile transfusion reactions and platelet refractoriness. Indicated for patients who require long term transfusion support and are at risk of becoming refractory to platelets, or with recurrent febrile reactions. Irradiated blood products: Products are irradiated to kill donor stem cells which (rarely) cause transfusion-associated GVHD. Indicated for BMT recipients, immunosuppressed patients, when donor and recipient are blood relatives, and patients receiving HLA matched platelets. CMV negative: Indicated for CMV seronegative patients who have received or are candidates for bone marrow or solid organ transplants. Patients should be tested if CMV status unknown. Saline washed RBC: RBC washed to remove plasma proteins, electrolytes, and antibodies. Indicated only in patients with history of severe transfusion reactions, hyperkalemia, paroxysmal nocturnal hemoglobinuria. Very expensive! RBC Transfusion Indications: Active bleeding and one of the following: Blood loss > 500cc or 15% of blood volume (70 cc/kg body weight) SBP < 100 mmHg or 20% fall in SBP Pulse > 100 bpm General anesthesia and Hgb < 9 g/dl Chronic, symptomatic anemia (generally Hgb < 9g/dl) Chronic transfusions to suppress endogenous Hgb in selected patients with sickle cell disease Hgb < 10 g/dl in patients with known coronary artery disease, unstable angina, or acute MI No RTC trial data to support this practice. One RCT (n=428) in patients undergoing CABG randomized patients to transfusion only if Hgb < 8 g/dL or standard practice (generally Hgb > 9.0) and found no mortality differences. ICU mortality data with clear evidence for more restrictive transfusion (Hgb<7.0) practices

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J service specifics: Hgb < 9 g/dl in J patients receiving chemotherapy/BMT/PSCT. Higher threshold as patients generally with insufficient marrow production. Remember to order leukocyte filtered, irradiated blood products for all patients on J service. Patients who are CMV negative must always receive CMV negative blood pre- and posttransplant. Dont forget to order CMV status on admission for all transplant candidates! Dose effect: 1 unit PRBC (volume = 350 cc) should raise Hgb by about 1 g/dl Other considerations: Patients with chronic anemia increase plasma volume in order to maintain an adequate cardiac output. The volume associated with transfusion will cause overload and must be done slowly to avoid precipitating CHF (4 hours per unit vs. 5-10 min/unit in a hypotensive patient with acute blood loss). Consider transfusing in splits of volume over same time (4 hours per split is the slowest rate at which blood may be transfused). Consider Lasix 20-40 mg IV to avoid fluid overload during transfusion of multiple units. Platelet Transfusion General: 1 unit single donor platelets (SDP) = 7 units of random donor platelets (a hemostatic dose for bleeding in an adult patient) General dose is 1 unit random donor platelets per 10 kg body weight 1 unit single donor platelets for a 70 kg person. For every 1 unit of SDP, the patient receives hemostatic levels of coagulation factors equivalent to 1 unit of fresh frozen plasma. Indications: Platelet count < 5-10K in ITP or significant purpura Platelet count < 10K in J patients, or patients not predisposed to spontaneous bleeding No change in bleeding events in RCT when compared to < 20K as transfusion threshold Platelet count < 20K and a clinical factor that would be associated with risk of spontaneous bleeding Temperature > 38.5C Infection Concurrent coagulopathy Disseminated intravascular coagulopathy (DIC) Hepatic or renal failure Marked splenomegaly Platelet count < 50K and surgery or post-op bleeding Platelet count < 50K and invasive procedure (LP, indwelling lines, liver or transbronchial biopsy, epidural puncture) Platelet count < 100K with active bleeding Dose effect: 1 unit/kg body weight of platelets (1 unit SDP) should increase platelet count by 50K by 10-60 minutes, and by 40K at 18-24 hours post-transfusion. Premedication: Tylenol 650 mg p.o. 1, Benadryl 25-50 mg p.o. OR IV 1 Refractoriness to platelet transfusions: a patient is considered refractory to platelets if 3 transfusions within 2 weeks fail to yield an adequate post-transfusion response. There are specific formulas for calculating an expected response, but in general, each unit should platelets by 35-40K. Causes: fever, sepsis, splenomegaly, DIC, drugs, platelet consumption, s/p BMT (likely multifactorial etiology, in one series < 40% post-BMT transfusions resulted in appropriate rise in platelet count), alloimmunization with antibody mediated destruction of circulating platelets (towards HLA class I antigen)

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Diagnosis: check rise 60 minutes after transfusion. Appropriate rise with decrease over next 24 hourssepsis, DIC, post BMT, etc. No rise at 60 minutesalloimmunization. Order platelet antibody screening test (results in 2-3 days). Treatment: if test positive, or while results pending, order HLA matched platelets and check platelet count 10 minutes to 1 hour following transfusion to document appropriate rise. Minimal options in acute bleed situation. Effort should be made to avoid alloimmunization in at risk patients through irradiation, leukocyte reduction (comparable in RCT) or both. Fresh Frozen Plasma (FFP) Description: FFP is made by separating plasma from a unit of whole blood. Contains all clotting factors. One unit of FFP contains: 200-250 cc volume 400 mg fibrinogen 200 units of other factors (factors V, VII, XI, ATIII, Protein C, Protein S) Indications: Active bleeding or risk of bleeding if PT and/or PTT> 1.5-1.8 normal. Patient with massive bleeding at high risk for clotting factor deficiency while coags pending. Common causes of factor deficiency: liver disease, vitamin K deficiency, DIC, hemorrhage, TTP (treatment with plasma exchange) Reversal of warfarin therapy Minimal evidence that FFP can correct mildly elevated INR (< 1.8). Guidelines for use: Starting dose 15 cc/kg = 4-6 units (dose needed to replace 25% clotting factors, minimum amount necessary to obtain hemostasis) Maximum effect declines after 2-4 hours, so infuse rapidly at time of bleeding or no more than 1 hour prior to anticipated bleeding. Administer fewer units of FFP when transfusing platelets since 1 unit SDP contains equivalent clotting factors to 1 unit FFP. Consider Lasix IV when multiple units FFP given rapidly to avoid fluid overload. Cryoprecipitate Contains fibrinogen, factor VIII, and von Willebrand factor. Indications: Fibrinogen < 100 mg/dl (as in DIC) Preparation of topical fibrin glue for surgical hemostasis Concentrated factor VIII and von Willebrand factor are preferred treatments of Hemophilia A and von Willebrands disease since cryoprecipitate not virus inactivated, thus carrying a higher risk for virus transmission. Dose effect: Usual starting dose is 10 units. Each unit raises fibrinogen by about 8 mg/dl. Follow fibrinogen levels every 6-8 hours to guide frequency and quantity of administration. Intravenous Immunoglobulin (IVIG) Indications: passive antibody prophylaxis for susceptible individuals exposed to certain infectious diseases (tetanus, rabies, hepatitis B), toxic shock syndrome complicating strep or staph infections, primary immune globulin deficiency, ITP or AIDS associated thrombocytopenia, Guillain-Barr syndrome, prophylaxis following allogenic-BMT. Available forms:

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Standard immune serum globulin: routine disease prophylaxis. Hyperimmune globulin: high titer antibody against specific diseases IVIG: Provides immediate maximum IgG levels after infusion. Dose based on weight (generally 1 g/kg). Avoid sucrose containing preparation if any underlying renal insufficiency Caution if possible IgA deficiency, chance of anaphylactic reaction

VITAMIN K Required for the post-translational modification of factor II, VII, IX, X, protein C and S. Severe deficiency will prolong PT and PTT. Indications for supplementation: Reversal of warfarin Severe vitamin K deficiency Causes: decreased dietary intake, broad spectrum antibiotics (eradicate gut flora), cholestasis of chronic liver disease, ileal disease, T-tube biliary drainage Vitamin K is stored in the liver, but chronically ill patients with poor intake will become deficient in 7-10 days. Dose: Prophylaxis: 10 mg p.o. (may not be reliable with malabsorption). In large meta-analysis SQ route no better than placebo in reversing anti-coagulation. Can attempt if necessary but should be 3rd option Active treatment: 1 mg IV daily x 3 days. Because of small risk of anaphylaxis, must have strong indication for IV route. Risk reduced significantly by infusion of dose over 1 hour. Effect begins 6-12 hours after administration, with maximal effect after 36 hours. Vitamin K supplementation will not be useful in severe liver disease when synthetic function is impaired. GROWTH FACTORS Indications for Erythropoietin Anemia of chronic renal failure (Cr > 1.8) Multiple recent studies demonstrating goal Hgb 10.0-12.0 with mortality for correction > 12.0. Dose: 50-100 units/kg IV or SQ 3 per week. Can titrate up dose if no response. Should respond within 1-2 months. Anemia with HIV Myelodysplastic syndromes No longer giving to cancer patients receiving chemotherapy given new black box warning issued. Initial data on improved quality of life for patients but more recent data with concerns of mortality. Contraindicated in uncontrolled hypertension Indications for G-CSF To accelerate myeloid recovery in patients with non-Hodgkins lymphoma, Hodgkins lymphoma, acute lymphoblastic leukemia, or following autologous-BMT To decrease incidence of febrile neutropenia in patients with non-myeloid malignancies receiving chemotherapy associated with significant incidence of neutropenia and fever. Current ASCO recommendations for patients with risk of febrile neutropenia > 20% (difficult to estimate) Secondary use (after development of febrile neutropenia) has demonstrated decreased duration of neutropenia, decreased length of hospital stay, but no mortality benefit. Relative contraindication: excess myeloid blasts (> 10%) in marrow or peripheral blood.

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TRANSFUSION REACTIONS Acute Hemolysis Caused by ABO incompatibility Incidence: rare Signs: fever/chills, hypotension, flushing, dyspnea, flank pain Fever often initial sign (rational for attempting to prevent non-hemolytic transfusion reaction) Complications: acute renal failure, shock, DIC, death Diagnosis: RUA (hemoglobinuria) Positive direct Coombs test Agglutination of RBCs on smear Workup: type and cross of donor and recipient blood (post-transfusion blood sample) with order for posttransfusion workup (sample is visually inspected for hemolysis) Treatment: Stop transfusion immediately if reaction suspected! Maintain blood pressure and urine output with vigorous NS hydration via new infusion set. Lasix 80-100 mg, or mannitol IV to maintain urine output with goal >100 cc urine/hr. Follow strict I/Os. Close monitoring for any electrolyte abnormalities (hyperkalemia) Anaphylaxis Incidence: 1 in 150,000 Cause: recipient antibodies react with donor plasma forming immune complexes which activate complement. Reported in patients with congenital IgA deficiency and high titers of anti-IgA IgG. Signs: sudden onset flushing and hypertension followed by hypotension, edema, respiratory distress, shock. Workup: none (no evidence of RBC incompatibility) Treatment: 0.2-0.5 cc of epinephrine 1:1000 SQ/IM. Repeat every 3-5 minutes as necessary. NS infusion to maintain urine output and BP. Treat hypoxia with supplemental O2. Prevention: patients with history of anaphylaxis to blood should receive components depleted of plasma (saline washed RBCs). Acute Lung Injury Cause: not completely clear. Likely mediated by leukocyte agglutinating antibodies in donor plasma reacting with recipient leukocytes in pulmonary vasculature Incidence: 1 in 2,000 RBC transfusions Signs: acute respiratory distress, cyanosis, fever, bilateral pulmonary infiltrates without other signs of heart failure. Onset: within 6 hours of transfusion Treatment: ventilatory assistance (i.e. ARDSNET protocol), diuretics, steroids (no data for use of steroids) Prevention: assay donors blood, generally bar donor from future donation. Delayed Hemolysis Incidence: 1 in 2,500 Cause: patients with undetectable antibodies when typed and crossed develop antibodies to minor antigens, leading to extravascular hemolysis. Sometimes these antibodies persist indefinitely after transfusion or following exposure to fetal antigens during pregnancy. Onset of symptoms: 4-14 days post-transfusion Signs: fever, jaundice, anemia, hemoglobinuria

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Workup: identify responsible antibody to avoid acute hemolysis in future! Patient should carry a transfusion alert card. Send H/H, total and direct bilirubin, direct Coombs, type and screen of donor and recipient blood. Bacterial Contamination Incidence: uncertain, more common in platelet transfusion Signs: fever, hypotension Onset: within 4 hours of transfusion Workup: culture of remaining product and immediate antibiotics for the patient. Febrile, Non-Hemolytic Transfusion Reaction Incidence: 1% of packed RBCs, up to 20% of platelet transfusions Cause: recipient antibodies to passenger donor leukocytes or donor cytokines produced by stored leukocytes. Signs: fever, rigors, nausea, vomiting, back/chest pain, HTN Onset: within 2 hours of transfusion Workup: similar to hemolytic reaction (difficult to differentiate based on clinical signs alone) Treatment: leukocyte reducing filters for transfusion dependent patients. Only 15% of patients with 1 reaction have a repeat episode; if a 2nd reaction does occur, give leukocyte reduced RBC and platelets. Urticaria Cause: soluble substances in donor plasma react with IgE which stimulates mast cell degranulation. Symptoms: rash, pruritus Treatment: monitor for anaphylaxis. Benadryl 50 mg IV. If rash or symptoms resolve within 30 minutes, may resume transfusion. Massive Transfusions Hypothermia: warm blood products. Hypocalcemia: secondary to citrate, provide IV calcium gluconate (generally only a problem for patients with hepatic dysfunction) Bleeding complications: follow platelet count and coags. No role for empiric transfusion of coagulation factors.

NEUTROPENIA Definition: absolute neutrophil cell count (ANC) < 500 ANC = WBC count % polymorphonuclear cells (PMNs) Risk of serious infection dramatically when ANC falls below 1000. Management: when ANC reaches 500 or less, or in patients with impending neutropenia (i.e. patients receiving conditioning chemotherapy with ANC 1000 or less and dropping), institute: Neutropenic precautions (hand washing for all contact with patient; masks, gowns or gloves are not necessary unless the health care worker in contact with the patient is ill, i.e. has a cold or URI) Neutropenic diet (low bacterial, i.e. no fresh fruits or vegetables) Gut sterilizers (pre-printed antibiotic form) Norfloxacin 400 mg p.o. BID Clotrimazole troche 10 mg to dissolve in mouth 4 daily OR nystatin swish and swallow 5 cc 5 daily Nystatin powder to apply to axilla and groin TID Nystatin tablets 1 million units p.o. 4 daily Patients on systemic antifungal prophylaxis (i.e. fluconazole or itraconazole IV) do not require p.o. nystatin or clotrimazole. Neutropenic patients should NOT receive medications per rectum or rectal exams as this can increase risk of gram negative bacteremia and sepsis. Avoid foley catheters if possible.

HEMATOLOGY/ONCOLOGY Antibiotic prophylaxis is shown to decrease febrile episodes but no mortality benefit. Not currently recommended by IDSA. However, recent meta-analysis demonstrating mortality benefit may change practice.

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NEUTROPENIC FEVER May be due to transient bacteremia from translocation of GI bacteria, exacerbated in setting of mucositis, constipation, or rectal manipulation. Suppression of normal flora (i.e. anaerobes) by broad spectrum antibiotics leads to overgrowth of yeast and gram negative aerobic bacteria. If ANC < 500, and patient has temperature > 38.0C), immediately start neutropenic fever workup, examine patient, and administer broad spectrum antibiotics within one hour! (do NOT just write the antibiotic orders, make sure antibiotics are running into the patient as these patients can get septic and hypotensive very quickly). Workup (source identified in < 30% patients): Bacterial blood cultures 2 (2 different sites, include peripheral stick as well as from central line). Fungal blood culture Consider blood CMV quantitative DNA (especially if patient has received allogeneic transplant) Routine urinalysis, urine bacterial and fungal cultures and sensitivity Sputum for gram stain (if coughing or respiratory symptoms), bacterial culture, fungal stain and culture, CMV culture, viral culture, and viral respiratory antigen direct (especially during flu season, Nov-Mar) Stool for C. difficile if patient has diarrhea or has been on antibiotics STAT portable CXR (Consider early CT if high suspicion for PNA) Examine patient for signs of infection (look at line sites, lungs, oral and anal mucus membranes, skin lesions) Swab all mucosal lesions for HSV (dont forget to ask about/look for rectal and genital lesions, but do not do a rectal exam!) Consider LP if significant altered mental status Antibiotic regimen: MUST INCLUDE BROAD SPECTRUM GRAM NEGATIVE COVERAGE Please refer to latest recommendations per J/SO pharmacy handout as recommendations change, and check if patient is eligible for a study protocol. Dosages that follow are for normal renal functioncalculate CrCl and adjust dose as necessary for renal insufficiency. Increasing number of gram positive infections (central venous catheters). The following antibiotics have been compared in head-head RCT without differences in mortality: Imipenem 500 mg IV q6hrs (this is first line) OR cefepime 2 gm IV q12hrs Penicillin allergy: aztreonam 1 gm IV q8hrs (dont forget you need gram positive coverage) Consider addition of antifungal agent if > 3-5 days of fever on antibacterial agents (50% patients will have resolution of febrile neutropenia s/p initiation of antifungals) Amphotericin B traditional 1st line agent. RCT have found similar efficacy for ABLC, itraconazole, voriconazole, and caspofungin. Consider alternative to amphotericin B as less side effects. Emerging role for posaconazole (only newer agent with Mucor activity) If decision made to use amphotericin B: Dose: 0.5 mg/kg/day (if cultures positive for fungus, dose is 1-1.5 mg/kg/day) Typical dose infusion lasts 4 hours. No test dose necessary, as this delays treatment, but be aware of risk for severe reaction. Premedication:

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Tylenol 650 mg p.o. 1, Benadryl 25-50 mg IV/PO 1, NS 250 cc bolus prior to infusion. May use Demerol 25-50 mg IV as needed for rigors (consider making this a standing order if patient consistently has rigors) Consider hydrocortisone 25 mg added to infusion if patient is poorly tolerant of amphotericin. Low dose amphotericin B (0.5 mg/kg/day) for patients with renal failure. If creatinine climbs during treatment, change to ABLC. Aggressive electrolyte repletion while giving amphotericin B (causes K and Mg wasting) Other hints: Add vancomycin only when indicated (i.e. erythematous line site or cultures positive for coagulasenegative staphylococcus) since empiric vancomycin leads to VRE selection pressure Consider adding Bactrim in patients with persistent fever (for possible Stenotrophomonas) Treat all positive cultures (never assume anything is a contaminant in an immunosuppressed patient!) Consider vitamin K supplementation if on antibiotics with poor appetite (dose at 10 mg p.o. daily) Give G-CSF 5-10 mcg/kg SQ daily for neutropenic patients following marrow suppressive chemotherapy or autologous-BMT No mortality benefit in RCT but decreased duration of neutropenia and decreased hospital stay

BONE MARROW TRANSPLANTATION Definition The intravenous infusion of hematopoietic progenitor cells designed to establish marrow and immune function in patients with a variety of malignant and nonmalignant disorders, such as leukemia, lymphoma, myeloma, and aplastic anemia. Bone marrow transplant (BMT): stem cells from bone marrow harvested from donor under anesthesia in an operating room (almost never performed anymore). Peripheral blood stem cell transplant (PBSCT): stem cells are collected after a donor is primed with G-CSF to promote circulation of stem cells in peripheral blood. Circulating stem cells are then collected by leukophoresis. Note that BMT often is used to mean both BMT and PBSCT Allogeneic BMT Bone marrow from a patients HLA-identical sibling or unrelated donor is transplanted. Used in cases of primary hematologic malignancy that would preclude the collection of autologous stem cells (i.e. AML, CML, or lymphomas that are refractory to chemotherapy). Need to specify whether donor is related or unrelated and if the HLA match is 5/6 or 6/6 Advantages: Absence of malignant cells contaminating the stem cell product. Potential graft versus tumor effect (useful in malignancies that are incurable with conventional chemotherapy). Disadvantages: Difficulty in finding an HLA-matched donor Development of graft versus host disease (GVHD) wherein donor T cells attack host tissues Limited to patients < 65 years old Prolonged neutropenia prior to engraftment (typically 3 weeks) Chronic immunosuppression (typical regimen is cyclosporine and prednisone) Complications: Infections: CMV pneumonitis within first 100 days after BMT, PCP, CMV viremia. Toxicities from chemotherapeutic regimen Acute graft versus host disease (GVHD) within first 100 days after BMT.

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Chronic graft versus host disease (GVHD) which occurs about 6 months to 3 years after BMT. Increased risk for development of secondary malignancies of skin, buccal cavity, CNS, thyroid, and connective tissue. Autologous BMT The patients own bone marrow cells are harvested (when in remission) and cryopreserved before administration of chemotherapy and/or high-dose radiation therapy. After chemotherapy and/or radiation, cells are thawed and infused into the patient to re-establish hematopoiesis. Useful when underlying disease is chemo/radiation responsive, but patient is at statistically high risk for relapse (i.e. AML, HD, NHL in remission, multiple myeloma) Advantages: No need for finding an HLA-matched donor Can be used to treat patients up to 70 years old No risk of GVHD Shorter neutropenia No prolonged immunosuppression Disadvantages: Potential for residual diseased cells being re-infused into patient No graft versus tumor effect Complications: Toxicities from high-dose chemotherapy and radiation therapy (EF must be > 40%) Infections (possible anti-fungal prophylaxis, Bactrim prophylaxis) Veno-occlusive disease of the liver early after BMT, especially with busulfan BCNU-related interstitial pneumonitis (late complication) Timeline Terminology Day of transplant = day 0 Days before transplant = day -x (i.e. day -2 is 2 days before the transplant) Days after transplant = day +x (i.e. day +2 is 2 days after the transplant) TIMELINE OF FREQUENT COMPLICATIONS AFTER BONE MARROW TRANSPLANTATION (TIME IN MONTHS) 0 1 2 3 4 5 6 7 8 9 10 11 12 Bacteria Bacteria (pneumococcal > staph or gram negatives) Aspergillus Candida HSV VZV PCP CMV Acute GVHD Chronic GVHD VOD Acute Renal Failure

BMT COMPLICATIONS AND PREVENTION Infections HSV (Herpes Virus): reactivates before marrow engraftment in 70-80% of seropositive recipients of allogeneic BMTs. Think of HSV in patients with mucositis. Swab oral lesions for HSV I/II with direct Immunofluorescence kit. Treat mucocutaneous HSV infection with IV acyclovir 5 mg/kg IV q8hrs; CNS HSV with 10 mg/kg IV q8hrs; zoster with 12-15 mg/kg IV q8hrs.

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PCP prophylaxis for BMT recipients: Autologous: Pre-BMT from admission until day -2: Bactrim DS 1 tab p.o. t.i.d. Post-BMT when ANC > 1000 3 consecutive days for 1 month: Bactrim DS 1 tab p.o. t.i.d. every Saturday/Sunday and Leucovorin 5 mg p.o. once a day every Saturday/Sunday Allogenic: Pre-BMT from admission until day -2: Bactrim 2 amps IV t.i.d. Post-BMT when ANC > 1000 3 consecutive days: Bactrim DS 1 tab p.o. t.i.d. every Saturday/Sunday and Leucovorin 5 mg p.o. once a day every Saturday/Sunday Continue for 2 weeks after all immunosuppression is stopped For patients with sulfa allergy: Mepron 750 mg p.o. daily OR pentamidine 300 mg inhaled monthly Prophylaxis for CMV-seropositive allogeneic BMT recipients: require antiviral drugs to prevent reactivation of latent virus. Pre-BMT from admission until day -2: ganciclovir 6 mg/kg/day IV until day -2 Post-BMT when ANC > 1000 3 consecutive days until day +100: ganciclovir 6 mg/kg/day IV every Monday-Friday Monitor ANC. Will need to decrease dose if neutropenic. Prophylaxis for CMV-seronegative allogeneic BMT recipients: ALWAYS use CMV-seronegative blood products for all transfusions. This almost eliminates the risk for primary CMV infection, and no ganciclovir prophylaxis is required. Antifungal prophylaxis: (generally reserved for high risk allogeneic transplants) Itraconazole 200 mg IV q12hrs 2 days then 200 mg IV daily until day +100. Can switch to p.o. suspension when tolerating orals. Graft Versus Host Disease (GVHD) GVHD prophylaxis: IVIG: 500 mg/kg (round off to the nearest 1 gm) IV weekly from admission until day +100, then monthly for the first year. Start IVIG infusion at 50 cc/hr 30 min, then increase to 75 cc/hr 30 min and to final rate of 125 cc/hr if no reaction. IVIG is rarely associated with anaphylaxis. Premedicate with Benadryl 50 mg p.o. and Tylenol 650 mg p.o. Cyclosporine: loading dose (3 mg/kg IV over 12 hours) on day -2 then 3 mg/kg/day continuous IV infusion starting on day -1. Change to Neoral after day +21 if tolerating orals (Neoral dosing is double the IV dose divided b.i.d.) Check levels on day +1, +4, then weekly with goal level 150-350 (if switched to Neoral, check levels 2 days and 7 days after switch) Solu-Medrol: patients 40, mismatched donor, unrelated donor, aplastic anemia. Start 1 mg/kg/day IV on day +3 and continue until day +30, then taper if no GVHD. Methotrexate: patients 40, mismatched donor, unrelated donor, CML patients in chronic phase, aplastic anemia. Given on days +1 (at least 24 hours after completion of stem cell transfusion), +3, and +6 Acute GVHD: Onset: about 30 days Organ involvement: skin, liver, GI tract Target cell involved: epidermal cells Incidence: 40-70% grade II to IV Histologic grading: stages I IV, highly recommended since signs and symptoms can be nonspecific

HEMATOLOGY/ONCOLOGY Treatment: high dose steroids, anti-thymocyte globulin (ATG) Acute GRAFT VERSUS HOST DISEASE CLINICAL GRADING Skin Liver GI (Total Bilirubin) (Diarrhea) Rash < 25% of body 1.5-3.5 500-1000 cc/day Rash 25-50% of body 3.6-8.0 1000-1500 cc /day Rash > 50% of body 8.1-15.0 1500-2500 cc/day OR diffuse erythroderma Bullae, desquamation > 15.0 > 2500 cc/day or ileus

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Grade Grade I Grade II Grade III Grade IV

Chronic GVHD: Onset: about 100 days Organ involvement: skin, liver, salivary glands, mucous membranes, muscles CHRONIC GRAFT VERSUS HOST DISEASE ORGAN INVOLVEMENT AND COMPLICATIONS Organ/Organ System Complication Eye (lens) Cataracts Eye (conjunctiva) Dry, red eyes Oral mucosa Decreased salivation, tooth decay, mouth ulcers Pulmonary Bronchiolitis obliterans, sinus and lung infections Liver Primary biliary cirrhosis-like syndrome Immune System Immunodeficiency, bacterial and viral infections Muscle Myositis Skin Scleroderma, skin rash Gut Malabsorption, diarrhea, abdominal pain Hematopoietic Pancytopenia Reproductive Decreased libido, vaginal dryness Multisystem Cancers in areas of previous GVHD

Target cell: mesenchymal cells Incidence: 20-50% (severe about 5%) Clinical grading: based on extent of disease, either limited or extensive Treatment: none proven effective; high dose steroids, ATG may increase survival. Mucositis cocktail: Benadryl elixir 25 mg/10 ml + Maalox 10 ml + viscous lidocaine 2% 10 ml swish and swallow 5 ml of the mix q4hrs as needed for mouth pain Veno-occlusive Disease (VOD): incidence of VOD in patients with pre-existent liver disease, allo-BMT, certain conditioning regimens, fever during cytoreductive therapy, and treatment with estrogens-progestins, amphotericin or methotrexate. About 70% recover from VOD Onset: generally occurs within 2-3 weeks of after transplant Signs/Symptoms: jaundice, tender hepatomegaly, ascites Up to 50% of patients develop 2 of 3 primary symptoms of VOD Diagnosis: requires RUQ ultrasound, and at times, liver biopsy Prophylaxis: evidence for ursodeoxycholic acid (UDCA), low dose heparin

HEMATOLOGY/ONCOLOGY Treatment: primarily supportive. Studies to evaluate heparin/tPA (response rate 30-40%, significantly increased bleeding), defibrotide (encouraging preliminary results.) Acute Renal Failure: Causes: 0-5 days after BMT: tumor-lysis syndrome (rare), stored marrow-infusion toxicity (probably due to DMSO used for cryopreservation of stem cells) 10-28 days after BMT: 90% due to VOD-associated hepatorenal-like syndrome 1 month after BMT: often due to BMT-associated HUS, cyclosporine-associated HUS, or chronic cyclosporine nephrotoxicity. Other causes of ARF which can occur at any time during or after BMT include: Nephrotoxic drugs (gentamicin, amphotericin B, cisplatin) ATN due to hemorrhagic or septic shock AIN due to penicillins, cephalosporins, allopurinol Obstructive uropathy due to hemorrhagic cystitis with clots or urogenital fungal infections.

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ONCOLOGIC EMERGENCIES Hypercalcemia Most common paraneoplastic syndrome, especially in breast cancer, squamous cell cancers of head and neck, renal, and multiple myeloma. Etiology: Bone destruction by metastases Mediators elaborated by tumor cells (PTH-related protein, TGF-) Osteoclast activating factors (IL-1, TNF) produced by hematologic malignancies Signs: see hypercalcemia in Nephrology section Treatment: (also see Nephrology section). Restore intravascular volume: NS hydration at 200 cc/hr (sodium ion competitively inhibits renal tubular absorption of calcium). Rehydration alone should decrease total calcium by 1 mg/dl. Furosemide: start with 20 mg IV. Works by preventing Ca resorption at ascending loop of Henle. NS and furosemide should produce maximum effect within 24 hours Steroids: prednisone 40-100 mg/day. Predominantly useful for treating symptoms caused by breast or hematologic malignancies. Works by inhibiting GI absorption of calcium, preventing release of osteoclast activating factors, and may cause lysis of tumor cells. Calcitonin: 4 international units /kg SQ/IM q12hrs. Decreases ionized calcium 1-2 mg/dl in 4-6 hours. Tachyphylaxis common problem. Nasal delivery not effective. Pamidronate: 90 mg IV 1. Potent inhibitor of osteoclast function, with effect lasting 1 month! Delayed action up to 48 hours before effect. 30mg IV if renal failure. Caution in patients with recent dental work Zoledronic Acid: 4mg IV over 15 minutes. In two RCT improved response rate as compared to pamidronate. Do not use if in renal failure. Caution in patients with recent dental work. Can use hemodialysis for severe hypercalcemia with significant side effects Some evidence for prophylactic bisphosphonate therapy in patients with known bone metastasis Superior Vena Cava Syndrome (SVCS) Etiology: Malignancy: usually primary lung (especially small cell), lymphoma, mets to mediastinum. Other: aortic aneurysm, goiter, fibrosing mediastinitis from prior infection (histoplasmosis) or XRT, catheter associated DVT. Signs/Symptoms: rate of compression corresponds to symptoms (amount of collateral formation). Progressive erythema/edema of unilateral upper extremity with ipsilateral face and neck involvement.

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Dyspnea, cough, hoarseness, headache, nasal congestion, epistaxis (worse with bending forward or lying down) Physical exam: dilated neck veins, collateral vessels covering chest wall, cyanosis and edema of upper extremity. Radiology: CXR: widened superior mediastinum (> 80% sensitivity), usually R>L, ipsilateral pleural effusion, or may be normal. Duplex ultrasound of neck and upper extremities: rule out thrombosis. Chest CT with contrast: gold standard. Mass, decreased opacification of central veins, prominent collateral circulation. Treatment: intervention depends on tissue diagnosis. If clinically stable may want to delay radiation therapy to make tissue diagnosis. SVCS is an emergency if there is tracheal obstructionemergent tracheostomy versus intubation versus surgery. Endovascular stent: (>90% effective). May need ongoing low dose warfarin therapy, no RCT data. Small cell lung cancer or lymphoma: steroids, chemo, XRT Non-small cell lung cancer: XRT DVT: Emergent thrombolysis by interventional radiology. Symptomatic: head of bed elevation, supplemental O2, low dose diuretics. Tumor Lysis Syndrome Cause: usually follows chemotherapy in malignancies with high tumor burden (high grade lymphoma, acute or chronic leukemia, rarely in solid tumors). May occasionally be seen prior to treatment due to spontaneous tumor necrosis. Antecedent risk factors: High tumor bulk (numerous sites of disease or large tumor mass) LDH or uric acid Azotemia with oliguria Hypovolemia Diagnosis: Hyperkalemia Hyperuricemia Hyperphosphatemia with hypocalcemia (danger of renal tubular calcification if calcium-phosphate product > 60) Treatment: NS hydration to achieve adequate urine output (4-5 L/day). Alkalinize urine: keep urine pH > 7 by administering sodium bicarbonate with IVF (1 amp HCO3 in 1 L NS, or 2 amps in D5W) (for uric acid related renal failure (more common with spontaneous tumor lysis)) Caution if hyperphosphatemia as can initiate renal tubular precipitation of calcium phosphate. Allopurinol: 300 mg t.i.d. incidence of uric acid nephropathy incidence of hyperphosphatemic renal failure Rasburicase: degrades uric acid. Rapid decrease in uric acid levels. Data primarily in children. Monitor K, PO4, Ca, uric acid, BUN, Cr q2-4hrs Consider emergent hemodialysis if K > 6, uric acid > 10, oliguria/anuria with rising BUN/Cr, PO4>10, CaPO4 product > 60. Treat DIC with supportive transfusions of blood products if indicated

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Treat hypocalcemia only if symptomatic Spinal Cord Compression Cause: metastases to vertebral bodies or spinal canal (lung, breast, prostate, lymphoma, multiple myeloma) Signs: localized back pain, neurologic deficits (sensory loss 1-2 levels below site of compression, weakness of involved extremities, spasticity, hyperreflexia, autonomic or sphincter dysfunction) Diagnosis: neurologic exam, spinal series, MRI Treatment: Decadron 6 mg IV q6hrs (no RCT data). Consider high dose (96mg x 1, 24mg q6hrs) for patients with paraplegia per one RCT. Radiation Oncology consult for emergent XRT. Neurosurgical consult for surgical release (especially with evidence of spinal instability, XRT failure, rapidly evolving symptoms, or to obtain tissue diagnosis) Prognosis: 75% of patients treated while still ambulatory remain so, while only 10% of paraplegics will recover. Aggressive intervention needed. Increased Intracranial Pressure Cause: metastases (breast, lung, renal, melanoma) causing edema, hydrocephalus; spontaneous hemorrhage into mets, carcinomatous meningitis Signs: headache, nausea/vomiting, altered mental status, focal neurologic deficits Diagnosis: papilledema, CT with IV contrast, LP for carcinomatous meningitis (increased opening pressure, high protein, low glucose) Treatment: Intubation with hyperventilation to decrease cerebral blood flow Mannitol 1 g/kg IV q6hrs Decadron 6 mg IV q6hrs Emergent XRT Surgical resection of isolated lesions Intrathecal chemotherapy for carcinomatous meningitis Pericardial Tamponade Cause: intrathoracic cancer (lung, breast, leukemia, lymphoma), prior XRT, drugs, hypothyroidism, infection Signs: elevated JVP, hepatomegaly, pedal edema, friction rub Diagnosis: pulsus paradoxus, low voltage on EKG, CXR, transthoracic echocardiogram Treatment: pericardiocentesis, pericardial window, chemotherapy, XRT

HEMATOLOGY/ONCOLOGY ANTIEMETICS FOR CHEMOTHERAPY PATIENTS Drug Diphenhydramine (Benadryl) 25-50 mg PO/IV Scopolamine Lorazepam (Ativan) 1-2 mg PO/IV

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Class Mild Potency Antihistamines Anticholinergics Benzodiazepines

Mild to Moderate Potency Phenothiazines Prochlorperazine (Compazine) 5-10 mg PO/IV or 25 mg PR Chlorpromazine (Thorazine) Promethazine (Phenergan) 25 mg PO/IV/PR Butyrophenones Droperidol 0.625-1.25 mg IV Haloperidol 2 mg IV Corticosteroids Dexamethasone 10-20 mg IV Methylprednisolone 60 mg IV Cannabinoids Dronabinol (Marinol) 10 mg PO Nabilone High Potency Serotonin antagonists Ondansetron 8 mg PO or 10 mg IV Granisetron (Kytril) 10 mcg/kg IV Palonosetron-Aloxi 0.25 mg IV 30 minutes pre-chemo (do not give more than once weekly as it is long acting) High-dose substituted Metoclopramide (Reglan) 10 mg IV benzamides Trimethobenzamide Alizapride Aprepitant (Emend) a neurokinin/substance P blocker. Given the day of chemo and 2 days after chemo orally for highly-emetogenic chemotherapy. Combination regimen for highly emetogenic chemotherapeutic regimens: 1) Dexamethasone 20 mg IV + metoclopramide 3 mg/kg IV q2h 2 + diphenhydramine 25-50 mg IV q2h 2 + lorazepam 1-2 mg IV 2) Dexamethasone 20 mg IV + ondansetron 32 mg IV (in divided doses)

HEMATOLOGY/ONCOLOGY COMMON TUMOR MARKERS Associated Illness Hepatocellular carcinoma, gonadal germ cell tumor, cirrhosis, hepatitis Medullary cancer of the thyroid Adenocarcinomas of the colon, pancreas, lung, breast, ovary, pancreatitis, hepatitis, IBD, smoking Pheochromocytoma Ovarian cancer, some lymphomas, menstruation, peritonitis, pregnancy, breast cancer, bland ascites Cancer of the colon, pancreas, breast, pancreatitis, ulcerative colitis Hairy cell leukemia, adult T-cell leukemia/lymphoma Hodgkins disease, anaplastic large cell lymphoma Gestational trophoblastic disease, gonadal germ cell tumors, pregnancy Lymphoma, Ewings sarcoma, hepatitis, hemolytic anemia, and many others Multiple myeloma, infection, monoclonal gammopathy of unknown significance (MGUS) Small cell cancer of the lung, neuroblastoma Prostate cancer, prostatitis, benign prostatic hypertrophy

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Tumor Marker -fetoprotein (AFP) Calcitonin Carcinoembryonic antigen (CEA) Catecholamines CA-125 CA 19-9 CD25 CD30 Human chorionic gonadotropin (-HCG) Lactate dehydrogenase (LDH) Monoclonal immunoglobulin Neuron-specific enolase (NSE) Prostatic acid phosphatase Prostate-specific antigen (PSA)

HEMATOLOGY/ONCOLOGY COMMON CHEMOTHERAPEUTIC AGENTS Emetogenic Potential Significant Side Effects Moderate (> 1gm/m2) Low Moderate (> 250 mg/m2) Cerebellar dysfunction, conjunctivitis (high dose) Cerebellar symptoms, hand-foot syndrome, diarrhea Mucositis, dermatitis, interstitial pneumonitis, crystal nephropathy Hepatotoxicity Neurotoxicity Interstitial pneumonitis, hemorrhagic cystitis VOD, hyperpigmentation, Addison-like syndrome Encephalopathy, hemorrhagic cystitis (use MESNA) Peripheral neuropathy, ototoxicity, renal toxicity Pulmonary toxicity (acute pneumonitis/delayed fibrosis), delayed myelosuppression Test dose for possible anaphylaxis, erythroderma, interstitial pneumonitis, mucositis Vesicant Cardiotoxicity (cumulative dose > 550 mg/m2) Cardiotoxicity Myelosuppression, cardiomyopathy Vesicant, neuropathy Vesicant, neuropathy Anaphylaxis (premedication), neuropathy

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Drug Name Antimetabolites Cytarabine (ara-C) 5- FU Methotrexate

6-MP Low Fludarabine Low Alkylating Agents (Sterility) Cyclophosphamide High (> 1500 mg/m2) Busulfan Moderate Ifosfamide Moderate Cisplatin High (> 50 mg/m2) BCNU High (Carmustine) Antimicrobials Bleomycin Low Doxorubicin Mitoxantrone Plant Alkaloids Etoposide Vinblastine Vincristine Paclitaxel Other Irinotecan High/Moderate Low Moderate Minimal Minimal Low

Moderate Diarrhea, fever, abdominal pain High: > 90% frequency of emesis; moderate: 30-90%; low: 10-30%; minimal: < 10%

HEMATOLOGY/ONCOLOGY NOVEL CHEMOTHERAPEUTIC AGENTS Mechanism of Action Clinical Use Anti-VEGF Colon Cancer, NSCLC, Renal, Breast ABL Kinas Anti-EGFR Gleevec Resistant CML Colon Cancer, NSCLC, Head/Neck SCC NSCLC, Pancreatic NSCLC CML, GIST Colon Cancer NHL Renal Cell, HCC Investigation (breast, colon, NSCLC, ovarian, pancreatic ) Renal Cell Breast Cancer Infusion reaction, immunosuppression, mucocutaneous Diarrhea, rash, hand-foot syndrome

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Drug Name Bevacizumab (Avastin) BMS-354825 (dasatinib) Cetuximab (Erbitux)

Side Effects Proteinuria, hypertension, gastrointestinal perforation, and arterial embolic events Weakness, fever, headache, acneiform rash, nausea, and hypersensitivity reactions Rash, diarrhea, pulmonary toxicity Rash, diarrhea, pulmonary toxicity Nausea, vomiting, cytopenias, heart failure

Erlotinib (Tarceva) Gefitinib (Iressa) Imatinib (Gleevec) Panitumumab (Vectibix, ABX-EGF) Fully Humanized Rituximab (Rituxan) Sorafenib

EGFR TK EGFR TK ABL, ARG, c-KIT, and PDGFR kinases Anti-EGFR Anti-CD20 Raf/VEGFR kinase inhibitor (multiple other targets) VEGF Kinase, (Multiple other targets) Anti-HER2 (EGFR)

Sunitinib (Sutent) Trastuzumab (Herceptin)

Infusion reaction, Cardiomyopathy, Pulmonary toxicity

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KEY CONCEPTS OF ANTI-MICROBIAL THERAPY Pharmacokinetics: relates to the absorption, distribution, and elimination of a drug. Absorption: important for determining IV vs PO as well as drug-drug interactions (i.e. PPI + iron) Distribution: important to note drugs which are lipophilic, protein bound and site of infections (i.e. in poorly vascularized sites). Elimination: important to adjust for renal or hepatic insufficiency. Pharmacodynamics: describes the relationship between the drug and its intended antimicrobial effect. Synergy: when two antibiotics used together have bactericidal activity greater than the sum of the two used alone. Antagonism is the opposite, use of a second agent decreases the efficacy of the either used individually. Post-antibiotic effect: the continued bactericidal activity of an antibiotic after the serum levels have fallen below the MIC. Time-dependent killing: an antibiotic is effective for as long as its serum concentration is above the MIC, concentration-independent. Examples: -lactams, glycopeptides (Vancomycin), macrolides, clindamycin. This is the rationale for continuous infusion therapy. Aim >40% time greater than the MIC. Concentration-dependent killing: An antibiotics effectiveness is proportional to the degree which its serum concentration exceeds its MIC. Examples: aminoglycosides, fluoroquinolones, metronidazole. This is the rationale for once-daily dosing of aminoglycosides and increased doses of fluoroquinolones. THERAPEUTIC DRUG MONITORING Vancomycin Dosed based on weight, aim 10-15mg/kg (not everyone gets 1 gram) Monitor serum trough for long-term treatment and in patients with varying renal function or on HD Aim for trough 2-4x MIC (5-10), but for some infections (i.e. deep tissue infections, endocarditis) may want higher (15-20) If trough is out of desired range, change INTERVAL of dosing No need to monitor peak levels Aminoglycosides Required for prolonged AG therapy as adverse effects (renal and ototoxicity) are related to drug levels DOSE is determined based on weight INTERVAL is determined by drug levels When using traditional dosing (every 8 hours): Peak: to check for efficacy, if out of range change DOSE Trough: to check for safety, if out of range change INTERVAL When using once-daily dosing: Obtain an extended interval level (6-14 hours after dose) and then use normogram to determine proper INTERVAL of dosing. Can call pharmacy for help. FEVER Definition Average normal oral body temperature is 36.8oC (normal range 36.4-37.2) Rectal temps are 0.5oC degrees higher, axillary temps are lower

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Elderly patients have a lower mean body temperature and they may not mount a fever when septic and can even be hypothermic Work-up when T 38.3oC or one hour of T 38.0oC o If immunosuppressed, concern when 38.0 C (see neutropenic fever) Evaluation (when called evaluate patient immediately) Review patients medical problems Obtain vital signs and mental status (tachycardic? tachypneic? hypotensive?) Focus on specific complaints: cough, SOB, N/V/D, urinary symptoms, erythematous IV or CVC line site? Has patient had fever work-up in the last 48 hours? Thorough but efficient exam: Eyeball test Vital Signs CVC or other indwelling devices (Foley, drains, etc.) Often overlooked sites: periodontal, oropharynx (mucositis, parapharyngeal abscess), sinuses, abdomen (abscess), perineum, skin, nails Differential Diagnosis Quick: Wind: Pneumonia, atelectasis, pharyngitis Water: UTI Wound: Incisions, cellulitis, skin abscesses Wires: IV/CVC sites Wonder drugs: Drug fever Walk: DVT Causes of nosocomial infection in the ICU: Sinusitis (think NGT-related), catheter sepsis, drug fever, wound infection (remember decubital ulcers), pneumonia, pulmonary embolism, acute MI, endocarditis, pericarditis, acalculous cholecystitis, perforated ulcer, pancreatitis, enterocolitis, bowel infarction, urosepsis, DVT, systemic inflammatory response syndrome (SIRS) Complete differential: Infections: bacterial, viral, rickettsial, fungal, parasitic Autoimmune diseases: lupus, polyarteritis nodosa, rheumatic fever, polymyalgia rheumatica, giant cell arteritis, Stills disease, Wegeners granulomatosis, vasculitis, relapsing polychondritis; less prominent in dermatomyositis, adult RA CNS disease: Cerebral hemorrhage, head injuries, brain and spinal cord tumors, degenerative central nervous system disease (i.e. multiple sclerosis), spinal cord injuries (due to interference with thermal regulatory process rather than true fever) Malignancy (tumor fever) Hematologic disease: lymphomas, leukemia, hemolytic anemia Cardiopulmonary/Vascular disease: myocardial infarction, thrombophlebitis, pulmonary embolism, DVT. Gastrointestinal disease: inflammatory bowel disease, liver abscess, alcoholic hepatitis, granulomatous hepatitis Endocrine disease: hyperthyroidism, pheochromocytoma may raise temperature due to altered thermal regulation. Diseases due to chemical agents: drug reactions (including serum sickness), neuroleptic malignant syndrome, malignant hyperthermia or anesthesia, serotonergic syndrome. Miscellaneous: sarcoidosis, familial Mediterranean fever, tissue injury, postoperative fever, hematoma, febrile transfusion reaction (due to anti-leukocyte antibodies), factitious fever

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For persistent or recurrent fevers think secondary infection, resistant bacteria, or abscess Management Basic Workup: Blood cultures (bacterial and fungal) from at least 2 sites (peripheral and each lumen on central line), CXR, RUA and Urine culture, sputum/trach culture For transplant/immunosuppressed patients consider: Blood: bacterial culture, fungal culture, CMV DNA quant, cocci Ab EIA, aspergillus Ag EIA, crypto Ag, EBV, AFB Sputum: bacterial culture, fungal culture, Influenza direct Ag A and B, AFB, mycoplasma ab, HSV IgM, RSV Ag, PCP direct stain Urine: Legionella Ab Also consider other catheter sites with induration or drainage LP if CNS infection suspected If diarrhea present, check C. difficile stool toxin (routine stool cultures are not indicated if diarrhea develops after >48 hours of hospitalization). C. difficile can be associated with markedly elevated WBC. Consider additional imaging if indicated (i.e. RUQ U/S, sinus CT, LE duplex, abdomen/pelvis CT) In the absence of an identifiable infection, empiric antibiotic therapy should be used only in those with hypotension/impending septic shock or who are immunocompromised. If clearly infected, hang antibiotics yourself avoid delay! Other things to consider: Fluid replacement if volume depleted. Removal of heat (i.e. cooling blanket) and antipyretic agents if patient is uncomfortable Note: do not write antipyretics as a standing PRN so that you can see if an infection is being treated or developing.

PNEUMONIA Community acquired Pneumonia in Immunocompetent Hospitalized Patient Organisms: S. pneumoniae, H. influenzae, Polymicrobial, Aerobic GNRs, Legionella species, S. aureus, C. pneumoniae, Respiratory viruses Other agents: M. pneumoniae, M catarrhalis, M. tuberculosis, endemic fungi Diagnostic Evaluation: CXR, CBC, Chem7, LFTs, 2 sets of blood cultures; gram stain and sputum culture and pulse oximetry. ABG (if hypoxic) Consider HIV test (if age<55yo, homeless or other risk factors) (everyone?), urine Legionella Ag (in elderly smoker), AFB stain and culture (if cough>1mo, homeless, other risk factors) Empiric Therapy: First antimicrobial dose within 3 hours of initial assessment! Expanded spectrum fluoroquinolone (levofloxacin) OR 3rd gen Cephalosporin AND macrolide (azithromycin) NOTE: This regimen misses MRSA and highly resistant Strep pneumoniae In severe (ICU) community acquired pneumonia: Antipseudomonal 4th generation cephalosporin (cefepime) AND macrolide (azithromycin) OR fluoroquinolone OR other antipseudomonal agent AND aminoglycoside (gentamicin or tobramycin) for first few days If suspect aspiration: Ceftriaxone or Levofloxacin

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If h/o long term residence facility, need anti-pseudomonal coverage: Levofloxacin or Zosyn or Ceftazidime If h/o severe periodontal disease, necrotizing PNA on CXR, or EtOH: Add anaerobic coverage: Levofloxacin PLUS (clindamycin OR metronidazole) OR -lactam with -lactamase inhibitor Risk Factors associated with increased morbidity and mortality: Age > 65 Coexisting illnesses: DM, renal failure, CHF, chronic lung disease, EtOH, aspiration, recent hospitalization, altered mental status PE: RR>30, BP<90/60, T38.3C, confusion or lethargy Labs: WBC <4,000 or >30,000, PaO2<60, PCO2>50, Cr>1.2, BUN>20, Hct<30, coagulopathy; multilobar disease or effusions on CXR References: Community Acquired Pneumonia in Adults: Guidelines for Management. Clin Infect Dis. 2000;31:34782. Mandell LA, Bartlett JG, Dowell SF, et. al. Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis. 2003;37:1405. Halm EA, Teirstein AS. Clinical practice. Management of community-acquired pneumonia. N Engl J Med. 2002;347:2039. Marik PE. Aspiration pneumonitis and aspiration pneumonia. N Engl J Med. 2001;344:665. Hospital acquired Pneumonia Organisms: Staph aureus, Strep pneumoniae MRSA, Enteric gram negative rods (Enterobacter species, E. coli, Klebsiella, Proteus species, Serratia marcescens), Haemophilus influenzae, Anaerobes, Pseudomonas aeruginosa, Acinetobacter, Fungi (candida, aspergillus) in neutropenic patients Diagnostic evaluation: Suspect in hospitalized patients who have new or progressive lung infiltrates and at least 2 of the following: fever, purulent sputum, leukocytosis See diagnostic evaluation for CAP Consider bronchoscopy for bronchoalveolar lavage Empiric therapy: Fluoroquinolone + anti-pseudomonal -lactam (ceftazidime) + vancomycin aminoglycoside Example: Levofloxacin + piperacillin/tazobactam + vancomycin gentamicin Consider imipenem after initial double coverage with anti-pseudomonal -lactam and gentamicin Add macrolide (IV erythromycin or azithromycin) if Legionella suspected Add clindamycin if aspiration suspected (controversial) Add vancomycin if MRSA suspected Add Amphotericin B in neutropenic patients if high suspicion for fungi (Amphotericin B traditional 1st line agent. Consider alternatives such as Itraconazole, Voriconazole, Caspofungin as less side effects (similar efficacy per RCT). Emerging role for posaconazole (only newer agent with Mucor activity) References Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcareassociated pneumonia. Am J Respir Crit Care Med. 2005;171:388. Pneumonia in HIV positive patient (see HIV section for more information) Organisms:

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S. pneumoniae, H. influenzae, PCP, M. tuberculosis, Aerobic GNRs (E. coli, Klebsiella), MAI, Fungi (Cryptococcus, Histoplasmosis), CMV, Toxoplasmosis, Diagnostic evaluation: See diagnostic evaluation for CAP Induced sputum for PCP and TB (if negative perform bronchoscopy) Remember to isolate patient as indicated Empiric therapy: Use therapy for CAP AND high-dose trimethoprim/sulfamethoxazole to cover PCP (add prednisone for PaO2<70) AND high-dose ganciclovir to cover CMV

TUBERCULOSIS Criteria for a Positive Tuberculin Skin Test Induration of 5 mm HIV positive Recent contacts of patients with TB Fibrotic changes on CXR consistent with prior TB Organ transplant recipients Other immunosuppressed patients (those taking the equivalent of >15mg/d of prednisone for 1 month or those taking TNF-a antagonists) Induration of 10 mm Recent (<5yrs) immigrants from high prevalence countries Injection drug users Clinical conditions increasing risk: DM, CRF, leukemia or lymphoma, head, neck or lung cancers, silicosis, weight loss 10% of ideal body weight, gastrectomy or jejunoileal bypass Residents of and employees of high risk congregate settings: Prisons, nursing homes, hospitals, homeless shelters Children 4yo or children exposed to adults at high risk Mycobacteriology laboratory personnel Induration of 15 mm No risk factors Active Tuberculosis Diagnosis Signs/Symptoms: Prolonged cough, chest pain, weight loss, fever, chills, night sweats, anorexia, fatigue, sputum production, and hemoptysis History: History of TB exposure/infection/disease, past TB treatment, demographic risk factors, medical conditions that increase risk for disease CXR: Cannot confirm diagnosis Abnormalities in apical or posterior segments of upper lobe or superior segment of lower lobe Appearance may be unusual in HIV patients Specimen collection: AFB stain and culture (with susceptibility testing) on induced sputum x 3 Skin testing: 10-25% of people with TB will have a negative skin test

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False positives: non-tuberculous mycobacterium, BCG vaccine False negatives: anergy, recent TB infection, <6 months of age, live virus vaccine, overwhelming disease QuantiFeron-TB test: Whole blood test used to detect M. tuberculosis infection Treatment Treat based on clinical suspicion! Do not wait for skin test results (can be negative) and culture and susceptibility (may not be available for 3-6 weeks) Isolation: Hospitalize very sick patients and those living in congregate or high risk setting; respiratory isolation is recommended for 2 months of treatment until disease is probably not communicable Empiric Regimens: 4 drugs (isoniazid, rifampin, pyrazinamide, ethambutol OR streptomycin) Isoniazid 5mg/kg/d (max dose 300mg) Rifampin 10mg/kg/d (max dose 600mg) Pyrazinamide 15-20mg/kg/d (max dose 2g) Ethambutol 25mg/kg/d x 2mos then 15mg/kg/d Streptomycin 15mg/kg/d IM Department of Health approval for discharge 72 hours before discharge: call ext 4-0187 (hospital epidemiology) for assistance with DHS discharge care plan Weekends/holidays: M.D. must call DHS TB physician on call (213)974-1234 to obtain discharge approval References David Pegues Noon conference lecture Blumberg HM, Burman WJ, et. al. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis. Am J Respir Crit Care Med. 2003;167:603. Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection. Am J of Respiratory Critical Care Medicine. 2000;161:S221.

MENINGITIS Obtain informed consent from the patient or family member prior to doing lumbar puncture (LP) Bacterial meningitis is an infectious emergency with a 25% case mortality rate When acute meningitis is suspected, prompt therapy with antibiotics is the standard of care. Perform funduscopic exam and consider head CT if you suspect increased intracranial pressure (in patients with coma, papilledema, or focal neurologic findings) Do NOT perform LP in this setting as herniation may result If imaging is indicated, obtain blood cultures, institute empiric antibiotic therapy (see below), and THEN obtain CT Perform LP immediately after the imaging if there is no intracranial mass lesion Instituting antibiotics 1-2 hours before LP will not decrease diagnostic sensitivity if CSF culture is done in conjunction with blood culture and CSF bacterial antigen testing Always check the opening pressure (normal < 20cm) unless LP has to be done with patient sitting up.

INFECTIOUS DISEASE CEREBRAL SPINAL FLUID STUDIES Studies Cell count and differential Glucose and protein Gram stain, bacterial culture, fungal culture and stain, AFB culture and smear, India Ink, VDRL, cryptococcal Ag 4 1 cc Cell count and differential If indicated, send for cocci Ab (CF & ID), toxo IgG, HSV PCR, CMV PCR, VZV PCR, TB PCR, lyme, histo Ag, viral culture, bacterial Ag panel, MEM (viral panel) If cancer: cytology If MS: IgG synthesis, oligoclonal bands, myelin basic protein If CNS lupus: antineuronal Ab (75-90% +) and antiribosomal P protein (45-80% +) Tube 1 2 3 Amount 1 cc 1 cc 3-5 cc CSF FINDINGS IN VARIOUS TYPES OF MENINGITIS Bacterial Viral TB nl to mod 100-1000, PMNs predominate 10-500, lymphs predominate except first few days where PMNs often predominate Nl or slightly , <100mg/dl nl 25-100, lymphs predominate except early stages where PMNs often predominate 100200mg/dl

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Finding Opening pressure WBCs & diff

Normal 6-20 cm H2O 0-5, 85% lymphs

Cocci 50-1000, initially PMNs predominate then monos, eos occ. present min. 20-40mg/dl, may be nl in early disease gm stain & culture usually negative

Cryptococcal 0-800, lymphs predominate (can be very low or zero in patients with AIDS) 20-500mg/dl, avg 100mg/dl 10-40mg/dl

Protein Glucose

18-45 mg/dL 45-80 mg/dL or (0.6 x serum glucose) For traumatic LPs, add 1WBC/1000 RBCs

100-500, occ > 1000mg/dl 5-40mg/dl, occ nl gram stain + in 60%, culture + in 2/3 of cases

Other

AFB smear + in < 25%, culture + in 2/3 of cases after >4 wks

CSF or serum crypto Ag + in 95% of cases, India Ink + in 75%

Empiric Treatment (Adapted from The Sanford Guide to Antimicrobial Therapy, 2006) Bacterial/CSF Gram stain negative/Immunocompetent patient (note that if Gram stain positive, see specific therapy in Sanford) Age<50yr Likely etiology: S. pneumoniae, meningococci, H. influenzae Treatment: ceftriaxone 2gm IV q12h + dexamethasone 10mg IV q6h x 4d with or just before 1st antibiotic dose + vancomycin 15mg/kg IV q6h NOTE: IV vancomycin has very poor CNS absorption; if confirmed high level resistant S. pneumoniae, may need to give intrathecal vancomycin which carries risk of seizure.

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Age>50yr or other debilitating disease (i.e. alcoholism) Likely etiology: S. pneumoniae, listeria, Gram-negative bacilli Treatment: ampicillin 2gm IV q4h + ceftriaxone 2gm Ivq12h + dexamethasone 10 mg/kg q6h IV x 4d with or just before 1st dose of antibiotic (NEJM 347;1549, 1613, 2002;4:139, 2004) Any age with impaired cellular immunity Likely etiology: Listeria, Gram-negative bacilli Treatment: ampicillin 2gm IV q4h + ceftazidime 2gm IV q8h Post-neurosurgery or head trauma Likely etiology: S. pneumoniae if CSF leak; S. aureus, coliforms, P. aeruginosa Treatment: vancomycin (until proven non-MRSA) 500-750gm IV q6h + cefepime or ceftazidime 2gm IV q8h Ventriculitis/meningitis due to infected V-P shunt Likely etiology: S. epidermidis, S. aureus, coliforms, diphtheroids, P. acnes Treatment: vancomycin 500-750gm IV q6 + cefepime or ceftazidime 2gm IV q8h Chronic Meningitis (symptoms and CSF pleocytosis>4wks) Likely etiology: M. tuberculosis, cryptococci, neoplastic, unknown Treatment: depends on etiology; usually no need for urgent treatment Bacterial meningitis in HIV+ patient Likely etiology: same as adults>50yr, also cryptococci, M. tuberculosis, syphilis, HIV aseptic meningitis, Listeria monocytogenes Treatment: as for adult>50yr Viral Meningitis/Encephalitis Likely etiologies: HSV, VZV, enterovirus Treatment: acyclovir 10mg/kg IV q8h x 14-21d (pending viral PCRs and cultures)

BACTERIAL ENDOCARDITIS Clinical Manifestations Signs/Symptoms: fever, chills, sweats, anorexia, weight loss, malaise, myalgias, arthralgias, heart murmur, arterial emboli, splenomegaly, petechiae, peripheral manifestations (Oslers nodes, subungual hemorrhages, Janeway lesions, Roths spots) and signs of CHF. Laboratory manifestations: anemia, leukocytosis, microscopic hematuria, elevated ESR, CRP, RF, circulating immune complexes, decreased serum complement Microbiology S. aureus (30-40%), viridans group strep, enterococci (1%), coagulase-staph, culture negative (2-20%) Risk Factors Structural heart disease, IVDU, indwelling vasc devices, bacteremia with other infection, prior history of infective endocarditis Work-Up Blood Cultures: If not critically ill: 3 blood cultures over 12-24 hours (can delay treatment) If critically ill: 3 blood cultures over 1 hour (treat) Echo (TTE or TEE) EKG: evaluate for conduction abnormalities, ischemia, infarction CXR: evaluate for septic emboli, valvular calcification, CHF

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Diagnosis Modified Duke Criteria (2 major OR 1 major and 3 minor OR 5 minor criteria) Major Criteria Positive blood cultures Typical microorganisms from two separate blood cultures: viridans strep, Strep bovis, HACEK, or community acquired Staph aureus or enterococci in absence of primary focus Persistently positive blood culture: recovery of organism from blood cultures drawn > 12hrs apart OR all of 3 or majority of 4 or more separate blood cultures with first and last > 1hr apart Evidence of endocardial involvement Positive echo: oscillating intracardiac mass or abscess or new partial dehiscence of prosthetic valve New valvular regurgitation Minor Criteria Predisposing heart condition or injection drug use Fever 38.0C Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, Janeway lesions Immunologic phenomena: glomerulonephritis, Oslers nodes, Roths spots, RF Microbiologic evidence: positive blood culture but not meeting above major criteria or serologic evidence of active infection with organism consistent with infective endocarditis Empiric Treatment (for culture-positive endocarditis, use Sanford Guide to determine regimen) Unless the pt has a toxic appearance or clinical or echo evidence of progressive valvular regurgitation or CHF, empiric antibiotics should be delayed until blood cultures are drawn. Administration of antibiotics before blood cultures are obtained reduces recovery rate of bacteria by 30-45%. Native valve without IVDU: [Penicillin G 20 million units q24h continuous or divided q4h OR ampicillin 12gm IV q24h continuous or divided q4h] AND oxacillin 2 gm IV q4h AND gentamicin 1mg/kg IV q8h Alternative regimen is vancomycin + gentamicin Native valve with IVDU (S. aureus) Vancomycin 1gm IV q12h OR daptomycin 6mg/kg q24h Prosthetic valve Vancomycin 15mg/kg IV q12h + rifampin 600mg PO q24h + gentamicin 1mg/kg IV q8h Indications for use of aminoglycosides for synergy Shorter course regimen in right-sided endocarditis Enterococcal endocarditis Prosthetic valve Prophylaxis (indirect evidence, no randomized trials) Cardiac lesions for which endocarditis prophylaxis is advised: High risk: prosthetic valves, prior bacterial endocarditis, complex cyanotic heart disease (except isolated secundum ASD and completely corrected PDA, VSD or pulmonary stenosis), PDA, coarctation of the aorta, surgically constructed systemic-pulmonary shunts Moderate risk: congenital cardiac malformations, VSD, bicuspid AV, acquired AV and MV, hypertrophic CMY, MVP with valvular regurgitation and/or thickened leaflets Procedures for which endocarditis prophylaxis is advised (moderate and high risk patients): Dental procedures: extractions, periodontal procedures, implant placement, root canal, surgery beyond apex, subgingival placement of antibiotic fibers/strips, placement of orthodontic bands but not brackets, intraligamentary injections Respiratory procedures: operations involving mucosa, rigid bronchoscopy

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GI procedures: Esophageal variceal sclerotherapy, stricture dilatation, ERCP, biliary tract surgery, bowel surgery involving the mucosa GU procedures: urethral dilation, prostate or urethral surgery, cystoscopy Antibiotic regimens for prophylaxis of endocarditis in adults at moderate or high risk: Oral cavity, respiratory tract, or esophageal procedures Amoxicillin 2gm orally 1 hour before procedure Unable to take oral medications: ampicillin 2gm IV or IM within 30mins of procedures PCN allergy options: Clarithromycin 500mg PO 1h before procedure Cephalexin 2gm PO 1h before procedure Clindamycin 600mg PO 1h before procedure or IV 30mins before procedure Cefazolin 1gm IV/IM 30mins before procedure GU/GI procedures High risk: ampicillin 2gm IM/IV and (gentamicin 1.5mg/kg within 30min of procedure); repeat ampicillin 1gm IM/IV or amoxicillin 1g PO 6h later High risk with PCN allergy: vancomycin 1gm IV over 1-2h AND gentamicin 1.5mg/kg IV/IM completed within 30 minutes of procedure Moderate risk: amoxicillin 2g PO 1h before procedure or ampicillin 2g IV/IM within 30min before procedure Moderate risk with PCN allergy: vancomycin 1g IV over 1-2h completed within 30 min of procedure References Matthew Leibowitz Noon conference lecture Infective Endocarditis Baddour LM, Wilson WR, et. al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation. 2005;111:e394. The Sanford Guide to Antimicrobial Therapy, 2006.

CLOSTRIDIUM DIFFICILE History Recent exposure to antibiotics. Any antibiotic, but newer data show that fluoroquinolones and 3rd generation cephalosporins (not clindamycin) seem to be most highly associated with this complication. However, exposure to other patients with C. difficile colitis in a hospital or other group facility can result in infection. Signs/Symptoms: Diarrhea, abdominal pain, fever, leukocytosis (can cause leukemoid reaction with WBC >30,000) Diagnosis Send 2 stool samples for C. difficile toxin (do not order C. difficile toxin x3!) Sensitivity of one C. difficile toxin assay (our lab runs BOTH A and B, even though sometimes the computer reports toxin A) is about 80%, sensitivity of 2 is over 90%. Therefore, the lab will only run 2 samples in a 7 day period. Management Discontinue broad-spectrum antibiotic agent or change to another agent with a more narrow spectrum specifically targeting known or suspected etiology Supportive measures: correct fluid losses and electrolyte imbalance Avoid antiperistaltic agents Contact isolation precautions for hospitalized patients

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Avoid using vancomycin for treatment while patient is hospitalized to avoid selecting for VRE Specific Treatment Antimicrobial Agents Metronidazole: 500 mg PO TID x 10 days: always the first drug of choice. PO is preferred to IV, but both work fairly equally. It may take several days for signs and symptoms to improve, rare Flagyl failure. Do not panic and add PO vancomycin (very expensive!) if pt. not better in 2 days. Treat for total 10 days. No need to repeat C. difficile toxin at end of Rx as test of cure, may still be positive. Vancomycin: 125 mg PO QID x 7-14 days Parenteral agent (to be used only until oral agents are tolerated): metronidazole 500 mg IV q6hrs Older agents that may be added in severe disease- Rifampin or Bacitracin: 25,000 U PO QID x 7-14 days (see below) Newer agents that may be effective: Rifaximin and nitazoxanide. Recurrences and Relapses Flagyl is still first drug of choice for repeat/recurrent C. difficile. Flagyl-resistant C. difficile rare, even after recent Rx with Flagyl, so choose Flagyl again Vancomycin or Metronidazole PO x 10-14 days. Vancomycin + rifampin (600 mg PO BID) x 7-14 days Many protocols for long-term Rx for patients with several recurrences, lactobacillus unlikely to be helpful while pt. is still on antibiotics, and cholestyramine is of questionable efficacy, consult ID if assistance is required. Emerging pathogen: more virulent epidemic C. difficile. Seen even in outpatients with no predisposing risk factors (N Engl J Med. 2005;353:2442).

LINE INFECTIONS Infected IV catheters are usually due to gram positive cocci, most often coagulase-negative staphylococcus or S. aureus Empirically treat with vancomycin If severe sepsis without other obvious source, remove CVC Remove CVC if any evidence of infection at catheter site References Infectious Diseases Society of America, Society of Critical Care Medicine, Society for Healthcare Epidemiology of America. Guidelines for the Management of Intravascular Catheter-Related Infections. Clinical Infectious Diseases. 2001;32:1249. URINARY TRACT INFECTIONS General Considerations Although a urine Gram stain may be useful in guiding therapy, all antibiotics recommended as empiric therapy are effective against Gram-negative bacilli (pyelonephritis is not treated empirically with ampicillin or sulfonamides alone due to E. coli resistance to these antibiotics). In patients with nosocomial pyelonephritis, a history of recurrent UTI, or prior infection with a resistant organism, initial antimicrobial therapy should cover Pseudomonas aeruginosa (I.e. cefepime, tobramycin, imipenem, ciprofloxacin, or piperacillin/tazobactam). In all cases, antibiotic therapy should be revised once susceptibility data are available. If bacteriuria persists > 24-48 hours, switch the antibiotic based on susceptibility data. If fever or toxicity persists despite adequate antibiotics, consider perinephric or renal cortical abscess and evaluate with imaging of kidneys. Signs of pyelonephritis (i.e. fever, leukocytosis) may not be present in the elderly.

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Categories and Empiric Treatment Acute, uncomplicated cystitis in women Dysuria, urgency, frequency, suprapubic pain No prior urinary symptoms in last 4 weeks No fever or flank pain Treatment: 3 days of oral TMP/SMX (DS) OR FQ DM, >7 days of symptoms, recent UTI, age > 65, or diaphragm use: treat for 7 days with above Pregnant: 7 days of oral amoxicillin, nitrofurantoin, cefpodoxime, OR TMP/SMX (do not use near term) Acute, uncomplicated pyelonephritis in women Fever, chills, dysuria, urgency, frequency, suprapubic pain, CVA tenderness and/or flank pain No history of urologic abnormalities Treatment: Mild/moderate symptoms without nausea/vomiting: oral FQ x7 days OR amoxicillin/clavulanate or cephalexin or TMP/SMX (DS) x14 days rd Severe/urosepsis requiring hospitalization: IV FQ OR (ampicillin + gentamicin) OR 3 generation cephalosporin OR piperacillin/tazobactam until afebrile then oral TMP/SMX (DS) or FQ x14 days Pregnancy: IV ceftizoxime OR gentamicin ampicillin OR aztreonam OR TMP/SMX until afebrile then oral amoxicillin OR cephalosporin OR TMP/SMX (DS) x14 days Complicated UTI Any combination of findings in above categories Men or patients with post-void residual > 100 mL, outlet obstruction, calculus, urinary catheter, vesicoureteral reflux, prior renal disease with azotemia Treatment: Mild/moderate symptoms without nausea/vomiting: oral FQ x10-14 days Severe/urosepsis requiring hospitalization: IV ciprofloxacin OR (ampicillin + gentamicin) OR ceftizoxime OR aztreonam OR piperacillin/tazobactam OR imipenem until afebrile then oral TMP/SMX (DS) or FQ x14-21 days Asymptomatic Treat only those who are pregnant, diabetic, and/or immuno-compromised. Asymptomatic Bacteriuria 5 Definition: >10 bacteria/mL of urine obtained by sterile technique on consecutive samples. If symptomatic, treat the patient. If asymptomatic, treat only those patients who are pregnant, have obstructive uropathy, or prior to genitourinary instrumentation. Prevalence is increased in elderly or patients with a condom catheter or indwelling Foley catheter. Women with diabetes have 3-fold higher rates of asymptomatic bacteriuria and may benefit from an initial attempt at eradication with a 2-week course of antibiotics. Often, bacteriuria is difficult to eradicate and routine antimicrobial therapy is not recommended. Pyuria Diagnosis: leukocyte esterase positive on dipstick (50% PPV; 92% NPV). Definition: more than 10 WBCs per mm3 of urine Most symptomatic women with pyuria but without bacteriuria do have UTIs, either with bacteria at levels 5 less than 10 /mL or with Chlamydia trachomatis. Patients with catheter-associated bacteriuria and pyuria are more likely to have true infection.

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Differential diagnosis of sterile pyuria includes: perinephric and renal cortical abscesses, urethral syndrome, chronic prostatitis, renal tuberculosis or fungal infection, renal papillary necrosis (esp. diabetes, sickle cell disease, chronic alcoholism), genital herpes, chlamydia, uric acid and hypercalcemic nephropathy, lithium and heavy metal toxicity, GU malignancy, sarcoidosis, transplant rejection, interstitial cystitis, polycystic kidney disease, and s/p TURP (several months). Candiduria Diagnosis: Species include: C. albicans, C. tropicalis, C. parapsilosis, and C. glabrata. May represent contamination, colonization, cystitis, pyelonephritis, or disseminated infection. Candida may contaminate urine cultures as a result of coincident perineal colonization, vulvovaginitis or balanitis (esp. diabetes). If candiduria is noted, first confirm with clean-cath specimen. In the absence of an indwelling bladder catheter, a colony count > 10,000/mL typically indicates infection. Risk factors favoring colonization of the bladder: diabetes, indwelling catheter, broad-spectrum antibiotics, immunosuppressive therapy, and pregnancy. In elderly and diabetic patients, this diagnosis may be elusive and is suggested by vague constitutional symptoms, a decline in renal function, and persistence of candiduria despite topical antifungal therapy, e.g., amphotericin bladder irrigation. Disseminated candidiasis is suspected in patients with risk factors for blood-borne disease: malignancy (esp. leukemia/lymphoma), postoperative status, intravascular catheters, immunosuppression, broadspectrum antimicrobial therapy, and malnutrition. Check RUA for pyuriafunguria without pyuria is unlikely an infection. Treatment: Asymptomatic candiduria is treated by eliminating the predisposing factor. Cystitis: as above and Fluconazole 200 mg p.o., then 100 mg p.o. qd x 4-7 days. Pyelonephritis and disseminated disease: Fluconazole (800mg iv x 1 dose, then 400 mg IV qd x 7d, then 400 mg p.o. qd x 14d) or Amphotericin B (0.5 mg/kg IV qd to a total cumulative dose of 5-7 mg/kg). For non-candida fungal UTI (e.g. C. glabrata): First try hi dose (2x normal dose) fluconazole Then try low dose IV Amphotericin B Then consider Amphotericin B bladder irrigation but use with caution in Renal transplant or pt. with abnormal GU anatomy. IV Caspofungin has virtually no penetration into urine/bladder and has little role in Rx of candiduria. LACTOSE FERMENTING STATUS OF GRAM NEGATIVE ORGANISMS Lactose Positive (CEEK) Lactose Negative (SPAM) Citrobacter freundii Serratia Escherichia Coli Salmonella Enterobacter Shigella Klebsiella pneumoniae, oxytoca Stenotrophomonas maltophilia Proteus Providencia Pseudomonas Plesiomonas Acinetobacter Aeromonas Morganella

INFECTIOUS DISEASE QUICK GUIDE TO EMPIRIC ANTIBIOTIC MANAGEMENT Adapted from Martha Lewis Noon conference lecture Guide to Empiric Antibiotic Management General Considerations: What are you treating and how? Site of Infection: drug penetration, common organism Host: immune status, past pathogens, drug-drug interactions, allergies Susceptibility data Infection Meningitis* If post-op Ventriculitis due to an infected VP shunt Bugs S. pneumoniae N. Meningitidis, H. influenzae Listeria Staphylococcus sp. Gram negative rods (GNR) S. epidermidis S. aureus Coliforms Diphtheroids P. acnes Herpes simplex virus Varicella zoster virus West Nile virus S. pneumoniae M. catarrhalis Staphylococcus sp. Group A, C, G streptococcus N. gonorrhoea Streptococcus sp. Oral anaerobes S. pneumoniae H. influenzae Chlamydia Mycoplasma Legionella S. pneumoniae S. aureus Enteric GNR (i.e. klebsiella) P. aeruginosa MRSA Acinetobacter Multidrug resistant GNR Stenotrophomonas PCP Cytomegalovirus Drugs Ceftriaxone + vancomycin ampicillin Ceftazidime + vancomycin Vancomycin + rifampin

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Encephalitis (viral) Sinusitis Mastoiditis Pharyngitis Retropharyngeal/neck abscess Pneumonia Community-acquired

Acyclovir Amoxicillin or Augmentin (if prior antibiotic exposure) Ceftriaxone vancomycin Penicillin Ceftriaxone (IM) + treat for Chlamydia with azithromycin OR doxycycline Clindamycin Levaquin OR Ceftriaxone + azithromycin

Hospital-acquired (48 hours) Ventilator-associated (48-72 hours)

Levaquin + Zosyn OR Ceftriaxone/ceftazidime + vancomycin gentamicin Imipenem + levofloxacin (vancomycin OR linezolid if suspect MRSA)

Pneumonitis

High-dose Bactrim OR High-dose Ganciclovir

INFECTIOUS DISEASE Infection Endocarditis Bugs S. aureus (MRSA) Viridans streptococcus Enterococcus Coagulase-negative staph Enteric GNR Candida Coagulase-negative staph S. aureus Enteric GNR P. aeruginosa Staphylococcus sp. Viridans streptococcus Enteric GNR P. aeruginosa Staphylococcus sp. Viridans streptococcus Campylobacter E. coli Salmonella Shigella Giardia C. difficile Enteric GNR Anaerobes Enterococcus sp. Enteric GNR Anaerobes Enterococcus sp. Enteric GNR Streptococcus sp. Enterococcus sp. Enteric GNR Enterococcus sp. S. saprophyticus Enteric GNR Enterococcus sp. S. saprophyticus N. gonorrhoea C. trachomatis S. aureus Streptococcus sp. MRSA Drugs Blood cultures first! Vancomycin + gentamicin + rifampin (if valve) Caspofungin Vancomycin (Ceftazidime gentamicin) OR Imipenem/Zosyn/Cefepime vancomycin (if possible line infection) Ceftriaxone + gentamicin + metronidazole

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Line Infections Neutropenic Fever

Sepsis

Diarrhea

Mild to moderate diarrheano antibiotics! Severe diarrhea use ciprofloxacin and/or metronidazole (if C. difficile suspected)

Diverticulitis Biliary Sepsis Spontaneous Bacterial Peritonitis (SBP) Cystitis Pyelonephritis STD Cellulitis Boils, Furuncles, Spider bites

Ciprofloxacin + metronidazole (outpatient) Zosyn OR imipenem (inpatient) (Ceftriaxone + metronidazole) OR Zosyn Ceftriaxone (Prevention of SBP with Bactrim 5 days per week or weekly ciprofloxacin) Ciprofloxacin Cephalexin Cefpodoxime (Ceftriaxone + gentamicin) OR (ampicillin + gentamicin) Ceftriaxone (IM) Azithromycin OR doxycycline Cefazolin (IV), cephalexin (PO) Vancomycin Bactrim Doxycycline Rifampin Linezolid

INFECTIOUS DISEASE Infection Diabetic Foot Bugs Mixed flora: MSSA/MRSA Enteric GNR Anaerobes Streptococcus sp. S. aureus Clostridium Anaerobes MSSA/MRSA Enteric GNR Anaerobes P. aeruginosa Enteric GNR Anaerobes P. aeruginosa Coagulase-negative staph Drugs Augmentin Ceftriaxone + metronidazole vancomycin

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Necrotizing Fasciitis

Osteomyelitis with diabetic foot with hardware

Imipenem OR Penicillin + clindamycin + (fluoroquinolone OR 3rd generation cephalosporin OR aminoglycoside) Consider IVIG & Xigris Oxacillin OR vancomycin (Oxacillin OR vancomycin) + metronidazole and ceftriaxone Vancomycin + cefotaxime

*Dexamethasone (N Engl J Med 2002;347:1549) Coliforms include Escherichia, Enterobacter, Klebsiella, Citrobacter

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Trotman RL et al. Antibiotic Dosing in Critically Ill Adult Patients Receiving Continuous Renal Replacement Therapy. Clinical Infectious Disease 2005: 41: 1159-66.

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HUMAN IMMUNODEFICIENCY VIRUS (HIV) TESTING Who do you test for HIV? New CDC guidelines recommend offering it to everyone! HIV screening is recommended for patients in all health-care settings after the patient is notified that testing will be performed unless the patient declines (opt-out screening). Persons at high risk for HIV infection should be screened for HIV at least annually Separate written consent for HIV testing should not be required; general consent for medical care should be considered sufficient to encompass consent for HIV testing. Prevention counseling should not be required with HIV diagnostic testing or as part of HIV screening programs in health-care settings Injection drug users, patients receiving injections in countries where needles are reused, piercing, tattoos; partners of people in any of these categories: Gay or bisexual men and their partners Exchanging sex for drugs or money Unprotected sex Patient request Patients transfused with blood products prior to 1986 in US, or at any time in other countries where blood is not routinely screened All pregnant women Occupational exposure Hepatitis Tuberculosis Women with HPV Anyone with any STD Any hospitalized homeless patient Symptoms suggesting possible HIV Infection or an opportunistic infection: Young adults (age <50) with shingles Non-diabetic women with recurrent (>3 per year) yeast infections Patients with thrush without a clear cause Patients with idiopathic thrombocytopenic purpura (ITP) or other cytopenias Patients with primary pulmonary hypertension Lobar pneumonia in a young person (age <55) Anyone with symptoms of primary infection: fever, rash, lymphadenopathy, myalgias, headache Active tuberculosis Unexplained dementia Aseptic meningitis Peripheral neuropathy Fever of unknown etiology Unexplained diarrhea and/or weight loss Lymphoma Presentation with any unusual illness suggestive of cell mediated immunodeficiency LABORATORY DIAGNOSIS OF HIV HIV enzyme-linked immunosorbent assay (ELISA) Screening serology detecting HIV antibodies

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Antibodies to HIV can be detected 2-8 weeks after acquisition of infection, but can be delayed up to 6 months >99.9% sensitivity, but less specific for HIV infection False positive results may occur as a normal biological variant, with recent Influenza vaccine or other disease states (i.e. connective tissue diseases) If 2 ELISA tests of the same sample are positive, a confirmatory Western blot test is done by the laboratory Western Blot (WB) >99.99% specificity of positive result when combined with ELISA The indeterminate rate of HIV-1 WB is too high to permit Western blotting to be used as a screening assay Identifies the presence of specific antibodies to individual HIV viral proteins ASTPHLD/CDC guidelines: Two bands (either p24, gp41, or gp120/160)positive result One bandindeterminate result Indeterminate results may occur with early HIV infection, HIV-2 infection, auto-immune disease, pregnancy and recent tetanus toxoid administration Zero bandsnegative result Risk factors for HIV-2 infection should also be reviewed, and HIV-2 western blots should be performed in individuals with opportunistic infections or other AIDS-associated conditions. HIV DNA PCR Measures amount of actively replicating HIV Standard HIV RNA assays are not designed for diagnosis Use with caution to diagnose acute HIV infection during the window period when serology is negative or indeterminate Low levels (<5000 copies/mL) could represent a false positive resultcan confirm with p24 antigen

THE CDC DEFINITION OF AIDS Definitive AIDS Diagnosis (with or without laboratory evidence of HIV infection): Opportunistic infections and malignancies that rarely occur in the absence of severe immunodeficiency (i.e. PCP, CNS lymphoma, Kaposis, PML, etc.) Definitive AIDS Diagnosis (with laboratory evidence of HIV infection): Certain infections and malignancies that occur in immunocompetent hosts but are more common in immunodeficiency (i.e. invasive cervical cancer, pulmonary TB, recurrent PNA, etc.) Non-specific conditions like dementia and wasting CD4 count <200 cells/L at any time INITIAL WORK-UP OF HIV+ PATIENT Complete History and Physical: History: Testing history: include info such as last negative test and first positive test PMH: HIV related illnesses (anything that may indicate a defect in cell-mediated immunity) Vaccination history (dT, hepatitis A and B, Pneumovax) Tuberculosis history, including last PPD and results STDs Hepatitis Pancreatitis Meds: do not forget the OTCs

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GYN: pregnancy history, including during the time of known infection, LMP/menstrual history, last PAP, oral contraceptive use. Social situation: include support system (who is aware of the diagnosis), drug/alcohol use, behaviors (putting others at risk, taking risks by exposures), sexual history, domestic violence screen Travel history: ascertain if the patient lives in areas endemic for cocci, histo, blastomycosis (all of which may reactivate with advanced disease) Review of systems (especially for HIV related symptoms): fever, night sweats, weight loss, fatigue, diarrhea, rash, thrush, neuropathy, neuro/mental status changes including depression Patient education: long life span if they are compliant with medications, safer sex, partner notification/testing, injection drug use and crystal meth cessation, power of attorney, travel precautions, patient information web sites: TheBody.com, aidsinfo.org, GMHC.org, HIVLA.org Physical Exam: general exam including GU exam with and pelvic/Pap for all women at earliest occasion Laboratory Testing Repeat HIV: only for those who tested anonymously or those without documentation; consider repeat test if asymptomatic or CD4+ count is normal. Viral Load (baseline every 3-4 months): Use: assess prognosis, determine need for therapy, and provide baseline. Types: HIV RNA PCR, bDNA, nucleic acid sequence based amplification (NASBA) Expect high (>100,000) viral loads at seroconversion, disease progression/therapy failure, and with concurrent illnesses T-Cell Subset: Absolute CD4+ count (baseline Q3-4 months): Use for disease staging, assess risk of development of opportunistic infections and need for prophylaxis, assess response to therapy Fluctuations can be due to diurnal variation, steroid use, concurrent illness, lab variation, and/or variations in WBC count components CD4 %: more stable, especially with increased WBC counttherefore may be more accurate over time than the absolute CD4+ count Genotype: if viral load >1,000 copies and recent infection suspected, use to check for drug resistance CBC with differential, chemistry panel, fasting lipid panel Annual VDRL/RPR: Follow up with fluorescent treponemal antibody-absorption test (FTA-ABS) for positives LP probably necessary for latent syphilis or early syphilis with neurologic signs/symptoms, treatment failure, and those in whom standard therapy cannot be used. Tuberculosis: annual PPD for those in high risk populations. Do you need an anergy panel? NOT recommended! High variability, poor predictive value, and prophylaxis in anergics has prevented few cases Toxoplasmosis: baseline anti-toxoplasma IgG, repeat when CD4+ <100-200 Cytomegalovirus (CMV): baseline serology recommended only for persons not at high risk for CMV (99% of gay males are CMV positive) Gonorrhea and chlamydia: screening based on risk assessment Varicella Zoster Virus (VZV): serology only in those who cannot give a positive history of chicken pox or shingles. It is probably worth checking the anti-varicella IgG to determine in advance the need for post-exposure prophylaxis with VZIG and acyclovir Hepatitis: Hepatitis A:

HUMAN IMMUNODEFICIENCY VIRUS Pre-vaccine screening is cost effective Consider administer to all men who have sex with men (MSM) without prior exposure Vaccine should be administered in all hepatitis C positive patients Hepatitis B: Check HBsAg, HBsAb, anti-HBc at baseline, and on an as needed basis Check HBsAb post-vaccination Hepatitis C: Check HCV Ab in all patients at baseline, especially IVDU, and patients with elevated LFTs G6PD: at baseline in genetically susceptible patients prior to oxidant drug therapy (i.e. dapsone) CXR: consider at baseline, especially in those at risk for tuberculosis

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VACCINATIONS AND PROPHYLAXES FOR HIV INFECTED INDIVIDUALS For all HIV infected individuals: INH for those PPD positive (>5 mm induration) Pneumococcal vaccine initially then every 5 years thereafter Yearly influenza vaccine Hepatitis A for all MSM and HCV coinfected persons Hepatitis B vaccine for all those never exposed Diphtheria and tetanus toxoid vaccine every 10 years For those with CD4 count < 200 cells/L: Pneumocystis jiroveci prophylaxes: Bactrim DS one tablet orally daily (1st line prophylaxis, will also cover toxoplasmosis) Dapsone 100 mg orally 2-3 times per week (2nd line, use if intolerant to Bactrim) Aerosolized pentamidine 300 mg monthly (3rd line) Consider discontinuing prophylaxes if CD4 count increases to >200 for >3 months on HAART For those with CD4 count <50 cells/L: Mycobacterium avium prophylaxes: Clarithromycin 500 mg orally twice daily OR azithromycin 1200 mg orally weekly Consider discontinuing prophylaxes if CD4 count increase to >100 for >3 months on HAART For those with CD4 count <50cells/L: Consider CMV prophylaxes (only in patients CMV IgG positive): Oral ganciclovir approved for prophylaxis, but can cause neutropenia In CMV negative HIV patients, use CMV negative blood HIV COMPLICATIONS BY CD4+ COUNT Any CD4+ Count: Persistent generalized lymphadenopathy Aseptic meningitis Idiopathic thrombocytopenic purpura (ITP) Community acquired pneumonia Tuberculosis Kaposis sarcoma Varicella zoster virus CD4+ counts <500 cells/mm3: Herpes simplex virus Candida species

HUMAN IMMUNODEFICIENCY VIRUS Varicella zoster virus Epstein-Barr virus Lymphoma CD4+ counts <200 cells/mm3: Pneumocystis jiroveci CD4+ COUNT < 100 CELLS/MM3 Infection Clinical Manifestations Toxoplasma gondii Encephalitis Microsporidia Diarrhea Cryptosporidia Diarrhea Cryptococcus neoformans Meningitis, pulmonary Mycobacterium tuberculosis Disseminated or extrapulmonary tuberculosis Herpes simplex virus Disseminated or aggressive herpes Varicella zoster virus Disseminated herpes zoster Epstein-Barr virus Primary CNS lymphoma Mycobacterium avium complex Disseminated Mycobacterium avium complex Cytomegalovirus Retinitis, GI disease, CNS disease, pneumonitis HIV Wasting syndrome, neuropathy, dementia, myelopathy AIDS INDICATOR CONDITIONS Candidiasis of bronchi, trachea, or lungs Candidiasis, esophageal Cervical cancer, invasive Coccidioidomycosis, disseminated or extrapulmonary Cryptococcosis, extrapulmonary Cryptosporidiosis, chronic intestinal (> 1 month) Cytomegalovirus disease (other than liver, spleen, or nodes) Cytomegalovirus retinitis (with loss of vision) Encephalopathy, HIV-related Herpes simplex: chronic ulcer(s) (> 1 month); or bronchitis, pneumonitis, or esophagitis Histoplasmosis, disseminated or extrapulmonary Isosporiasis, chronic intestinal (> 1 month) Kaposi's sarcoma Lymphoma, Burkitt's (or equivalent term) Lymphoma, immunoblastic (or equivalent term) Lymphoma, primary, of brain Mycobacterium avium complex or M. kansasii, disseminated or extrapulmonary Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary) Mycobacterium, other species or unidentified species, disseminated or extrapulmonary Pneumocystis carinii pneumonia Pneumonia, recurrent Progressive multifocal leukoencephalopathy Salmonella septicemia, recurrent Toxoplasmosis of brain Wasting syndrome due to HIV

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ANTIRETROVIRAL THERAPY INITIATION AND TREATMENT CONSIDERATIONS Indications for initiating antiretroviral therapy: Antiretroviral therapy is recommended for all patients with a history of an AIDS-defining illness or severe symptoms of HIV infection regardless of CD4+ T cell count (AI). 3 Antiretroviral therapy is also recommended for asymptomatic patients with <200 CD4+ T cells/mm (AI). Asymptomatic patients with CD4+ T cell counts of 201350 cells/mm3 should be offered treatment (BII). 3 Asymptomatic patients with CD4+ T cell of >350 cells/mm and plasma HIV RNA >100,000 copies/mL Most experienced clinicians defer therapy but some clinicians may consider initiating treatment (CII). Therapy should be deferred for patients with CD4+ T cell counts of >350 cells/mm3 and plasma HIV RNA <100,000 copies/mL (DII). Treatment Considerations: Preserving immune function, including HIV specific immunity Response to therapy is better with baseline viral load <100,000 and CD4+ >200 Mortality and morbidity is improved if therapy is started when CD4+ >200 Balance the risk of drug side effects versus the risk of HIV related complications Resistance, cross resistance, mutation rate Future options Other Factors Affecting Decisions to Start Treatment: Willingness of patient to adhere to a complex regimen with side effects 3 Starting therapy at a CD4+ <200 cells/mm is associated with greater risk of virologic failure Higher viral loads at baseline are associated with a greater risk of subsequent virologic failure, independent of baseline CD4+ cell count. The level of viral load suppression after a few months of therapy is predictive of a durable viral load response, independent of the baseline viral load and CD4+ cell count. Increasing the CD4+ cell count in the severely immunocompromised, even to > 50 cells/mm3, can result in substantial reductions in the subsequent incidence of new AIDS events and death. Goal of Initial Therapy (ICONA Study): Suppression of the viral load to below the limits of detection: HIV RNA < 20-50 copies/mL. Median time for viral load < 200 is 3.8 weeks ANTIRETROVIRAL REGIMENS: NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTIS) Inhibit reverse transcriptase (RT) through false incorporation into DNA virus Generic Names Trade Names Zidovudine (ZDV, AZT) Retrovir Didanosine (ddI) Videx Zalcitabine (ddC) Hivid Stavudine (d4T) Zerit Lamivudine (3TC) Epivir Abacavir (ABC) Ziagen Emtricitabine (FTC) Emtriva Zidovudine/Lamivudine Combivir Tenofovir (TFV) Viread

HUMAN IMMUNODEFICIENCY VIRUS NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTIS) Inhibit reverse transcriptase (RT) through a different mechanism Generic Names Trade Names Nevirapine (NVP) Viramune Delavirdine (DLV) Rescriptor Efavirenz (EFV) Sustiva PROTEASE INHIBITORS (PI) Prevent successful assemblage and release from CD4+ cells Generic Names Trade Names Saquinavir (SQV) Invirase, Fortovase Ritonavir (RTV) Norvir Indinavir (IDV) Crixivan Nelfinavir (NFV) Viracept Fosamprenavir Lexiva Tipranavir Aptivus Lopinavir + ritonavir Kaletra Atazanavir Reyataz Darunavir Prezista FUSION INHIBITORS Prevent fusion of virus to CD4 cell Generic Names Trade Names Enfuvirtide Fuzeon Other: Ritonavir- Protease inhibitor that is used as a booster for other PIs as it inhibits CYP 3A4, slowing drug metabolism of them, thus allowing for less frequent dosing COMBINATION DRUGS Generic Names Trade Names Efavirenz/emtricitabine/tenofovir Atripla Abacavir/lamivudine Epzicom Zidovudine/lamivudine Combivir Zidovudine/lamivudine/abacavir Trizivir Emtricitabine/tenofovir Truvada Recommended Combinations: NNRTI based: 1 NNRTI + 2 NRTIs Examples (pick one from each column with preferred regimen bolded): NNRTI Efavirenz Nevirapine NRTI(s) Zidovudine + Lamivudine (Combivir) Zidovudine + emtricitabine Tenofovir + emtricitabine (Truvada) Tenofovir + lamivudine

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Protease Inhibitor (PI)-Based: Boosted PI + 2 NRTIs Examples (pick one from each column with preferred regimen in bold) PI Lopinavir/ritonavir (Kaletra) Atazanavir/ritonavir Fosamprenavir/ritonavir NRTI(s) Zidovudine + Lamivudine (Combivir) Zidovudine + emtricitabine Tenofovir + emtricitabine (Truvada)

Pregnancy Considerations: Recommended: Lamivudine + Zidovudine Nelfinavir or Lopinavir/Ritonavir Not recommended (i.e. do not offer!): Monotherapy Saquinavir as single PI Atazanavir + indinavir Stavudine + didanosine OR zidovudine OR zalcitabine Zalcitabine + lamivudine OR didanosine Emtricitabine + lamivudine

COMPLICATIONS OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY: Nucleotide/Nucleoside Reverse Transcriptase Inhibitors: Class common side effects: Nausea/vomiting Hepatic steatosis Lactic acidosis Drug specific side effects: Didanosine (ddI, Videx) and Zalcitabine (ddC, Hivid): Pancreatitis and peripheral neuropathy Zidovudine (Retrovir, AZT): Bone marrow suppression, macrocytosis, headache, myopathy, may increase HMG-CoA reductase inhibitor toxicity, lipodystrophy Abacavir (Ziagen): Hypersensitivity syndrome (may be fatal after rechallenging with this agent) Stavudine + Didanosine: In pregnancyfatal lactic acidosis Non-Nucleoside Reverse Transcriptase Inhibitors: Class common side effects: Stevens-Johnson Hepatic transaminitis Drug specific side effects: Efavirenz (Sustiva): CNS manifestations (insomnia, altered thinking, dizziness, euphoria), teratogenic Nevirapine (Viramune): Stevens-Johnson

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Protease Inhibitors: Class common side effects: Clinically significant inhibition or induction of P450 enzymes GI intolerance Hepatic transaminitis cholesterol, triglycerides and glucose intolerance Fat redistribution Increased bleeding complications in hemophiliacs Drug specific side effects: Nelfinavir (Viracept): Diarrhea Indinavir sulfate (Crixivan): Interstitial nephritis and nephrolithiasis Atazanavir (Reyataz): Hyperbilirubinemia and prolonged PR Tenofovir (Viread): Fanconis syndrome Contraindicated medications with protease inhibitors: St. Johns wort, lovastatin, simvastatin, pimozide, inhaled fluticasone, rifampin, benzodiazepines, ergot derivatives, and cisapride

POST EXPOSURE PROPHYLAXIS (PEP) Risk of Seroconversion: 1:300 risk of acquiring HIV after needle stick 0.09% risk from mucous membrane exposure from an HIV+ patient Procedure: Obtain baseline HIV test, then at 6 weeks, 3 months, and 6 months Contact occupational health (also the National HIV phone number is (800) 933-3413) Treatment: Post-exposure prophylaxis NOT recommended for skin intact exposures or urine-source exposures Treatment should start ASAP after exposure (regimens at www.hivatis.org): Example basic regimens for low risk exposure: Combivir (zidovudine 300 mg + lamivudine 150 mg) twice daily for 4 weeks Truvada (tenofovir + emtricitabine) daily for 4 weeks Example expanded regimen for high risk exposures: Basic regimen plus Kaletra (lopinavir/ritonavir) Combivir + Kaletra is in pregnancy PULMONARY DISEASE IN HIV Those with HIV may have non-specific symptoms of infection such as cough, dyspnea, sputum production, and wheezing without having demonstrable pulmonary pathology. Always consider the obvious, such as asthma, bronchitis, and symptoms secondary to cigarette smoking. Upper respiratory tract infections, acute bronchitis, and acute sinusitis are common in both seronegative and seropositive patients, but bronchitis and sinusitis may be more common in seropositive patients. General Risk Factors: Degree of immunosuppression HIV risk group

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Prophylactic treatments History of opportunistic infections Geographic considerations CD4+ Levels and Associated Disease: <400: bacterial pneumonia and pulmonary tuberculosis <300: recurrent pneumonia and nontuberculous pulmonary mycobacterioses <200: PCP, Kaposi's sarcoma, and disseminated tuberculosis <100: disseminated fungal infections, CNS toxoplasmosis, and cytomegalovirus disease (bronchitis, bronchiectasis, and nontuberculous mycobacterioses are rare) Mode of HIV Infection (Influences risk for different complications of AIDS): Kaposis sarcoma: male to male sex confers a 10-times increased risk Tuberculosis and bacterial pneumonia: IVDU confers greater risk Many infections that patients with AIDS contract are not eradicated, or re-exposure is unavoidable, so knowing previous OIs and current medications is important. The diagnoses of cryptococcosis, toxoplasmosis, MAC and cytomegalovirus (CMV) disease in the setting of HIV, usually obligates a patient to lifelong prophylaxis unless antiviral therapy is successful in improving CD4+ counts. Geographic Considerations: Incidence of PCP in the United States and Europe much greater than that seen in Africa. United States: TB is associated with HIV highest in the Northeast Coccidiomycosis, histoplasmosis, and blastomycosis follow their usual geographic distribution. Always consider reactivation of latent infections, making travel history important. Bacteria: Bacterial pneumonia may accelerate the course of HIV diseaseit is an independent predictor of progression to AIDS and mortality. Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus are still the most common pathogens, with others including Moraxella catarrhalis and Pseudomonas aeruginosa. Bacterial pneumonias recur in about 25% of HIV-infected patients, and some experts recommend prophylaxis if there is recurrence. Clinical presentation in those with HIV is similar to presentation in non-infected individuals. May be community-acquired and not necessarily related to neutropenia or steroid use (cavitation may be seen in those with CD4+ level <50) Mycobacterium tuberculosis: May occur at any point in HIV infection Radiographic findings more common with CD4+ counts <200, and disseminated disease more likely with CD4+ counts <100 Presentation: intrathoracic adenopathy, lower lobe infiltrates, and pleural effusions are common; upper lobe infiltrates seen in only 20-30% of HIV/AIDS patients, compared to 70-80% in the non-HIV infected population Diagnosis: Sputum evaluation: 30% of patients are AFB smear negative Bronchoscopy with/without biopsy (biopsy increases diagnostic yield): high transmission rate to medical personnel involved in procedure Pleural fluid: in 15% of cases, pleural fluid is AFB smear positive; cultures are positive in 91% for AFB when the pleura is involved. Pleural biopsy: indicated if TB suspected or adenopathy seen on CXR; AFB positive in 69% and granulomas are seen in 88%.

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Treatment: same as non-HIV (see infectious disease section), but must pay attention to drug-drug interactions, especially with protease inhibitors. Mycobacterium avium-intracellulare: Diagnosis: Radiographic evidence of disease Sputum, rare in AIDS (need one of the following): Positive sputum culture with 2+ growth 1 acid fast smear with 2+ growth 2 positive cultures + 1 smear <1 year 3 positive cultures <1 year Pulmonary biopsy with positive cultures or histology consistent with MAC and a positive sputum culture Primary Prophylaxis: Must first rule out disseminated MAC disease If CD4+ count is <50, chemoprophylaxis against disseminated MAC should be initiated with one of the following regimens: Clarithromycin 500 mg orally twice daily Azithromycin 1200 mg orally weekly Azithromycin + rifabutin 300 mg orally daily (more effective than azithromycin alone, but no proven survival benefit and increased side effects and drug interactions) Rule out tuberculosis prior to initiation of rifabutin because of possible development of tolerance to rifampin Rifabutin only (only if azithromycin and clarithromycin are not tolerated) Consider discontinuing prophylaxis when CD4+ count is >100 for >3-6 months while on HAART therapy OR plasma HIV RNA levels are suppressed for >3-6 months Cervical adenitis and pulmonary nodules may require surgical resection Pulmonary disease alone requires treatment with clarithromycin, ethambutol, rifampin/rifabutin and 2-4 months or streptomycin Streptomycin (1 gram 3-5 days/week for 6-12 weeks) may be added initially for cavitary disease Pneumocystis jiroveci (formally Pneumocystis carinii): Epidemiology: In the beginning of the AIDS epidemic, nearly of infected people developed PCP during their disease. With effective prophylaxis, the incidence has declined and bacterial pneumonia infections have been on the rise. PCP is rare in patients with CD4+ counts >200 and CD4+ counts <200 with prophylaxis PCP becomes more common once CD4+ count <100 despite prophylaxis PCP recurs in about 50% of patients off prophylaxis Presentation: Often insidious in onset and gradually progressive (may be present for weeks to months prior to diagnosis) Fever, nonproductive cough, dyspnea on exertion, fatigue Examination: Unremarkable exam relative to symptoms Approximately 50% of patients are clear to auscultation and percussion, and basilar rales may occasionally be appreciated. Labs: Serum antibodies to PCP are not clinically useful

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Serum lactate dehydrogenase (LDH) may be elevated Radiology: Bilateral, diffuse reticular or granular opacities. Pneumatoceles may be found, which may burst and cause pneumothorax/tension pneumothorax Lungs may also be clear on films High-resolution CT shows areas of ground-glass opacifications Sputum induction: false-negative rate of 17% to 26% PFTs: DLCO may be decreased Bronchoscopy with BAL: When performed in HIV-infected patients with a negative induced sputum for PCP the sensitivity is high, so if negative, no further diagnostic workup for PCP is necessary. Prophylaxis: Primary prophylaxis indications: CD4+ counts <200/mm Oropharyngeal candidiasis Unexplained fever (>37.7C) for 2 weeks Consideration for primary prophylaxis: CD4+ T-lymphocyte <14% History of AIDS-defining illness If CD4+ monitoring occurs less than every 3 months, initiate prophylaxis if the CD4+ count is >200 but <250 Drug options: Bactrim DS one tablet daily OR Bactrim SS one tablet daily OR Bactrim DS one tablet three times per week. Bactrim prophylaxis also reduces the risk of developing bacterial pneumonia Adverse reactions are reported in 50%, serious enough to require discontinuation in 30-40% For non-life threatening adverse reactions try: Reinstitution once adverse reaction is resolved Desensitization Reintroduction at smaller dose or frequency For true Bactrim intolerance: Dapsone (100 mg daily OR 50 mg daily with pyrimethamine 50 mg weekly and leucovorin 25 mg weekly) Aerosolized pentamidine (300 mg in Respirgard nebulizer monthly) Less effective than Bactrim and dapsone Less expensive as well Contraindicated in presence of active tuberculosis Atovaquone (1500 mg daily) If seropositive to toxoplasmosis, good alternatives to Bactrim are pyrimethamine and dapsone OR atovaquone with or without pyrimethamine. Stop primary prophylaxis for a response to HAART (CD4+ level >200 for >3-6 months). No data are available concerning when to restart primary prophylaxis. It is reasonable to restart prophylaxis under same criteria for initiation of primary prophylaxis.

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Treatment: Severe disease: Bactrim: Administered orally, or IV as trimethoprim (TMP) 15-20 mg/kg/day and sulfamethoxazole (SMX) 75-100 mg/kg/day in 3-4 divided doses Because of high organism burden in HIV infected individuals, continue for 21 days Side effects may include skin rash, fevers, cytopenias, nausea, vomiting, hepatitis, pancreatitis, nephritis, hyperkalemia, metabolic acidosis, CNS manifestations, and an anaphylactoid reaction. Pentamidine: Administer as 4 mg/kg IV daily Can be toxic: hypotension, torsades, marrow suppression, electrolyte disorders, islet cell destructionhypoglycemia or hyperglycemia, metallic taste Trimetrexate: 2 Administer as 45 mg/m daily (bone marrow suppression prevented with folinic acid) Clindamycin + Primaquine: Administer as 600-900 mg IV every 6-8 hours and Primaquine (contraindicated in G6PD deficiency) Milder disease: TMP (15-20 mg/kg/day orally) with Dapsone (100 mg/day orally) Dapsone contraindicated in G6DP deficiency Clindamycin and Primaquine (15-30 mg orally daily) Atovaquone (poor bioavailability, especially in the presence of diarrhea) Hypersensitivity reactions to both Bactrim and dead Pneumocystis may cause clinical deterioration in the first few days of therapy. Steroids: Use in patients with a PaO2 <70 mmHg and/or an A-a gradient of >35 Prednisone (or equivalent IV) should be administered as follows: 40mg PO BID X 5 days, then 40mg PO QD X 5 days, then 20mg PO QD X 10 days Patients with HIV and PCP should respond to therapy after seven days. If there is no response by about this time, consider drug failure (consider switching regimens) and rule out additional pathogens. CMV Pneumonitis: Diagnosis of CMV Pneumonia: Clinical and radiographic evidence of interstitial pneumonia Demonstration of CMV antigen or nucleic acids in alveolar macrophages obtained by BAL or open lung biopsy Isolation by culture of CMV from BAL fluid or lung tissue Absence of other pathogens that might explain the interstitial pneumonitis Viremia may be present without pulmonary involvement, so CMV PCR or CMV cultures are not diagnostic but may help with treatment decisions (serologic studies have the same problem) Prophylaxis: If CD4+ T-cell count is <50 and CMV antibody status is positive, prophylaxis with ganciclovir has been approved, but efficacy is not well established. Problems with ganciclovir prophylaxis: anemia, neutropenia, questionable efficacy, lack of proven survival benefit, risk of development of ganciclovir resistance

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No definitive cure is available, so secondary prophylaxis is recommended for life after recovery from serious infection until CD4+ >100 for > 3 months Ganciclovir 5-6 mg/kg IV daily OR oral Valcyte 900 daily (marrow toxicity) OR Cytovene 1000 mg orally three times daily Foscarnet 90-120 mg/kg IV daily (renal toxicity, electrolyte disturbances) Ganciclovir IV and Foscarnet IV combined Consider halting secondary prophylaxis in patients with inactive CMV disease and CD4+ counts >100 for > 3 months and HIV plasma RNA levels <200. Fungal Infections: Severe immunosuppression predisposes to disseminated fungal infections Pulmonary involvement is usually present Aspergillus fumigatus: Ubiquitous pathogen frequently found in BAL studies; frequent colonizer Cryptococcus neoformans: Course may run from colonization to ARDS Symptoms: fever, cough, malaise, scant sputum, pleuritic pain, hemoptysis is rare Radiography: patchy pneumonitis, solitary or multiple nodules, cavitations and effusions less common Tissue retrieval: bronchoscopy, open lung biopsy, or thorascopic biopsy Sputum wet preps: positive 20% Once pulmonary diagnosis is established, LP should be performed Treatment: antifungals Blastomyces dermatitides, Coccidioides immitis, Histoplasma capsulatum: Important causes of mortality in HIV infected patients Candida pneumonitis is rare even in severely immunocompromised patients and usually requires a lung biopsy to document tissue invasion. Malignancies The risk of developing the following is related to the area of residence, degree of immunosuppression, HIV risk group, and the use of prophylactic therapies Kaposi's Sarcoma (KS): Cutaneous disease precedes pulmonary disease. Up to 1/3 of those with KS have clinical pulmonary findings, and have autopsy findings (parenchymal lesions, endobronchial lesions, pleural disease, and adenopathy) Presentation: dyspnea, cough, fever, occasional blood streaking of sputum (gross hemoptysis rare), and chest pain Physical examination: often unremarkable; endobronchial KS may cause wheezing; endotracheal lesions may rarely lead to stridor Radiology: interstitial infiltrates may be focal or diffuse, typically following septal lines; there is usually a perihilar predominance; ill-defined nodular infiltrates may also be present; pleural effusions are common CT: nodules, masses, bronchovascular thickening, and pleural effusions all common; ground-glass opacities and mediastinal adenopathy uncommon Gallium: not taken up by pulmonary KS PFTs: not specific Histology: difficult to confirm Treatment: chemotherapy Non-Hodgkin's Lymphoma: Occasionally, the lung is the initial or only site of disease and is usually found during the staging process Involvement includes parenchyma, bronchi, pleura, and nodes

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Presentation: most common is parenchymal involvement showing multiple nodular densities and diffuse interstitial infiltrates A solitary nodule or mass may occur Endobronchial lesions are rare Intrathoracic nodes are uncommon as compared with the same diagnosis in the general population Diagnosis: thoracentesis and pleural biopsy Other pulmonary manifestations of HIV Carcinoma of the lung Lymphocytic interstitial pneumonitis Nonspecific interstitial pneumonitis Bronchiolitis obliterans organizing pneumonia Primary pulmonary hypertension

ADDITIONAL INFORMATION Please see the following web sites for more complete and up to date information: http://www.hivatis.org (treatment guidelines) http://hivinsite.ucsf.edu/InSite http://hopkins-id.edu/ http://projectinform.org

NEPHROLOGY N Solution D5W D10W D50W NS NS 3%NS D5NS D5NS LR D5LR E Na+ P H R O L O G Y Dextrose 50 100 500

160

154 77 513 154 77 130 130

GUIDE TO INTRAVENOUS FLUIDS K+ ClLactate mOsm/L 278 556 2780 154 286 77 143 513 1026 154 564 77 421 4 109 28 272 4 109 28 524

50 50 50 50

1 amp NaHCO3 = 50 ml = 44 mEq 1 amp 7.5% KCl = 20 ml = 20 mEq 1 amp 14.9% KCl = 20 ml = 40 mEq 1 amp 46% KPO4 = 15 ml = 66 mEq K, 45 mM PO4 1 amp 10% CaCl2 = 10 ml = 14 mEq 1 amp 10% Ca gluconate = 10 ml = 4.7 mEq

URINALYSIS INTERPRETATION Urine Dipstick Specific gravity: Estimate of UOsm. Typical range = 1.005-1.030 Each 0.001 in specific gravity above 1.0 implies a 30 mOsm/kg in UOsm such that SG 1.010 ~ UOsm 300 pH: Varies between 4.5-8.0 with a number of metabolic conditions May be useful in differential diagnosis of RTA Protein: Typically negative. Positive test implies significant albuminuria Positive test implies > 300-500 mg/day, but should always prompt quantitative assessment (24 hour urine or urine total protein/Cr ratio) False positives with contrast and concentrated or alkaline urine Less sensitive for immunoglobulins or light chains (can be detected with sulfosalicylic acid test) and microalbuminuria Leukocyte esterase: Typically negative. Positive test implies WBCs present False positives with vaginal secretion contamination False negatives associated with proteinuria, glucosuria, SG Nitrites: Typically negative. Positive test suggests presence of Gm- bacteria Enterobacteriaceae frequently convert nitrates to nitrites Blood: Reflects presence of heme, presumably as intact RBCs False positives with myoglobinuria or free hemoglobin (hemoglobinuria) False negatives with Vitamin C Gross hematuria with negative blood on dipstick suggests medication (deferoxamine, rifampin, phenazopyridine, etc), food dye (beets, blackberries, etc), bile pigments, or porphyria Ketones: Better detects acetoacetate and acetone than -hydroxybutyrate (i.e. detection of DKA better than ETOH ketoacidosis)

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Bilirubin: Usually conjugated Often suggestive of liver disease Glucose: Proximal tubule transport maximum (Tmax) of glucose = 180-200 mg/dl Glucosuria suggests serum glucose level greater than Tmax or proximal tubule dysfunction (Fanconis syndrome) Urine Microscopy (Urine Sediment) Cells: RBCs: GN suggested by small, dysmorphic RBCs caused by osmotic injury while passing through tubules WBCs: PMNs suggest UTI Eosinophils suggest AIN, atheroembolic disease, prostatitis, or RPGN Sterile pyuria suggests tuberculosis Renal tubular epithelial cells: Often seen with renal tubular damage (i.e. ATN) Oval fat bodies: Sloughed tubular cells containing fat droplets (seen with nephrotic syndrome) Casts: Hyaline: Consists of protein alone. Not specific for disease, and can be seen with concentrated urine and a number of pathologic conditions RBC: Indicative of GN due to intraparenchymal bleeding WBC: Indicative of pyelonephritis, GN, AIN Granular: Consists of sloughed tubular casts seen with tubular injury (coarse granular = classic ATN) Crystals: Rhomboid: uric acid. Bipyramidal: calcium oxalate. Dumbell-shaped: calcium oxalate. Hexagonal plates: cystine. Lipids: suggests nephrotic syndrome, oval fat bodies, maltese cross. PROTEINURIA Definition: Urinary protein excretion > 150-300 mg/day Causes: Glomerular: Often associated with nephrotic syndrome Pathophysiology: filtration of macromolecules (i.e. albumin) due to disruption of filtration barrier (i.e. DM, GN, etc) Tubular: Usually less than 2 grams in 24 hours Pathophysiology: excretion due to proximal tubule reabsorption of LMW filtered proteins (i.e. ATN, tubulointerstitial disease, etc) Overflow: May have proteinuria as high as those with glomerular disease Pathophysiology: excretion of LMW proteins due to marked overproduction (i.e. MM, MGUS, etc) Finding of disparity between weakly positive urine dipstick for protein and highly positive protein quantitation is highly suggestive of overflow proteinuria Tissue: Usually less than 500 milligrams in 24 hours Pathophysiology: Tissue inflammation leads to protein leaking into urine (i.e. UTI, malignancy) Proteinuria quantitation: 24 hr urine collection: Measure concurrent Cr to assess adequacy (15-20 mg/kg/day in females and 20-25 mg/kg/day in males) Urine total protein/Cr ratio: Spot estimate of 24 hr output per 1.73m2 (i.e. total protein/Cr ratio of 3.5 ~ 3.5 grams in 24 hr collection)

NEPHROLOGY Assumes patient excretes on the order of 1 gm of Cr at steady state. So less accurate at extremes of body habitus and in ARF DDx massive proteinuria (>10g/24hr): only 4 things Minimal change, membranous nephropathy, diabetes, amyloidosis.

162

NEPHROTIC SYNDROME Definition: Heavy proteinuria (24 hour urine collection >3.5 gm or urine total protein/Cr ratio > 3.0-3.5 mg/mg) Hypoalbuminemia (serum albumin <3 g/dl) Peripheral edema Dyslipidemia Differential Diagnosis: Common primary renal diseases Minimal change disease: Causes: Idiopathic (most common), genetic, allergic (some associate with atopic disease), post-URI, malignancy (Hodgkins disease in particular), NSAIDs, heavy metals (lead, mercury, lithium) Pathology: Normal LM and IF. Fusion of epithelial foot processes on EM Most common cause of nephrotic syndrome in children Focal segmental glomerulosclerosis: Causes: Idiopathic (most common), genetic, heroin, HIV-associated nephropathy/parvovirus B19 (collapsing variant), obesity, healed prior injury/reduced nephron mass (reflux nephropathy, renal agenesis, renal dysplasia) Pathology: Focal segmental sclerosis on light microscopy. No immune deposits except non-specific IgM and C3 in lesions on IF. Fusion of epithelial foot processes on EM More common in African American. Important to distinguish between primary and secondary (associated with adaptation to hyperfiltration) Membranous nephropathy: Causes: Idiopathic (most common), autoimmune disease (SLE, RA, etc), malignancy (solid tumor, nonHodgkins lymphoma in particular), Hep B, syphilis, malaria, penicillamine, gold, NSAIDs Pathology: Spike and dome pattern with thick GBM on LM. IF and EM show immune complex deposits in subepithelial space Most common GN in adults in U.S Membranoproliferative glomerulonephritis: Causes: Idiopathic, Hep C (most common), subacute bacterial endocarditis, cryoglobulinemia, SLE Pathology: Thickened GBM with splitting appearance of capillary wall and cell proliferation on LM. IF and EM show immune complex deposits in subendothelial space Frequently has features of nephritic syndrome as well Differential Diagnosis: Common systemic causes Amyloidosis: Causes: Idiopathic, MM/MGUS, chronic inflammatory diseases. Pathology: Glomeruli filled with amorphous material positive for congo red stain and green birefringence with polarized light. Immunohistology can identify protein subtype Diabetic nephropathy: Causes: Type 1 or 2 DM Pathology: Classic = nodular glomerulosclerosis (Kimmelstiel-Wilson nodules) Work-up: Standard H&P (assess for systemic disease and review medications)

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Labs: CBC, chemistry panel, albumin, ANA, RF, ESR, CRP, HIV, Hep B/C serologies, RPR, ASO, Ca, SPEP/UPEP, cryoglobulin, Hba1c Fasting lipid panel Proteinuria quantitation: 24 hr urine or spot urine total protein/Cr ratio Renal ultrasound: Large kidneys suggest DM, HIV, infiltrative disease (amyloid, lymphoma) Renal consultation for possible renal Bx, particularly if new or rapid onset Treatment of complications: Proteinuria: Uncontrolled proteinuria independently associated with progressive loss of renal function ACE-I/ARB: intraglomerular pressure protein excretion Spironolactone: Evidence growing in literature of ability to protein excretion, particularly in DM 1Dietary protein intake should replace urinary protein loss. Beware malnutrition in CKD patients placed on restricted protein diet Edema: Due to renal Na retention Dietary salt restriction (2-3g NaCl/day) Diuretic therapy: Loop diuretics usually required and at higher dose due to albumin Dyslipidemia: Aggressive treatment with lipid lowering agents (statin first line) Hypercoagulable state: risk (10-40%) of thromboemboli due to urinary loss of ATIII, protein C and S Incidence of DVT disproportionately high in membranous GN Consider WITHU of renal vein thrombosis in setting if ARF Anticoagulation if evidence of thrombosis and some propose prophylaxis for membranous with severe hypoalbuminemia Infections: Low level of IgG may play role. Pneumococcal infection especially common. SBP may develop in some patients with ascites ARF: May be associated with development of renal vein thrombosis (dull back pain may be sole symptom). Also, crescentic GN may rarely occur in membranous GN Low C3/Low C4 MPGN type 1 Lupus Cryoglobulinemia Low C3 (normal C4) MPGN type 2 Post-infectious GN

DECREASED URINE OUTPUT Oliguria: Urine output < 500 ml/day; Anuria < 200 ml/day Assess volume status: History: Check if NPO, N/V/D, dehydrated. Check I/Os over past few days to see if patient persistently positive or negative PE: Check for orthostatics, tachycardia, JVP, crackles on pulmonary exam, abdominal exam (palpable bladder), and edema Labs: Consider chemistry panel to rule out ARF. BUN/Cr ratio > 20 suggests pre-renal cause Radiology: Consider CXR for evidence of CHF If thought to be volume depleted, attempt fluid challenge (250-500 ml NS) If thought to be volume overloaded or in CHF, try diuresis with furosemide. Start at 20 mg IV if furosemide naive; may need higher doses (up to 200mg IV) if the patient has significant renal impairment. If patient already on furosemide, try doubling usual dose If patient has a Foley and is anuric (<100 ml/day), ask RN to flush Foley to make sure that it is not clogged

NEPHROLOGY If post-renal obstruction is suspected, check a post-void residual. If volume is > 150-200 ml, then leave the Foley in place If unable to place Foley, try larger size catheter and/or Coude tip catheter with Uro-jet (Lidocaine jelly in syringe); if this fails, call Urology

164

GFR ESTIMATION Cr-based GFR estimations are most accurate in steady-state, therefore estimations will underestimate true GFR in ARF with rising Cr. Normal values for GFR are 120 ml/min for men and 100 ml/min for women, though GFR will vary depending on size, age, and physiologic state. For example, true GFR in a cachectic female with a Cr of 1.0 mg/dl is much lower than a muscular male with the same Cr MDRD equation: Logarithmic 4 variable equation used by UCLA lab system to estimate GFR in ml/min/1.73m2. A 6 variable equation (age, sex, race, Cr, BUN, albumin) is also available. Estimated GFR

( ml/min/1.73m ) =
2

( 186 ) ( 0.74 if female ) ( 1.21 if African American ) ( Serum Cr )

1.154

( Age )

0.203

Cockroft-Gault equation:

( 140 age ) weight in kg ( 0.85 in women )

Estimated GFR (ml/min) = 72 Serum Cr 24 hr urine collection:

( Urine Cr in mg/dl ) ( Urine Volume in ml/day )

Measured GFR (ml/min) =

( Plasma Cr in mg/dl ) ( 1440 min/day )

Factors other than decreased GFR that may cause elevation of creatinine: Decreased secretion: Trimethoprim, cimetidine Interference with assay: Ketoacidosis (acetone, acetoacetate), cefoxitin, flucytosine, ascorbic acid, nitromethane Enhanced production: Large meat meals, rhabdomyolysis (conversion of creatine to creatinine)

NEPHROLOGY
ACUTE RENAL FAILURE (ARF)/ACUTE KIDNEY INJURY (AKI) Definition: No formal definition though some have considered the use of the proposed RIFLE classification scheme Classification Risk Injury Failure RIFLE CLASSIFICATION FOR ACUTE RENAL FAILURE GFR Criteria UOP Criteria UO < 0.5 ml/kg/h x 6 hours Baseline Cr x 1.5 OR GFR > 25% UO < 0.5 ml/kg/h x 12 hours Baseline Cr x 2 OR GFR > 50% UO < 0.3 ml/kg/h x 24 hours Baseline Cr x 3 OR OR anuria x 12 hours GFR > 75% OR SCr > 4 mg/dl with in Cr by 0.5 mg/dl Persistent ARF = complete loss of kidney function > 4 weeks End stage kidney disease > 3 months

165

Loss ESKD

Causes: Prerenal: Associated with renal perfusion (40-70% of cases of ARF) Intravascular volume: Hemorrhage (i.e. GIB, retroperitoneal hematoma, trauma) Urinary loss (i.e. excess diuresis) Third spacing GI losses (i.e. vomiting, diarrhea) SVR: Sepsis Anaphylaxis Cirrhosis/HRS Effective circulating volume: CHF Intraglomerular pressure (small vessel): ACEI/ARB, NSAIDs, cyclosporine, tacrolimus Vascular (large vessel): Dissection, embolism, thrombosis, renal artery stenosis with ACE-I, vasculitis Intrinsic renal failure: Associated with renal parenchymal injury (30-50% of cases of ARF) Acute tubular necrosis (ATN): Exogenous nephrotoxins: Aminoglycosides, amphotericin, acyclovir, contrast Endogenous nephrotoxins: Myoglobinuria, hemoglobinuria, uric acid, paraproteinemia Renal ischemia: Hypotension, severe dehydration, shock, sepsis, hypoxia Acute interstitial nephritis (AIN): Drugs: Antibiotics (B-lactams most common, though most classes of antibiotics have known associations), phenytoin, allopurinol, NSAIDs, diuretics, PPI Infections: Legionella, leptospirosis, CMV, histoplasmosis, Rickettsia Immunologic: SLE, Sjgrens, sarcoidosis, cryoglobulinemia, TINU syndrome Glomerulonephritis (GN): Anti-GBM: Goodpastures and primary anti-GBM glomerulonephritis Immune complex: SLE, IgA, post-infectious, membranous, MPGN, cryoglobulins

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Pauciimmune (ANCA-associated): Wegners granulomatosis, microscopic polyangiitis, Churg-Strauss Vascular: Malignant HTN, scleroderma renal crisis, DIC, preeclampsia, TTP/HUS, cholesterol emboli Post-renal failure: Associated with urinary obstruction (2-5% of cases of ARF) Urethral/bladder dysfunction/obstruction (i.e. BPH, urethral stricture) Bilateral ureter or pelvic obstruction (i.e. stones, malignancy, retroperitoneal fibrosis) Work-up: Strongly consider Foley if not present. If post void residual is > 150-200ml, keep catheter in place Calculate the fractional excretion of Na (FENa; see below) Urinalysis: Assess for active sediment or casts ATN: Coarse granular casts AIN: WBC casts, urine eosinophils GN: RBC casts and dysmorphic red cells Renal ultrasound: Assess for stones, masses, hydronephrosis, size, and echogenicity Consider acute GN work-up based on history and urinalysis (i.e. active sediment with dysmorphic RBCs and RBC casts): Blood cultures, ASO, C3, C4, CH50, ESR, CRP, ANA, RF, DSDNA, ANCA, anti-GBM, Hep B/C serologies, cryoglobulins Treatment: Basic goals: Treat underlying cause Minimize fluid/electrolyte imbalance Avoid nephrotoxins and renal dose medications Ensure adequate nutrition Dialysis: ARF severe enough to cause dialysis dependence is associated with upwards of 50% in-hospital mortality Indications: No definitive guidelines but most would agree with starting for following indications Acidosis, particularly if pH < 7.1 Electrolyte imbalance: K, PO4 (especially in tumor lysis), severe Ca or Mg Intoxication: Lithium, toxic alcohols, theophylline, salicylates Overload (volume): After failing diuretic management Uremic complications: Encephalopathy, seizures, pericarditis, platelet dysfunction Dialysis dose: Controversial though most would advocate for steady state BUN below 80-100 mg/dl May be done every other day or daily if indicated. Some evidence that daily dialysis associated with improved outcomes Types of dialysis: Hemodialysis (HD): Physiology: Intermittent solute removal via diffusion (dialysis) + fluid removal via transmembrane pressure (ultrafiltration) Advantages: Rapid solute removal and acid-base correction. May use any vascular access (catheter or AV shunt) Complications: Hypotension, arrhythmia, dialysis disequilibrium syndrome (nausea, vomiting, seizures), bleeding, membrane reaction, access malfunction Continuous renal replacement therapy (CRRT): Physiology: Continuous solute removal via diffusion (dialysis) + fluid removal via transmembrane pressure with additional dilutional component from replacement fluid (hemofiltration) Continuous dialysis + hemofiltration (CVVHDF):

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Advantages: More hemodynamically stable than HD. Excellent for removal of large fluid volumes over 24 hours versus intermittent HD. Complications: Similar to HD but less cardiovascular and neurological side effects (slower rates of removal). AV fistulas/grafts should not be used as access for CRRT. Peritoneal Dialysis (PD): Physiology: Peritoneum is used as dialysis membrane with solute removal via diffusion + fluid removal dependent on dialysate glucose/icodextrin concentration Advantages: Ambulatory. Can be done during day or evening at home (home HD not as available at present). More hemodynamically tolerable than HD Complications: Peritonitis, hyperglycemia with glucose based solutions, access malfunction. Generally not used for ARF as it takes 4 weeks for inserted PD catheter site to heal prior to use Evaluation of urinary composition in ARF Fractional Excretion of Sodium (FENa):

( Urine Na ) ( Plasma Cr )
% Fractional Excretion of Sodium =

( Plasma Na ) ( Urine Cr )

More accurate than urinary Na at assessing prerenal state More specific in oliguric than non-oliguric renal failure Intrinsic renal diseases that occasionally have low FENa include acute GN, pigment nephropathy, AIN, contrast nephropathy FENa may be inaccurate in setting of diuretic use given false elevations in urinary Na. However, low FENa in setting of diuretics suggests severe prerenal state Fractional Excretion of Urea (FEUrea):

( Urine BUN ) ( Plasma Cr )

% Fractional Excretion of Urea =

( Plasma BUN ) ( Urine Cr )

May be used in patients on diuretics (can also use FE uric acid) Differentiating prerenal azotemia from intrinsic renal failure
Test

EVALUATION OF URINARY COMPOSITION IN ACUTE RENAL FAILURE Prerenal Azotemia Intrinsic Renal Failure (ATN) FENa <1% >2% FEUrea <35% >50% Urinary Na (mmol/L) <20 >40 Urinary Sediment Normal or occasional granular casts Brown granular casts, cellular debris

Note the parameters listed above may not be true in someone with underlying CKD because of defects in urinary concentration and Na reabsorption. In such patients a cautious trial of fluids may be indicated despite contrary urinary studies

HEPATORENAL SYNDROME (HRS) Definition: ARF in the setting of cirrhosis or fulminant hepatic failure in the absence of other renal diseases Pathophysiology: Splanchnic arterial vasodilation due to accumulation of local vasodilators (i.e. nitric oxide, etc) from portal HTN SVR Activation of compensatory mechanisms (i.e. sympathetic nervous system,

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Avid sodium and H2O retention and renal renin-angiotensin-aldosterone system, endothelin, etc) prerenal ARF vasoconstriction Clinical presentation: Often exacerbated by infection (SBP most common), acute hepatic injury superimposed on cirrhosis, GIB, or overdiuresis Type I HRS: Rapidly progressive ARF with doubling of Cr to > 2.5 mg/dl or fall in GFR to 20 ml/min in less than 2 weeks Associated with poor prognosis and 50-80% mortality upon onset due to progressive circulatory, hepatic, and renal failure Type II HRS: Slowly progressive increase in Cr to > 1.5 mg/dl or fall in GFR to 40 ml/min Work-up: Diagnosis of exclusion though the following have been proposed as diagnostic criteria Chronic or acute advanced liver failure and portal HTN Cr > 1.5 mg/dl or GFR < 40 ml/min Absence of shock, ongoing bacterial infection, fluid loss, or current/recent treatment with nephrotoxins No sustained improvement in renal function after withdrawal of diuretics and volume challenge with 1.5 L of NS Proteinuria < 500 mg/day Absence of obstructive uropathy or parenchymal disease on U/S Other helpful criteria include: Urine volume < 500 ml/day, urine Na < 20 mmol/L, UOsm > serum Osm, urine RBC count < 50/hpf, serum Na < 130 mmol/L Treatment: Definitive treatment is liver transplant with all other therapies serving as bridges to transplant Diet: Na restriction to prevent edema and refractory ascites Diuretics: Spironolactone as first line therapy. Furosemide to be added for refractory edema or ascites. However, need cautious use to avoid overdiuresis and exacerbation of HRS Arterial vasoconstrictors: Terlipressin (V1 receptor agonist): IV infusion along with albumin may have beneficial effects. However, limited availability in U.S. and may be associated with ischemic adverse events Midodrine (alpha-agonist; 5-15 mg PO tid) and octreotide (somatostatin analogue; 100-200 g SQ tid): Octreotide alone not shown to be effective. Limited data regarding beneficial effects of dual treatment or midodrine alone in addition to albumin. Transjugular intrahepatic portosystemic shunt (TIPS): Decompresses portal HTN and may be associated with suppression of renin-angiotensin-aldosterone system and improved renal perfusion. Major side effect includes hepatic encephalopathy and shunt dysfunction Dialysis as needed until liver transplantation: if dialysis has been prolonged > 1 month, patient may qualify for a dual liver-kidney transplantation

CHRONIC KIDNEY DISEASE Definition per National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI): Evidence of structural or functional kidney abnormalities (abnormal urinalysis, imaging, histology, etc) for > 3 months OR GFR < 60 ml/min/1.73 m2 for > 3 months NKF-KDOQI Stages: Stage I: GFR > 90 ml/min/1.73m2 + persistent albuminuria Stage II: GFR 60-89 ml/min/1.73m2 + persistent albuminuria Stage III: GFR 30-59 ml/min/1.73m2 Stage IV: GFR 15-29 ml/min/1.73m2 Stage V: GFR < 15 ml/min/1.73m2 or dialysis dependence

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Symptoms: Azotemia = BUN, Cr, and other waste products. Uremia = symptomatic azotemia General: Anorexia, malaise, pruritus GI: Nausea, vomiting CV: Pericarditis, HTN, accelerated atherosclerosis, lipids, edema Heme: Anemia, platelet dysfunction Neuro: Peripheral neuropathy, encephalopathy, seizures Metabolic: K, PO4, Ca, acidosis, PTH, osteodystrophy General treatment: Treat reversible causes of renal dysfunction including causes of renal perfusion (i.e. hypovolemia, hypotension, infection, drugs) Avoid nephrotoxins Consider restricting dietary protein intake to 0.8-1.0 g/kg of high biologic value protein for predialysis patients (some possible retardation of CKD progression). Must weigh risks of such strict limitations and potential for malnutrition. Renal dietician should be involved Nephro-Vite 1 tab PO daily (high in Vitamin B, low in Vitamin A and C) BP control < 130/80 per K/DOQI guidelines with ACEI/ARB preferred particularly in DM ACE-I/ARBs for proteinuria (goal: protein excretion to < 500-1000 mg/day) and BP control (< 130/80) Treatment of complications: Edema: Dietary Na and diuretic therapy, typically a loop diuretic Metabolic acidosis: Risks of bone disease given H+ buffering along with skeletal muscle breakdown and albumin synthesis. Sodium bicarbonate tabs (0.5-1.0 mEq/kg/day) to goal TCO2 > 22 mEq/L. Sodium citrate may be considered by patients as more tolerable K: Low K diet (no OJ, dairy, bananas, melons, potatoes) +/- loop diuretic +/- Kayexalate. Avoidance of drugs that serum K such as NSAIDS. Cautious use of ACEI/ARB and Aldactone PO4: Dietary PO4 restriction of 800mg/day. Oral PO4 binders (Ca carbonate, Ca acetate, sevelamer, or lanthanum) as needed with meals. Goal Ca-PO4 product < 55mg2/dl2. Avoid aluminum based binders given risks of aluminum toxicity Secondary hyperparathyroidism: Associated with Ca, PO4, and Vitamin D 1,25-OH production among other factors in CKD. Goal to control PO4 and consider supplementation with Vitamin D analogues or cinacalcet (Ca sensing receptor agonist) Anemia: Normocytic and normochromic due to erythropoietin production among other factors in CKD. Supplemental erythropoietin for goal hemoglobin 11-12 g/dl after ruling out other causes (i.e. Fe, folate, or Vitamin B12 deficiency, etc). Note that worse outcomes may be associated with Hgb correction > 13 g/dl Dyslipidemia: CKD equivalent to CAD, so current goal LDL < 100 mg/dl, and some would consider lower target Renal replacement therapy: Early identification and early referral to nephrologist. Preparation for renal replacement therapy in Stage IV CKD (HD, PD, or renal transplant). Dialysis typically initiated when GFR < 15 ml/min in diabetics, GFR < 10 ml/min in non-diabetics, or when symptoms or other metabolic indications occur.

REQUIREMENTS FOR OUTPATIENT HEMODIALYSIS Prior to being accepted for outpatient hemodialysis, ALL patients need Hep B serologies, Hep C serologies, HIV, CXR and PPD placed and read. These tests usually take 3-4 days so as soon as you think a patient will need outpatient dialysis, you should preemptively send them. HYPONATREMIA Definition: Na < 135 mmol/L.

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Causes: Initial classification based on serum osmolality Isoosmotic (275-295 mmol/L) = Pseudohyponatremia Hyperproteinemia Hyperlipidemia Hyperosmotic hyponatremia (> 295 mmol/L) Hyperglycemia: Every 100 mg/dl in glucose > 150 measured Na by 1.6 mmol/L Hypertonic infusion (mannitol, sucrose, maltose, glycine) Hypoosmotic hyponatremia (< 275 mmol/L): Most common form of hyponatremia with further work-up based on volume status of patient Hypovolemic: Associated with effective circulatory volume as stimulus for ADH secretion Causes: Diuretics, osmotic diuresis, salt wasting nephropathy, diarrhea, vomiting, third spacing, sweat, burns, cerebral salt wasting, NPO Treatment: IVF hydration Euvolemic: Causes: Primary polydipsia, SIADH, adrenal insufficiency, hypothyroidism, reset osmostat, beer potomania Treatment: Free H2O restriction (<1-1.5 L/day) and treat underlying cause Hypervolemic: Associated with effective circulatory volume as stimulus for ADH secretion Causes: CHF, cirrhosis, nephrotic syndrome Treatment: Free H2O restriction and diuresis Work-up: Urine Osmolality: UOsm < 100 mOsm/kg suggests primary polydipsia, malnutrition (beer potomania), or reset osmostat UOsm > 100 mOsm suggests continued ADH secretion despite hyponatremia Urine Sodium: More informative than FENa, which in setting of normal renal function is reflective of Na balance. For instance, a euvolemic SIADH patient on a normal diet may have a FENa < 1% UNa < 20 mmol/L suggests effective circulatory volume UNa > 40 mmol/L suggests SIADH Serum uric acid and urea tend to be elevated in prerenal state and low in SIADH Treatment: Serial sodiums should initially be followed q2-6 hours depending on rate of correction and severity of hyponatremia Asymptomatic hyponatremia: Correct no more than 10-12 mmol/L in 24 hours and 18 mmol/L in 48 hours to avoid osmotic demyelination syndrome. Patients with chronic hyponatremia, elderly, and women are at a high risk. Symptomatic hyponatremia: Severe symptoms (seizures, coma): Na 3-5 mmol/L at a rate of 1-2 mmol/L/hr but not more than 10-12 mmol in 24 hours Moderate symptoms (AMS, lethargy): Na 3-5 mmol/L at a rate 0.5mmol/L/hr but not more than 10-12 mmol in 24 hours Androgue-Madias Equation shows effect of 1L of any fluid on serum Na: (Infusate Na + K ) Serum Na Na = TBW + 1 TBW = 0.6 x weight (kg) for men and 0.5 x weight (kg) for women

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Caution in treatment of hypovolemic state as restoration of euvolemia will abolish ADH stimulus for H2O conservation resulting in more rapid self-correction of hyponatremia than anticipated by above equation Available Na solutions: 3% Saline = 513 mmol Na/L 0.9% Saline (NS) = 154 mmol Na/L 0.45%Saline (NS) = 77 mmol Na/L

. SYNDROME OF INAPPROPRIATE ADH SECRETION (SIADH) Definition: Hypo-osmolality (Serum Osm < 275 mOsm/kg) Inappropriately high urinary concentration (UOsm > 100 mOsm/kg) in setting of hypo-osmolality Clinical euvolemia Elevated urinary Na (> 40 mmol/L) while on normal salt and H2O intake Normal thyroid, adrenal, and kidney function Causes: Tumors: Small cell lung carcinoma, mesothelioma, pancreatic carcinoma, duodenal carcinoma CNS disorders: Tumor, abscess, ischemia, hemorrhage, infection, trauma Medications: Phenothiazine, TCAs, SSRIs, clozapine, desmopressin, oxytocin, carbamazepine, vincristine, cisplatin, cyclophosphamide, Ecstasy, chlorpropamide, clofibrate Pulmonary disease: Infection, tumor, mechanical ventilation, COPD exacerbation, ARDS Other: Pain, nausea, HIV Treatment: Free H2O restriction Increased solute input (i.e. salt tabs or high salt, high protein diet) leads to urinary excretion of excess solutes in larger body of water and negative H2O balance Loop diuretic (i.e. furosemide) interferes with countercurrent concentrating mechanism and leads to excretion of free H2O in excess of Na Demeclocycline or lithium to induce nephrogenic DI in refractory patients Vasopressin receptor (V2) antagonists once available
HYPERNATREMIA Causes: Unreplaced water losses: Insensible loss (sweating, tachypnea, burns). UOsm often > 800 mOsm/kg GI loss (vomiting, diarrhea). UOsm often > 800 mOsm/kg Renal losses: Central or nephrogenic DI. UOsm often < 250 mOsm/kg Osmotic diuresis. UOsm often 300-400 mOsm/kg Sodium overload: UOsm often > 800 mOsm/kg Hypertonic solutions (3% NaCl). Mineralocorticoid excess (rare) Water redistribution: rare, transient Excessive exercise or seizures Treatment:

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Plasma [Na] 140 Free Water Deficit = 0.6 weight ( kg) 140

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Rate of repletion: As general guide, may give half of free water deficit in first 24 hours and remainder over next 1-2 days However, need to check frequent serial Na and correct no more than 10-12 mEq/L change in 24 hours to avoid cerebral edema Remember to take into account insensible losses (approx. 30 ml/hr) and ongoing urinary/stool losses when calculating the amount of free H2O to give

POLYURIA Definition: > 3L urine output per 24 hours without exogenous diuretic use Causes: Central DI: Deficient ADH secretion. Spot UOsm often < 250 mOsm/kg Causes: Familial, neurosurgery, tumor, trauma, infection (TB, meningitis), infiltrative disease (sarcoid, Histiocytosis X), Sheehans Nephrogenic DI: Renal resistance to ADH. Spot UOsm often < 250 mOsm/kg Causes: Familial, hypercalcemia, hypokalemia, demeclocycline, lithium, sickle cell anemia, cystic kidney disease, pregnancy Primary polydipsia: Excess free H2O intake. Spot UOsm often < 250 mOsm/kg Causes: psychogenic, hypothalamic disease, anticholinergics Osmotic diuresis: Associated with high solute excretion. Spot UOsm often > 300 mOsm/kg Causes: Hyperglycemia, post-obstructive diuresis, high-protein tube feedings, saline load (IVFs, etc), contrast Work-up: Check 24 hr urine osmoles: < 600-900 mosm/24 hours implies water diuresis > 900 mosm/24 hours implies solute diuresis Check 24 hr urine for Na and K: 2 (Na + K ) 24 hour UOsm

If > 70% implies electrolyte diuresis If < 70% implies non-electrolyte solute diuresis Water restriction test: Check urine volume every hr and UOsm, serum Osm, and serum Na at baseline and every other hr. Check plasma ADH at baseline Cease water restriction when 1) UOsm normal (>600 mOsm/kg; suggests primary polydipsia), 2) UOsm stable x 3 yet with rising serum Osm, or 3) serum Osm > 295 mOsm/kg Check plasma ADH level before DDAVP given Administer DDAVP 10 g nasally or 4 g subcutaneous and continue serial urine volume and urine Osm Interpretation: Complete central DI: > 50-100% rise in UOsm (often > 450 mOsm/kg) Complete nephrogenic DI: < 10-15% rise in UOsm Partial central or nephrogenic DI: 15-50% rise in UOsm Plasma ADH low or low normal likely partial central DI Plasma ADH normal or high likely partial nephrogenic DI

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Treatment: Central DI: Exogenous DDAVP for replacement Nephrogenic DI: Treatment aimed at reducing symptoms. Low Na diet, thiazide diuretics, NSAIDs, trial of DDAVP

HYPOKALEMIA Definition: K < 3.5 mmol/L Clinical manifestations: Proportionate to degree and duration Neuromuscular: Weakness, paralysis, rhabdomyolysis (K < 2-2.5) CV: Arrhythmia (VT, VF), prolonged QT, PVCs, U waves Renal: Nephrogenic DI, increased ammoniagenesis, metabolic alkalosis Causes: K intake (rare except in extreme malnutrition) Transcellular shift: Alkalemia, insulin excess, B-adrenergic stimulation (i.e. albuterol), hypokalemic periodic paralysis, high cell proliferation (i.e. AML, RBC production after EPO, WBC production after GM-CSF) GI losses: Diarrhea, laxatives, villous adenoma, VIPoma. Loss of K with intestinal secretions largely due to high K in fluid Renal losses: Diuretics, mineralocorticoid excess, vomiting, NGT suction, DKA, osmotic diuresis, RTA I and II, hypomagnesemia, PCN, amphotericin B, gentamicin, foscarnet, salt-wasting nephropathy Loss of K with gastric loss (i.e. NGT suction) due to metabolic alkalosis causing distal Na delivery (accompanies excreted HCO3 load) with associated K exchange and aldosterone causing distal K secretion Other: Dialysis, plasmapheresis, sweat loss Work-up: Assess symptoms, BP, acid-base status, and EKG Calculate transtubular K gradient:

TTKG =

(Urine K )(Plasma Osm ) (Urine Osm )(Plasma K )

TTKG > 4 = renal or endocrine defect TTKG < 2 = extrarenal causes Other: Check 24 hr urine K UK > 30 mmol/day suggests renal losses UK < 25 mmol/day suggests extrarenal losses Treatment: General rule for replacement: Desired K Measured K Estimated mEq KCl Needed = 100 Serum Cr If Cr<1, still calculate as if Cr=1. Preferred method = oral replacements up to 40 mEq/hr (more may result in GI upset/diarrhea/esophagitis) Err towards under-correction in renal failure and consider using moderate oral doses with rechecking of K frequently Replete IV for symptomatic and EKG changes Peripheral line: Max IV rate = 10 mEq/hr Central line: Max IV rate = 20 mEq/hr (use cardiac monitor and frequent serum K checks). Generally avoided except in severe cases of arrhythmia

NEPHROLOGY Remember you can give IV and PO simultaneously for rapid input Replete Mg in setting of hypomagnesemia or patient will be refractory to K repletion

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HYPERKALEMIA Definition: K > 5.5 mmol/L Pseudohyperkalemia: K may be falsely elevated if intra-tube hemolysis (often mentioned by lab), WBC > 100,000 or platelets > 800,000 (redraw in heparinized tube), tourniquet draw, hereditary spherocytosis Clinical manifestations: Neuromuscular: weakness, paralysis EKG abnormalities: Acute rises are most dangerous and associated with arrhythmia K = 6-7: peaked T waves K = 7-8: widened QRS, P amplitude K = 8-9: sine waves K > 9: AV dissociation, VT, VF Causes: K intake: Salt substitutes, dietary indiscretion (with renal failure), overzealous K replacement Transcellular shift: Acidemia, insulin deficiency, hyperosmolality (glucose, contrast), cell destruction (tumor lysis, rhabdomyolysis, hemolysis, blood transfusion), B-adrenergic blockade, digoxin overdose, vigorous exercise, succinylcholine, hyperkalemic periodic paralysis renal excretion: Renal failure Hyporeninemic hypoaldosteronism: DM nephropathy, NSAIDs, cyclosporine Hypoaldosteronism: Adrenal insufficiency, CAH, ACEI/ARB, heparin, spironolactone Diminished aldosterone action: Amiloride, triamterene, trimethoprim, pentamidine, tacrolimus, type II pseudohypoaldosteronism, tubulointerstitial disease Hyperkalemic type I RTA effective circulatory volume Work-up: Assess symptoms, diet (including TPN), med list, BP, acid-base status, and EKG Calculate transtubular K gradient: TTKG > 10 = external causes TTKG < 7 = renal or endocrine defect Treatment: K = 5.5-6.5, no EKG changes D/C any offending drugs and external sources of K. Chang to low K diet Kayexalate, a cationic exchange resin, 15-45 grams PO q4-6 hours PRN. Kayexalate takes up K and releases Na in the gut. Side effects include volume overload and intestinal necrosis (caution in patients with ileus or bowel surgery). Often given with sorbitol to prevent constipation. Loop diuretic PRN. Thiazides generally less effective, particularly with renal failure. K > 6.5 + EKG changes or K > 8 CaCl or Ca gluconate 1 gram IV over 2-5 min PRN with cardiac monitoring q5 min. Ca infusion antagonizes the proarrhythmic effects of hyperkalemia. Effect lasts up to 30 min. DO NOT USE IF DIGOXIN TOXICITY SUSPECTED. Insulin 10 units regular IV push with 1 amp D50W IV push. D50 prevents hypoglycemia so should avoid if patient already hyperglycemic. May K by 1 mmol/L, works in 15-30 min, and lasts hours. NaHCO3 1 amp IV over 5 min q30 min. Less effective if patient not acidotic or has ESRD. May K by 0.5-1 mmol/L, works in 30-60 min, and lasts hours. Watch for Na load

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Albuterol 10-20 mg hand held nebs (note this is 2-8x the usual dose) or 0.5mg by IV infusion (rarely given). May K by 1 mmol/L, works in 60-90 min nebulized or 30 min IV, and lasts about 4 hours. Major side effects include -stimulation (arrhythmia) and not as effective in ESRD Kayexalate and diuretics as above Dialysis: May consider holding insulin/D50, NaHCO3, and albuterol if patient without dangerous EKG findings and plans are to dialyze immediately. Each measure shifts K intracellular and will make removal of K by dialysis less effective Important to note that of the above measures, only Kayexalate, diuretics, or dialysis will remove total body K rather than redistribute

HYPOCALCEMIA Calcium relationships: Total Ca = Protein bound (primarily albumin) + complexed (primarily to anions like PO4) + free (ionized Ca) Primary determinant of clinical manifestations of Ca disorders is the ionized Ca. Approximately 45-50% of total Ca is ionized Conversion factors of total Ca (mg/dl) and ionized Ca (mmol/L): Molecular weight of Ca = 40 grams, so 40 mg/L = 1 mmol/L = 4mg/dL So if total Ca = 10 mg/dl then it is 2.5 mmol/L. Assuming that 50% of total Ca is ionized then a total Ca of 10 mg/dl is approximately equivalent to 1.25 mmol/L ionized Ca Total Ca is effected by changes in albumin concentration and the proportion of bound Ca is effected by systemic pH Every 1 g/dL of albumin below 4 0.8 mg/dL in total Ca Every 0.1 of pH below 7.4 0.12 mg/dL in ionized Ca Clinical manifestations: Depends on rate of onset and are potentiated by alkalosis, Mg, K, catecholamines Neuro: Mild: circumoral numbness, paresthesias, cramps Severe: seizure, tetany, laryngospasm, carpopedal spasm Signs: Trousseaus = carpal spasm with cuff inflation. Chvosteks = twitching of facial muscles with facial nerve tapping Psych: Irritability, anxiety, depression CV: Arrhythmia, prolonged QT interval on EKG, depressed function Optho: Papilledema Chronic: Dry puffy skin, alopecia, cataracts, basal ganglia calcification, extrapyramidal disorders Causes: Loss of Ca from circulation: Extravascular deposition: PO4 (renal failure, rhabdomyolysis, tumor lysis), acute pancreatitis (precipitation of Ca soaps) Intravascular binding: Ca chelation (citrate or EDTA in massive blood transfusion, lactate, foscarnet), ionized fraction) acute respiratory alkalosis ( albumin binding Osteoblastic metastases Entry of Ca into circulation: Hypoparathyroidism ( production or action): post-surgical, autoimmune, infiltrative disease, cinacalcet, autosomal dominant hypocalcemia (activating mutation of Ca sensing receptor results in low PTH secretion), Mg, pseudohypoparathyroidism Hypovitaminosis D ( production or action): dietary intake, malabsorption, 25-hydroxylation in liver failure, 1-hydroxylation in renal failure, metabolism

NEPHROLOGY Bisphosphonates Critical illness: Appears related to inflammatory cytokines diminishing PTH and vitamin D production and PTH action. Examples include sepsis or burns Work-up: Confirm with ionized Ca measurement or corrected total Ca Other useful tests include: intact PTH, Mg, PO4, Vitamin D 25-OH, Vitamin D 1,25-OH, and Cr PTH must be interpreted with concomitant Ca measurement A normal PTH with a low Ca is inappropriate and suggestive of hypoparathyroidism
DIFFERENTIAL DIAGNOSIS OF HYPOCALCEMIA BASED ON LAB FINDINGS Disorder PTH PO4 25-OH-D Hypoparathyroidism Low High Nl Pseudohypoparathyroidism High High Nl High Low Low Vitamin D 25-OH deficiency: (dietary, malabsorption, cirrhosis) Vitamin D 1,25-OH deficiency: High Low Nl or high (renal, hereditary) Vitamin D 1,25-OH resistance High Low Nl Hypomagnesemia Low, nl or high High Nl Nl or high Low nl Nl bone formation: Healing, mets, hungry bone syndrome Soft tissue calcification Nl or high High Nl

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1,25-(OH)2-D Low Low Low, nl, or high

Low Very high Low or nl Nl or high Nl, high or low

Treatment: Mild asymptomatic: Oral replacement with extra 1000 mg elemental Ca daily (500 mg CaCo3 ~ 200 mg elemental Ca) Consider IV replacement in those unable to take PO Severe or symptomatic: (iCa < 0.7-0.8 mmol/L or total < 7 mg/dL) IV Ca: 1-2 grams Ca gluconate or Ca chloride over 20 min. Do not give any faster given possible side effect of inducing cardiac arrhythmia. May follow by infusion of 0.5 mg/kg/hr. Follow serum Ca q4-6 hr and gradually taper infusion Correct hypomagnesemia Treat underlying condition Chronic: Frequent complication of CKD given hyperphosphatemia and Vitamin D 1,25-OH production. Consider addition of calcitriol or other Vitamin D analogues If patient is on dialysis, dialysate Ca bath may be altered Watch Ca repletion with hyperphosphatemia. Beware of calciphylaxis if Ca-PO4 product (Total serum Ca x PO4) > 70

HYPERCALCEMIA Clinical manifestations: Renal: ARF (prerenal, vasoconstriction), polyuria (nephrogenic DI), dehydration, nephrolithiasis GI: Anorexia, nausea, vomiting, constipation CV: Short QT on EKG, enhanced sensitivity to digitalis, bradyarrhythmia Neuro: Apathy, depression, coma, hyperreflexia Musculoskeletal: Chondrocalcinosis, pseudogout, osteitis fibrosa cystica (associated with hyperparathyroidism)

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Soft tissue: Ectopic calcification Causes (CHIMPANZEES): Calcium supplementation Hyperparathyroid (primary or tertiary)/Hereditary (Familial hypocalciuric hypercalcemia): Hyperparathyroidism accounts for 90% of ambulatory cases Note: Secondary hyperparathyroidism associated with low Ca Immobility/Infections (TB, histoplasmosis, coccidiomycosis, leprosy) Milk-alkali/Medications (Thiazides, diuretics, lithium, estrogens, antiestrogens) Pagets disease, Parenteral nutrition Addisons disease/Adrenal insufficiency Neoplasm: accounts for majority (65%) of hospitalized cases PTH-RP mediated (squamous cell lung carcinoma, renal, breast) Vitamin D 1,25-OH mediated (lymphoma) Osteolytic mediated (multiple myeloma, metastases, lymphoma) Zollinger-Ellison Endocrine (non-parathyroid): Thyrotoxicosis, pheochromocytoma Excess Vitamin D 25-OH, Vitamin D 1,25-OH, Vitamin A Sarcoidosis Work-up: Ionized Ca, PO4, Cl, TCO2, Vitamin D 25-OH, Vitamin D 1,25-OH, PTH, PTHrP, TFTs, SPEP/UPEP, alkaline phosphatase Consider Vitamin A, skeletal survey, nuclear bone scan, and BM Bx depending on level of clinical suspicion

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TREATMENTS FOR HYPERCALCEMIA Mechanism Onset Duration Hours Temporizing Na-induced volume while IVF expansion reverses running dehydration and inhibits proximal tubule Ca reabsorption Hours Temporizing Na-induced while diuretic in natriuresis and effect inhibits ascending limb Ca reabsorption (Note: thiazides may worsen hypercalcemia) Inhibits osteoclast2-4 days Weeks to mediated bone months resorption

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Treatment NS Hydration: 200-300 ml/hr titrated to UOP 100-150 ml/hr

Side effects Volume overload, rarely effective alone

Loop diuretic (i.e. furosemide)

Bisphosphonate: Zoledronic acid (4mg over 15 min) or Pamidronate (90mg IV over 24 hours or 60mg IV over 4 hours) Calcitonin (4-8 IU/kg IM/SQ q6-12 hours) Prednisone (20-40mg PO daily)

Other electrolyte abnormalities (K, Mg), volume depletion (ensure patient volume replete before instituting) Mg, PO4, caution in renal failure given prolonged half-life (use lower dose) Rarely side effects, nausea, flushing, hypersensitivity Typical side effects of steroid usage

Gallium nitrate (200 mg/m2/day continuous IV for 5 days) Oral PO4 (0.5-1 gm PO tid) Dialysis

Inhibits osteoclastmediated bone resorption Inhibits Vitamin D 1,25-OH synthesis by mononuclear cells (effective versus lymphoma or granulomatous disease) Inhibits osteoclastmediated bone resorption Complexes Ca in gut Removes systemic Ca via diffusion

Hours 2-4 days

Tachyphylaxis at 48 hours Days

3-5 days Days Immediate

Weeks Temporizing while in use Temporizing while in use

Nephrotoxic, requires continuous infusion, rarely used Calciphylaxis (do not use if Ca-PO4 product > 55) Use for patients with severe hypercalcemia

OTHER ELECTROLYTE REPLACEMENT Magnesium: General rule: Every 1.0 gm of MgSO4 given IV will serum Mg 0.1 mEq/L (if Cr is <1) Oral replacement may also be used with Mg Oxide though absorption is 15-50% and may cause diarrhea Patients with renal failure will require lowering of dose by 50% or more Phosphate: Phosphate > 2.0 mg/dl Replete orally with Neutra-Phos or KPhos (2 tablets/packets TID)

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Phosphate 1.5-2.0 mg/dl 0.08 mmol/kg IV NaPhos or KPhos over 6 hours Phosphate < 1.5 mg/dl 0.16 mmol/kg IV NaPhos or KPhos over 6 hours Be careful with phosphate replacement in patients with hypercalcemia as chance of metastatic calcification Patients with renal failure will require lowering of dose by 50% or more

IDENTIFYING ACID/BASE DISORDERS Step 1: Check ABG and chemistry panel. Identify changes in pH, HCO3, and pCO2, and see if the perturbation in PCO2 or HCO3 explains the trend in pH. VBG may be used to estimate arterial pH (add ~ 0.05) and pCO2 (subtract ~ 5) except in cases of circulatory failure. In most clinical cases, venous chemistry total CO2 can substitute for blood gas HCO3 If pH is low and pCO2 is high, patient has a primary respiratory acidosis If pH is low and HCO3 is low, patient has a primary metabolic acidosis If pH is high and pCO2 is low, patient has a primary respiratory alkalosis If pH is high and HCO3 is high, patient has a primary metabolic alkalosis Step 2: Check anion gap to look for an anion gap acidosis (even if pH is normal): Anion Gap = Na (Cl + HCO3) Low albumin will cause lower AG (for every in albumin by 1, AG by 2.5). Other causes of low anion gap include unmeasured cations (paraproteinemia, lithium, K, Ca, Mg), bromide intoxication, hyperlipidemia If high, calculate anion gap (AG): AG = Patients AG Normal AG (use patients baseline AG, or, if unknown, 12 at UCLA) Step 3: Add the AG to patients HCO3 (AG + patients HCO3) If < 24: a non-gap metabolic acidosis AND/OR a respiratory alkalosis is present in addition to gap metabolic acidosis If > 24: a metabolic alkalosis AND/OR a respiratory acidosis is present in addition to gap metabolic acidosis Step 4: Identify any additional respiratory or metabolic process by using the formulas below to calculate expected pCO2 and serum HCO3 based on serum HCO3 and compare to actual pCO2 and HCO3 If actual pCO2 = expected pCO2 pure metabolic process If actual pCO2 > expected pCO2 primary respiratory acidosis also present If actual pCO2 < expected pCO2 primary respiratory alkalosis also present If actual HCO3 = expected HCO3 pure respiratory process If actual HCO3 > expected HCO3 primary metabolic alkalosis also present If actual HCO3 < expected HCO3 primary metabolic acidosis also present ACID/BASE FORMULAS The formulas below predict expected pCO2 based on serum HCO3 in the following settings: Metabolic Acidosis For every in HCO3 by 10, pCO2 should by 10-12 OR Winters Formula: Expected pCO2 = 1.5 x HCO3 + 8 2 (Use in simple acidosis) Metabolic Alkalosis For every in HCO3 by 10, pCO2 should by 7 The formulas below predict expected serum HCO3 based on pCO2 in the following settings: Acute Respiratory Acidosis For every in pCO2 by 10, HCO3 should by 1 and pH should by 0.08

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Chronic Respiratory Acidosis For every in pCO2 by 10, HCO3 should by 3.5 and pH by 0.03 Acute Respiratory Alkalosis For every in pCO2 by 10, HCO3 should by 1-2 Chronic Respiratory Alkalosis For every in pCO2 by 10, HCO3 should by 5

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Remembering the renal compensation for a respiratory problem is as easy as A-B-C, 1-2-3! Just use THE BOX!! For every change in pCO2 of 10, the bicarb (HCO3) will change by the number in the box for the given respiratory process. For example, in an acute respiratoy acidosis with a pCO2 of 60 (20 pts above normal), you would expect the HCO3 to rise by 2 points.
Acid Base

Acute
Chronic

1 3.5

2 5

ACID/BASE DIFFERENTIAL DIAGNOSES Metabolic Acidosis: Anion gap metabolic acidosis (MUDPILES): Methanol Uremia (renal failure) Diabetic ketoacidosis, Dilutional acidosis Paraldehyde, Pyroglutamic acid (acetaminophen), Phenformin INH, Iron Lactic acidosis Ethylene glycol, ETOH ketoacidosis Salicylates, Starvation ketoacidosis Anion gap and osmolal gap metabolic acidosis: If suspect toxic ingestion calculate osmolal gap: Calculated serum osmolality = (2 Na) + (BUN 2.8) + (glucose 18) Osmolal gap = Measured serum osmolality Calculated serum osmolality Normal osmolal gap 10 mOsm/kg Conditions include methanol ingestion, ethylene glycol ingestion, ethanol intoxication, renal failure, paraldehyde, ketoacidosis, lactic acidosis Other substances that cause osmolal gap without anion gap acidosis include isopropanol, mannitol, contrast, severe hyperproteinemia Non gap metabolic acidosis (HARDPUT): Hyperalimentation Acetazolamide RTA, Renal failure (early) Diarrhea Pancreatic fistula Ureteral diversion (ureterosigmoidostomy, ileal loop, etc)

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Toluene ingestion Urine anion gap may help distinguish GI and renal causes of non-gap metabolic acidosis: Urine Anion Gap = Urine Na + Urine K Urine Cl If negative, GI HCO3 loss (diarrhea) is likely cause (Negative means below the belt) If positive, renal HCO3 loss (RTA) is likely cause (Positive means above the belt) Metabolic Alkalosis: Check urine chloride to divide into chloride responsive and chloride resistant Chloride responsive (UCl < 20 mmol/L): NGT suction, vomiting Diuretics (late) Posthypercapnea Cystic fibrosis Low chloride intake Laxative-induced diarrhea Chloride resistant (UCl > 40 mmol/L): Mineralocorticoid excess (frequently hypertensive): May include primary hyperaldosteronism, reninsecreting tumors, Cushings syndrome, Liddles syndrome, renovascular disease, apparent mineralocorticoid excess, licorice ingestion Diuretics (early) Alkali load, antacids Bartters or Gitelmans syndrome Severe hypokalemia Respiratory Acidosis: Respiratory depression COPD Neuromuscular weakness/kyphoscoliosis Pleural effusions Pneumothorax Pneumonia Pulmonary edema Bronchospasm/laryngospasm Respiratory Alkalosis: Sepsis Respiratory distress (PE, CHF, hypoxemia, restrictive lung disease) Head trauma Liver disease Salicylates Hyperthyroidism Pregnancy, progesterone Central hyperventilation Anxiety

RENAL TUBULE ACIDOSES Proximal (Type II): Failure to reabsorb HCO3 in the proximal tubule DDx: Congenital, Fanconis, myeloma, ifosfamide, heavy metals, hyperparathyroidism, aminoglycosides, cystinosis, glycogen storage disease, acetazolamide, amyloidosis, topiramate

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Work-up: Fractional excretion of HCO3 (FEHCO3) > 15% (calculate like FENa) after normalization of serum HCO3 Distal (Type I & IV): Failure to acidify urine in the cortical collecting duct Type I (classic distal): Failure of H+-ATPase to secrete H+ into urine DDx: Collagen vascular disease (Sjgrens, rheumatoid arthritis) congenital, chronic hyperglobulinemia Amphotericin may cause holes in luminal membrane allowing back-leak of H+ ions Often associated with hypokalemia, hypercalciuria, and nephrolithiasis Type IV: Lack of aldosterone production or action leads to failure to reabsorb Na and secrete H+ and K DDx associated with hyporeninemic hypoaldosteronism: Diabetic nephropathy, tubulointerstitial diseases, ACEI, NSAIDs, cyclosporine, obstructive uropathy Primary hypoaldosteronism will give similar clinical picture except renin DDx associated with aldosterone resistance: Spironolactone, epithelial Na channel blockage (amiloride, triamterene, trimethoprim, pentamidine), pseudohypoaldosteronism (type I & II), distal chloride shunt (tacrolimus) Often associated with hyperkalemia and metabolic acidosis Work-up: Urine PCO2 - Blood PCO2 < 30 Urine PCO2 will be lower than normal (70) because urine will not be acidified and subsequently less drive H2CO3 H2O + CO2 for H+ + HCO3 Send ABG on urine (have patient urinate in cup with mineral oil to prevent PCO2 diffusion to air) and check blood gas Serum HCO3 must be normal before obtaining the above studies (will likely need to give HCO3 IV)

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Hyperchloremic Metabolic Acidosis

Urine Net Charge

Negative (High Urine NH4+)

-Gastrointestinal HCO3 losses? -HCl, NH4Cl used? -Acetazolamide used? -Unmeasured ions? -Proximal RTA?

Positive (Low Urine NH4+)

FeHCO3

Urinary pH 5.5 >5.5

Exclude UTI, primary hypokalemia, volume

No Potassium

Potassium

Potassium

No Potassium

Urine-blood PCO2

Type IV RTA

-Voltage distal RTA -Postobstructive uropathy

Low

High

Measure serum aldosterone

(+) Amphotericin B

(-) Amphotericin B

Rate-limited secretory distal RTA

NH3 Defect

= Aldosterone deficiency = Aldosterone resistance

-Gradient-limited secretory distal RTA -Low urine-blood PCO2

-Permeability defect -High urine-blood PCO2

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DIURETIC THERAPY Tolerance: After long term use of loop diuretics, the distal segments hypertrophy Thiazides (often metolazone 2.5-5 mg PO 30 minutes prior to loop diuretic dose) are then used to block the distal sites Clinical conditions of diuretic resistance: Renal insufficiency: Frequently need higher doses due to inherent diuretic resistance from dysfunctional tubules. Can give up to 160 mg IV Lasix. If no effect, start an IV Lasix drip after a loading dose. Need to watch for ototoxicity with high doses If still little response, add metolazone Dialysis if fluid overload state is refractory to high dose diuretics Nephrotic Syndrome: Diuretics bound to albumin and transported to renal tubules for secretion into intraluminal space intravascular albumin leads to diffusion of diuretics into extravascular space and decreased transport to renal tubules binding of diuretic to filtered urinary albumin and free diuretic to interact with appropriate channels May need to dose of diuretic by 2-3x of normal amount Consider concomitant infusion of albumin with furosemide (controversial if more effective than furosemide alone) Cirrhosis: Spironolactone (50-100 mg/day titrated to max 400 mg/day) as first line Add loop diuretic (furosemide 40-160 mg/day) for refractory edema or ascites CHF: Loop diuretics at frequency. Diuretic free periods allow rebound Na retention to occur so frequent dosing (i.e. furosemide q6-8 hours) or drip may be appropriate Add metolazone if lack of response with loop diuretic Sulfa allergy: Ethacrynic acid does not contain sulfa Check K, Mg q6-12 hours depending on the frequency and strength of diuretic administration and replete to keep K > 4.0 and Mg > 2.0 RHABDOMYOLYSIS Definition: Necrosis of skeletal muscle with release of intracellular muscle enzymes and pigments into circulation Causes: Crush injuries, severe exertion, alcoholism, seizure, infection, drugs (statins, cocaine, etc), hypokalemia, hypophosphatemia, malignant hyperthermia/NMS, metabolic myopathies, inflammatory myopathies, mitochondrial disorders Clinical manifestations: Asymptomatic with mild rhabdomyolysis to severe cases with myalgias and myoglobinuria ARF: Possible mechanisms include renal ischemia due to volume depletion, tubular obstruction from the heme pigment casts, and tubular injury from the free iron DIC: Thromboplastin released from damaged cells Work-up: CK (skeletal fraction): Typically > 10,000 to cause injury, but can be > 100,000 IU/L. CK peaks within 24 hours and ~40%/day, so if delayed presentation, CK on admission may be markedly lower than at time of initial insult

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Electrolytes: K, PO4, Ca, uric acid, metabolic acidosis Urinalysis: Reddish/brown urine with urinalysis noted positive for heme but negative for cells (similar to hemoglobinuria; unlike hemoglobinuria where it is red, plasma color is clear in myoglobinuria). Urine sediment may show reddish-gold pigmented casts Gross pigmenturia may not be present because myoglobin more rapidly cleared from serum than CK Other: Serum AST/ALT Treatment: Goal is to treat underlying illness and prevent/manage ARF. Similar management as for hemoglobinuria, the other type of pigment nephropathy Monitor frequent electrolytes (K, Ca, PO4) Hypocalcemia common in early phase, but avoid Ca replacement unless symptomatic or severe as risk of Ca-PO4 precipitation and development of hypercalcemia during recovery phase. Fluid resuscitation: Normal saline to enhance renal tubular perfusion and prevent tubular obstruction Begin NS 0.5-1 L/hr and titrate to urine output of 200-300 ml/hr Monitor for fluid overload and compartment syndrome which can worsen with vigorous hydration If diuresis not achieved with volume repletion, add diuretic Urine alkalinization: Theoretical benefit of decreasing pigment cast formation and release of free iron from myoglobin. Conflicting reports and no controlled trials. Use only if adequate urine output achieved. Consider 1-2 amps of NaHCO3 in NS @ 100ml/hr titrated to goal urine pH > 6.5 Side effects include worsening hypocalcemia, Ca-PO4 precipitation, and hypokalemia Mannitol: Theoretical benefit of forced diuresis to flush out pigment as well as act as free radical scavenger Conflicting reports and no controlled trials. Use only if adequate urine output achieved Side effects include osmotic diuresis with volume depletion and hypernatremia, hyperosmolarity and associated volume overload (Monitor serial plasma osmolality D/C if osmolal gap > 55 mOsm/kg), and ARF Dialysis: May be needed for hyperkalemia, hyperphosphatemia, or volume overload

CONTRAST-INDUCED NEPHROPATHY Definition: Differs study to study, but often defined by 25% or absolute of 0.5 mg/dL of serum Cr within 1 week of contrast administration Epidemiology: Estimates depend on definition and population, though likely 1-2% of all patients, and relatively common cause of hospital-acquired ARF (~12%) Risk factors: DM, CKD (Cr > 1.5 mg/dl or GFR < 60 ml/min), volume depletion, myeloma, CHF, contrast factors (high osmolality, large volume, ionic) Prophylaxis: Optimal treatment unclear, but should be done for all patients at risk IV hydration: Should be considered for all patients NS 1 ml/kg/hr beginning 6-12 hours prior to contrast and 6-12 hours afterwards Limited evidence for benefit of NaHCO3 over NS. May consider NaHCO3 if limited time for IVF hydration, but need to monitor for alkalemia and hypocalcemia Consider 3 amps of NaHCO3 added to 1L sterile H2O (~150-175 mEq/L NaHCO3) as bolus of 3 ml/kg 1 hr prior to contrast and continued for 6 hours afterwards N-acetylcysteine: Conflicting reports of efficacy, but often given due to minimal side effects N-acetylcysteine 1200mg PO BID given day before and 24-48 hours after contrast exposure Some evidence for IV N-acetylcysteine so may consider for patients unable to take PO or for emergency procedures. However, side effects include fair rate of anaphylactoid reactions Consider 1200 mg N-acetylcysteine IV bolus prior to contrast and then 1200 mg IV BID for 48 hours after contrast exposure

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Continuous hemofiltration: Limited evidence with positive results using serum Cr (which is eliminated from serum with hemofiltration) as measure of ARF Discuss with renal service prior to institution as may be useful in patients already with access. However, use requires presence of vascular access and ICU stay for day of CVVH Note hemodialysis alone is not effective Other: Withhold diuretics and NSAIDs if possible 24 hours prior to and after contrast and metformin 48 hours prior to and after contrast. Forced diuresis with mannitol and dopamine has been associated with worse outcomes. Some limited data available regarding possible beneficial effects of theophylline and Vitamin C

VASCULAR ACCESS FOR HEMODIALYSIS Acute, short-term catheter (i.e. Quinton, Mahurkar): Double lumen, non-cuffed, non-tunneled catheter May be inserted at bedside into femoral, jugular or subclavian (less preferable because of risk of subclavian stenosis or thrombosis) vein via modified Seldinger technique Typical longevity of catheter by insertion site: Internal jugular: 2-4 weeks Femoral vein (in non-ambulatory patient): ~7 days Femoral vein (in ambulatory patient): Single use only Tunneled catheter (i.e. PermCath): Double lumen, cuffed catheter that is tunneled under the skin Inserted into jugular, femoral or subclavian (less preferable) vein by interventional radiology or vascular surgery Typical longevity of catheter is 6 months to one year Often used as a bridge until maturation of AV fistula or graft Arteriovenous Access: AV Fistula: Placed by vascular surgery under regional anesthesia via a subcutaneous anastomosis of an artery to an adjacent vein Safest and longest lasting permanent vascular access for hemodialysis Requires minimum 1 month, and possibly 4-6 months, maturation time prior to use AV Graft: Placed by vascular surgeon under regional anesthesia via a synthetic tube graft connecting an artery and vein Used when patient vasculature inadequate for AV fistula Allow 2-3 weeks for maturation prior to use Clotting and infection risk higher with AV graft than AV fistula Complications associated with hemodialysis access: Catheter insertion related complications: Arterial puncture, pneumothorax/hemothorax, pericardial tamponade, air embolism, brachial plexus injury, mediastinal hemorrhage, arrhythmias Catheter infectious complications: Prevention: Aseptic insertion and handling of catheters Infection of uncuffed catheters: Localized exit site or tunnel infection: If erythema present but no purulent discharge, treat with antibiotics for 2 weeks

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Remove catheter if systemic signs of infection are present (e.g. fever, leukocytosis, hypotension), if positive blood cultures, if pus can be extruded from the catheter insertion site, or if the erythema does not clear after treatment with antibiotics Systemic infection: Signs of local infection may or may not be present Remove catheter if there are signs of systemic infection without another obvious source or if fungemia On removal, the catheter tip should be cultured using sterile technique and consideration may be made for blood cultures from line and peripherally Antibiotic therapy should be continued for a minimum of 2 to 3 weeks Infections in cuffed catheters (PermCath): Tunnel site infections without bacteremia: Can be given a brief trial of antibiotics but failure to respond within 36-72 hours requires removal of catheter Catheter-related bacteremia without tunnel site infection or signs of sepsis: Initial course of parenteral antibiotics Given patients may be difficult access, catheter may be left in patients who become asymptomatic on antibiotic therapy and have no evidence of tunnel or exit site infection Catheter should be removed in all patients who are still symptomatic after 36-72 hours of antibiotic therapy Catheter related fungemia: Catheter should be removed Complications of catheter related infections: Endocarditis Osteomyelitis Suppurative thrombophlebitis Spinal epidural abscess Sepsis Catheter dysfunction: Early catheter dysfunction: Intracatheter thrombosis: Treatment with intraluminal administration of tPA Malposition or catheter tip thrombosis: Persistent low flow despite intracatheter thrombolytics requires examination under fluoroscopy to diagnose malposition of the catheter tip or tip thrombosis Late catheter dysfunction (> 5 days): Fibrin sleeves and mural thrombi: Fibrin sleeves begin developing 1-3 weeks after insertion of the catheter May cause intraluminal obstruction and serve as a nidus for infection Suspected in catheters that infuse but are difficult to aspirate Diagnosis made by interventional radiology with a catheter venogram Treatment with either thrombolytics, snare stripping of the fibrin or replacement of the catheter Complications with AV fistulas or grafts: Stenosis: Caused by thrombosis, myointimal hyperplasia, pseudoaneurysm, needle stick injury Signs and symptoms: Recurrent clotting Difficulty with needle placement or hemostasis after needle withdrawal Persistently swollen arm

NEPHROLOGY High venous pressures during dialysis Positive recirculation study Pulse with absent thrill (suggests low flow) or discontinuous water hammer type pulse over the graft Work-up: Doppler ultrasound Angiography Treatment: Thrombolysis or surgical thrombectomy if clot Percutaneous transluminal catheter angioplasty Surgical revision Infections: More common in AV grafts than fistulas Initial antibiotics should cover gram negatives, gram positives (including enterococcus). Total antibiotics for 3 wks with graft and 6 wks with fistula (similar to endocarditis treatment) Extensive infection or septic embolus warrants surgical excision of graft/fistula Consider a tagged white cell scan in FUOs Distal ischemia/Steal: More common in DM, PVD, elderly May require surgical revascularization and ligation of access Aneurysm (fistula)/Pseudoaneurysm (graft): Avoid needle insertion Vascular surgery assessment should be pursued and may require revision, particularly for pseudoaneurysms

188

RENAL TRANSPLANT Differential of Renal Transplant Graft Dysfunction Immediate graft dysfunction (hours post-transplant): Ischemic renal injury Calcineurin inhibitor nephrotoxicity Hyperacute rejection Urinary leak or urinary tract obstruction Vascular thrombosis Volume depletion/prerenal Recurrence of primary renal disease (particularly primary FSGS) Early graft dysfunction (days to weeks post-transplant): Acute rejection (cellular, humoral or both) Calcineurin inhibitor nephrotoxicity, including TTP/HUS Urinary leak or urinary tract obstruction/ Volume depletion/prerenal Infection Recurrence of primary renal disease (particularly primary FSGS) Delayed graft function (perioperative ATN) Late onset graft dysfunction (months to years post-transplant): Acute rejection (cellular, humoral or both) Calcineurin inhibitor nephrotoxicity, including TTP/HUS Chronic allograft nephropathy

NEPHROLOGY

189

Recurrence of primary renal disease or de novo glomerulonephritis Transplant renal artery stenosis (RAS) BK virus nephropathy Post-transplant lymphoproliferative disease (PTLD) Note: Donor characteristics will affect graft function at all stages (i.e. poor prognostic factors include donor elderly age, history of stroke, donor hypertension, glomerular and interstitial scarring on biopsy, etc) Work-up of renal allograft dysfunction Physical exam: Vital signs: Fever and oliguria are not necessarily present with acute rejection. Given effect of potent immunosuppression, fever likely more suggestive of infection Monitor for hypertension Volume status (i.e. JVP, edema, urine output) Consider transplant RAS in the edematous patient Palpate renal graft looking for tenderness or enlargement which may represent acute rejection or pyelonephritis Excruciating graft pain suggestive of urine leak Auscultate for a new bruit which may represent transplant RAS Laboratory exam: Standard chemistry panel CBC with platelets and differential: Low platelets in setting of ARF should make one worried nephrotoxicity associated with calcineurin inhibitor-induced thrombotic microangiopathy Urinalysis and culture: Pyuria can indicate either acute rejection or infection Proteinuria may represent recurrence of primary disease (especially FSGS) or chronic allograft nephropathy Calcineurin inhibitor levels (cyclosporine, tacrolimus): Most useful drawn as trough levels. Draw cyclosporine and tacrolimus daily. May help differentiate between calcineurin inhibitor nephrotoxicity and rejection Sirolimus trough: Most useful drawn as trough level. Draw intermittently during hospital course rather than daily given long half-life Doppler renal ultrasound: Anatomic and surgical problems must be excluded Renal graft biopsy: Technique: Core needle (18 gauge spring loaded) biopsy performed with local anesthetic and ultrasound guidance Post-biopsy monitoring: Vitals every 15 min and 2 hours post-biopsy then hourly for 6 hours Patients should remain lying flat, relatively immobile, and can begin ambulating within 6-8 hours of bed rest Gross hematuria should be noted to renal fellow on call Complications: Perinephric or urinary bleeding Post-biopsy arteriovenous fistula Ureteral obstruction from blood clots

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190

Immunosuppressive Medications In Renal Transplant Note that decisions about immunosuppressive medications should be made by the renal transplant fellow and attending Corticosteroids: Class: Corticosteroids Mechanism: Inhibits lymphocyte proliferation and cell mediated immune response Toxic effects: Immunosuppression, glucose intolerance, osteonecrosis, cosmetic changes, impaired wound healing, cataracts, hyperlipidemia, psychosis Maintenance immunosuppression: Varies according to protocol Following steroid pulse, prednisone 20 mg daily immediately post-transplant and then usually tapered to 5 mg daily within 3 months Recently, select patients are being transferred to steroid-sparing regimens immediately posttransplant Monitoring: Monitor blood sugars for hyperglycemia Cyclosporine (Neoral, Gengraf, Sandimmune): Class: Calcineurin inhibitor Mechanism: Inhibits calcineurin which blocks T-cell function and IL2 secretion Toxic effects: Nephrotoxicity (acute and chronic), HTN (higher degree than tacrolimus), hyperlipidemia, glucose intolerance, neurotoxicity, hyperuricemia, gout, malignancy, infection, HUS/TTP, hirsutism, and gingival hyperplasia (higher degree than tacrolimus), hyperkalemia, hypomagnesemia, RTA Drug interactions: Due to interaction with p450 enzyme CYP3A4 cyclosporine levels: Anti-epileptics (barbiturates, phenytoin, carbamazepine), rifampin cyclosporine levels: Calcium channel blockers (verapamil, diltiazem, amlodipine), antifungal agents (-azoles), erythromycin, protease inhibitors, amiodarone Dosing: Note: Sandimmune is an older generic form of cyclosporine and is not equivalent to Neoral or Gengraf, which have more consistent bioavailability If cyclosporine and not Neoral or Gengraf is ordered through pharmacy, the patient may receive the older generic form Maintenance immunosuppression: varies according to protocol. Some centers and the outpatient clinic have adopted use of 2 hour peak level. 0-1 month: Trough 200-300 1-3 months: Trough 150-250 3-6 months: Trough 125-175 >6 months: Trough 100-175 Tacrolimus or FK 506 (Prograf): Class: Calcineurin inhibitor Mechanism: Inhibits calcineurin which blocks T-cell function and IL2 secretion Toxic effects: Nephrotoxicity (acute and chronic), HTN, hyperlipidemia, glucose intolerance (higher degree than cyclosporine), neurotoxicity (higher degree than cyclosporine), hyperuricemia, gout, malignancy, infection, HUS/TTP, hair loss, hyperkalemia, hypomagnesemia, RTA Drug interactions: Similar to cyclosporine Maintenance immunosuppression: Varies according to protocol 1-3 months: Trough 8-12 >3 months: Trough 6-10 Mycophenolate mofetil (CellCept, Myfortic): Class: Inosine monophosphate dehydrogenase inhibitor

NEPHROLOGY

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Mechanism: Inhibits B- and T-cell proliferation Toxic effects: Diarrhea, nausea, vomiting, dyspepsia, leukopenia, anemia, thrombocytopenia, opportunistic infections, lymphoproliferative disorders Dosing: Note: Myfortic is enteric-coated and may be associated with less GI side effects. Equivalent dose of Myfortic 720 mg ~ CellCept 1 gm Maintenance immunosuppression: No formal protocol for measuring drug levels at present Typically dosed 1-1.5 gm PO bid Higher doses frequently given to those who are African American, larger size, or prior history of rejection Sirolimus (Rapamune): Class: Macrolide antibiotic compound Mechanism of action: Inhibits mTOR which blocks T-cell function and IL2 signal transduction Toxic effects: Hyperlipidemia, thrombocytopenia, leukopenia, anemia, HUS/TTP, skin ulcers, pneumonitis, delayed wound healing, infection (PCP prophylaxis should always be given for 1 year), malignancy, hypokalemia, leg edema Dosing: Combination with calcineurin inhibitors may increase risk of calcineurin inhibitor toxicity Everolimus, a newer mTOR inhibitor, is presently being studied Drug interactions: Similar to cyclosporine Maintenance immunosuppression: 1-6 months: Trough 8-15 >6 months: Trough 6-12 Rabbit antithymocyte globulin (Thymoglobulin): Class: Polyclonal T-cell antibody Mechanism: Cytotoxic antibodies directed against various T-cell markers leading to depletion of peripheral blood T-cells Toxic effects: Fever, rigors, arthralgias, anaphylaxis, thrombocytopenia, leukopenia, delayed opportunistic infection (CMV prophylaxis should always be given), lymphoma Dosing: Daily dose must be infused into central vein usually for 7-14 days Premedication generally given with methylprednisolone, Benadryl, and Tylenol Doses may be given by RN via IVPB with frequent monitoring of vital signs (q15 min for 1 hr then q hr until infusion complete) Muromonab-CD3 (OKT3): Class: Anti-CD3 monoclonal antibody Mechanism: Antibody directed against T-cell receptor function inhibits T-cell function Toxic effects: Fever, rigors (common first-dose reaction, should still always consider infections), arthralgias, anaphylaxis, non-cardiogenic pulmonary edema, nephrotoxicity, neurological complications (aseptic meningitis), delayed opportunistic infection (CMV prophylaxis should always be given), lymphoma, coagulopathy, thrombocytopenia, TTP/HUS Dosing: Daily dose may be given via peripheral line usually for 7-14 days Premedication generally given with methylprednisolone, Benadryl, and Tylenol First few doses must be given by MD in the hospital with frequent monitoring of vital signs (q15 min for 2 hours then q30 min for 2 hours). CD3 levels may be followed Doses of other immunosuppressives may be lowered

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If second course of OKT3, should always check for OKT3 antibodies prior to administration Intravenous gammaglobulin (IVIG): Class: Polyclonal Ig produced from pooled plasma of multiple donors Mechanism: Multiple complex mechanisms involving suppression or elimination of anti-HLA T- and Bcells as well as altered cytokine signaling Toxic effects: Nephrotoxicity (osmotic mediated ATN from sucrose, maltose, and other additives), hemolytic anemia, dilutional and pseudohyponatremia, headache, fever, chills, myalgia, arthralgia, aseptic meningitis Dosing: Daily dose may be given via peripheral line usually for 2-4 days Premedication generally given with methylprednisolone, Benadryl, and Tylenol Renal Transplant Rejection Decisions about rejection treatment should be made by the renal transplant fellow and attending Banff Classification System: (1) Normal (2) Antibody-mediated (humoral) rejection: Rejection associated with at least 3 of the 4 following criteria: graft dysfunction, histologic evidence of tissue injury, positive staining for C4d, demonstration of donor specific antibody. This may be concurrent with categories 3, 4, and 5. Histologic types include the following: Type I: An ATN-like histology, with minimal inflammation Type II: A capillary glomerulitis, with margination and/or thromboses Type III: Arterial-transmural inflammation/fibrinoid changes (3) Borderline changes: Characterized by no intimal arteritis, the presence of foci of mild tubulitis (1-4 mononuclear cells/tubular cross section), and at least 10-25% involvement of interstitium. Findings are suspicious, but not diagnostic, for acute rejection (4) Acute/active cellular rejection: Histologic types include the following: Type IA: Significant interstitial inflammation (>25% of parenchyma) and moderate tubulitis (>4 mononuclear cells/tubular section) Type IB: Significant interstitial inflammation (>25% of parenchyma) and severe tubulitis (>10 mononuclear cells/tubular section) Type IIA: Mild to moderate arteritis found in at least one arterial cross section Type IIB: Severe arteritis, which is associated with > 25% loss of luminal area Type III: Transmural arteritis, and/or arterial fibrinoid alterations, and necrosis of medial smooth muscle cells occurring in association with lymphocytic inflammation of the vessel (5) Chronic allograft nephropathy: Fibrosis is observed, with or without alloimmune injury. This may be concurrent with categories 2, 3, and 4 Treatment: Varies per protocol and center Acute cellular rejection, tubulointerstitial type (Banff 4, Type IA or IB): Pulse methylprednisolone, 3-5 mg/kg for 3-5 days, is first line therapy. Conversion of maintenance cyclosporine to tacrolimus as well as addition of mycophenolate if not already present Antithymocyte globulin for steroid resistant or recurrent acute cellular rejection. Consider muromonab as third-line agent but must weigh potential risks Acute cellular rejection, vascular type (Banff 4, Type IIA, IIB, or III): Pulse methylprednisolone along with Thymoglobulin is first line therapy. Conversion of maintenance cyclosporine to tacrolimus as well as addition of mycophenolate if not already present .

NEPHROLOGY Consider muromonab for steroid resistant or recurrent acute vascular rejection but must weigh potential risks Acute humoral rejection (Banff 2): Pulse methylprednisolone along with IVIG is first line therapy Consider additional antithymocyte globulin if severe acute cellular rejection is also present Some data regarding use of concurrent plasmapheresis

193

NEUROLOGY
N E U R O L O G Y

194

GLASGOW COMA SCALE Adapted from Lancet 1974:2(872):81-84. System Best Result # of Points 6 Motor Response Obeys commands 5 Localizes 4 Withdraws 3 Abnormal flexion 2 Extends 1 No response Verbal Response Oriented 5 Confused conversation 4 Inappropriate words 3 Incomprehensible sounds 2 No response 1 Eye Opening Spontaneous 4 To speech 3 To pain 2 No response 1 Score 3-5 >60% mortality in head injury Score 6-8 12% mortality in head injury Score 9-12 2% mortality in head injury Total possible score of 30 FOLSTEIN MINI-MENTAL STATUS EXAM (MMSE) Adapted from J Psychiatric Res 1975;12:189 Tasks Year, season, date, day, month State, county, town, hospital, floor Patient recites 3 consecutive objects named (i.e. rose, baseball, car) Serial 7s or spell WORLD backwards Patient to name 3 objects registered from before Name an object (i.e. pen, watch) Repeat NO if, ands, or buts 3-stage command: Take this paper in your right hand, fold it in half, and put it on the table. Read and obey: Close your eyes. Write a sentence Copy the design to the right Assess along continuum: Alert-drowsy-stuporous-comatose

Category Orientation Registration Attention/Calculation Recall Language

Score 5 5 3

5 3 2 1 3 1 1 1 0

Level of consciousness

Maximum possible score of 15

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DELIRIUM VERSUS DEMENTIA Adapted from Intern Intake 1999-2000 by Dr. Joel Isackson and Dr. Susan Charette Delirium Dementia Onset: over hours to days Onset: over months to years Disturbance of consciousness such as reduced Level of attention not initially compromised awareness, inability to sustain attention Altered cognition: memory, language, Multiple cognitive impairments: language, motor disorientation, perceptual disturbance activities, agnosia, executive function Caused by medical condition Not explained by any medical condition Evaluation: check medications, infections, CBC, Evaluation: obtain thorough history from the patient electrolytes, creatinine, glucose, liver function panel, and family members, physical exam (with focus on cardiac enzymes, UA, CXR, EKG, pulse oximetry neurologic testing), MMSE, functional status, CBC, and/or ABG. Consider Head CT and LP. TSH, vitamin B12, electrolytes, VDRL, HIV. Consider neuroimaging and LP if onset <60, abrupt onset or rapid decline, or history of cancer or anticoagulant use DELIRIUM PROPHYLAXIS Adapted from Noon conference by Dr. Michael Galindo (September 2006) Risk factors: Age >70, comorbidities, male, dementia, history of alcohol use, malnutrition. Admission Risk Factors Infection, dehydration, severe pain, fracture, heart failure, abnormal blood pressure Preventative Measures Orientation: accurately assess baseline, provide orientation clues, perception aids (hearing aids, glasses), regulate sleep-wake cycle, active involvement of family/caregivers Minimize iatrogenesis: stop inappropriate/unnecessary medications, minimize urinary catheters, minimize restraints Housekeeping measures: oxygen delivery, hydration, monitor electrolytes/glucose Prophylaxis: bowel regimen, nutrition, early mobilization, pain control Common medication culprits: benzodiazepines, anticholinergics, muscle relaxants, antiemetics, GI antispasmodics, narcotics overdose, antihistamines, tricyclic antidepressants Treatment Behavior: sitters, family, reorientation, bed rails, minimize restraints Drug therapy: Haloperidol 0.5 mg to 1 mg IV t.i.d. then 1-2 mg IV qhs short term, taper quickly. Caution with prolonged QT, check EKG routinely, optimize electrolytes. Generally want to avoid lorazepam, but in conjunction with haloperidol can be useful ALTERED MENTAL STATUS Differential Diagnosis (MOVE STUPID) Metabolic: vitamin B12 or thiamine deficiency, acidemia, hepatic encephalopathy Oxygenation: hypoxemia, anemia Vascular: ischemic or hemorrhagic stroke, vasculitis, TTP, DIC, hyperviscosity, hypertensive encephalopathy Endocrine: hypoglycemia or hyperglycemia, hypothyroidism or hyperthyroidism, high or low cortisol states. Electrolytes: hyponatremia or hypernatremia, hypercalcemia Seizures

NEUROLOGY Tumor Trauma Temperature Uremia Psychogenic (diagnosis of exclusion) Infection/Intoxication Drugs Degenerative diseases: Alzheimers, Parkinsons Evaluation Assess ABCs Check vital signs including blood glucose check Neurologic examination: include responsiveness, orientation, pupil size, symmetry, motor response to stimuli in all 4 extremities, reflex symmetry, gag reflex and meningismus Emergent neuroimaging (consider): head CT to evaluate for bleed, MRI stroke protocol to evaluate for stroke Lab: blood cultures, CBC, chemistry panel, LFTs, ABG, toxicology screen, RUA, CXR, EKG, LP Treatment Treat readily reversible conditions and hopefully, the underlying cause! Thiamine 100 mg IV D50W if hypoglycemic Naloxone 0.4-1.2 mg IV Oxygen If you suspect cerebral edema and ICP: begin steroids (dexamethasone 6-12mg IV q4-6hrs) and mannitol infusion (1 g/kg), phenytoin, and intubate with hyperventilation Well-lit, calm environment. Soft restraints as needed to protect patient. Consider a sitter. In combative patient: Haldol 1-5 mg IV/IM/PO or Droperidol 2.5-5 mg IV/IM

196

STATUS EPILEPTICUS Adapted from Status Epilepticus/Stroke 2/22/01 by Dr. Steve Lee Definition Continuous seizures lasting > 5 minutes OR 2 discrete seizures between which there is incomplete recovery of consciousness. Etiologies Structural: brain trauma, tumor, stroke, hemorrhage CNS infection: encephalitis, meningitis Drugs: penicillins, lidocaine, normeperidine, theophylline, flumazenil, cocaine, imipenem Drug withdrawal: alcohol, opiates, barbiturates, benzodiazepines Metabolic: glucose, glucose, Na, Ca, Mg, osmolarity, hypoxia, uremia Precipitation of idiopathic epilepsy: change in anticonvulsant drug levels, intercurrent infection, alcohol excess or withdrawal Evaluation/Initial management Establish ABCs. Intubate if necessary. Establish at least 2 IVs. Obtain vitals including oxygen saturation. Keep the patient on monitor. Frequently monitor rectal temperature. Obtain blood glucose level. If hypoglycemia is documented or if it is impossible to obtain the measurement, give 100 mg IV thiamine followed by D50.

NEUROLOGY
Labs: ABG, comprehensive chemistry panel, CBC with differential, anticonvulsant drug levels, PT/PTT, cultures (if patient is febrile) Consider: urine/serum toxicology screen, LP, EEG, CT, and/or MRI Treatment Anti-epileptic drugs should be initiated whenever a seizure has lasted >5-10 minutes. Administer drugs sequentially until the seizure is aborted Lorazepam or diazepam: Lorazepam: 1-2 mg IVP/dose to maximum dose of 0.1 mg/kg Use of lorazepam is preferable to diazepam because diazepam redistributes from the CNS to peripheral tissues too quickly and the patient goes back into status again within minutes. Diazepam: 5-10 mg IVP/dose or PR Phenytoin: Load at 20 mg/kg IVP to run at maximum rate of 50 mg/min. Can rebolus 5 mg/kg to maximum total of 30 mg/kg if patient is still seizing. Run at slower rate if the patient is hypotensive. Get level 2 hours after IV loading. Adjustment formula for low albumin:

197

Effective Phenytoin Level =

measured phenytoin level measured albumin level 0.9 = 0.1 4

Adjustment formula for renal failure:

Effective Phenytoin Level =

measured phenytoin level 0.48 measured albumin level 0.9 = 0.1 4

Dose of phenytoin to load in mg to bring patient to therapeutic level: Dose of phenytoin = (15 measured phenytoin level) weight (kg) Maintenance dose is usually 4-5 mg/kg/day IVP or PO Fosphenytoin: May also be used at same loading dose and rate if hypotension is a problem with phenytoin, though it also can cause hypotension. Phenobarbital or pentobarbital: Intubate patient before placing patient in phenobarbital or pentobarbital coma. Phenobarbital: 20 mg/kg IVP to run at maximum rate of 100 mg/min Pentobarbital: 5 mg/kg IVP load, then 5 mg/kg IVP as needed until EEG shows burst-suppression, then 0.5-2 mg/kg/hr IV continuous infusion. Miscellaneous: Call the Neurology Consult chief on call and ask for a STAT consult. Continuous EEG telemetry per Neurology.

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ACUTE STROKE Adapted from Status Epilepticus/Stroke 2/22/01 by Dr. Steve Lee and Stroke 2006 by Nereses Sanossian, MD Evaluation Establish ABCs. Obtain vitals including oxygen saturation. Keep patient on a continuous cardiac monitor and obtain frequent vital sign measurements and neurologic checks every 1-2 hours. Blood glucose check: Keep BS <200 avoiding dextrose-containing solutions for the first 24 hours. Normal saline infusion at a rate of 100 cc/hr Antipyretics if febrile Workup History and Physical: focus on when symptoms began (i.e. when patient was last know to be symptom/deficit free as this will determine possible eligibility for thrombolytics), look for focal neurologic findings Labs: CBC with differential, chemistry panel, Ca, Mg, Phos, PT/PTT, and cardiac enzymes Studies: EKG, CXR, RUA Stat head CT without contrast to rule out bleed Stat MRI/DWI of brain and MRA of brain and neck Later consider: TTE, carotid duplex, hypercoagulable labs in young patients Treatment Ischemic strokes: Withhold anti-hypertensive drugs unless SBP >220 or MAP >130. When severe arterial hypertension needs to be treated, parenteral agents that allow rapid, controlled titration are useful (i.e. labetalol, enalapril, or nitroprusside drip) Antiplatelet agents versus thrombolytics versus MERCI clot removal? ACTIVATE STROKE TEAM TO HELP WITH DECISION! CRITERIA FOR DETERMINING THROMBOLYTIC USE (TPA) IN ISCHEMIC STROKES Inclusion criteria Exclusion criteria 1. Age >18 years 1. Prior intracranial hemorrhage 2. Clinical diagnosis 2. History of intracranial neoplasm, AVM or aneurysm of ischemic 3. Stroke or serious head trauma within past 3 months stroke with a 4. Major surgery or biopsy of parenchymal organ <14 days defined onset of 5. GI or urinary tract hemorrhage <21 days symptoms <3 6. Recent post-MI pericarditis hours from time 7. Seizure at onset of stroke tPA is to be 8. History of known hereditary or acquired abnormal hemostasis started 9. Rapidly improving neurological signs 3. CT scan shows 10. Isolated mild neurological deficits (such as ataxia, dysarthria, or sensory loss no evidence of alone) intracranial 11. SBP >185 or DBP >110 or aggressive treatment required to reduce BP hemorrhage 12. Current use of anticoagulants with INR >1.7 13. Use of heparin within 48 hours with an elevated PTT 14. Platelets <100,000 15. Glucose < 50 or > 400 16. Evidence on CT of major hypodensity of sulcal effacement (>1/3 of MCA territory)

NEUROLOGY
Hemorrhagic strokes: Keep MAP <130, but SBP >90 ICP: Managed through osmotherapy, controlled hyperventilation, and barbiturate coma Avoid corticosteroids In general: Activate the STROKE TEAM (call page operator) Q2-4 hour neuro checks. PT, OT, speech therapy. Passive full ROM exercises of paralyzed limbs should be started during the first 24 hours. NPO if patient is at risk of aspiration.

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BRAIN DEATH CRITERIA Two licensed physicians are required to declare brain death. Neurologists need not be involved. Must be known cause of condition. Diagnosis must be made in absence of hypothermia (temperature <32.2C) and CNS depressants. Cerebral unresponsiveness (lack of response to auditory or tactile stimuli) Absence of brain stem reflexes Pupillary: lack of any change in pupil size with shining of light into each eye. Extraocular (tests vestibulo-ocular reflex = VOR) Dolls eyes reflex: with head tilted forward 30, turn head side to side. Any eye movement excludes brain death. Caloric reflex: with head tilted forward 30, irrigate ear canals with 10 cc ice water. Any eye movement excludes brain death. Corneal: lack of eyelid movement in response to cornea being touched with a piece of cotton. Gag: lack of movement of uvula or gagging with stimulation of back of pharynx with tongue depressor. Cough: lack of movement or coughing with stimulation of tracheobronchial tree by passing cannula or irrigating endotracheal tube. Patient needs two neurologic exams at least 6 hours apart to ensure lack of change in neurologic status prior to declaring brain death. No spontaneous respirations on apnea test Pre-oxygenate with 100% FIO2 and draw ABG Disconnect ventilator Give O2 at 8-12 L/min by tracheal cannula (DO NOT EXTUBATE!) Observe for spontaneous respirations After 10 minutes, draw an ABG The pCO2 has to be >60 mmHg for an accurate test Reconnect the ventilator Patient is apneic if pCO2 >60 mmHg, and there is no respiratory effort. If hypotension and/or arrhythmia develop, immediately reconnect the ventilator, and consider other confirmatory test. Condition irreversible Duration of observation depends on clinical judgment Recommend 12 hours when an irreversible condition is well established and no confirmatory test Recommend 24 hours for anoxic brain damage and no confirmatory test Per California state law, an EEG or CBF (cerebral blood flow study) are not mandatory, but if performed, must be consistent with brain death.

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HEADACHES HEADACHE ALARMS AND WORKUP Adapted from Neurologic Clinics 1998;16(2):285-303 Headache Alarm Differential Diagnosis Workup Headache begins after age 50 Temporal arteritis, mass lesion ESR, neuroimaging Very sudden onset of headache Subarachnoid hemorrhage, Neuroimaging, lumbar puncture if pituitary apoplexy, hemorrhage CT is negative into a mass lesion or vascular malformation, mass lesion Headaches increase in Mass lesion, subdural Neuroimaging, drug screen frequency and severity hematoma, medication overuse New-onset headache in patient Meningitis, brain abscess Neuroimaging, lumbar puncture if who has risk factors for HIV, (including toxoplasmosis), neuroimaging is negative cancer metastasis Headache with systemic illness Meningitis, encephalitis, Lyme Neuroimaging, lumbar puncture, (fever, stiff neck, rash) disease, systemic infection, serology collagen vascular disease Focal neurological symptoms or Mass lesion, vascular Neuroimaging, collagen vascular signs of disease (other than malformation, stroke, collage evaluation (including typical aura) vascular disease antiphospholipid antibodies) Papilledema Mass lesion, pseudotumor, Neuroimaging, lumbar puncture meningitis Headache following head trauma Intracranial hemorrhage, Neuroimaging of brain, skull, and subdural hematoma, epidural possible cervical spine hematoma, posttraumatic headache

HIV and Headaches (Adapted from Emergency Medicine Clinics of North America 1999;17(1):127-152) All stages of HIV: Acute aseptic meningitis Chronic headache and persistent pleocytosis Syphilitic meningitis Non-HIV-related headaches Advance disease (CD4+ count < 500): Opportunistic infections and tumors Meningitis (cryptococcal, tuberculous, syphilitic, lymphomatous) Focal brain lesions (toxoplasmosis, CNS lymphoma, PML, abscess, cryptococcoma) Medication use Zidovudine-induced headaches Primary Headache Disorders Migraines: Unilateral (not always the same side) throbbing headaches that are associated with nausea, vomiting, photophobia, phonophobia, and osmophobia. Common migraines have no aura

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Classic migraines have auras: scotoma (blind spot), teichopsia (bright wavy lines), fortification (zigzag pattern), photopsia (flashing lights), visual and auditory hallucinations, paresthesias, metamorphopsia (distorted size of objects) Temporary neurologic deficits: hemiplegic, ophthalmoplegic, and basilar deficits Acute or abortive treatments: acetaminophen, aspirin, NSAIDs, triptans, ergotamine derivatives. Prophylactic treatments: -blockers (propranolol), TCAs (amitriptyline), SSRIs (fluoxetine), anticonvulsants (valproate, gabapentin), calcium channel blockers (verapamil). Tension headaches: Bilateral, mild to moderate headache with a pressing or tightening quality not exacerbated by routine physical activity. Often associated with neck stiffness. Chronic tension headache patients should be screened for comorbid depression and overuse of medications. Cluster headaches: Severe, excruciating, sharp unilateral headaches that usually last from 30 to 90 minutes and occur one to two times daily for several weeks at a time. Associated with eyelid edema, ptosis, miosis, conjunctival injection, lacrimation, nasal congestion, and rhinorrhea. Male to female ratio 8:1 50% occur within 2 hours of sleep 70% are triggered by alcohol Treatment: oxygen can help. Prevention: prednisone 40-60 mg daily with 10 day taper, lithium, verapamil, melatonin Temporal Arteritis: Classically in patients >55 years old Recent onset of headaches with possible jaw claudication Exam: temporal artery tenderness to palpation. Labs: ESR >50, then order temporal artery biopsy Treatment: Vision loss if untreated! Prednisone 60 mg daily if suspected, can biopsy later (but not too much later). Pseudotumor Cerebri: Idiopathic intracranial hypertension. Classic: premenopausal, obese woman, more likely in pregnancy. Clinical: horizontal diplopia, headache, peripheral visual field loss (often asymptomatic), 10% severe, irreversible visual loss. Exam: papilledema, LP shows CSF pressures >25 cmH2O Treatment: Mild: acetazolamide or furosemide Severe: prednisone 60 mg daily Other Causes of Headaches Sinusitis Postherpetic neuralgia Intracranial hypotension: Systemic infection, dehydration, hyperpnea, profound hyperglycemia, and post-lumbar puncture Pain is aggravated by upright position and is relived with recumbency Eye pain:

NEUROLOGY Ocular disease Eyestrain, corneal abrasions, uveitis, iritis, ischemic ocular pain, orbital cellulites, orbital pseudotumor, and orbital or retro-orbital mass lesions Acute angel glaucoma: acute pain associated with nausea and vomiting Referred eye pain Aneurysms, tumors, and venous sinus thrombosis

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MEDICATIONS AND CHEMICALS KNOWN TO CAUSE HEADACHES Class of drugs Pathophysiology Examples Vasodilators Involves nitric oxide Nitroglycerin, beta-blockers, mechanism by activating the nifedipine, ACE inhibitors, trigeminal vascular pathway hydralazine Histamine Cimetidine H1/H2 receptor antagonists NSAIDs Vasoconstriction of the carotid Indomethacin, Ibuprofen arteries resulting in reduction of cerebral blood flow; aseptic meningitis Serotonin agonists Activates serotonin receptors SSRIS Amino Acids MSG, Aspartame (NutraSweet) Sex Hormones Estrogen withdrawal, progestin, tamoxifen Chemotherapeutic drugs Aseptic meningitis Intrathecal methotrexate and diaziquone Methodichlorophen, interferonbeta, interleukin-2 Immunomodulating drugs Cyclosporin, FK-506, thalidomide, antithymocyte globulin Antimicrobial and Idiopathic intracranial Tetracycline, Amphotericin, antimalarial drugs hypertension griseofulvin, sulfonamides, chloroquine Ergotamine Other chemicals Alcohol, cocaine, carbon monoxide PERIPHERAL NEUROPATHY Differential Diagnosis (DANG THERAPIST) Drugs: phenytoin, isoniazid, hydralazine, amiodarone, metronidazole, vincristine Alcohol Nutritional: deficiencies of vitamin B12, thiamine, pyridoxine, folate Guillain-Barr syndrome Toxins: heavy metals, industrial agents and pesticides Hereditary Endocrine: diabetes mellitus, hypothyroidism Renal failure: uremia Amyloidosis

NEUROLOGY Porphyria Infection: HIV, CMV, lyme disease, syphilis Systemic (rheumatologic): sarcoidosis, vasculitis Tumors: paraneoplastic, multiple myeloma Workup Check: CPK, B12, TSH, RPR, SPEP, HgbA1c, HIV, Hepatitis C, ANA, RF, anti-SSA/SSB/dsDNA, Jo-1 Consider: EMG, muscle biopsy, nerve biopsy, LP for demyelinating disorders, sarcoid, lymphoma

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DERMATOME MAP

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NUTRITION
N U T R I T I O N

Every patient must have a diet order written in the chart within 8 hours of admission.
ORAL DIETS Modified Consistencies Indicated for patients with problems chewing and/or swallowing All diets are of a regular consistency unless otherwise specified (i.e. mechanical soft or puree) Modified consistency liquids ordered as needed per swallow evaluation recommendations Speech Pathologists/Dysphagia Team are available for bedside swallow evaluations and modified barium swallow studies (MBSS) Disease Specific Modifications (liberalize restrictions for patients with poor oral intake) Coronary Artery Disease: Sodium: 3-4gm Na Total/saturated fat and cholesterol: order Low Fat, Low Cholesterol Congestive Heart Failure: Sodium: 2 gm Na restriction Fluid: 1.5-2.0 L fluid restriction Diabetes: Carbohydrate controlled diet Renal Failure: Sodium (based on urine output, edema, and fluid status) Potassium (based on K+ (with corrected acidosis) levels and renal function) Phosphorus (only in face of calciphylaxis; if phos elevated should be on phosphorus binder) Protein (restrict only if severely uremic/pre-dialysis) Fluid (restriction based on urine output, edema and fluid status) Liver Failure: Sodium (2 gm or 3-4 gm based on severity of ascites and fluid retention) Fluid (only if progressive ascites and/or hyponatremia) Protein (only if encephalopathic) Nutritional Supplements (order these for patients with poor oral intake or poor nutritional status) Boost (general; lactose free) OR Carnation Instant Breakfast (general; milk-containing) Nepro (Renal failure/Dialysis) Suplena (Renal failure/Pre-dialysis) Glucerna (Diabetic) Can order Snack TID and patient can choose ENTERAL NUTRITION (see enteral feeding order form) If the gut works, use it! Consult dietitian for assessment prior to initiation of enteral feeds and for assistance with management of feeding as needed. See Nutrition notes in Essentris for diet recommendations. Specify route of administration (type of tube) on order form. Available enteral formulas summarized on order form Aspiration precautions: head of bed elevated at least 30 degrees, blue coloring added to feeds

NUTRITION
PARENTERAL NUTRITION (see TPN order form and UCLA Enteral/Parenteral Handbook) Consult dietitian for nutritional assessment prior to initiating PPN/TPN. Indications Bowel obstruction and unable to feed distal to obstruction, bowel ischemia/necrotic bowel, true small bowel ileus, malabsorption, enteral feeding intolerance/high gastric residuals with failure of jejunal feedings, intractable vomiting Peripheral Parenteral Nutrition (PPN) Incomplete nutritional needs: short term use 5-7 days. Can be administered via peripheral line, with standard concentration of D10 and 3.5% AA plus Intralipid Intralipid 20% (soybean oil based), 2 kcal/ml (available in 100 ml, 250 ml, and 500 ml) Total Parenteral Nutrition (TPN) Longer term use >1 week to months. Must have central line access, standard concentration D25, 4.25% AA or D28 6% AA Intralipid 20% (soybean oil based), 2 kcal/ml (available in 100 ml, 250 ml, and 500 ml) APPROVED DIET ORDERS FOR WESTWOOD, SANTA MONICA, AND RNPH UCLA MEDICAL CENTERS Diet Order Name Diet Purpose/Indication NPO, NPO except meds, NPO except No food sent to patient, nothing by mouth sips NPO except ice chips Clear Liquid Fluids, electrolytes and energy in a form that requires minimal digestion/stimulation of GI tract Bariatric Clear Liquid Broth and juice only in measured quantities for after bariatric surgery (WW ONLY) Blenderized Liquid To provide food in a liquid form for patients who are unable to chew, swallow or tolerate solid foods Mechanical Soft Cut up, soft, moist and easy to chew and swallow foods for chewing or swallowing problems. Ground To provide moist, soft and ground up foods for chewing or swallowing problems (SMH ONLY) Low Fiber Low fiber, esophageal soft, previously known as GI Soft. Puree To provide thick, smooth, homogeneous, semi-liquid textures for severely reduced swallowing ability Kosher To provide foods for patients observing Jewish dietary laws and the practice known as kashrut Regular To provide food appropriate for adults, with no restrictions Pediatric To provide foods appropriate for pediatric age patients Pediatric 3 gram Sodium To provide age appropriate foods with a 3000 mg sodium restriction. Pediatric Renal To provide age appropriate food for pediatric patients that are lower in potassium, sodium and phosphorous. 2 gram Sodium To limit sodium provided to tissues to prevent accumulation of fluid in a 2000 mg Na restriction Low Potassium To achieve normal potassium levels in patient at risk for hyperkalemia with a 3000 mg K+ restriction Low Bacteria To eliminate foods that may be contaminated with bacteria for patients undergoing chemotherapy or BMT

NUTRITION
APPROVED DIET ORDERS FOR WESTWOOD, SANTA MONICA, AND RNPH UCLA MEDICAL CENTERS Diet Order Name Diet Purpose/Indication Carbohydrate Controlled To provide a consistent amount of carbohydrate to achieve blood glucose control Low Fat To provide foods lower in saturated and trans fats for patients with heart disease No Red Meat To limit the amount of aromatic amino acids for patients with hepatic encephalopathy Low Lactose To provide foods that contain minimal amounts of lactose for patients with lactose intolerance Gluten Free To provide adequate energy for patients unable to tolerate gluten Low Iodine To deplete the body of iodine for radioiodine scan Gestational DM Different calorie levels: 1800, 2000, 2200 and 2500 calories per day for pregnancy Ketogenic To induce and maintain a state of ketosis for an antiepileptic effect (WW ONLY) Metabolic Diet To provide moderate carbohydrate and low fat options (NPH ONLY) No caffeine Restricts main sources of caffeine from diet: no coffee, no black tea. Thickened Liquids Options: Nectar, honey or pudding thickened liquids Fluid Restrictions Options for Adults and Pediatrics: 1000 ml, 1200 ml, 1500 ml, 1800 ml, 2000 ml fluid restriction levels Options for Pediatrics: 500 ml, 550 ml, 600 ml, 650 ml, 700 ml, 750 ml, 800 ml, 850 ml, 900 ml, 950 ml No diabetic clear liquid tray: The American Dietetic Association recommends that patients requiring a clear liquid diet should receive approximately 200 grams of carbohydrates per day in equally divided amounts, at meals and snack times. Liquids should not be sugar free. Patients require carbohydrates and calories, and sugar free liquids do not meet these needs. Diabetes medications may need to be adjusted to achieve and maintain metabolic control. Diet orders no longer accepted: advance diet as tolerated (ADAT), resume diet, ADA, Diabetic, Renal, Cardiac, CCU, 1 gm Na, Liver diet, No Salt, No Concentrated Sweets, No fat, Soft and Full Liquid.

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PULMONARY FUNCTION TESTS Definitions: FVC=maximal volume of air exhaled with maximal effort from maximal inhalation. FEV1=volume of air expired during the 1st second of FVC. PEF or FEFmax=largest expiratory flow achieved during FVC. FEF25%-75%=mean forced expiratory flow during the middle of FVC (reflects small airway disease). RV=volume of air remaining at the end of maximal exhalation. TLC=total lung capacity Positive bronchodilator response=12% (200mL) increase in FEV1 or a 15% increase (200mL) in FVC.

Normal Flow-Volume Loop

(J Respir Dis. 2005;26:26-40) Interpretation: Was the test performed adequately (look at flow-volume loop)? Cough? Premature termination? Poor maximal inhalation? Poor effort? Look at FEV1:FVC ratio: Less than the predicted lower limit of normal (<70%)obstructive pattern. Look at FEV1. FEV1>80% predicted: borderline obstruction. FEV1 60-80% predicted: mild obstruction. FEV1 40-60% predicted: moderate obstruction. FEV1<40% predicted: severe obstruction. Look at FVC. FVC<80% predicted: low vital capacity Within normal limit or elevatednormal spirometry or restrictive pattern. Look at FVC. FVC>80% predicted: normal spirometry. FVC 60-80% predicted: mild restriction. FVC 50-60% predicted: moderate restriction. FVC <50% predicted: severe restriction.

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Look at FEV1. If FEV1 is disproportionally reduced relative to FVC, then a mixed picture may be present (obstruction and restriction). Bronchodilator Response: Look at the FEV1 and/or FVC to see if there was an appropriate change in response to bronchodilators. Lung volumes: Obstructive pattern: TLC (hyperinflation) RV (gas trapping) Restrictive pattern: TLC RV Diffusion Capacity (DLCO2): DLCO2 + normal spirometry: early ILD, pulmonary vascular disease, anemia, early emphysema. DLCO2 + obstruction: emphysema, bronchiolitis obliterans, cystic fibrosis, bronchiectasis. DLCO2 + restriction: ILD, hypersensitivity pneumonitis, drug toxicity, CHF. DLCO2: polycythemia, pulmonary hemorrhage!

ASTHMA Definition: Asthma: Chronic inflammatory disorder of the airways causing reversible airflow limitation and increased airway responsiveness to various stimuli. This results in recurrent episodes of wheezing, breathlessness, chest tightness, and cough particularly at night and/or in the early morning. Classifications based on severity and control: SEVERITY Intermittent ASTHMA SEVERITY CLASSIFICATION SYMPTOMS NIGHT SYMPTOMS <1/week 2/month LUNG FUNCTION FEV1 or PEF 80% predicted, with variability <20% FEV1 or PEF 80% predicted, with variability 20-30% FEV1 or PEF 60-80% predicted, with variability >30% FEV1 or PEF 60% predicted, with variability >30%

Mild Persistent Moderate Persistent Severe Persistent

>1/week but <1/day Daily Daily with frequent exacerbations and activity limitation

>2/month >1/week Frequent

SEVERITY

Intermittent Mild Persistent Moderate Persistent Severe Persistent

ASTHMA TREATMENT SHORT ACTING BETA LONG ACTING BETA AGONIST AGONIST Yes, PRN No Yes, PRN Yes, daily Yes, PRN Yes, daily

CORTICOSTEROIDS

Low dose inhaled Medium dose inhaled High dose inhaled High dose inhaled + oral steroids.

Yes, PRN

Yes, daily

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CHARACTERISTIC

Daytime symptoms Limitations of activities Nocturnal symptoms/awakening Need for rescue treatment Lung function (PEF or FEV1) Exacerbations

GINA LEVELS OF ASTHMA CONTROL CONTROLLED PARTLY CONTROLLED (ALL OF THE FOLLOWING) (ANY PRESENT IN ANY WEEK) 2/week >2/week None Any None Any

UNCONTROLLED

2/week Normal None

>2/week

3 features of partly controlled asthma present in any week

<80% predicted or personal best 1/year One in any week From GINA asthma guidelines at http://www.ginasthma.com

Risk Factors for Asthma-Related Death: Currently using or have recently stopped using systemic steroids, or those not using inhaled steroids History of intubation for asthma History of non-compliance History of psychiatric disease Long-acting 2 agonist use or excessive short-acting 2-agonist use Recent hospitalization or emergency visit for asthma within the past year Sedative use Treatment for Asthma Exacerbation: Step 1: Initial assessment and treatment Obtain history and physical, vital signs, oxygen saturation, PEF, ABG Peak flow normals (PEF): Male 450-650 L/min, Female 350-500 L/min depending on pt height and age. Give supplemental oxygen (goal SaO2>90%) Give continuous albuterol nebulizer for 1 hour Give oral prednisone 60mg or IV Solu-Medrol 80mg 1. One dose is likely to cause no harm but may be very beneficial. Step 2: Reassessment (~1 hour) and classification-based treatment Recheck physical exam, vital signs, PEF Mild episode: PEF>80% predicted No dyspnea at rest, mild wheezing Treatment: Discharge home with oral steroid taper, inhaled steroids, 2-agonist, and close followup. Moderate episode: PEF 60-80% predicted Moderate symptoms and/or accessory muscle use Treatment: Continue oxygen, albuterol and ipratropium inhaler every hour, and oral steroids. Severe episode: PEF<60% predicted Chest retractions and/or severe symptoms at rest No improvement from initial treatment

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Treatment: Continue oxygen, continuous albuterol nebulizer, oral or IV steroids, and add IV magnesium 2gm IV over 20 minutes. Step 3: Reassessment (~1-2 hours) and triage for further care Good response (normal exam, PEF>70%, SaO2>90% on room air): Discharge home with oral steroid taper, inhaled steroids, 2-agonist, and close followup. Incomplete response (risk factors above, PEF<60%, no improvement of SaO2 or physical exam): Admit to hospital and continue oxygen, albuterol, steroids, and add magnesium and ipratropium if not done already. Poor response (PEF<30%, PaCO2>45mmHg, PaO2<60mmHg): Admit to ICU, continue albuterol and ipratropium, IV Solu-Medrol 125mg IV Q6H and consider Heliox (poor data), and/or invasive or non-invasive mechanical ventilation.

CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) Definitions: COPD: Airflow limitation that is not fully reversible, though usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases. GOLD STAGING CRITERIA FOR COPD SPIROMETRY FEV1/FVC<70% FEV180% predicted FEV1/FVC<70% 50%FEV1<80% predicted

STAGE Stage I

SYMPTOMS Mild

TREATMENT

SABA prn SABA prn LABA, daily Rehabilitation SABA prn LABA, daily Rehabilitation ICS SABA prn LABA, daily Rehabilitation ICS Home O2 Consider surgery

Stage II Stage III

Moderate Severe

FEV1/FVC<70% 30%FEV1<50% predicted FEV1/FVC<70% FEV1<30% predicted or FEV1<50% predicted plus chronic respiratory failure

Stage IV

Very severe

SABA = short-acting beta agonist. LABA = long-acting beta agonist. ICS = inhaled corticosteroids.
Executive Summary for the GOLD. http://www.goldcopd.com

COPD Exacerbation: An acute change in the natural course of COPD characterized by dyspnea, cough, and/or sputum requiring changes in medication. Exacerbations are typically due to infection (50-60%), air pollution (10%), and unknown trigger (30%).

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COPD EXACERBATION TRIAGING INDICATIONS FOR HOSPITAL ADMISSION INDICATIONS FOR ICU ADMISSION Marked increase in symptoms Severe dyspnea that does not respond to ER therapy Severe underlying COPD (Stage III-IV) Confusion, lethargy, or coma Outpatient failure PaO2<40 mmHg PaCO2>60 mmHg Significant comorbidities (i.e. renal failure) Mechanical ventilation New arrhythmia Hemodynamically unstable Old age/poor home support

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Treatment for COPD Exacerbations: Supplemental oxygen to maintain PaO2>60 mmHg or SaO2>90% It is a good idea to check a blood gas an hour after starting oxygen to assess for adequate oxygenation and CO2 retention. Remember that adequate (not excessive, as this will cause worsening respiratory acidosis due to worsening V/Q mismatch) oxygenation trumps CO2 retention! Bronchodilators Albuterol nebulizer 2.5mg Q1-2H is first line. Can add ipratropium nebulizer 0.5mg Q2-4H. Steroids It is generally accepted that steroids treatment failures and hospital stay, however the optimal dosage is unknown. Base your dosage decision on the severity of the exacerbation: Not requiring an ICU, give oral prednisone 30-40mg daily for 7-10 days, you can taper after that if you wish. Requiring ICU admission, give IV Solu-Medrol 60-125mg IV daily to Q6H for 3 days then switch to oral prednisone. Longer courses than 2 weeks have not been shown to be beneficial. Dont forget about hyperglycemia! Antibiotics Consider antibiotics in patients who have at least 2 of 3 cardinal symptoms: dyspnea sputum volume sputum purulence. Give antibiotics to any patient requiring mechanical ventilation (invasive or non-invasive). Choose anti-pseudomonal antibiotics (i.e. piperacillin/tazobactam). Ventilatory support Strongly consider NIPPV (i.e. BiPAP) See acute respiratory failure for more information Vaccinations Make sure your patients get pneumococcal and influenza vaccines before they leave the hospital! Home O2 Qualifying criteria peripheral SaO2 88% or PaO2 55 mmHg on ABG

PULMONARY EMBOLISM Definitions: Pulmonary embolism (PE): a blanket statement for anything that embolizes to the vasculature of the lungs, including air, tumors, amniotic fluid, etc.

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Lower extremity deep veins: External iliac, superficial femoral (dont let the name fool you), deep femoral (profunda), popliteal, anterior tibial, posterior tibial, and peroneal veins. Lower extremity superficial veins: Greater saphenous and lesser saphenous veins. Upper extremity deep veins: Radial, ulnar, brachial, axillary, and subclavian veins. Upper extremity superficial veins: Digital, metacarpal, cephalic, basilic, and median veins. Clinical Signs and Symptoms: No clinical sign or symptom can help you rule in or rule out PE. While these clinical observations may help you focus your differential, remember that the studies that obtained this data state that the patients without PE had similar signs and symptoms. Likewise, EKG and chest radiography are of limited value as their findings are nonspecific. Signs: Tachypnea (RR 20) is most common (73%) Rales (55%) Tachycardia (HR >100) (30%) Hemoptysis (rare) 4th heart sound (rare) Symptoms: Dyspnea is most common symptom (78%) Age-discrepancy found: 85% 65 years old vs. 76% <65 years old Pleuritic chest pain (59%) Age-discrepancy found: 48% 65 years old vs. 79% <65 years old Cough (43%) Chest Radiography: Atelectasis and/or pulmonary parenchymal abnormality (69%) Pleural effusion (47%) Cardiomegaly Rare classic signs: Westermarks sign (focal decreased vascularity) Hamptons hump (peripheral wedge-shaped density above the diaphragm) Pallas sign (enlarged right descending pulmonary artery) Electrocardiogram: Nonspecific ST-T wave changes (70%) Tachycardia (42%) SIQIIITIII (11.6%) Of note, this classic finding was present in 13.5% of those without PE! Diagnosis: In patients who cannot tolerate a CT angiogram (i.e. 2 to renal insufficiency), substitute a V/Q scan. A high probability scan + likely pretest probability would be positive for PE. A normal scan would be negative for PE. Any other combination should warrant further testing (i.e. ultrasound for DVT). If your pretest probability is very high, even a negative CT angiogram should warrant further workup. (i.e. Ultrasound for DVT, pulmonary angiogram)

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SIMPLIFIED WELLS CRITERIA FOR PRETEST PROBABILITY OF PE Variable Points Clinical signs and symptoms of DVT (minimum of leg swelling 3.0 and pain with palpation of deep veins) Alternative diagnosis less likely than PE 3.0 Heart rate >100/min 1.5 Immobilization (>3 days) or surgery in previous 4 weeks 1.5 Previous PE or DVT 1.5 Hemoptysis 1.0 Malignancy (receiving treatment, treated in last 6 months, or 1.0 palliative) Probability: <2=low; 2-6=intermediate; >6=high V/Q SCAN AND CLINICAL PROBABILITY IN PREDICTING PE FROM PIOPED Clinical Probability Scan Category 80-100% 20-79% 0-19% All High Probability 96% 88% 56% 87% Intermediate Probability 66% 28% 16% 30% Low Probability 40% 16% 4% 14% Near Normal/Normal 0% 6% 2% 4%

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CTA AND CLINICAL PROBABILITY IN PREDICTING PE FROM PIOPED II PPV NPV CTA CTA+CTV CTA CTA+CTV High Probability 96% 96% 60% 82% Intermediate Probability 92% 90% 89% 92% Low Probability 58% 57% 96% 97% PPV=positive predictive value; NPV=negative predictive value CTA=CT chest angiogram; CTV=CT lower extremity venogram Probability based on Simplified Wells Criteria (<2=low; 2-6=intermediate; >6=high) Clinical Probability

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Algorithm for Diagnosis of PE (Using Simplified Wells Criteria for Pretest Probability) Adapted from JAMA 2006;295:172-179
Pretest Probability 4 Unlikely Pretest Probability >4 Likely

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D-Dimer

Start Anticoagulation if no Contraindications

Negative D-Dimer

Positive D- Dimer

CT Angiogram CT LE Venogram

No Treatment

PE Excluded

Inconclusive

PE Confirmed

Consider DVT workup if clinical suspicion high

Consider: V/Q Scan DVT Workup Pulmonary Angiography

Treat and Workup for Cause if Idiopathic

Treatments: Anticoagulants: Step 1: Begin anticoagulation with your choice of heparin, Lovenox, or Arixtra, all approved for use in acute PE. If clinical suspicion high, can begin while still making the diagnosis. Step 2: Begin therapy with warfarin, 5mg nightly, within 72 hours of starting one of the above anticoagulants (unless contraindicated or cancer-related). Warfarin should not be used alone because it takes ~5 days for true anticoagulation to occur (2 factor II) even though the INR may be therapeutic (2 factor VII which has a life of ~6 hours).

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Heparin may prolong the INR by 0.5, so a goal INR of 2.5 may produce better results. Do not start warfarin until the PTT is therapeutic because a hypercoagulable state may occur as the life of protein C is < factor II Step 3: When INR is 2.0-3.0 and warfarin has been used for >5 days, stop the other anticoagulant and continue warfarin at goal INR. Step 4: Continue treatment with warfarin for: Transient, reversible causes: 3-6 months Idiopathic: 6-12 months Cancer-related: LMWH for 3-6 months then warfarin indefinitely or until resolution of cancer Hypercoagulable state: 6-12 months to indefinitely Antithrombin III, protein C, or protein S deficiency Factor V Leiden or prothrombin 20210 mutation Antiphospholipid antibodies (at least 12 months) Homocystinemia Factor VIII levels >90% of normal Persistent residual thrombosis on repeated ultrasound Recurrent PE/DVT: indefinitely Inferior Vena Cava (IVC) Filters: In patients who can tolerate anticoagulation, there is no benefit in adding an IVC filter. In patients who fail anticoagulation (i.e. have another PE despite anticoagulation), an IVC filter in addition to continued anticoagulation may be of some benefit. In patients with a severely compromised pulmonary vascular bed (i.e. had multiple large PEs), a filter may be of some benefit. In patients who cannot tolerate anticoagulation, an IVC filter may decrease the short-term risk of PE, but consider this: There is little information on IVC filters without anticoagulation. Perhaps there is a benefit to placement of an IVC filter for short-term protection until the patient can tolerate anticoagulation (i.e. after surgery) Perhaps there is a benefit to a removable IVC filter for short-term protection until the patient can tolerate anticoagulation and then remove the filter. Antithrombotic Therapy: Use in patients with acute PE who are hemodynamically unstable and do not seem prone to bleeding. Use the agent with the shortest infusion timetPA (100mg infusion over 2hrs) versus Streptokinase (24hrs) and Urokinase (12hrs). Thrombectomy: Can be considered in hemodynamically unstable patients who have failed all of the above treatments. Highly dependent on surgical expertise.

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PULMONARY HYPERTENSION Etiology idiopathic pulmonary HTN/familial associated with connective tissue disease, congenital heart disease (R-->L shunts), portal HTN, HIV infection, drugs (fen-Phen, cocaine, methamphetamine) venoocclusive disease associated with L heart disease associated with chronic hypoxemia: COPD, OSA, pulmonary fibrosis/ILD chronic thromboembolic disease Diagnosis formal diagnosis is made via right heart cath with a mean pulmonary artery pressure > 25 at rest or 30 with excercise a transpulmonary gradient of greater than 15 is suggestive of PH. TPG=mean pulmonary pressure PCWP. [mean pulm pressure is (2xdiastolic + systolic/3] during swan, pt can be challenged with short-acting vasodilator; if responsive, suggests better prognosis and better response to CCB the diagnosis of PH is also suggested on echo with a calculated pulmonary pressure of greater than 40. An enlarged pulmonary trunk on CT is also suggestive Initial Presentation chronic SOB, DOE, exertional syncope, +/- peripheral edema *these pts are often hospitalized with a known diagnosis of PH and are commonly admitted for fluid overload/RHF, line infections, initiation of remodulin, flolan, etc Work up PFTs, echo, sleep study, VQ scan, HRCT, ECG LFTs (to screen for portopulmonary htn), ANA, HIV, RF, ANCA RH cath, +/- vasodilator challenge Treatment if pulm HTN is 2/2 to known cause, attempt to tx underlying cause in general, all pts treated with diuetics, 02, +/- coumadin +/- CCBs (if pt responds to vasodilator challenge during swan, it suggests that the pt will be responsive to CCB) +/- digoxin endothelian receptor antagonists: bonsentan (aka Tracleer) PDE 5 inhibitors: sildenafil (aka viagra, revatio) IV prostacyclins: flolan, remodulin (remodulin also can be delivered via subq pump) Management Pearls to initiate tx with IV prostaglandins, the pt must be hospitalized on a monitored bed (usually MOU/COU, MICU), due to concern for possible hypotension, anaphalaxis. There needs to be a dedicated line (nursing usually requires a central line) if IV prostaglandins are suddenly d/c'ed, there is a risk for severe rebound pulmonary HTN and florid RH failure

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PLEURAL EFFUSIONS Types of pleural effusions: Transudates CHF (80% are bilateral), cirrhosis (usually right-sided), nephrotic syndrome, hypoalbuminemia, pulmonary embolus, atelectasis, malignancy (lymphatic obstruction), peritoneal dialysis, urinothorax, IVF from misplaced catheter, ovarian hyperstimulation syndrome Exudates Infection (25%), PE (10%), malignancy (15%), pancreatitis, rheumatologic (RA, SLE, sarcoid, Wegeners), drug reaction, radiation pneumonitis, variceal sclerotherapy, myxedema, familial Mediterranean fever, congenital lymphatic hypoplasia, asbestosis, silicosis, post-MI, uremia, GVHD Note that borderline transudates in the horizontal position may become exudates when sitting up. When to do a thoracentesis: Any new pleural effusion, not thought to be due to CHF or viral infection. When the amount of fluid present is >1cm in height (~200mL) on a decubitus CXR. Imaging pleural effusions for possible thoracentesis: Upright CXR (get PA and lateral views) 75mL of fluid required to obliterate the posterior costophrenic angle 175mL of fluid required to obliterate the lateral costophrenic angle 500mL of fluid to obscure the diaphragm Supine CXR 175mL of fluid required to identify an effusion, though it typically can produce apical caps and a slight opacity to the lung field (without air bronchograms and with clear pulmonary vasculature) Decubitus CXR (ipsilateral to side of effusion). Can tell you if effusion layers Can see as little as 10mL of fluid And of course, a CT without contrast. Pleural fluid studies: (*should always send) Cell count and differential* Gram stain* LDH* (make sure to send serum LDH) Total protein* (make sure to send serum total protein) Culture (bacterial, fungal, mycobacterial) Cytology pH (send in ABG syringe on ice) Glucose Amylase Triglycerides and/or chylomicrons

PULMONARY AND CRITICAL CARE Diagnosis:

219

TEST Pleural:serum TP Pleural:serum LDH Pleural LDH

LIGHTS CRITERIA FOR DIAGNOSING A PLEURAL EFFUSION AS AN EXUDATE (98% SENSITIVE, 83% SPECIFIC) TRANSUDATE EXUDATE <0.5 >0.5 <0.6 >0.6 <2/3 of upper limit of normal serum value >2/3 of upper limit of normal serum value (<149) (>149) Only one of the above criteria need to be met to qualify as an exudate

RBCs > 100,000: typically seen in TB, pulmonary infarct, chest wall trauma, malignancy, post-operative. Pleural:serum hematocrit > 0.5: hemothorax. WBC < 1500: normal. With >50% lymphocytes, TB or malignancy are likely. TB is less likely if mesothelial cells are >5% or eosinophils are >10%. pH < 7.2: empyema, complicated parapneumonic effusion, rheumatoid, TB, malignancy, hemothorax, or systemic acidosis. pH < 6.0: esophageal perforation or urinothorax. Glucose < 30: suggests TB or RA. Glucose < 60: suggests cancer or parapneumonic effusion. Triglycerides > 110 and/or chylomicrons: chylothorax Cytology: This will be positive in only 60% of malignant effusions. Food particles or squamous cells suggest esophageal perforation. Multinucleated giant cells are seen in RA. LE cells can be seen in SLE. Additional Treatments: Chest tube placement: Uncomplicated, but symptomatic parapneumonic effusion involving at least half the hemithorax Complicated parapneumonic effusion (pH<7.2, positive Gram stain or cultures, OR glucose <60, OR LDH > 1000) Empyema VATS + chest tube placement: Loculated effusion Pleurodesis + chest tube placement Recurrent malignant effusion

CHEST TUBES Purpose: To drain air (pneumothoraces), blood (hemothoraces), fluid (pleural effusions, chylothorax) or pus (empyemas or complicated parapneumonic effusions) from the pleural space. Function: A tube (28 French is most common size) is placed into the pleural space usually in the fourth or fifth intercostal space (above the rib) just anterior to the mid-axillary line. They are always connected to an underwater seal, and may be left to straight drainage (no suction) or to suction.

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Chest Tube Insertion

Wall Suction Hookup

Suction Control Chamber

Water Seal

Collection Chamber

Complications: Air Leak: If the tube was inserted to resolve a pneumothorax, then an air leak (i.e. bubbling in the water seal chamber during inspiration and coughing) is to be expected. If the tube was inserted to drain fluid, then an air leak represents either loose tubing connections, air leaking into the chest from the tube insertion site, or the development of a pneumothorax. Disconnect the suction and check all the tubing connections to confirm an airtight seal by clamping each section and looking for bubbles. Check the entry site of the chest tube for an excessively large incision which might need to be sutured or covered with petrolatum gauze occlusive dressing. Check a CXR to ensure the tip of the chest tube is in the thorax and not too close to mediastinal structures and for a pneumothorax. Drainage of an excessive volume of blood: May represent erosion of an artery, vein or great vessel by the chest tube. If > 500cc of blood loss over 8 hours consider immediate thoracic surgery consult for emergency thoracotomy. Remember basic resuscitation (fluids, type and cross), and hold anticoagulation.

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Loss of tidaling in the underwater seal container (i.e. no respiratory deviation of the fluid): Often due to a kinked tube, or occlusion of the tube by blood clots and debris. Check for kinks and check a CXR to assess positioning of tube. Subcutaneous emphysema: A small amount of subcutaneous emphysema around the entry site is normal, however extension into the neck may rarely result in tracheal compression Note that in the absence of a chest tube, subcutaneous emphysema strongly suggests a pneumothorax, especially following line placement May occur when one of the chest tube apertures is in the chest wall or abdominal cavity, or when there is inadequate suctioning. Check the entry site of the tube for a visible drainage hole; if misplaced, insert new tube; do not reintroduce the partially dislodged tube. If tube is in place, but has been to water seal, try placing it to suction. If the emphysema is severe and is causing stridor with tracheal compression immediate intubation and consider CT surgery consult. Shortness of breath: Increasing pleural effusion/hemothorax Reexpansion pulmonary edema Tension pneumothorax Increasing pneumothorax secondary to tube malposition Inadequate suction Bronchopulmonary fistula

When to remove: Effusion draining < 50cc/day Empyema draining < 20cc/day Pneumothorax, no further air leak? set to waterseal CXR no pneumo? pull out chest tube! x24hrs

CXR

no pneumo?

clamp chest tube

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SHOCK Distributive Inability to maintain vascular resistance Warm Flat initially then Sepsis Anaphylaxis Spinal injury Drugs that lower SVR Adrenal insufficiency DIFFERENTIAL DIAGNOSIS OF SHOCK Cardiogenic Obstructive Inability to pump blood Inability to pump effectively 2 to heart blood effectively 2 dysfunction to obstruction to blood flow Cold Cold Distended Distended Hypovolemic Loss of blood

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Main Defect Extremities Neck Veins CO SVR SVO2 PCWP Etiology

Cold Flat Normal then

Variable Myocardial Large Trauma resulting in infarction pulmonary hemorrhage Bradycardia embolus Retro/intraperitoneal Ventricular Tension bleed tachycardia pneumothorax GI bleed Ventricular Pericardial Aortic rupture from fibrillation tamponade dissection or Acute mitral/aortic Constrictive aneurysm regurgitation pericarditis Osmotic diuresis Myocarditis Atrial myxoma (i.e. diabetes) Congestive heart Left ventricular Severe failure free wall rupture diarrhea/vomiting Heart transplant resulting in rejection tamponade Sepsis Drugs that cause arrhythmias or reduce inotropy Cardiotoxic drugs Contusion CO=cardiac output; SVR=systemic vascular resistance; SVO2=mixed venous oxygen saturation; PCWP=pulmonary capillary wedge pressure

RESPIRATORY FAILURE Definitions and Pathophysiology: Causes of hypoxic respiratory failure (PaO2<60 mmHg): 1. Ventilation perfusion (V/Q) mismatch (i.e. an imbalance between alveolar ventilation and capillary blood flow; improves with supplemental O2) 2. Shunt (i.e. blood bypasses areas where oxygenation takes place; does not improve with supplemental O2) 3. Diffusion capacity 4. FiO2 (normal Aa oxygen gradient) 5. Hypoventilation (normal Aa oxygen gradient)

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Causes of hypercarbic respiratory failure (PaCO2>45 mmHg; except in cases of respiratory compensation for metabolic alkalosis): 1. Dead space 2. Obstructive diseases 3. Restrictive diseases 4. CNS respiratory depression 5. Neuromuscular respiratory drivehypoventilation Differential Diagnosis:
Organ System Pulmonary DIFFERENTIAL DIAGNOSIS OF ACUTE RESPIRATORY FAILURE Disease Obstructive (asthma, COPD, cystic fibrosis, anaphylaxis) Restrictive (pulmonary fibrosis) Pleural (effusion, pneumothorax, hemothorax) Upper airway obstruction (mucus plug, aspiration, vocal cord dysfunction, angioedema) Pneumonia Pulmonary embolism ARDS Ischemia CHF Arrhythmias Pericardial tamponade (malignancy, post-MI, post-cardiac surgery) Valvular heart disease Aortic dissection Sepsis Metabolic acidosis ALS Botulism Myasthenia gravis Drug overdose Anemia Methemoglobinemia Anxiety (diagnosis of exclusion)

Cardiac

Metabolic Neuromuscular

Hematologic Psychiatric

Diagnostic Evaluation: History: Duration of onset (i.e. acute, chronic) Underlying lung pathology (i.e. COPD, asthma) Associated symptoms (i.e. chest pain, cough, fever, nausea, vomiting, delirium) Preceding events (i.e. surgery, medications, IVF, trauma, line placement) Physical Exam: Vital signs (note that the RR is usually NOT accurate) Fluid balance Lung exam (air movement, wheezing, flail chest, retractions, accessory muscle use) Cardiac exam (rubs, new murmurs, JVP) Extremities (symmetric or asymmetric edema, warmth vs. cool) Mental status (delirium, obtunded)

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Labs and Studies: (note that these should be performed after the patient has been stabilized (i.e. supplemental oxygen, transfer to ICU, BiPAP, intubation) Obtain ABG and chemistry panel simultaneously Calculate Alveolar-arterial oxygen gradient:

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Aa oxygen gradient = PAO2 PaO2 = {[FiO2 x (Patm Pwater)] PaCO2/Respiratory quotient} PaO2
At sea level on room air where Patm=760 mmHg; Pwater=47 mmHg; respiratory quotient=0.8 at steady state. The formula reduces to {150-PaCO2/0.8} PaO2
Expected Aa oxygen gradient = 2.5 + 0.21 age ( in years )

Etiology of an increased Aa gradient: Parenchymal (PNA, ARDS, ILD) Vascular (PE, pulmonary edema, AVM, congenital heart disease) Hemoglobin affinity for O2 (CO poisoning, pH) Portable CXR 12-lead EKG Any additional labs or studies based on patient history: CBC Cultures Methemoglobinemia (fractionated hemoglobin) Cardiac enzymes BNP CT chest angiography (to look for PE) Management: Step 1: Stabilize the patient Ventilatory Support: It is not necessary to start with nasal cannula and work your way up. You can go right to a nonrebreather face mask or BiPAP to reduce fatigue and maybe stave off intubation. Supplemental oxygen: Nasal canula : FiO2 21% + (3 LPM) (maximum 40%) Simple face mask = up to an FiO2 of 50% Venturi face mask = based on color-coded adaptor, up to an FiO2 of 50% Nonrebreather face mask = always at an FiO2 of ~60%

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Noninvasive mechanical ventilation: TYPES OF NONINVASIVE MECHANICAL VENTILATION Continuous Positive Airway Bilevel Positive Airway Pressure Pressure (CPAP) (BiPAP) CPAP, FiO2 IPAP, EPAP, RRset, FiO2 TV, RR TV Not applicable Patient determines

225

Set Variables Dependent Variables End-Inspiration Trigger Notes

Equivalent to EPAP (on BiPAP) and continuous PEEP (on invasive ventilation) CPAP=5 cmH2O

Initial Settings

IPAP=inspiratory positive airway pressure (i.e. PS); EPAP=expiratory positive airway pressure (i.e. PEEP) IPAP=10 cmH2O, EPAP=5 cmH2O

The maximum FiO2 for a given LPM of O2 is very variable, though with no leak may approach 100%. Realistically, at 15LPM (highest O2 flow), expect a mean FiO2 of 60%. Noninvasive mechanical ventilation has been shown to reduce mortality and rates of intubation in COPD exacerbations, cardiogenic pulmonary edema (CPAP only), immunosuppressed patients in respiratory failure with bilateral infiltrates, and hypoxic respiratory failure. Do not use if you answer NO to any of these questions: Can the patient protect their airway? Is the patient alert and cooperative? Is their face free of surgical wounds? Can you monitor the patient closely (i.e. hourly, usually in ICU setting)? Will the mask fit properly over their mouth and nose? If it is okay to use, give a trial of one hour and reassess. If no clinical improvement, intubate! Noninvasive mechanical ventilation algorithm:

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Invasive mechanical ventilation (i.e. intubate): There are no perfect indicators to determine which patients need invasive mechanical ventilation. Experience is perhaps the best determinant in making this decision. Some things to think about include: Persistent hypoxic respiratory failure after supplemental O2 is administered Use of accessory muscles of respiration and/or paradoxical breathing (abdomen moves out on inspiration) Worsening neuromuscular disease Hyperventilationnormal ventilationhypoventilation with no improvement in oxygenation indicating respiratory muscle fatigue Airway protection (i.e. prolonged seizures, status asthmaticus, altered mental status) Upper airway obstruction (i.e. copious secretions) Cardiovascular support: place the patient on a cardiac monitor. If the patient becomes hypotensive, intubate! Step 2: Treat the underlying cause Wheezing: albuterol, ipratropium nebulizers Suctioning: mucus plugging, secretions Volume overload (edema, JVP, BNP, cool extremities): IV furosemide, hemodialysis

PULMONARY AND CRITICAL CARE Sepsis (fever, hypotension, WBC count): broad spectrum antibiotics MI (chest pain, troponin, EKG changes): urgent revascularization

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INVASIVE MECHANICAL VENTILATION Variables: Variable Tidal volume (TV) MECHANICAL VENTILATOR VARIABLES Description Volume of air inspired or expired per regular breath (TV = VDead Space+VAlveolar Space) Number of breaths per minute Percent of oxygen in inspired air Normal Value 6-8 mL/kg

Respiratory rate (RR) Fraction of inspired oxygen (FiO2) Positive end expiratory pressure (PEEP) Peak inspiratory pressure (PIP) Plateau pressure (Pplat)

12-20 21% 0 cmH2O <35 cmH2O

Inspiratory to expiratory time ratio (I:E) Inspiratory Time (IT) Minute ventilation (VE) Inspiratory flow rate (IFR) Resistance

Remaining pressure (>atmospheric) in the lungs at the end of expiration Pressure reached at the end of inspiration (pressure needed to expand the lungs and chest wall + pressure needed to push air through the airways) Pressure obtained at the end of inspiration during a pause between inspiration and expiration (pressure needed to expand the lungs and chest wall) Ratio of the amount of time spent in inspiration to expiration in a single breath Amount of time set for inspiration in a single breath (also expressed as a percentage of time spent in the inspiratory phase) TV RR Rate at which air is passed into the lungs during inspiration
Pressure Flow Rate = PIP Pplat IFR

<30 cmH2O

1:2-4 ~1-2 sec (33%) 72-120 mL/kg/min 1 L/sec <10 cmH2O/L/sec 100 mL/cmH2O

Compliance

Volume Pressure

TV Pplat PEEP

PULMONARY AND CRITICAL CARE Modes:

ASSIST-CONTROL (AC) Volume-Cycled (VCV)* TV, FiO2, RRset, PEEP, IFR PIP, I:E or IT Total TV delivered Pressure-Cycled (PCV) PIP, FiO2, PEEP, (I:E + RRset) or IT TV, IFR I:E or IT reached

228

Set Variables Dependent Variables End-Inspiration Trigger Pros Cons

Will not exceed set PIP Does not guarantee adequate TV or VE; If peak inspiratory flow inspiratory demand, patient may have work of breathing (similar to that of unsupported breaths) Notes The I:E ratio is determined by the TV depends on IT and the pattern of total RR (RRset + patient-initiated the inspiratory flow (which depends on the dynamic pressure gradient breaths), the TV, and the IFR. between the alveoli and airways) *Note that pressure-regulated volume control (PRVC) is a type of VCV that adjusts the pressure of the air delivered to reduce PIP while maintaining the selected TV
PRESSURE-SUPPORT (PS) PPS, FiO2, PEEP TV, PIP, IFR, I:E + RR or IT Patient determines Less discomfort and anxiety, more physiologic (patient and ventilator work in synchrony) Does not guarantee adequate TV or VE Patients respiratory drive must be intact in order to trigger each breath

Always delivers set TV Cannot control PIP and may have high PIP at selected TV

Set Variables Dependent Variables End-Inspiration Trigger Pros Cons Notes

SYNCHRONOUS INTERMITTENT MANDATORY VENTILATION (SIMV) Volume-Cycled (VSIMV) Pressure-Cycled (PSIMV) Set Variables TV, FiO2, RRset, PEEP, IFR, PPS PIP, FiO2, PEEP, I:E + RRset or IT Dependent Variables PIP, Spontaneous TV TV, Spontaneous TV End-Inspiration Total TV delivered, Spontaneous I:E or IT reached, Spontaneous Trigger patient determines patient determines Pros Unlike PS alone, the patient will receive a minimum number of breaths Cons Has not been shown to reduce time on ventilator, though SIMV with PS has not been adequately studied Notes May paradoxically increase the work of breathing and respiratory muscle fatigue. May be uncomfortable for the patient having to adapt to the intermittent full support and minimal support modes.

PULMONARY AND CRITICAL CARE Initial Settings:

TYPICAL INITIAL SETTINGS FOR MECHANICAL VENTILATION Variable VCV PCV TV 6-8 mg/kg Variable PIP Variable 30 cmH2O FiO2 100% 100% RRset 12 12 PEEP 5 cmH2O 5 cmH2O IFR 1 L/sec Variable I:E or IT Variable 1:2 or 33%

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Adjustments:
ADJUSTING THE MECHANICAL VENTILATOR Goals To Improve Notes Avoid O2 toxicity when PaO2>60 mmHg FiO2 SaO2>90% FiO2<60%; IT may lead to PEEP FiO2<60% PIP IT (IFR, I:E) Does not account for pH>7.20 TV or PIP permissive hypercapnia (see 30<PaCO2<50 mmHg RR ARDS); IT may lead to PIP IFR (I:E, IT) PIP-Pplat=airway resistance <30 cmH2O (<35 TV or PIP cmH2O) (think bronchospasm, mucus IT plugging) Each patient-initiated May also switch to flow Trigger breath triggers the triggering; auto-PEEP may sensitivity ventilator make it hard for patient to develop enough negative pressure to trigger a breath

Oxygenation

Ventilation

Pplat (PIP) Asynchrony

Ventilator Emergencies: Step 1: Remove the ventilator (not the ETT) and bag the patient with 100% FiO2. If you experience resistance while bagging the patient without improvement in SaO2, there most likely is an obstruction to flow (i.e. mucus plug, ETT obstruction or kink, patient biting on ETT). Consider suctioning, tube exchange with bronchoscopy, and/or removal of ETT and reintubation. If there is minimal resistance while bagging the patient but no improvement in SaO2, consider PE, PTX, pulmonary hemorrhage, pulmonary edema, atelectasis, or misplaced ETT (i.e. one lung ventilation). Step 2: Reattach the ventilator circuit and assess PIP and Pplat. The difference between PIP and Pplat is the airway resistance. PIP-Pplat>5 cmH2Oupper airway obstruction PIP-Pplat<5 cmH2Oparenchymal problem

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DIFFERENTIAL FOR VENTILATOR EMERGENCIES BASED ON PIP AND PPLAT PIPPplat<5 cmH2O PIPPplat>5 cmH2O (Parenchymal) (Upper Airway) Wrong ventilator settings/mode Mucus plug PTX Bronchospasm Pulmonary hemorrhage ETT kinked/obstructed Pulmonary edema Secretions Auto-PEEP Atelectasis Pneumonia PE Abdominal distention Malpositioned ETT (i.e. right mainstem bronchus)

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Step 3: Make appropriate interventions (i.e. change ventilator settings, place chest tube, etc.) Recheck ABG to ensure proper oxygenation and ventilation. Weaning the Ventilator: Step 1: Daily screening of patients for possible weaning. Look for: PaO2/FiO2>200 PEEP5 cmH2O Intact airway reflex (i.e. coughing during suctioning) Rapid shallow breathing index (RR/TV)105 Absence of pressors (except dopamine at 5 g/kg) and continuous sedatives Scant respiratory secretions Patient can protect airway Alert and awake or easily arousable (though those with brain injury and are not responsive can still be extubated successfully) Spontaneous breathing efforts Temperature 38C Hemoglobin > 8 mg/dL Correction of the underlying problem that necessitated intubation Step 2: Spontaneous breathing trial with T-piece or minimal pressure support of 5-7 cmH2O for 30-60 minutes (thought to overcome the resistance of the ETT) Step 3: Obtain weaning parameters, specifically RSBI, MIP, and VC. Note that if these parameters are obtained on minimal PS, they will be less accurate.

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PREDICTIVE INDICES OF EXTUBATION (OBTAINED DURING T-PIECE TRIAL) Parameter Value Sensitivity Specificity Notes 95% 42% +LR=1-2 Maximum <-16 to -20 inspiratory cmH2O -LR=0.1-0.3 pressure (MIP) Rapid shallow 100-105 91% 16% +LR=1.4-2.7 breathing index -LR=0.2-0.3 (RSBI=RR/TV) Vital capacity (VC) >11 mL/kg 59% 79% 40% of patients can perform test satisfactorily* Tidal volume (TV) >5 mL/kg 82% 53% Taken over 2 minutes 12 L/min 77% 11% If elevated, think about Minute Ventilation (VE) PaCO2, dead space Airway occlusion 95% 11% Used to assess respiratory 4 cmH2O pressure (P0.1) drive and mechanical load on the system J Inten Care Med 2001;16:270-286 Intensive Care Med 2004;30:830-836 *Chest 1992;102:1829-1832

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Step 4: Extubate the patient after the breathing trial if: RSBI 105 SaO2>90% VC>11 mL/kg MIP<-20 cmH2O Patient is comfortable without wide variations in vital signs

SEDATION: Sedatives do not provide analgesia. Dont forget the morphine! Patients typically do not need to be heavily sedated. Often, a good combination of analgesia and sedation will make the patient very comfortable while still allowing them to be responsive. Daily interruption of sedatives has been shown to reduce days on mechanical ventilation and days in the ICU so consider daily drug-holidays for your patients.

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Sedative

Midazolam (Versed)

PROPERTIES OF SEDATIVES COMMONLY USED IN THE ICU Half-Life Onset of Dosages Notable Elimination Action Adverse Effects 1-4 hr 1-5 min 0.02-0.08 mg/kg None Q5-15min; 0.040.2 mg/kg/hr infusion

Notes

Propofol (Diprivan)

4-7 hr (1-3 days after 10 days of infusion) 20-50 hr; metabolite 50-100 hr 12.9 hr

1-2 min

Diazepam (Valium)

2-5 min

Initiate at 5 g/kg/min; increase at 5-10 mcg/kg/min every 5-10 minutes 0.03-0.1 mg/kg Q30min-6hr

Hyperlipidemia; must titrate off

t prolonged with CHF, obesity, cirrhosis; prolonged sedation with renal failure Monitor Zinc levels after 5 days of use; may potentiate effects of vecuronium Not available as a continuous infusion; caution advised with renal and liver failure ESRD t to 3270 hr; unlabeled use for agitation/sedation in ICU

Contains propylene glycolacidosis; phlebitis Contains polyethylene glycol and propylene glycolacidosis

Lorazepam (Ativan)

5-20 min

0.02-0.06 mg/kg Q2-6hr; 0.01-0.1 mg/kg/hr infusion

PARALYSIS: Per the ACCM guidelines, paralytics should be used to manage ventilation, managed ICP, treat muscle spasms, and O2 consumption only when all other means have been tried without success. (Crit Care Med 2002;30:142-156) Paralytics have been shown to duration of mechanical ventilation, weaning time, ICU stay, and mortality. Pancuronium is typically the agent of choice however, because of its associated tachycardia and vagolysis, this agent should be avoided in patients who cannot tolerate HR Monitoring of patients should include both Train-of-Four (TOF) and clinical assessment Paralytics should be adjusted to a TOF of 1-2 twitches Always remember to sedate patients before administering a paralytic as paralytics do not provide any sort of sedation (or analgesia) Pearls: Always call attending or fellow before starting paralytics Always make sure you can bag-mask ventilate a patient before starting paralytics

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Paralytic

Atracurium (Tracrium)

Cisatracurium (Nimbex) Pancuronium (Pavulon) Rocuronium (Zemuron) Succinylcholine (Anectine) Vecuronium (Norcuron)

PROPERTIES OF PARALYTICS COMMONLY USED IN THE ICU Onset Duration Dosage Notable (Initial; Infusion) Adverse Effects 2-3 min 20-35 0.4-0.5 mg/kg; Metabolite is a min CNS stimulant; 5-10 g/kg/min may cause histamine release 2-3 min 20-35 0.15-0.2 mg/kg; Less histamine min release than 3-10 g/kg/min atracurium 2-3 min 60-100 0.05-0.1 mg/kg; Tachycardia and min vagolysis 0.8-1.7 g/kg/min

Notes

No changes needed in renal or liver failure More potent than atracurium Significant adjustments for renal and hepatic disease required Newer agent Used basically for rapid intubation drug requirements in renal and liver disease

1-4 min 30-60 sec 2.5-3 min

30 min 4-6 min 20-40 min

0.6-1.2 mg/kg; 10 g/kg/minute 1-1.5 mg/kg; 10-100 g/kg/min 0.05-0.1 mg/kg; 0.8-1.7 g/kg/min

None Malignant hyperthermia More commonly associated with prolonged blockade

ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS) Definition: Acute lung injury (ALI): Acute onset Bilateral infiltrates on CXR Pulmonary capillary wedge pressure (PCWP) 18 mmHg or the absence of clinical evidence of left atrial hypertension (or LVEDP) PaO2/FiO2 300 (regardless of PEEP level) Acute respiratory distress syndrome (ARDS): ALI + PaO2/FiO2 200 (regardless of PEEP level) Pathophysiology: Injury to the capillary-alveolar membrane from: Pro-inflammatory cytokines (TNF, IL-1, IL-8) Recruitment and activation of neutrophils with release of toxic mediators Defects in the coagulation systemplatelet-fibrin thrombi in small vessels and impaired fibrinolysis in distal damaged airspaces Risk Factors: Sepsis Aspiration of gastric contents Near drowning

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Pulmonary contusions Multiple blood transfusions (>15 units/24 hours) Trauma Treatment: Low tidal volume ventilation: ARDS network showed a 22% mortality with low TV ventilation. (NEJM 2000;342:1301-1308) TV = 6 mL/kg of ideal body weight (IBW) IBWmen= 50 + 0.91(height in cm 152.4) or 2.3xheight (inches) 60. IBW women= 45.5 + 0.91(height in cm 152.4) or 2.3xheight (inches) 60. Permissive Hypercapnia is a side-effect of low TV ventilation and is tolerated up to a PaCO2 < 80 and pH > 7.15. The high PaCO2 is a powerful stimulus to breath, and may require heavy sedation to prevent asynchrony. Just write for ARDS Net protocol and the respiratory therapists will adjust the ventilator settings accordingly.

GENERAL CARE OF ICU PATIENTS Blood glucose control: Maintain blood glucose 80-110 mg/dL. This likely decreases mortality (controversial as a study looking at patients in the MICU did not show a statistically significant difference unlike the SICU trial) and definitely decreased morbidity. Use the insulin drip protocol for the best titration of insulin based on glucose. Note that the patient must have some source of glucose (i.e. tube feeds, D5W) before placing them on an insulin drip. GI prophylaxis: Major risk factors for developing a stress ulcer are mechanical ventilation and coagulopathy. Place every patient on GI prophylaxis that is intubated! First line is oral PPIs (need to load with two doses 6-8 hours apart) In patients who cannot tolerate oral PPIs, IV H2 receptor antagonists should be used (typically given as a bolus followed by a continuous infusion) Keep HOB > 30 to reduce risk of ventilator-associated pneumonia. Nutrition: Feed patients as soon as possible with an NG tube. This is by far the best way to provide nutrition. There is no good evidence that TPN improves mortality, not to mention its costs and risk of infection. Prealbumin is not a great marker for nutritional status. Clinical status is a better marker, but go ahead, order a prealbumin! Remember, ICU patients aspirate their own saliva and gastric contents, so always keep HOB elevated and check tube feed residuals to prevent overfeeding. DVT prophylaxis: VERY IMPORTANT! Up to a 8x increased risk of DVT in patients in the ICU. If there are no contraindications to anticoagulation (i.e. recent surgery, spinal cord injury, intracranial bleed), use Lovenox 40mg SC QD (low risk) or 30mg SQ Q12H (high risk). Heparin 5000 units SQ Q12H (low risk) or Q8H (high risk) should be used in those with renal insufficiency/failure, also consider in cirrhotics/patients with coagulopathy. Mechanical devices like TED stockings and SCDs are okay, though there is poor evidence that SCDs do anything except annoy patients.

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Lab holidays: If you dont need an ionized calcium daily (which you dont), dont order it! Only check labs you need and when you need them. PM labs are not always necessary in ICU patients. Daily CXR: This is mainly used to check ETT placement, which should be about 2-4 cm above the carina. Usually, order daily CXRs on intubated patients unless the attending says otherwise. Daily CXR not needed if trached. Central lines: There is a lot of debate as to when central lines need to be changed and if changing them over a wire is as good as placing it at another site. Ask yourself these questions regarding central lines: If the patient is febrile, could it be the source of infection? If so, this is a good reason to change the line and culture the tip. Do I need the central line in the first place? Does the blood pressure cuff do as good a job as the arterial line (if so, take it out!)? And of course, it is up to the attending if and when lines should be changed, as each has their own style.

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ARTHROCENTESIS GENERAL CONCEPTS Indication for Joint Aspiration: Presence of an effusion in a single joint with unclear etiology Symptomatic relief in a patient with a known arthritic condition Monitor therapeutic response in a patient with infectious arthritis Indication for Joint Injection: Suppression of inflammation for up to a few peripheral joints once infection is ruled out As much fluid as possible should be aspirated before intra-articular glucocorticoid therapy Steroid injection works in 1-7 days, benefit may last weeks to 1 yr. Contraindication to Joint Aspiration and Injection: Absolute: overlying infection Relative: significant coagulopathy, bacteremia Normal Colorless Transparent High <200 <25% Negative None SYNOVIAL FLUID ANALYSIS Noninflammatory Inflammatory Xanthochromic Yellow Transparent Translucent High Low 200-3,000 3,000-50,000 <25% >50% Negative Negative None May be positive Osteoarthritis Gout Trauma Pseudogout Charcot joint Rheumatoid arthritis Polymyalgia rheumatics Scleroderma Aseptic necrosis Ankylosing spondylitis Scleroderma Psoriatic arthritis Polyarteritis nodosum Behets Septic Variable Opaque Low >50,000 >75% May be positive Negative Bacterial Tuberculosis

Color Clarity Viscosity WBC/mm3 PMN Culture Crystals Examples

ACUTE MONOARTHRITIS DIFFERENTIAL DIAGNOSIS Infectious: Bacterial: Gonococcal, Staphylococcus, Streptococcus, Enterobacteriaceae, Lyme Fungal Mycobacterium tuberculosis Crystal: Monosodium urate (gout) Calcium pyrophosphate dihydrate deposition disease (pseudogout) Trauma: Hemarthrosis Fracture Ligamentous injury Meniscal injury Systemic disease:

RHEUMATOLOGY Reactive arthritis Psoriatic arthritis Rheumatoid arthritis Inflammatory bowel disease Other: Foreign body reaction Tumor Avascular necrosis

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GONOCOCCAL BACTERIAL ARTHRITIS Predisposing factors: Young, sexually active H/o complement deficiency Clinical: Migratory polyarthralgia Fever Tenosynovitis Dermatitis 80% with asymptomatic gonococcal STD infection. Treatment: Ceftriaxone 1g IV qday. NONGONOCOCCAL BACTERIAL ARTHRITIS Etiology: Hematogenous spread (~70%) Bite/trauma Direct inoculation or contiguous spread from adjacent to the joint Underlying arthritis Predisposing factors: Immunosuppression Intravenous drug use Indwelling catheters Neonates Elderly Infective endocarditis Prosthetic joints Microbiology: Staphylococcus aureus (most common in adults) Staphylococcus epidermidis (post-op, prosthesis) Streptococci (2nd most common, splenic dysfunction) Gram-negative bacilli (IVDU, neonates, elderly, DM, immunosuppressed, sickle cell) Clinical: Acute onset monoarticular arthritis (80%) Knee (>50%), wrist, ankles, hips Can be oligoarticular or polyarticular, usually in the setting of rheumatoid arthritis, connective tissue diseases, or sepsis

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Fever is common Associated skin, urine, or respiratory tract infection may be present Diagnosis: Labs: leukocytosis with left shift, blood cultures (+ in 50% of cases). Synovial fluid aspiration: Gram stain & culture (usually +) Cell count (average WBC 50,000-150,000) and differential (mostly polymorphonuclear cells) Radiographs: usually normal at presentation but useful to rule out concurrent osteomyelitis or joint disease CT/MRI: useful to detect effusions/inflammation in hip and spine Differential Diagnosis: Crystal-induced arthritis Reactive arthritis Rheumatoid arthritis Lyme disease Mycobacterial arthritis Psoriatic arthritis Treatment: Intravenous antibiotics: Initially can base choice on gram stain or likely organism given history Gram-positive cocci: vancomycin Gram-negative rods: 3rd generation cephalosporin Joint drainage: Notify orthopedics immediately as they may want to clean out the joint in the OR Other option is daily aspiration (need to see improving WBC count in synovial fluid)

CRYSTAL DEPOSITION ARTHRITIDES Gout Definition: a term for clinical syndromes of urate crystal deposition disease: Acute inflammatory arthritis Tophaceous deposits Uric acid nephrolithiasis Uric acid nephropathy Natural history: acute gouty arthritisinterval goutchronic tophaceous gout Acute gouty arthritis: Predisposing factors: any acute change in the uric acid concentration (i.e. diuretics, allopurinol, excess alcohol consumption, diet, surgery) Clinical features: Severe pain, erythema, swelling 80% of initial attacks are monoarticular, typically in the lower extremities Most often at first metatarsophalangeal joint (i.e. podagra) with inflammation often extending beyond involved joint Fever, leukocytosis, and ESR can occur (difficult to distinguish from acute septic arthritis) Diagnosis: At least 10% have normal uric acid levels. Joint aspiration of synovial fluid shows:

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Needle-shaped, negatively birefringent crystals (intracellular monosodium urate) under polarized light microscopy Sensitivity > 85%, specificity ~100% WBC 3000-50,000 (>50% polymorphonuclear cells) Note that gout and septic arthritis can coexist, so always also a check gram stain and culture! Treatment: Anti-inflammatory therapy NSAIDs: 1st line (depending on renal function) Indomethacin 150 mg p.o. daily (divided b.i.d. or t.i.d.) usually for 7-10 days Reduce dose by half as soon as clinical improvement to reduce risk of GI intolerance If longer course of treatment needed, consider alternative NSAID PPI Glucocorticoids (intraarticular or orally) Intraarticular: option if few inflamed joints (must rule out infection first!) Systemic: for patients who cannot take NSAIDs, COX-2 inhibitors, or colchicine and who are not candidates for intraarticular injection. Consider oral prednisone versus intravenous methylprednisolone Colchicine (orally only, do not give intravenously!) Effective especially when stared early Main side effects are GI: nausea, vomiting, diarrhea Must reduce dose in hepatic or renal disease (risk of bone marrow suppression) Dose at 0.6 mg/hr orally until relief of symptoms OR total daily dose of 6 mg reached OR adverse effects limits use Once symptoms are improving, can reduce dose to 0.6 mg orally b.i.d. until resolution Allopurinol Do not start if acute gout attack. Dose 100mg po daily, raise weekly to desired dose. Treatment options for special cases Hospitalized patients who are NPO: intravenous or intraarticular glucocorticoids Decreased GFR: glucocorticoids (avoid colchicine and NSAIDs) Renal transplant patients: defer to renal transplant team Pseudogout (calcium pyrophosphate dihydrate deposition disease) Definition: acute self-limited synovitis induced by calcium pyrophosphate dihydrate deposition Clinical features: resembles gout, acute to subacute monoarticular or pauciarticular arthritis Typically located in the knees (>50%), wrists, and/or metatarsophalangeal (MTP) joints Etiologies: trauma, surgery, severe illness (similar to gout) Diagnosis: synovial fluid aspiration Polarized microscopy shows rhomboid-shaped, weakly positive birefringent crystals WBC count typically 2,000-10,000 with >50% polymorphonuclear cells Treatment: treat like acute gout

CLASSIFICATION OF VASCULITIDES Large Vessel Vasculitis Takayasus arteritis: Primarily affects the aorta and its primary branches ACR classification criteria (3 out of 6 criteria): Age of disease onset 40 years

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Claudication of the extremities Decreased pulsation of one or both brachial arteries Difference of > 10 mmHg in systolic BP between arms Bruit over one or both of the subclavian arteries or abdominal aorta Arteriographic narrowing or occlusion of the entire aorta, its primary branches, or large arteries in the proximal upper or lower extremities not due to atherosclerosis, fibromuscular dysplasia, or other causes Giant Cell (temporal) arteritis: Chronic vasculitis of large and medium size vessels Associated with polymyalgia rheumatica ACR classification criteria (3 out of 5 criteria): Age 50 years at time of disease onset Localized headache of new onset Tenderness or decreased pulse of temporal artery ESR > 50 mm/h Biopsy of the temporal artery revealing necrotizing arteritis with predominance of mononuclear cells or a granulomatous process with multinucleated cells Medium-Sized Vessel Vasculitis Polyarteritis nodosa: Systemic necrotizing vasculitis without granulomas Not associated with p-ANCA (myeloperoxidase) antibody ACR classification criteria (3 out of 10 criteria): Otherwise unexplained weight loss 4 kg Livedo reticularis (a purplish network-like pattern of the skin) Testicular pain or tenderness Myalgias (excluding shoulder and hip girdle), weakness, or polyneuropathy Mononeuropathy or polyneuropathy New onset diastolic BP > 90 mmHg Elevated serum BUN (> 40 mg/dL) or Cr (> 1.5 mg/dL) Evidence of hepatitis B infection Characteristic arteriographic abnormalities (aneurysms, vessel occlusion) Biopsy of small or medium-sized artery containing polymorphonuclear cells Isolated CNS vasculitis: Rare disorder most commonly diagnosed in patients with CNS symptoms/signs with evidence of cerebral vasculitis by angiography and a positive leptomeningeal biopsy Small Vessel Vasculitis Churg-Strauss arteritis (allergic granulomatosis and angiitis): Classically involves arteries of the skin and lung but can be generalized ACR criteria (presence of 4 is 85% sensitive and 99.7% specific): Asthma Eosinophilia > 10% on differential Mononeuropathy or polyneuropathy Migratory or transient pulmonary infiltrated on chest x-ray Paranasal sinus abnormality Biopsy containing perivascular eosinophil accumulation Wegeners granulomatosis:

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Systemic vasculitis of medium/small arteries/venules/arterioles Typically produces granulomatous inflammation of upper and lower respiratory tracts and necrotizing pauci-immune glomerulonephritis Associated with c-ANCA (proteinase-3 antibody) ACR criteria (presence of 2 is 88% sensitive and 92% specific): Nasal or oral inflammation (ulcers, bloody nasal discharge) Abnormal chest x-ray showing nodules, fixed infiltrates, or cavities Abnormal urinary sediment (microscopic hematuria or RBC casts) Granulomatous inflammation on biopsy of an artery or perivascular area Microscopic polyarteritis: Primarily affects capillaries, venules, or arterioles. Pulmonary-renal vasculitic syndrome (pulmonary hemorrhage/renal failure) p-ANCA + in 40-80% patients Hypersensitivity vasculitis (3 vasculitic syndromes): Henoch-Schnlein purpura: Systemic vasculitis characterized by tissue deposition of IgA-containing immune complexes ACR criteria (presence of 2 is 87% sensitive and 88% specific): Age 20 years at disease onset Bowel angina Palpable purpura Biopsy showing granulocytes in the walls of arterioles and/or venules Hypersensitivity vasculitis (cutaneous leukocytoclastic angiitis): Includes drug-induced vasculitis and serum sickness ACR criteria (presence of 3 is 71% sensitive and 84% specific): Age > 16 years Palpable purpura Maculopapular rash Known medication taken prior to disease onset Biopsy showing granulocytes around vessels Essential cryoglobulinemic vasculitis: Immunoglobulins precipitate in the cold and dissolve on rewarming Type 1: monoclonal immunoglobulin (IgM or IgG) Type 2: monoclonal IgM with activity against polyclonal IgG (mixed) Type 3: polyclonal IgM with activity against polyclonal IgG (mixed) Often associated with hepatitis C Small vessel inflammation results from deposition of immunoglobulins and complement in the vessel walls

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ANTINUCLEAR ANTIBODY SUBTYPES Diseases Comments Does not occur in classic drugSLE induced lupus but may occur in lupus induced by anti-TNF agents Associated with lupus nephritis SLE May indicate an overlap of Sjgrens SLE and SLE Neonatal SLE Sjgrens Myositis May indicate an overlap of Sjgrens SLE and SLE Sjgrens Often seen with Raynauds Mixed connective tissue disease (MCTD) SLE Especially sensitive for lupus caused Drug-induced lupus by procainamide, hydralazine, SLE chlorpromazine, and quinidine < 5% of diffuse, 60-80% of limited Systemic sclerosis (Scleroderma) 40% diffuse, 15% of limited Systemic sclerosis (Scleroderma)

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Subtypes Anti-ds-DNA Anti-Sm Anti-Ro/SSA

Anti-La/SSB Anti-U1-RNP

Anti-histone Anti-centromere Anti-topoisomerase (anti-Scl-70)

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AMERICAN COLLEGE OF RHEUMATOLOGY CRITERIA FOR DIAGNOSIS OF SYSTEMIC LUPUS ERYTHEMATOSUS ( 4 yields a sensitivity and specificity of > 95%) Criteria Definition Malar rash Fixed erythema, flat or raised, over the malar eminences, tending to spare the nasolabial folds Discoid rash Erythematosus raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur in older lesions Photosensitivity Skin rash as a result of unusual reaction to sunlight, by patient history or physician observation Oral Ulcers Oral or nasopharyngeal ulcerations usually painless, observed by a physician Arthritis Nonerosive arthritis involving 2 or more peripheral joints, characterized by tenderness, swelling, or effusion Serositis Pleuritis (convincing history of pleuritic pain or a rub heard by a physician or evidence of a pleural effusion) OR pericarditis (documented by EKG, rub, or evidence of a pericardial effusion) Proteinuria ( > 0.5 gm/day or 3+ on dipstick if quantitation not performed) OR Renal disorder cellular casts (may be red cell, hemoglobin, granular, tubular, or mixed) Seizures OR psychosis (in the absence of offending drugs or known metabolic Neurologic disorder derangements such as uremia, ketoacidosis, or electrolyte imbalances) Hemolytic anemia (with reticulocytosis) OR leukopenia (< 4,000/mm3 on 2 Hematologic occasions) OR lymphopenia (< 1,500/mm3 on 2 occasions) OR disorder thrombocytopenia (< 100,000/mm3 in the absence of offending drugs) Antiphospholipid antibody OR anti-ds-DNA (antibody to native DNA in abnormal Immunologic titer) OR Anti-Sm (presence of antibody to Sm nuclear antigen) OR false positive disorders serologic test for syphilis known to be positive for 6 months and confirmed by a negative Treponema pallidum immobilization or fluorescent treponemal antibody absorption test Antinuclear An abnormal titer of antinuclear antibody by immunofluorescence or an equivalent antibody assay at any point in time and in the absence of drugs known to be associated with drug-induced lupus syndrome

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Drugs that cause lupus: Hydralazine, Isoniazid, Procainamide, Methyldopa, Quinidine, Chlorpranimide.

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SCLERODERMA RENAL CRISIS Clinical Characteristics Acute onset of renal failure usually in the absence of chronic kidney disease Abrupt onset of moderate to marked hypertension Due to ischemic activation of the renin-angiotensin system Often associated with hypertensive retinopathy Urine sediment: Usually normal but can have mild proteinuria Microscopic hematuria and granular casts may be seen Vascular sequelae of hypertension: Microangiopathic hemolytic anemia, pulmonary edema, headache, blurred vision, encephalopathy Pathology Acute: fibrin thrombi and fibrinoid necrosis Chronic: mucoid intimal thickeningconcentric onion-skin thickening Management Aggressive blood pressure control is the mainstay of treatment ACE inhibitors (not ARBs) are the agent of choice Achieve gradually (10-15 mmHg) Avoid nephrotoxins

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GENERAL APPROACH TO INTOXICATION/INGESTION Every patient who present with an acute intoxication or poisoning will require rapid diagnosis and treatment, but first must be stabilized and assessed thoroughly. Always have someone contact the poison control center at (800) 222-1222 to help you with your workup and management. Step 1: ABCs Intubation for respiratory failure and/or airway protection. Place at least 2 large bore (<18 gauge) IVs and/or a central venous catheter. Cardiac monitoring and pulse oximetry. Supplemental oxygenation. Step 2: Focused History Material (or materials) ingested Time of ingestion Amount ingested (empty pill bottles) Significant past medical history and prescription medications Step 3: Order appropriate laboratory and radiologic tests EKG, CXR CBC, chemistry panel including Ca, Mg, and Phos, LFTs, ABG, acetaminophen level, salicylates, ethanol level, serum osmoles. Urine toxicologic screen Step 4: Diagnose and treat based on agent (see below) ETHANOL INTOXICATION AND WITHDRAWAL Ethanol Properties 20% absorbed by the stomach with the rest absorbed in the small intestine >90% eliminated by the liver Clearance rates of ethanol are 20 mg/dL/hr 6 mg/dL/hr, with tolerant drinkers having a higher clearance rate Clinical Signs and Symptoms Based on Blood Alcohol Level Make sure to assess the patient from head-to-toe looking for trauma 1 shot = 1 beer = 1 glass of wine will raise the ethanol blood level of a 70 kg person by 25 mg/dL Note that a blood alcohol concentration (BAC) of 0.08 = 80 mg/dL

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BLOOD ALCOHOL CONCENTRATION AND ASSOCIATED CLINICAL SIGNS BAC (mg/dL) Drinks (55 kg person) Clinical Signs 50-100 1-3 drinks Impaired sensation, incoordination 100-150 3-5 drinks Behavioral changes, ataxia, cognitive and memory difficulties 150-200 5-7 drinks Marked incoordination, worsening ataxia, cognitive impairment 200-300 7-9 drinks Nausea, vomiting, diplopia, lethargy, aspiration risk 300-400 >9 drinks Decreased respiratory drive, hypoventilation, amnesia, hypothermia, cardiac arrhythmias (mostly atrial fibrillation) >400 >9 drinks Coma, respiratory arrest, death Adapted from Postgrad Med 2002;112:14-26

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Management Think ABCs (airway, breathing, circulation). Obtain baseline labs including a BAC, chemistry panel (including magnesium and phosphorous) to calculate an anion gap, liver function panel, serum ketones, blood glucose (alcohol can induce hypoglycemia) and possibly an illicit drug screen (either serum or urine) if additional drug use suspected. If the patient had a recent binge (usually within 1 hour), activated charcoal and/or gastric lavage can be considered. When a BAC is obtained, determine whether the clinical signs are worse than the measured BAC. If so, look for alternative causes (i.e. trauma, intracranial hemorrhage, infection, severe ketoacidosis). Administer IV fluids (normal saline, as they are usually dehydrated). Usually, add to 1L of IV fluids: IV thiamine 100 mg (poor absorption with concurrent ethanol use), IV folate 1 mg, and an IV multivitamin (this is often referred to as a Banana Bag as it is yellow). Traditional teaching is to give thiamine before glucose to prevent precipitating Wernickes encephalopathy. This is controversial and is only applicable to thiamine deficient individuals (i.e. chronic alcoholics). Measure serum glucose (can use fingerstick): If the patient is hypoglycemic, this is dangerous and should be corrected acutely. Give 5% dextrose in 1L normal saline + thiamine, folate, and a multivitamin (as above). If the patient is not hypoglycemic, give 1L normal saline + thiamine, folate, and a multivitamin (as above), then you can add 5% dextrose to the next liter of fluid (if applicable). Replete magnesium and phosphorus as indicated. Patients may have a large anion gap from alcoholic ketoacidosis. This should correct with administration of IV fluids with dextrose. Serum lactate should be normal (if high, look for reasons to explain this) Usually presents in chronic alcoholics days after a binge (i.e. BAC low or undetectable)

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Ethanol Withdrawal
Syndrome Minor withdrawal Onset 6-12 hours ETHANOL WITHDRAWAL SYNDROMES Signs/Symptoms Nausea, vomiting, tremulousness, anxiety, palpitations Notes Not all patients will have minor withdrawal before the other syndromes occur 25% incidence

Alcoholic hallucinations Seizures (Rum Fits) Delirium Tremens

10-48 hours 6-48 hours 48-96 hours

Tactile (formication), visual, or auditory hallucinations with a clear sensorium Generalized tonic-clonic seizures with a short postictal period with quick recovery of mental status Hypertension, tachycardia, tremors, diaphoresis, disturbance of consciousness (i.e. delirium) or change in cognition (i.e. memory deficit)

10% incidence, of those 3% experience status epilepticus 30-40% incidence in those with alcohol withdrawal seizures; Can last up to 2 weeks; 5% mortality

Assessment of alcohol withdrawal Use the Revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale. (Br J Addict 1989;84:1353-1357) *see reference for scale <9 = mild withdrawal 9-15 = moderate withdrawal >15 = severe withdrawal symptoms and an increased risk of delirium tremens and seizures Treatment Initial treatment (see management of ethanol intoxication) Minor withdrawal and alcoholic hallucinations Benzodiazepines Diazepam is the first-line drug choice because of its immediate onset and long half-life (20-50 hours) Dose at 10-20 mg IV every hour to achieve sedation but with normal vital signs and spontaneous respirations. Avoid in those with advanced liver disease (half life) Lorazepam can also be used as it has an onset of 5 minutes and a 13 hour half-life. Dose at 0.5-4 mg IV every hour to achieve sedation but with normal vital signs and spontaneous respirations. For patients with minor withdrawal, oral benzodiazepines are acceptable, with chlordiazepoxide being the drug of choice. Dose 50-100 mg every 8 hours as needed (reduce dose in hepatic and renal insufficiency). Can start with 10-20 mg IV or PO diazepam to achieve more rapid sedation. Clonidine can be used to control autonomic hyperactivity (i.e. tachycardia, hypertension) but should never be used as monotherapy, as it can mask the severity of alcohol withdrawal and may lead to underdosing of benzodiazepines. Two RCTs have shown that symptom-triggered dosing of benzodiazepines reduced total benzodiazepine use and duration of treatment without an increase in withdrawal seizures or other adverse events. (Arch Intern Med 2002;162:1117-1121) (JAMA 1994;272:519-523) There are issues, however:

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All patients were scored with the CIWA-Ar scale. They were assessed and dosed hourly. They were all in minor to moderate withdrawal (mean CIWA-Ar score of 9-11). Therefore, if you plan on using symptom-triggered dosing, you must be able to assess the patient hourly using the validated CIWA-Ar score to determine repeat dosing. Alcoholic withdrawal seizures Airway protection Fall protection IV lorazepam 2 mg IV every 5 minutes OR IV diazepam 10-20 mg IV every 5 minutes to stop the seizures, then continue either IV or oral lorazepam/diazepam to maintain adequate sedation with normal vital signs and spontaneous breathing. Consider additional causes (i.e. intracranial bleed, meningitis) and workup accordingly. Delirium tremens Cardiac monitoring Airway protection and fall precautions Judicious use of IV diazepam (or IV lorazepam) to achieve sedation with normal vital signs and spontaneous breathing. For patients who do not respond to benzodiazepines, consider ICU management and phenobarbital or propofol for sedation.

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OPIOID OVERDOSE Opioid Properties Drug PROPERTIES OF COMMON OPIOID DRUGS Brand Names Onset of Half Life Action Actiq IV immediate 2-4 hours Duragesic IM 7-15 min Diamorph IV 1-2 min 15-30 min Many street drug IM 15-30 min names Vicodin PO 10-20 min 3.3-4.4 hours Norco Dilaudid PO 15-40 min 1-3 hours IV 10-15 min IM 15 min Demerol PO 10-15 min 2.5-4 hours SQ 10-15 min (> in renal and IV 5 min liver disease) Dolophine PO 0.5-1 hr 7-59 hours IV 10-20 min Roxanol PO 30 min 2-4 hours MS Contin (long IV 5-10 min acting) Roxicodone PO 10-15 min 2-3 hours OxyContin (long acting) Percocet (contains acetaminophen) Darvon PO 0.5-1 hours 6-12 hours Duration

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Fentanyl Heroin Hydrocodone + Acetaminophen Hydromorphone Meperidine Methadone Morphine Oxycodone

IV 0.5-1 hours IM 1-2 hours 3-5 hours 4-8 hours PO 4-5 hours IV 2-3 hours IM 4-5 hours 2-4 hours 4-48 hours 4 hours (MS Contin 12 hours) 3-6 hours (OxyContin 12 hours) 4-6 hours

Propoxyphene

Clinical Signs and Symptoms Signs: Respiratory depression, miosis, orthostatic hypotension, bradycardia, flushing, sedation/coma, bronchospasm, non-cardiogenic pulmonary edema Seizures can occur with meperidine and propoxyphene Symptoms: Pruritus, constipation, euphoria, analgesia Laboratory Testing Opioid metabolites in the urine can be detected for 1-3 days False-positives can be caused by cocaine, rifampin, fluoroquinolones, and poppy seeds Management Gastric lavage and/or activated charcoal for recent oral administration Respiratory support (supplemental oxygen, intubation if needed) Bowel regimen Naloxone administration Can be given IV (preferred), IM, SQ, and intratracheal

TOXICOLOGY Dose at 0.4-2 mg (0.1-0.2 mg in opioid dependent or postoperative patients) and repeat every 2-3 minutes as needed up to 10 mg. Can place on naloxone drip, using 2/3 of the initial dose over an hour as a guide. VERY IMPORTANT: The duration of action of naloxone is 20-60 minutes while all of the opioids (see table above) have much longer durations. Therefore, if you achieve reversal of CNS and respiratory depression initially, monitor the patient closely as you probably will have to redose the naloxone approximately every 45 minutes. Side effects: opioid withdrawal, seizures, myocardial infarction, non-cardiogenic pulmonary edema.

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COCAINE OVERDOSE Cocaine Properties Administered IV, IM, inhaled, and snorted Onset of action 6-16 seconds, except when snorted (3-5 min) Half-life 30-90 minutes Works by blocking the reuptake of catecholamines in the brain, impairs nerve conduction by blocking fast sodium channels locally, and rate and amplitude of the action potential in cardiac myocytes. Clinical Signs and Symptoms Signs: Hyperthermia, tachycardia, tachypnea, hypertension, mydriasis, diaphoresis Symptoms: Agitation, delirium, psychosis, anesthesia locally, muscle pain, abdominal pain, chest pain, shortness or breath, wheezing Adverse Events CNS: seizure, coma, stroke, intracranial hemorrhage Pulmonary: edema, pneumothorax, alveolar hemorrhage, asthma Cardiac: coronary vasospasm and/or myocardial infarction (can occur up to 2 weeks after use), arrhythmias, dilated cardiomyopathy (chronic use) Abdominal: perforated ulcers, ischemic colitis, bowel obstruction (think body packing) Musculoskeletal: rhabdomyolysis Laboratory Testing Cocaine metabolites in the urine can be detected for 2-3 days False-positives can be caused by topical anesthetics containing cocaine, amoxicillin, tonic water Consider urine myoglobin, serum creatinine, cardiac enzymes, EKG, CT scans (intracranial hemorrhage, body packing, pulmonary edema/hemorrhage) Management Note that -adrenergic antagonists (i.e. -blockers) are ABSOLUTELY CONTRAINDICATED as they allow unopposed -adrenergic activity. Supportive care is the mainstay of therapy unless other signs/symptoms occur: Chest pain/MI: Give ASA, lots of oxygen, and morphine. Benzodiazepines and nitroglycerin have been shown to be beneficial. Phentolamine can be used for excessive hypertension/tachycardia. Heparins, clopidogrel, glycoprotein IIb/IIIA inhibitors can be considered in those patients with risk factors for coronary artery disease. Hypertension: Phentolamine, nitroglycerin Arrhythmias: Diltiazem (for rapid atrial fibrillation, SVT), lidocaine Seizures: Lorazepam or diazepam IV Hyperthermia: cooling blanket and/or sedation Rhabdomyolysis: large volumes of IV fluids

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Agitation: benzodiazepines (use midazolam or diazepam first)

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BENZODIAZEPINE OVERDOSE Benzodiazepine Properties PROPERTIES OF COMMON BENZODIAZEPINE DRUGS Brand Names Onset of Action Half Life Xanax PO 1-2 hours 11.2 hours (prolonged in LD) Chlordiazepoxide Librium PO 1-2 hours 6.6-25 hours (prolonged in LD, ESRD) Clonazepam Klonopin PO 20-60 min 19-50 hours Diazepam Valium IV immediate 20-50 hours PO 3-5 min (prolonged in LD) Lorazepam Ativan IM 20-30 min 13-16 hours IV 5-20 min (32-70 hours in ESRD) PO 30-60 min Midazolam Versed IM 15 min 1-4 hours IV 1-5 min (prolonged in LD) Temazepam Restoril PO 30 min 9.5-12.4 hours LD = liver disease; ESRD = end-stage renal disease Drug Alprazolam

Clinical Signs and Symptoms Signs: Respiratory depression, hypothermia, bradycardia Symptoms: Confusion, drowsiness, dysarthria, ataxia, coma Management Supportive care with specific attention to respiratory depression Flumazenil: Typically NOT indicated in overdose as it can precipitate seizures Its use is contraindicated in patients with seizure disorders and when tricyclic antidepressants may be co-ingested. A good rule of thumb is to consider its use in benzodiazepine-naive patients with severe respiratory depression. Dose at 0.2 mg IV over 15 seconds and can be repeated every minute (maximum dose 1 mg). Like naloxone, its duration of action (~1 hour) is typically less than the benzodiazepines, and patients who respond initially usually need redosing to prevent respiratory depression.

ACETAMINOPHEN OVERDOSE Acetaminophen Properties Rapid absorption with a half-life of 2-3 hours (may be prolonged in patients with liver disease) Overdose is typically defined as 7.5 grams ingested within a 4 hour interval. Acetaminophen is metabolized as follows: ~50% by hepatic conjugation to glucuronide. ~35% by hepatic conjugation to sulfate.

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~10% by oxidation by CYP2E1 to N-acetyl-p-benzoquinoneimine (NAPQI), which is toxic, but rapidly combines with glutathione creating non-toxic metabolites. <5% remains unchanged and is renally cleared. When the amount of acetaminophen ingested overwhelms the glutathione system, NAPQI builds up resulting in the toxic effects of acetaminophen overdose. Clinical Stages Stage I (<24 hours): Nonspecific symptoms including diaphoresis, pallor, nausea, and vomiting. Cannot detect hepatotoxicity on labs yet. Stage II (24-36 hours): Hepatotoxicity (defined as an AST>1000) can be detected at this time. Stage III (72-96 hours): Fulminant liver failure with abnormalities of liver function (i.e. prolonged PT, elevated bilirubin and lactate) that may result in death from sepsis, ARDS, hemorrhage, or multiorgan system failure. Stage IV (>5 days): Recovery phase for those who survive stage III, with full return of liver function within days to months. Laboratory Testing Serum acetaminophen levels (g/mL) should be drawn on presentation. It is important to determine the approximate time of ingestion. If the time of ingestion is <4 hours, a repeat level should be drawn after 4 hours to be able to use the Rumack-Matthew nomogram. If you do not know the time of ingestion, draw levels every 1-2 hours to try and find a peak level. A level of <10 g/mL within 4 hours of ingestion is not compatible with overdose. Liver function tests and complete chemistry panel

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Rumack-Matthew Nomogram Management If the patient presents within 1-2 hours of ingestion, activated charcoal 1 gm/kg (up to 100 gm) can be administered to prevent further absorption. Separate charcoal and N-acetylcysteine (NAC) doses by 1-2 hours, and if this is not possible, use IV NAC. Obtain a serum acetaminophen level (see above) and plot on Rumack-Matthew nomogram to determine if treatment with NAC is needed. Treatment is indicated if the acetaminophen level is above the bottom line. If the time of ingestion is unknown, treat any level >150 g/mL and consider treatment based on history. If toxic dose taken (7.5 grams), treat. When in doubt, always treat! N-acetylcysteine (NAC): Oral (Mucomyst) and IV (Acetadote) NAC are equally efficacious, with oral being the therapy of choice. Administer within 8-10 hours of ingestion for best prevention of liver toxicity. Use IV NAC in patients with fulminant liver failure, pregnancy, or recurrent vomiting. Dose the oral form as 140 mg/kg loading dose then 70 Adapted from Ann Emerg Med mg/kg every four hours for 17 doses total. 1991;20:1058. If vomiting occurs with 1 hour of dose, repeat the dose. Dose the IV form as 150 mg/kg loading dose over 15 minutes followed by 50 mg/kg infused over 4 hours then 100 mg/kg infused over 16 hours. Follow serum levels of liver enzymes and liver function and provide supportive care as needed (i.e. fresh frozen plasma).

SALICYLATE (ASPIRIN) OVERDOSE Salicylate Properties Acetylsalicylic acid (aspirin) and methylsalicylic acid (Oil of Wintergreen) are rapidly absorbed in the stomach and hydrolyzed to salicylic acid. The half-life varies on the concentration of salicylate in the body (i.e. at therapeutic concentrations the halflife is 2-4 hours, while at toxic concentrations, the half-life can be as high as 30 hours). Clinical Signs and Symptoms Signs: Fevers, tachypnea, convulsions, coma Symptoms: Nausea, vomiting, fatigue, restlessness Laboratory Testing A 6-hour salicylate level best correlates with toxicity, however this will not be accurate with enteric-coated or extended-release formulations. Mild toxicity = 30-60 mg/dL Moderate toxicity = 60-80 mg/dL

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Severe toxicity = >80 mg/dL The Done nomogram was evaluated in one study and found to have a predictive index of 0.42 (i.e. worse than chance) and therefore should not be used in guiding management. (Ann Emerg Med 1989;1811:11861190) Management It is important to first determine, if possible, the time, how much, and what type of aspirin (i.e. enteric-coated) was ingested. Gastric lavage should be considered in patients who have ingested salicylates within one hour of presentation or have ingested enteric-coated or extended-release pills. Activated charcoal 1 gm/kg (up to 100 gm) should be given to all patients. Toxicity may not correlate with amount ingested, especially in chronic users. Obtain basic labs, a serum salicylate level (preferably 6 hours after ingestion), and an ABG to determine pH. Determine the level of toxicity: Mild: salicylate level 30-60 mg/dL with nausea, vomiting, tinnitus, and fatigue. Rehydration. Moderate: salicylate level 60-80 mg/dL with restlessness, tachypnea, diaphoresis, hyperpyrexia, and dehydration. Rehydration + Urinary alkalization (1L D5W + 3 amps HCO3 over 3 hours) Monitor potassium levels closely and consider adding potassium to the maintenance fluids. Severe: salicylate level >80 mg/dL with coma, acute renal failure, pulmonary edema, convulsions, severe metabolic acidosis, and/or hypotension. Hemodialysis + urinary alkalinization. Continue to check salicylate levels every 2-3 hours or until peak. If the level continues to rise, give additional doses of activated charcoal 1 gm/kg (up to 100 gm). Continue to check urine pH hourly to maintain pH between 7.5-8.5. Adjust bicarbonate drip accordingly. Watch for hypokalemia!

TRICYCLIC ANTIDEPRESSANTS OVERDOSE Tricyclic Antidepressants (TCAs) Properties TCAs exert their effect by blocking the reuptake of serotonin and norepinephrine at the presynaptic membrane. PROPERTIES OF TRICYCLIC ANTIDEPRESSANTS Drug Name Brand Names Half-Life Amitriptyline Elavil 9-27 hours Nortriptyline Aventyl, Pamelor 28-31 hours Protriptyline Vivactil 54-92 hours Imipramine Tofranil 6-18 hours Desipramine Norpramin 7-60 hours Trimipramine Surmontil 16-40 hours Doxepin Adapin, Sinequan 6-8 hours Clomipramine Anafranil 20-30 hours

Clinical Signs and Symptoms Anticholinergic effects: Mydriasis, ileus, urinary retention, hyperthermia Cardiac effects: Hypotension, just about any arrhythmia (including torsades de pointes), AV block CNS effects: Seizures, coma, delirium, myoclonus

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Laboratory Testing TCA serum levels are not clinically useful (other than confirming that TCAs were ingested). Electrocardiographic findings suggesting severe toxicity: QRS duration > 100 ms aVR R-wave amplitude 3 mm Management Acute ingestions may benefit from NG lavage and activated charcoal administration. Inducing emesis may be dangerous as these patients tend to be at high risk for aspiration due to altered mental status and seizures. Obtain baseline labs, EKG, and ABG and place on a cardiac monitor. Consider mechanical ventilation if hypoxic or cannot protect airway. Hypotension: Use sodium bicarbonate 1-2 mEq/kg IV Q3-5 minutes for goal pH 7.45-7.55 first, then use norepinephrine. Arrhythmias: Use sodium bicarbonate first, then use lidocaine and magnesium (avoid class Ia and Ic drugs as they worsen cardiotoxicity, and class III drugs as they prolong the QT interval). Seizures: IV lorazepam 2 mg IV every 5 minutes OR IV diazepam 10-20 mg IV every 5 minutes to stop the seizures, then can place on midazolam or propofol drip if needed.

CARBON MONOXIDE INTOXICATION Carbon Monoxide (CO) Properties CO is an odorless, colorless gas that is the leading cause of poison-related deaths in the US. Half-life of 5 hours on room air ( to 1 hour on 100% FiO2). Binds to hemoglobin with a much higher affinity than oxygen resulting in carboxyhemoglobin reducing the amount of oxygen available to tissues. Decreases oxygen delivery to tissues via a left shift of the oxygen dissociation curve. Causes direct cellular toxicity, interfering with myoglobin, cytochromes, and guanylate cyclase. It also NO activity resulting in oxidative damage from free radicals. Clinical Signs and Symptoms Signs: Dyspnea/tachypnea, tachycardia, arrhythmias, hypotension, seizure, coma, noncardiogenic pulmonary edema Symptoms: Nausea, vomiting, headache, lightheadedness, confusion, weakness, chest pain Delayed effects may result in neurologic deterioration up to 40 days post-intoxication. Laboratory Testing Carboxyhemoglobin Nonsmokers = 1-2% Smokers = 5-10% Mild toxicity = 15-20% Intermediate toxicity = 20-60% (level does not correlate with symptoms or prognosis) Fatal = >60% Management Obtain baseline labs and a carboxyhemoglobin level from either an ABG or VBG. Start high-flow oxygen therapy (nonrebreather face mask with 15 LPM) and consider intubation and mechanical ventilation to provide 100% FiO2. Correct hypoglycemia and hypotension. Consider hyperbaric oxygen administration (usually at 2.5 ATM) in patients who have:

TOXICOLOGY Carboxyhemoglobin > 25% CNS manifestations (seizures, coma, altered mental status, abnormal neurologic exam, syncope) Cardiovascular dysfunction Severe metabolic acidosis Pregnancy

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DIGOXIN TOXICITY Digoxin Properties Digoxin is used in patients with heart failure to improve contractility via an intracellular calcium and in patients with SVT via direct suppression of the AV node. Onset of action is 1-2 hours (oral) or 5-30 minutes (IV). Half-life (in adults) is 38-48 hours (prolonged in renal insufficiency). Clinical Signs and Symptoms Acute intoxication: nausea, vomiting, lethargy, weakness, abdominal pain. Chronic intoxication: GI (nausea, vomiting, abdominal pain, anorexia), CNS (lethargy, hallucinations, delirium), and visual (blurring, photophobia, scotomata) Laboratory Testing Therapeutic serum concentrations: CHF: 0.5-0.8 ng/mL SVT: 0.8-2 ng/mL Toxic serum concentration is >2.5 ng/mL. Hyperkalemia (with levels higher than 5.5 mEq/L very worrisome for morbidity/mortality). Changes on electrocardiogram may include: Ectopic ventricular rhythm (i.e. PVCs) AV junctional block Enhanced automaticity Prolongation of PR interval AV dissociation Bidirectional ventricular tachycardia (i.e. a wide QRS with an alternating axis) is pathognomonic Management Obtain basic labs including a chemistry panel and digoxin level. Place on a cardiac monitor and obtain an electrocardiogram. Determine if the patient needs digoxin-immune Fab fragments, and if so, consult your pharmacist to determine dosing. #vials of digibind = [dig level (ng/ml) x weight (kg)]/100 and give over 15-30 min. Reasons to give antidote: Digoxin level 15 ng/mL (or 10 ng/mL 6-hours post ingestion) Potassium level > 5 mEq/L Severe clinical signs/symptoms Life-threatening arrhythmia Things to look out for: Hypokalemia following administration (make sure potassium is corrected before giving) Return of SVT (i.e. atrial fibrillation with rapid ventricular response) CHF Other management considerations: Symptomatic bradyarrhythmias: Atropine 0.5 mg IV. Symptomatic tachyarrhythmias: Phenytoin (either as a drip at 50 mg/min or in 100 mg boluses Q5 minutes, maximum dose of 1 gm) or lidocaine (1-1.5 mg/kg IV bolus followed by a drip at 1-4 mg/min).

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Hyperkalemia: Use insulin + dextrose and bicarbonate. Avoid calcium! GI Absorption: Cholestyramine 4 gm PO Q4 hours and/or activated charcoal 1 gm/kg (up to 100 gm) Q24 hours may half-life as digoxin is enterohepatically recirculated.

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PERIOPERATIVE MANAGEMENT Preoperative Cardiac clearance for noncardiac surgery (see Cardiology section page 60) Discontinue aspirin, nonsteroidal anti-inflammatories, and clopidogrel 1 week prior to the surgery, if possible. Typically, patients are NPO. It is usually okay for patients to have AM medications with small sips of water, especially -blockers. For diabetic patients, discontinue all oral hypoglycemics the night prior to surgery, start D5 NS or NS, and half the insulin dose in the morning. Postoperative It is important that postoperative patients that are sent back to the medicine wards are seen immediately. If you have a patient that is undergoing surgery and is not back by the time you leave, make sure to signout a postoperative check to the medicine float. Review: Operative note, blood loss, fluid balance, complications Antibiotic orders (both prior antibiotics and prophylactic antibiotics for the surgery) Any postoperative EKGs (for high-risk patients), labs, radiography Prophylaxis: Know when to begin DVT prophylaxis, especially after hip or knee surgery Aspiration precautions Remove Foley catheter within 24 hours of the surgery, if possible Early mobilization (call for physical therapy evaluation) Incentive spirometer every hour while awake to prevent atelectasis and postoperative pneumonia Nutrition: Know when the diet can be advanced, usually start with clear liquid diet Consider nutrition consultation, enteral feeding, supplements Pain control options: Patient-controlled analgesia (PCA) Standing IV or PO analgesia Symptom-triggered IV or PO analgesia See http://www.anes.ucla.edu/pain for more discussion about the choices of pain medications, setting the PCA, and how to assess pain. PAIN MEDICATION CONVERSIONS To convert from one pain medicine to another, use the following formula:

Reference value drug B Desired 24 hr dose of drug B = ( Current 24 hr dose of drug A ) (1- Cross-tolerance ( % ) ) Re ference value drug A The cross-tolerance % accounts for tolerance to a particular narcotic that the patient will not have with a different narcotic. For example, if a patient is on 100 mg of IV morphine per day, converting that to oxycodone would give you 200 mg of oxycodone per day. The patient has developed some tolerance to morphine, but not to oxycodone, so the 200 mg of oxycodone may act like 250 mg. Therefore, choose a cross-tolerance of at least 25%, which in our example would give a daily oxycodone dose of 150 mg. You can always titrate up!

MISCELLANEOUS
NARCOTIC EQUIVALENTS Analgesic Oral Dose (mg) Meperidine (Demerol) 150 100 Codeine (Tylenol #3 3) Hydrocodone 15 (Vicodin 3, Lortab 3) Morphine (MSIR, Roxanol) 15 Oxycodone 10 (Percodan 2, Percocet 2, Tylox 2) Methadone (Dolophine) 10 Hydromorphone (Dilaudid) 4 Levorphanol (Levo-Dromoran) 2 Fentanyl N/A

259

Parenteral Dose (mg) 50 60 N/A

5 N/A 5 0.75 1 0.05

General conversion from oral morphine to a fentanyl patch is: Morphine 45-134 mg/day = Fentanyl patch 25 g/hr Morphine 135-224 mg/day = Fentanyl patch 50 g/hr Morphine 225-314 mg/day = Fentanyl patch 75 g/hr Morphine 315-404 mg/day = Fentanyl patch 100 g/hr

STEROID CONVERSIONS STEROID EQUIVALENTS Steroid Dose (mg) Cortisone 25 Hydrocortisone 20 Prednisone 5 Prednisolone 5 Methylprednisolone (Solu-Medrol) 4 Dexamethasone (Decadron) 0.75 GASTRIC TUBES Compared with parenteral nutrition, it is the preferred delivery method of nutrition and medications because it uses the GI tract, has less infectious complications, and is more cost effective. Indications Dysphagia in a patient with intact mental status Head and neck cancer patients Gastric decompression Remember that feeding tubes have never been shown to improve either quality or length of life in severe dementia patients and can create new problems. Feeding tubes have also not been shown to be effective in preventing aspiration. Management Usually placed by Gastroenterology or Interventional Radiology, but can be done surgically in some situations. Check platelets, PT, and PTT prior to procedure. After placement, tube should not be used for 24 hours due to frequent ileus

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If there is low drainage (< 500 cc/24 hours), start feeding at 20 cc/hr and check residuals after 4 hours If the residuals are < 2 the rate (40 cc), then continue feedings and advance by 20 cc/hr until the goal feeding rate is met (usually determined by a nutrition consult) as long as residuals remain low. G-J tubes have 2 ports that allow simultaneous jejunal feeding & gastric drainage; indicated with gastric dysmotility or obstruction. For G-J tubes: medications ONLY go through the G-port and feedings generally go through the J-port Complications Infection: look for erythema, tenderness, and increased discharge at entry site Increased residual: consider ileushold feeds for 1-2 hours and recheck residual. If low, restart at previous or reduced rate, if prolonged consider intraperitoneal spilling Clogged tube: irrigate with warm water or carbonated beverage. If unsuccessful call IR to clear with guidewire or brush Tube accidentally removed: usually prevented by balloon or bumper. A sinus tract forms after a tube has been in place for > 1 week allowing for easy replacement at bedside. Ask the nurse to put a Foley in to keep the tract open Leakage of gastric contents: if causing irritation to skin, frequent dressing changes or ask for Ostomy Nurse consult. If leakage continues for > 2 days, have IR evaluate with contrast study. Intraperitoneal spilling can be a serious problem and may warrant a surgical consult (also consider this with a prolonged ileus) Aspiration: tube feeds have not been shown to prevent aspiration pneumonia and some studies have shown risk with tube feeds. Always use strict aspiration precautions and dental care t.i.d. Diarrhea: usually not due to tube feeding, so consider other causes like C. difficile.

PREMEDICATION FOR CONTRAST ALLERGY Carefully elicit allergy historyif allergic reaction severe, consider alternate study If reaction is rash alone, give Benadryl 50 mg IV 1 on call to scan. If reaction is unknown or more severe (but not anaphylaxis), give prednisone 50 mg p.o. q12hrs 3 doses or Solu-Medrol 40 mg IV q12hrs 3 doses prior to the study in addition to Benadryl 50 mg IV 1 on call to scan QUALIFYING FOR HOME OXYGEN Medicare will cover home oxygen only for patients with chronic, stable significant hypoxemia if the following conditions are met: Physician determines patient suffers from severe lung disease or hypoxia-related symptoms that may improve with oxygen. Patients arterial blood gas indicates a need for oxygen: PaO2 < 55 mmHg or O2sat < 88% at rest PaO2 56-59 mmHg or O2sat 89% AND dependent edema suggesting CHF OR pulmonary hypertension/cor pulmonale (measured PA pressure, echocardiogram, P pulmonale on EKGP wave > 3 mm in leads II, III, or aVF) Nocturnal oxygen therapy only if: PaO2 < 55 mmHg or O2sat < 88% while asleep AND PaO2 > 56 mmHg or O2sat > 89% while awake PaO2 > 10 mmHg or O2sat > 5% from waking to sleeping AND EKG shows P pulmonale or patient has documented pulmonary HTN and erythrocytosis Exercise oxygen therapy only if: PaO2 < 55 mmHg or O2sat < 88% during activity for a patient with PaO2 > 56 mmHg or O2sat > 89% during the day at rest, and it is documented that use of oxygen improves hypoxemia with exercise. Alternative treatment measures have been tried or considered and have failed

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Sample order (written on prescription): Home oxygen at 4 L/min by nasal canula. Patient with documented hypoxia to 85% during activity, improving to 92% with 4L nasal cannula oxygen.

VACCINATIONS This is a quick guide, not meant to be comprehensive. Please see the CDC website for more information and recommendations, particularly for international travelers. Vaccine Pneumovax Who >65, Q5 yrs Chronic disease*, aplenia, alcoholism >50, Q1 year Chronic disease* Nursing home resident Q10 years OK in pregnancy What Polyvalent 23 capsular polysaccharide antigens Inactivated virus Contraindication Pregnancy

Influenza (Oct-Nov)

Prior Guillain-Barre from flu shot

Tetanus-diphteria (Td)

Tetanus-diphteriapertussis (Tdap)

Measles-MumpsRubella (MMR)

Varicella

Once as adultalternative to Td as gives protection for pertussis as well Persons born 1957 ot later, consider in immigrants with no history. Health care workers, international travelers may need 2nd dose All adults who are not immune (can ask history or check titers if unsure) Age >60 years One time dose

Tetanus and diphteria toxoids Primary series 0, 1, 6 months then Q10 year booster Tetanus and diphteria toxoids

Td preferred over Tdap in pregnancy

Severe latex allergy Epilepsy Prior coma or seizure with DTaP as child Pregnancy or possible pregnancy within 3 months Immunocompromised Recipients of blood products or immune globulin in past 11 months

Live attenuated virus

Live attenuated virus Two doses 4-8 weeks apart Live attenuated

Zostavax

Pregnancy or possible pregnancy within one month Immunocompromised, active untreated TB, received blood products in last 6 months, lymphoma/leukemia Immunodeficiency, lives with patient who is immunocompromised, pregnant, active tuberculosis, high dose steroids, anaphylactic rxns to gelatin, neomycin or components of vaccine

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Who What Contraindication Currently Inactivated virus Pregnancy recommended for Three doses at 0, girls age 11-12. 2, 6 months Catchup vaccine for girls 13-26 Meningococcal Dose at high Polysaccharide Unclear in pregnancy school entry, vaccine Prior Guillain-Barre dormatory living, Conjugate vaccine military recruits, (preferred) aplenia, exposure, international travel Hepatitis A Liver disease**, Inactivated virus Unclear in pregnancy IVDU, MSM Two shots 6-12 Planned travel months apart outside US Hepatitis B Liver disease**, Recombinant IVDU, MSM, STD DNA risk factors, Three doses at 0, healthcare 1, 6 months worker, renal disease, prison inmate, internation travel, household contact *Diabetes, COPD, heart dz, kidney dz, sickle cell, HIV, cancer, pregnancy, steriod use, lives w/ at risk person **Chronic liver disease, HCV, HBV, clotting disorder Anaphylaxis to vaccine or components is contraindication to any vaccine

HPV

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Ventricular Fibrillation Unstable (Pulseless) Ventricular Tachycardia

Use For Every Shock: Monophasic: 360J Biphasic: 200J

Shock

5 cycles of CPR (1 cycle = 30 compressions and 2 breaths)

Note that once an airway is secured, proceed with continuous compressions at 100/min with 8-10 breaths/min

Check Rhythm and Pulse

Pulse Present

VF/Unstable VT (shockable)

Asystole/PEA (not shockable)

Postresuscitation Care

Shock

See Asystole/PEA Algorithm

Give Vasopressors During CPR: Epinephrine 1mg IV Q3-5min OR Vasopressin 40U IV

5 cycles of CPR (1 cycle = 30 compressions and 2 breaths) Consider Antiarrhythmics During CPR: Amiodarone 300mg IV x1 then 150mg IV x1 OR Lidocaine 1-1.5mg/kg IV x1 then 0.5-0.75mg/kg IV until a maximum of 3 doses or 3mg/kg Consider Magnesium During CPR: 1-2gm IV for torsades de pointes

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Asystole Pulseless Electrical Activity (PEA)

Note that once an airway is secured, proceed with continuous compressions at 100/min with 8-10 breaths/min

5 cycles of CPR (1 cycle = 30 compressions and 2 breaths)

Give Vasopressors During CPR: Epinephrine 1mg IV Q3-5min OR Vasopressin 40U IV Consider Atropine 1mg IV Q3-5min x3 for slow PEA rate or asystole

Check Rhythm and Pulse

Pulse Present

VF/Unstable VT (shockable)

Asystole/PEA (not shockable)

Postresuscitation Care

See VF/Unstable VT Algorithm

Think About Treatable Factors: Hypovolemia Hypoxia Hydrogen ion (acidosis) Hypo/hyperkalemia Hypoglycemia Hypothermia Toxins Tamponade Tension pneumothorax Thrombosis Trauma

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ACLS ALGORITHMS
Tachycardia (With Pulses)

267

Assess Patient (ABCs, telemetry, supplemental oxygen)

BP okay? Respiratory status okay? Mentating okay?

HR usually >150bpm

Yes

No

Narrow Complex (QRS <120ms)

Wide Complex (QRS >120ms) Perform Synchronized DC Cardioversion 1. Have suction, IV access, and intubation equipment at bedside 2. Premedicate when possible with a sedative an analgesic 3. Shock at 100J, 200J, 300J, then 360J for monophasic machines (or clinically equivalent doses for biphasic machines) *note that you may have to select synchronize after each shock

See Narrow Complex SVT Algorithm

See Wide Complex Tachycardia Algorithm

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Narrow Complex SVT (QRS<120 ms) Known pre-excitation: Avoid AV nodal blocking agents to prevent rapid conduction down accessory pathway

Irregular

Regular Have EKG Running!

AF MAT

AFL or AT with variable conduction

Vagal Maneuvers Adenosine (6mg rapid IV push, then 12mg rapid IV push x2)

No change in rate

Gradual rate then

Persistent AT with transient high-grade AVB

Termination

Inadequate Dose/Delivery VT

ST AT NPJT

AFT AT

AVNRT OAVRT SANRT AT

Rate control with -blockers or CCB

Treat recurrence with adenosine or longer acting agents (i.e. -blockers or CCB)

Abbreviations AAVRT = antidromic atrioventricular reciprocating tachycardia OAVRT = orthodromic atrioventricular reciprocating tachycardia ST = sinus tachycardia NPJT = Nonparoxysmal junctional tachycardia SANRT = SA node reentrant tachycardia SVT = supraventricular tachycardia AF = atrial fibrillation AFL = atrial flutter AT = atrial tachycardia MAT = multifocal atrial tachycardia BBB = bundle branch block

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NOTES

270

PROCEDURE REQUIREMENTS (OFFICIAL RECORD KEEPER IS MYRT YAMAMOTO) Procedure Medical Record Number Date Resident Central Venous 1. Catheter 2.

Attending

3. 4. 5.
Paracentesis

1. 2. 3.

Thoracentesis (or Chest Tube)

1. 2. 3. 4. 5.

Arterial Blood Gas (or Arterial Lines)

1. 2. 3. 4. 5.

Nasogastric Tube Lumbar Puncture

1. 2. 3. 1. 2. 3. 4. 5.

Major Joint Aspiration (or Injection)

1. 2. 3.

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