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Clinical Review & Education

JAMA | Review

Delirium in Older Persons
Advances in Diagnosis and Treatment
Esther S. Oh, MD, PhD; Tamara G. Fong, MD, PhD; Tammy T. Hshieh, MD, MPH; Sharon K. Inouye, MD, MPH

Author Audio Interview
IMPORTANCE Delirium is defined as an acute disorder of attention and cognition. It is a Supplemental content
common, serious, and often fatal condition among older patients. Although often
CME Quiz at
underrecognized, delirium has serious adverse effects on the individual’s function and quality
of life, as well as broad societal effects with substantial health care costs.

OBJECTIVE To summarize the current state of the art in diagnosis and treatment of delirium
and to highlight critical areas for future research to advance the field.

Author Affiliations: Department of
EVIDENCE REVIEW Search of Ovid MEDLINE, Embase, and the Cochrane Library for the past 6
Medicine, Johns Hopkins University
years, from January 1, 2011, until March 16, 2017, using a combination of controlled vocabulary School of Medicine, Baltimore,
and keyword terms. Since delirium is more prevalent in older adults, the focus was on studies Maryland (Oh); Department of
in elderly populations; studies based solely in the intensive care unit (ICU) and Psychiatry and Behavioral Sciences,
Johns Hopkins University School of
non–English-language articles were excluded. Medicine, Baltimore, Maryland (Oh);
Department of Pathology, Johns
FINDINGS Of 127 articles included, 25 were clinical trials, 42 cohort studies, 5 systematic reviews Hopkins University School of
Medicine, Baltimore, Maryland (Oh);
and meta-analyses, and 55 were other categories. A total of 11 616 patients were represented in
Department of Neurology, Beth Israel
the treatment studies. Advances in diagnosis have included the development of brief screening Deaconess Medical Center, Harvard
tools with high sensitivity and specificity, such as the 3-Minute Diagnostic Assessment; 4 A’s Test; Medical School, Boston,
and proxy-based measures such as the Family Confusion Assessment Method. Measures of Massachusetts (Fong); Aging Brain
Center, Hebrew SeniorLife, Boston,
severity, such as the Confusion Assessment Method–Severity Score, can aid in monitoring
Massachusetts (Fong, Inouye);
response to treatment, risk stratification, and assessing prognosis. Nonpharmacologic Division of Aging, Department of
approaches focused on risk factors such as immobility, functional decline, visual or hearing Medicine, Brigham and Women’s
impairment, dehydration, and sleep deprivation are effective for delirium prevention and also are Hospital, Harvard Medical School,
Boston, Massachusetts (Hshieh);
recommended for delirium treatment. Current recommendations for pharmacologic treatment Department of Medicine, Beth Israel
of delirium, based on recent reviews of the evidence, recommend reserving use of Deaconess Medical Center, Harvard
antipsychotics and other sedating medications for treatment of severe agitation that poses risk Medical School, Boston,
Massachusetts (Inouye).
to patient or staff safety or threatens interruption of essential medical therapies.
Corresponding Author: Esther S.
Oh, MD, PhD, Division of Geriatric
CONCLUSIONS AND RELEVANCE Advances in diagnosis can improve recognition and risk Medicine and Gerontology,
stratification of delirium. Prevention of delirium using nonpharmacologic approaches is Johns Hopkins University School of
documented to be effective, while pharmacologic prevention and treatment of delirium Medicine, 5200 Eastern Ave,
Seventh Floor, Baltimore, MD 21224
remains controversial.
Section Editors: Edward Livingston,
JAMA. 2017;318(12):1161-1174. doi:10.1001/jama.2017.12067 MD, Deputy Editor, and Mary McGrae
McDermott, MD, Senior Editor.

elirium, defined as an acute disorder of attention and cog- Delirium remains underrecognized, and rates of identification
nition, is a common, life-threatening, and often prevent- have not improved significantly over time. Rates of unrecognized
able clinical syndrome in older persons. Often occurring delirium, defined as delirium diagnosed by an expert assessor
after acute illness, surgery, or hospitalization, the development of after the diagnosis was not made by the patient’s treating physi-
delirium initiates a cascade of events culminating in loss of indepen- cians and nurses, ranged from 55% to 70% in 2000-20012,3 and
dence, increased morbidity and mortality, institutionalization, and still remain around 60% in 2015.4 Delirium is a complex and chal-
high health care costs. In the United States, more than 2.6 million lenging condition, and a synthesis of current evidence should
adults 65 years and older each year develop delirium and account optimize clinical care. The goals of this review were (1) to summa-
for an estimated more than $164 billion in annual health care rize the current approaches to diagnosis and treatment of
expenditures.1 Given its adverse effect on function and quality of life, delirium, (2) to highlight recent advances, and (3) to underscore
delirium holds significant societal implications for the individual, fam- critical gaps in knowledge where future research is needed to
ily, community, and the entire health care system. advance the field. (Reprinted) JAMA September 26, 2017 Volume 318, Number 12 1161

© 2017 American Medical Association. All rights reserved.

Downloaded From: by a Hospital Pablo Tobon Uribe User on 09/28/2017

gained widespread acceptance as the most effective strategy for fection. 2017. precipitating factors (eg. all patients presenting with delirium need rapid. cycle. cognitive changes (typically over months for dementia). plus tends to occur in later stages of dementia. lum. Number 12 (Reprinted) jama. such as hepatic or ure- Methods mic encephalopathy. tal status change (such as vasculitis or herpes encephalitis) must line mental status and the acuity of any changes. Because delirium can signify an acute Primary prevention of delirium with nonpharmacologic multi- medical by a Hospital Pablo Tobon Uribe User on 09/28/2017 . signs suspicious for meningitis 14 or cations and mortality. through March 16. and emotional lability. and the condition is easily Key Points overlooked. inattention. sion. however.22 While many pharmacologic approaches have been evalu- on information obtained from the history and physical examination.8 include an acute onset and fluctuating course outweigh the harms. It is important not son for a missed diagnosis.9. Delirium and dementia commonly coexist. the benefits do not Method (CAM). knowledge of the patient’s baseline is essential to make tionnaire on Cognitive Decline of the Elderly. multiple comorbidities). since the acute change might otherwise only to distinguish between delirium and dementia diagnostically be missed. Examination of cerebrospinal fluid is not required for most Concepts were created for the topics of (1) delirium or confusion.21 searching for possible causes. and psychosis (Table 1). The presence of depres- ture unique to delirium that is less common with dementia. hallucinations or mispercep- tions). memory impairment.16 Neglecting the baseline mental status assessment is a leading rea. Once the baseline mental status is determined.10 encephalitis. family. and is associated with higher rates of compli. in.19 and death.17 Conditions that may mimic delirium include dementia. 2011. at present there is no convincing. inappropriate or unsafe behavior. disorientation. derived nonpharmacologic multicomponent strategies is effective.6 Key diagnostic features.23 cognitive impairment.7 Delirium includes both hypoactive and hyperactive forms. inattention. which has important prognostic implications. Some con- ditions presenting with symptoms of delirium. and recommendations are to reserve treatment for patients with severe agitation that poses of symptoms. infections. from the DSM-5 and the widely used Confusion Assessment For pharmacologic management of delirium. prevention or treatment of delirium. institutionalization. This step is critical and ogy of delirium if the history suggests recent falls or examination requires obtaining the history from a knowledgeable informant. while common in delirium.20 can help establish the diagnosis. such as the Informant Ques- diagnosis. drugs). alcohol withdrawal de- lirium (delirium tremens). or both. The current reference management of delirium in older adults have been introduced standard diagnostic criteria are the Diagnostic and Statistical Manual in the last 6 years? of Mental Disorders (Fifth Edition) (DSM-5) from the American Psy- Findings Brief screening tools and improved delirium severity chiatric Association5 and the International Statistical Classification measurement tools have been developed for recognition of Diseases and Related Health Problems. The hypoactive form is more common among older persons. The specific selection of tests should be based delirium. Neuroimaging can be useful in identifying the etiol- changes typically occur over hours to days. an acute change Interview with a caregiver for baseline mental status. includ- Mini-Cog11 or the Short Portable Mental Status Questionnaire12 and ing accelerated rate of cognitive and functional decline. (3) randomized trials 1162 JAMA September 26. prior diagno- in mental status from baseline may distinguish delirium from other sis of mild cognitive impairment or dementia. and time course of conditions. reproduc- keeping in mind that delirium is often multifactorial in etiology and ible evidence that any of these treatments are effective for either can be influenced by a number of predisposing factors (eg. perceptual disturbances (eg. Embase. Search was conducted in Ovid MEDLINE. Depression Scale. ated in clinical trials. acute drug intoxication. safety risks.17 increased rating with a validated delirium instrument. using brief depression screening tools such as the Geriatric The next step is a careful physical and neurologic examination. using a combination of controlled vocabulary and keyword terms. with delirium. Alteration in the level of consciousness is another fea. reveals deteriorating mental status or focal neurologic findings. prevention. ing with fever. and the have specific treatments (eg. depres. the presence of an underlying dementia. and careful bedside observation of key features. (2) diagnosis or prevention or therapy. or Wernicke-Korsakoff syndrome (WKS). thiamine supplementation for WKS) and Cochrane Library from January 1. improve recognition and risk stratification. the be excluded. and disturbance of cognition indicating disorganization of thought (eg. For accurate differential administration of proxy-rated tools. older patients presenting with delirium and fever.1.19 compared with dementia alone. therefore should not be overlooked in the evaluation. sion should also be ruled out in the interview with the patient and sion. metabolic derangement.18 and higher rates of rehospitalization. 2017 Volume 318. Tenth Revision from the and risk stratification of delirium. or psychosis. depres. Delirium prevention with World Health Organization. or organ failure. or alteration in language) Meaning Advances in screening and diagnosis of delirium can (CAM algorithm in eFigure 2 in the Supplement). As described above.15 or when a specific neurologic cause of acute men- The cornerstone of diagnosis is determining the patient’s base. Furthermore. impaired level of consciousness. All rights reserved. Clinical Review & Education Review Advances in Diagnosis and Treatment of Delirium Current Approach to Diagnosis and Treatment of Delirium Delirium remains a clinical diagnosis.7. often bar puncture 13 should be strongly considered in patients present- goes unrecognized. older age. delusions. while implementation of nonpharmacologic delirium prevention strategies can portive of the delirium diagnosis include alterations in sleep-wake substantially improve outcomes among older patients. delirium but also to recognize when delirium is superimposed on a preexist- is diagnosed by using brief cognitive screening tests such as the ing © 2017 American Medical Association. component approaches has been shown to be effective and has targeted evaluation for electrolyte or metabolic derangements. Other features sup. headache. Downloaded From: http://jamanetwork. length of hospital stay.1 Recognition is based on brief cognitive screening and Question What advances in diagnosis.

ness. ICU 6 years. (using the Cochrane highly sensitive search strategy for identify. sensitivity. and Short CAM has been more recently adapted and validated across a these sections highlight key advances in diagnosis during the past large range of patient populations.8. clinical guidelines. For instance. and palliative care. lence of decreased mental status in the population. suggestive of cognitive impairment for which more detailed cogni- article quality was rated with the Cochrane Collaboration tool for tive testing is advised. Advances in Diagnosis and Treatment of Delirium Review Clinical Review & Education Table 1. and 10 observational items) that facili- search flow diagram are provided in eAppendix 1 and eFigure 1 in tates rating of the 4 core CAM features and demonstrated a sensi- the Supplement. the following new information has become available. and psy- original published studies to date and translated into 19 languages.40 Other screening tools with more recent validation studies Screening Instruments include the Nursing Delirium Symptom checklist (Nu-DESC). 2008 revision). The presence analyses. 2017 Volume 318. sedation. the mRASS has a low sensitivity of 64% to of which have been developed in the past 6 years (Table 2). of which 25 were clinical trials. overweighting of hyperactive or agitation symptoms and the risk of tion. specificity.28 Another screening tool is the 4A’s Test the current review and has been examined in comprehensive (4AT).40 The Since 2011. with memory. The 3-Minute Diagnostic Assessment (3D-CAM) cohort studies. The complete list of search strategies and a items. and (90%-95%). used in more than 4500 inappropriate communication. nursing home. 3 symptom probes. level of consciousness. One hundred twenty-seven conversations).com (Reprinted) JAMA September 26. drowsiness. Downloaded From: http://jamanetwork. Clinical Features of Diseases That Mimic Delirium Conditiona Feature Delirium Dementia Depression Psychosis Acute change in mental status + − − ± Inattention + ± ± ± Altered consciousness + − − − Disorganized thinking + ± − + Altered psychomotor activity + ± + + a “±” indicates that the feature may Chronic duration ± + + ± be present. and biomarker studies that were not also required. 4 attention treatment studies. or language. These 70%. ing and neurologic examination for fulfillment of key diagnostic We identified 2303 titles and abstracts from the electronic search features. Since screening tools have varying sensitivity and ing randomized trials in MEDLINE. All rights reserved. many delirium.25 In addition.and precision. 5 were systematic reviews and meta.92).27 More recently. however. search was limited to articles published in English.30 Both 3D-CAM and 4AT validation studies assessing risk of bias. sible delirium.30 reviews. inattention (reduced ability to sustain attention and follow were retrieved for manual review. Two hundred fifty-four full-text articles day. has been advocated as a screening tool for more than 20 delirium screening tools have been introduced. which The CAM. The Modified Richmond Agitation and consciousness7) and has high sensitivity (94%-100%).1%.26 have high ratings by the Standards for Reporting of Diagnostic Accuracy criteria. and 55 were other categories including methodological of an underlying organic etiology or multiple etiologies is papers. The checklist has sensitivity of 72% and The CAM algorithm is based on the presence of 4 core features of specificity of 80%41. disorganization of thought. we focused on studies in populations 65 years and older. and interrater reliability (κ = 0. including medical. The investigation for more definitive diagnosis of delirium. and either disorganized thinking or altered level of missing hypoactive delirium. which has been validated in various clinical settings. In addition to Definitive diagnosis of delirium should be conducted by randomized trials. a positive screening test result should lead to further maximizing version. and (4) elderly adults. since this setting was considered outside the scope of in hospitalized patients. Number 12 1163 © 2017 American Medical Association. inappropriate behavior. For 89.24. which measures arousal. chomotor retardation. continues to be the most widely includes assessment of disorientation. such as hypervigilance. In settings with jama. The 4AT provides a score range selected studies on pharmacologic prevention and by a Hospital Pablo Tobon Uribe User on 09/28/2017 . surgical. A total of 11 616 patients were represented in the provides a brief assessment (3 orientation items.43 and the usefulness of the scale depends on the preva- screening tools are used to alert clinicians to the presence of pos.39 In recent years. (CAM-ICU). However. tivity of 95% and specificity of 94% when compared with a clini- Studies based solely in the intensive care unit (ICU) were cal reference standard rating in a prospective validation study excluded. illusions or hallucinations. including disturbance in mental status that represents and also found an additional 37 eligible articles from the reference a change from baseline and fluctuates in severity during the lists of relevant studies. such as problems articles were used for this review. and impaired conscious- 42 were cohort studies. emergency department. specificity Sedation Scale (mRASS). inatten.7% and specificity of 84. many well-established delirium screening tools have been adapted or used in various clinical and research applica- Results tions. or stupor. since delirium is more prevalent in older This tool is also brief and easy to administer and has a sensitivity of adults. used delirium instrument worldwide. orientation.42. experienced clinician and would entail cognitive test- to find other types of studies (eAppendix 1 in the Supplement). limitations include the potential for delirium (acute onset and fluctuating course of symptoms.7 published in 1990. the CAM7 is often used as a reference standard Clinical Diagnosis in studies of more newly developed delirium screening tools. the overall search strategy was also designed a trained.

MOTYB.8) 7 s (average) Maximum score = 3. not applicable. then the rest of the PQI in that section and caregivers and geriatric psychiatrist ranged from 44% to 84% in agreement. kConstruction cohort N = 88.0) (11 CQI) thinking OR (4) altered level of consciousness I-AGeD33 Hospital 88 (27)k 86.9) κ = 0. FAM-CAM.4l 63.65-0. %b (95% CI) Question Items) 3D-CAM28 Hospital 201 (38) 84 (5. 10 (IQR. 4 A’s Test. 3D-CAM.34-0.1) 69 (27) NR Possible delirium if the patient failed MOTYB 93.Downloaded From: http://jamanetwork. 2017 Volume 318. gInformation available at http://www. 2 ORI) 4AT30. 3-Minute Diagnostic Assessment.5 90 64. observer rating items.8 (7.4) 3 min Possible delirium if (1) acute onset or fluctuation 95 (96) 94 (86) 95% Screening tool derived (median) AND (2) inattention AND EITHER (3) disorganized from the CAM thinking OR (4) altered level of consciousness (10 PQI.7 (71.4 (8.m Hospital 239 (49) 82 (6. y Assessment Time Scoring Impaired). it will not yield a delirium diagnosis but only quantify the intensity of delirium.4) 67 (42.5) 84.the4at. Sensitivity of 2 validation cohorts ranged from 70.9) <2 min Maximum score = 12. or N = 59 and N = 33. therefore. NR Short form. ICC = 0. comparison of agreement between if any item in a section is answered incorrectly or endorsed as yes. Months was validated in 2 different cohorts. 1 CQI. RADAR.5) NR Maximum score = 10. bSensitivity and specificity of the screening tool to detect delirium against 100%. nComparison of agreement between cognitive impairment. mDelirium screening tool consists of 4 observational delirium items from the Inter-RAI acute care the gold standard such the Diagnostic and Statistical Manual of Mental Disorders criteria.9%. Informant Assessment of Geriatric Delirium scale.65-1. Inter-Resident Assessment original CAM algorithm.0% to 88. %b Impaired). Recognizing Acute Delirium as Part of Your Routine. of Screening Tool Setting No. fCAM-S is a tool to quantify the intensity of delirium. ICC. possible delirium when score >4 77. 193 (40) 80. not reported. Delirium assessment 10-15 min. 7 (short form) NAf NA Long form. possible delirium when score ≥1 73 (71. iAll patients enrolled in the study had preexisting a Inclusion criteria: (1) study published during the defined search period. Inter-RAI. patient Recovery sample.2%. 2 ORI) © 2017 American Medical Association. specificity ranged from 66. Simple Query for Easy delirium screening tool does not apply. and easily distracted. episode of disorganized speech. CAM-Severity .76 Screening tool and (2) mental function varies over the course of the day for acute care (4 ORI) MOTYB + signs Hospital 265 (51. criteria: (1) study of delirium in the critically ill (intensive care unit). 2 validation cohorts of assessment was completed using Diagnostic and Statistical Manual of Mental Disorders (DSM) IV or 5. median. DelApp31 Hospital 156 85 (delirium group <5 min Maximum score = 10.4) NR Screening tool for acute care of confusion35 or was confused (subjectively or objectively) (2 PQI. caregiver questionnaire 3D-CAM was validated with administration of all items. Maximum score = 18. 6 (IQR. Number 12 (Reprinted) Clinical Review & Education Review Table 2.7% to of an existing delirium screening tool.d Hospital 1219 (41) 77-80e Long form. and those numbers are reported in parentheses. Characteristics of Delirium Screening Tools (Last 6 Years)a Sensitivity Specificity Interrater Description (Cognitively (Cognitively Reliability (No. mean age was 77 years in the SAGES Study and 80 years in the Project of the Year Backwards.2 NR Caregiver-based questionnaire (10 CQI) Inter-RAI34. 6 ORI) RADAR36 Hospital. CQI. Family-CAM. sustained attention counting task and is still in research phase.3 (8. eCAM-S Instrument. I-AGeD. cThere is a skip pattern option for which untrained nurses and geriatric psychiatrist calculated by each question. CAM-S. IQR.g Hospital 234 (36) 84 (5. dThe CAM-S is intended to be used in addition to the items. ICC = 0.3%-92. the jama.2% were derived from a cutoff score of DSM-derived criteria such as CAM.85 Screening tool for caregivers AND (2) inattention AND EITHER (3) disorganized (0. PQI. short form: 1 PQI. 1 PQI)h FAM-CAM32 Homei 52 (33)j 82 (8) NR Possible delirium if (1) acute onset or fluctuation (88) (98) κ = 0. All rights reserved. 10-10) in control group measurement of attention 75 (control group) (9 ORI.4% and 63.8 (87. (2) reference standard delirium cognitive impairment. NR.8%n Tool for informal caregivers 2-5 min (caregivers) and untrained nurses (7 ORI) Abbreviations: CAM.79 Tool for nursing staff (3 ORI) long-term care SQeeC37 Hospital 100 (40) 87 30 s to 3 min Possible delirium if unable to answer first question 83 (83) 81 (59) NR Tool for evaluating level or provides wrong answer to second question of consciousness (2 PQI) Sour Seven38 Hospital 80 (36) 81. Confusion Assessment Method.4) NR Possible delirium if (1) acute change in mental status 82 (90) 91 (69) κ = 0. Mean (SD). 4-7) 98 93 NR Software for objective 87 (dementia group) in delirium group.88. mental function varies over the determined the sensitivity and specificity of the screening tool for detecting delirium in individuals with course of the day. by a Hospital Pablo Tobon Uribe User on 09/28/2017 1164 JAMA September 26. Exclusion greater than 4 on the I-AGeD. possible delirium when score ≥4 90 (94) 84 (91) NR Screening tool for delirium and cognitive impairment (5 PQI. or Neelon and Champagne Confusion Scale. ORI. tool derived from the Short form. sensitivity and specificity as a Advances in Diagnosis and Treatment of Delirium questionnaire items. 10 ORI)c CAM-S29. hDelApp is a visual Evaluation of Consciousness. Maximum score: 19 (long form). However.9) 1-2 min (nurses). CAM (long form: 4 PQI.92 2 CQI. sensitivity and specificity in patients without dementia were 100% and 65. j52 dyads (patient and caregiver). Delirium Rating Scale. allowing administration of fewer questions (as few as 3). 4 ORI. lThe sensitivity and specificity of corresponding ORI can be skipped. SQeeC. (% Male) Age. (2) validation study of a non-English version respectively. intraclass correlation coefficient. Some studies also comprehensive assessment system: acute change mental status from baseline. 4AT. possible delirium when score ≥4 89. interquartile range.

such as the Table 3. and death. including inflammatory. nisms. and Approaches to Maximize Detection of Delirium medical records. Although numerous biomarkers have been studied. preferably with nonopioid medications ing language. such as the sum of all CAM-S substantial harm to self. A high-quality validation study involving 2 cohorts Multicomponent Delivered by interdisciplinary team when older adults totaling more than 1219 patients showed that the CAM-S has strong nonpharmacologic are diagnosed with postoperative delirium to improve interventions clinical outcomes psychometric properties and high predictive validity for important (for treatment) clinical outcomes related to delirium. All rights reserved. level of consciousness. mental status change. inOlderAdultsbestpracticestatement56 andabstractedclinicalpracticeguideline.45 The DRS-R-98 has scale items cover. nurses. consensus diagnosis based on comprehensive assessment using information gathered from patients. In a recent review. a new scoring system based on either the short or long ver. nursing home placement. tire hospital stay and compared 9 different measures reflecting in. but validation studies have not yet been completed. Number 12 1165 © 2017 American Medical Association. Widely used delirium severity measures have included the Medical evaluation Identify and manage underlying organic contributors Delirium Rating Scale–Revised-98 (DRS-R-98)44 and the Memorial to delirium Delirium Assessment Scale. Pain management Should be optimized. benzodiazepines. olanzapine. (eTable 1 in the Supplement). and recent studies have focused on in- review48 is the recommended approach when complete and highly flammatory markers.geriatricscareonline. or both scores across the hospitalization. But Level of Evidence or Potential Risks Limit Strength of Recommendation sion of the CAM. the combined method of interview plus chart pathogenesis of delirium. the detection of delirium can be especially challenging. since many cases of delirium will be missed. dihydropyridines) Cholinesterase inhibitors should not be newly cal intervention trials and has scale items for assessing disturbance prescribed to prevent or treat postoperative delirium in arousal. encounters and need to be applied multiple times a day to improve the detection of delirium. dard used. Advances in Diagnosis and Treatment of Delirium Review Clinical Review & Education high prevalence of sedation and depressed sensorium. various larly episodes occurring during night shifts. routine use of the mRASS is not recommended out- Recommendation Description side of these settings. and yield clues to potential underlying pathophysiologic mecha- nation with interviews to maximize detection of delirium. Downloaded From: http://jamanetwork. have been examined in the past comparison with a reference standard rating or clinical consensus 6 years. fluids. Because delirium can be due to different etiologies. Weak: Evidence in Favor of These Interventions. particu. Pain management Injection of regional anesthetic at the time of surgery pital costs. 2017 Volume 318. Standardized chart-based methods. provided for health care professionals nisms.23 Full guideline available at http://www. interventions Includes mobility and walking. this approach may be valu. risperidone. however. or ziprasidone) at the lowest tensity.29 A subsequent and postoperatively to improve pain control with the goal of preventing delirium study examined the severity of an episode of delirium over the en- Antipsychotics The use of antipsychotics (haloperidol. Strong: Benefits Clearly Outweigh Risks or Vice Versa Multicomponent Delivered by interdisciplinary team for at-risk Assessment of Delirium Severity nonpharmacologic older adults The measurement of delirium severity has assumed increased im. vation Screening scale is a new nurse-based delirium measure47 that correlates strongly with DRS-R-98 scores. effective dose for shortest possible duration may be considered to treat delirious patients who sures. duration. and nutrition sponse to treatment. Memorial Delirium Assessment Scale was designed for use in clini. Since sensitivity and specificity determinations Because of its fluctuating nature and frequent hypoactive presen. monitoring re. distressed. disoriented/ useful for identifying patients at higher risk for developing delirium reoriented) by trained clinician abstractors. portance for tracking clinical course and recovery. or a combination of these mea. can be used in combi. One of the problems in comparing different screening tools is that there is no uniform approach to delirium diagnosis by a clinical Novel Uses of Electroencephalography reference standard.45 Benzodiazepines and antipsychotics should be A recent advance is the development of the CAM-Severity Scale avoided for treatment of hypoactive delirium (CAM-S). none have yet been validated for clinical application.44 The delirium (eg. meta- been validated to show sensitivity of 74% and specificity of 83% in bolic. sleep by a Hospital Pablo Tobon Uribe User on 09/28/2017 . quetiapine. and evaluating pathophysiologic mecha. or threatening including both intensity and (Reprinted) JAMA September 26. hos. since they may be identification of keywords (eg. as well as cognitive function and Benzodiazepines should not be used as first-line treatment of delirium-associated agitation psychomotor activity. high-dose opioids. others. These methods have biomarkers. avoiding physical (for prevention) restraints. for each screening tool can vary depending on the reference stan- tation. American Geriatrics Society Clinical Practice Guidelines postoperative recovery room and ICU. including length of stay. Educational programs Ongoing. and neurotransmitter-based. neurodegenerative. including interleukins and C-reactive protein50 sensitive detection of delirium is needed. This study demonstrated that episode severity measures are severely agitated. Therefore.49 the reference standard The current role for electroencephalography (EEG) in the diagno- was found to range from a single physician’s clinical evaluation to sis of delirium is to aid in differentiating delirium from nonconvul- jama.46 The Delirium Obser. had the strongest association with a Adapted from American Geriatrics Society Expert Panel on Postoperative Delirium posthospital outcomes at 30 and 90 days. this may not be feasible in Biomarkers for Delirium many settings. and cognition Medications to avoid Any medications associated with precipitating that are designed to capture gradations of symptom intensity. cognitive change. antihistamines. however. thought processes. orienting to surroundings. motor symptoms. Refinement of Approaches for Definitive Diagnosis such as diagnosis or monitoring of delirium. family members. for the Prevention and Treatment of Postoperative Deliriuma able. more standardization will improve the ability to cross- Interview-based methods are sometimes conducted during brief validate and to directly compare different screening tools.48 based on Biomarkers have assumed increasing importance. adequate Inflammation is thought to play an important role in the panel.

consider parenteral reminiscence (for cognitive stimulation). patient populations. using a cost-effectiveness Infection prevention Look for and treat infections Avoid unnecessary catheterization threshold of £20 000 (US $31 423) per quality-adjusted life year. but their success is dependent on adher- In 2014. New recommendations included avoidance of drug treat. In 1 study of hospitalized patients with demen- quinolones. Clinical Review & Education Review Advances in Diagnosis and Treatment of Delirium Table 4. highlight the importance of multicomponent nonpharmaco. Pharmacologic Approaches dards. cancer patients.52 In a recent innovation. delirium prevention approaches. epine withdrawal. cal adult patients 16 years and older. or treat. Table 4 with comorbidities (heart failure.25-0. 0. Selected pharmacologic delirium prevention studies from the past logic prevention strategies. Multicomponent Nonpharmacologic Approaches Prevention to Delirium Prevention Multicomponent Nonpharmacologic Interventions Primary prevention with multicomponent nonpharmacologic Approach Description approaches has been consistently demonstrated to be the most Orientation and Provide lighting. 6 years are summarized in Table 5. and hearing and vision fluids if necessary Seek advice regarding fluid balance in patients optimization by using hearing and vision aids as needed. focal dyscognitive seizures. fective prevention strategies should be implemented together (typi- range-of-motion exercises cally 3 or more at a time) by a multidisciplinary team.59 Implement infection-control procedures This study took the novel approach of statistical modeling for Pain management Assess for pain. 0. methodologic limitations preclude a definitive recommendation at 1166 JAMA September 26. ef- at all times Encourage all patients to engage in active. consultants.38 [95% CI. and music therapy and psy- conditions. 0.63 However. how to implement delirium prevention strategies.38-0. sleep enhance- Facilitate regular visits from family. In a recent Cochrane review medical evaluation of delirium etiology. clocks therapeutic activities Reorient the patient to time. regular ambulation Keep walking aids (canes. Downloaded From: http://jamanetwork. findings suggestive of seizures results are not © 2017 American Medical Association. the effect of these interventions on delirium incidence has been Development of systematic reviews and guidelines have served more limited.64-66 Geriatric consultative approaches have been ap- to facilitate application of more evidence-based approaches. that examined prophylactic antipsychotics compared with control ment with nonopioids. using decision tree communication difficulties Begin and monitor pain management in patients analysis to explore deterministic and probabilistic sensitivity analy- with known or suspected pain ses. non- your role ICU medical and surgical patients. whereas after implementation. optimizing pain manage.54 and is currently under investigation in a large developed postoperative delirium. A Cochrane review of delirium prevention examined 39 trials Hypoxia protocol Assess for hypoxia and oxygen saturation involving 16 082 patients60 and found moderate-quality evidence Psychoactive Review medication list for both types and number that multicomponent nonpharmacologic interventions are effec- medication protocol of medications tive for prevention of incident delirium but less robust for decreas- ing delirium severity or duration. the American Geriatrics Society and the American College ence by the health care staff to recommendations made by the of Surgeons jointly released clinical practice guidelines for the pre. and avoiding high-risk medications for preventing delirium in hospitalized non-ICU medical and surgi- (Table 3).62 Multicomponent nonpharmacologic (eg. except in cases of alcohol or benzodiaz. bupropion). place. friends ment. These prevention strategies Introduce cognitively stimulating activities (eg. and terminal ill- Advances in Prevention and Treatment ness. 63 Prior to implementation of nonpharmacologic shown to be associated with a marked reduction in postop. walkers) nearby Because delirium is usually precipitated by multiple factors. plied in different settings.57.61. adequate hydration. reminiscing) include early mobilization. developed in accordance with Institute of Medicine stan. education of health care professionals. calendars. orientation to time and place. renal disease) provides details on these specific approaches to guide clinicians in Early mobilization Encourage early postoperative mobilization. in long-term care. 0. with antipsychotics can prevent postoperative delirium. In a meta- Feeding assistance Follow general nutrition guidelines and seek advice analysis of 14 interventional studies based on the Hospital Elder Life from dietician as needed Ensure proper fit of dentures Program. especially in patients with patients undergoing surgical hip fracture repair. and Ensure working hearing and visual aids are the risk of falls by 62% (odds ratio.51. history of brain trauma or stroke. there was no clear benefit of ment for hypoactive delirium and avoidance of benzodiazepines antipsychotics as a group.9% of patients became delirious. these approaches resulted in noticeable decreases in delirium EEG monitoring and adjustment of anesthetic depth has been incidence.47 [95% CI.58 these approaches significantly reduced the risk of in- Vision and hearing Resolve reversible cause of the impairment cident delirium by 53% (odds ratio. bispectral tia.22 Sleep enhancement Avoid medical or nursing procedures during sleep if possible Multicomponent nonpharmacologic approaches are cost- Schedule medications to avoid disturbing sleep effective. therapeutic activities such as Fluid repletion Encourage patients to drink. specialized geriatric units. but with a known history of seizures. Recent studies support the use of EEG in patients chotherapy have been examined for delirium prevention. however. Number 12 (Reprinted) jama. approximately 20% of patients erative delirium53. non-ICU patients 65 years and older. clinical trial. fluoro.1 vention and treatment of postoperative delirium.60]) among available and used by patients who need them hospitalized. with 1 study demonstrating an incremental net monetary Reduce noise at night benefit of £8180 (US $12 852 in 2014). approaches for delirium prevention have been examined in specific ment with medications that lower seizure threshold ( by a Hospital Pablo Tobon Uribe User on 09/28/2017 .23 The guide- lines.60 Some studies suggest that prophylaxis for treatment of delirium. signs. or psychiatric caregivers.55 only 4. effective strategy for delirium prevention among hospitalized. gaze deviation). All rights reserved.58).60 Educating nursing aides and sive status epilepticus. person. 2017 Volume 318.

73 RCT Hospital. Placebo Delirium incidence 295/3755 (8) vs 289/3752 (8) 6 2015 (2007-2013) intravenous (250 mg P = .03 postoperative day) subsyndromal delirium Vochteloo et al.79 RCT Cardiac surgery 183 (91/92) Dexmedetomidine Propofol Delirium incidence 16/91(17.75 RCT Noncardiac surgery 385 (184/201) Sevoflurane Propofol Delirium incidence 21/184 (11. postoperative P = .003 Perioperative Interventionse Ashraf et al.4) vs 29/205 (14. intravenous Placebo Delirium incidence 35/229 (15.40 Hatta et al.6) vs 16/30 (43. oral No haloperidol Delirium incidence 73/173 (42. Elective 119 (59/60) Haloperidol.5 mg/d) Placebo Delirium incidence 2/56 (3.3) vs 53/228 (23. oral (8 mg/d) Placebo Delirium incidence 1/33 (3) vs 11/34 (32) 6 2014 (2011-2012) P = . Last 6 Yearsa Overall jama.7) vs 17/50 (34) 6 2012 (2007-2010) (0. oral Placebo Delirium incidence 7/51 (13.4 μg/kg/h) 7/31 (22.03 0. intravenous Neostigmine.7 μg/kg/h) Liu et al80 2016 RCT Orthopedic surgery 197 (99/98) Dexmedetomidine Placebo Delirium incidence In 65.31 prospective surgery days 1-3) (2007-2012) Hakim et al. intravenous No haloperidol Delirium incidence 25/59 (42.6) vs 10/52 (19. intravenous © 2017 American Medical Association. Number 12 Review Clinical Review & Education 1167 . 5 (2014-2015) (0.5) 4 (2012-2014) (2 mg/kg) intravenous P = .com Sources by Setting Sample Size Results. 2017 Volume 318.5) vs 29/92 (31. RCT Hip fracture surgery 378 (186/192) Melatonin.67 Randomized.2) 5 2011 (2007-2008) P < .76 2016 Retrospective Hip fracture surgery 174 (78/96) Sugammadex.4 μg/kg bolus.70 RCT Noncardiac surgery 457 (229/228) Haloperidol.80 at induction and at initiation of cardiopulmonary bypass) Djaiani et al.4) vs 29/201 ( 75-year-olds.5 mg/12 h among those with P = .3) P < .01g (continued) (Reprinted) JAMA September 26.02d 72 de Jonghe et al. (0.67 Whitlock et al. Intervention vs Control.71 RCT Hospital.4) 6 2012 (2006-2010) P = .5) 6 2016 (2011-2014) (0. oral (0.01 mg/kg) Stoppe et al.5) 6 2014 (2008-2012) P = .05 mg/kg) + glycopyrrolate.1) 3 2011 (2008-2009) (1 mg/twice daily in lower-risk P < .2-0.7 mg/d. oral (3 mg/d) Placebo Delirium incidence 55/186 (29. All rights reserved. Quality Category Study Design (Study Duration) (Intervention/Control) Intervention Control Outcome No.2-0.(%) Scoreb Antipsychotics (Typical and Atypical) Fukata et al. GI/orthopedic (2. Selected Delirium Prevention Studies.77 RCT Cardiac surgery 30 (15/15) Xenon Sevoflurane Delirium incidence 3/15 (20) vs 4/15 (27) 4 2013 (2011) P = .5 mg/d. then (25-50 μg/kg/min) P = .4) vs 20/60 (33. medical 122 (61/61) Melatonin.03 day 1) Melatonin or Ramelteon Al-Aama et al.75 (0.78 RCT Cardiac surgery 7507 (3755/3752) Methylprednisolone.68 RCT Cardiac surgery 101 (51/50) Risperidone.3) vs 35/96 (36.38 Oh et al.3) 5 2014 open-label. Delirium incidence 26/78 ( by a Hospital Pablo Tobon Uribe User on 09/28/2017 and diazepam (5 mg) Lurati et al. medical 67 (33/34) Ramelteon.001c Advances in Diagnosis and Treatment of Delirium in high-risk patients) patients Wang et al.6) vs 49/192 (25.69 PCT Hip fracture surgery 378 (173/205) Haloperidol.74 RCT Elective cardiac 93 (47/46) Premedication with No premedication Delirium incidence 0/47 (0) vs 0/46 (0) 4 2015 cathertizationf diphenhydramine (25 mg) NS Downloaded From: http://jamanetwork. postoperative P = .4) 4 2012 (2009-2010) (1. Table 5.

Patients with normal cognition: dexmedetomidine vs placebo risk of bias. who did not receive haloperidol. g This study examined the effect of dexmedetomidine on patients with amnestic mild cognitive impairment b The quality rating was based on the Cochrane risk of bias overall quality score. gastrointestinal. stratified by age.6% vs 43. intervention type. 6 (low risk of bias in all domains). Selected Delirium Prevention Studies.(%) Scoreb Li et al. but the total number of individuals who Downloaded From: http://jamanetwork. experienced delirium in each group are not reported. with 1 point assigned for each and in individuals with normal cognition.07i Pesonen et al.83 2011 (2007-2008) over time P = . They were included because of the a study quality. Intervention vs Control. RCT.01) for those c 75 years or older.4 μg/kg/h) Dighe et al.01) for those aged 65 to 75 years and 37. intravenous Placebo Delirium incidence 18/51 (35. Confusion Assessment Method for the Intensive Care Unit. postoperative day 1: 5 2011 (2008-2009) on day 1.6 μg/kg bolus. Studies with overall quality score less than 2 were also Study duration not reported. excluded. d Numerator and denominators calculated after the prevalent delirium cases were subtracted (melatonin n = 5. All rights reserved. Low risk of bias. unclear risk of dexmedetomidine vs placebo (normal saline).53 Marcantonio et RCT Hip fracture surgery 16 (7/9) Donepezil. Whitlock et al78 [secondary outcome]). Patients with amnestic mild cognitive impairment: of 6 domains found to be at low risk of bias. there were 26 patients in the high-risk group Denominator was number of interviews.8% (P < . P = . less than 4 (high risk of bias on !2 domains). but the delirium incidences in these patients were not significantly different i Study reports statistical significance on postoperative days 3 to 5. 75 mg/12 h on 24/25 vs 21/25 postoperative days 1-5) P = .84 2014 (8 mg/d ×5 d) postoperative day 2 P = . 1168 Table 5.9% vs 30.3% (P < . jama. more than 1 interview per patient. 2017 Volume 318.5% bias = not enough information to make a clear judgment (high or unclear risk of bias on 1 or more domains). 22. placebo n = 9).30 then 0. Some studies were excluded if studies were conducted exclusively in the intensive care unit or the duration of f JAMA September 26. (Lurati et al75 [tertiary end point].94h Clinical Review & Education Review Papadopoulos et RCT Orthopedic surgeryf 106 (51/55) Ondansetron. In this study. the patients received prophylactic haloperidol if they were determined to be at high risk based on h the Risk Model for Delirium score.7% vs 36. Last 6 Yearsa (continued) Overall Sources by Setting Sample Size Results. j Modified Finnish CAM-ICU score (highest 25 points).8% (P < . and large study population. oral (5 mg/d) Placebo Delirium presence 7/11 (64) vs placebo 9/14 (64) 6 al.81 2017 RCT Cardiac surgery 285 (142/143) Dexmedetomidine Placebo Delirium incidence 7/142 (4.7) on 5 al.04 e Abbreviations: Advances in Diagnosis and Treatment of Delirium .85 RCT Cardiac surgery 70 (35/35) Pregabalin.01) for those 75 years or older. Because of protocol by a Hospital Pablo Tobon Uribe User on 09/28/2017 from those of patients who received prophylaxis. (normal saline) 11.9) vs 11/143 (7. post hoc Cardiac surgery 161 (83/78) Gabapentin (200 mg Placebo Delirium incidence 10/83 (12) vs 7/78 (9) 4 2014 analysis (2007-2011) 3 times daily ×4 d) P = .3) vs 29/55 (52.7) 6 (2014-2015) (0. high vs 90% (P < .01) for those aged 65 to 75 years and 16. oral (150 mg/d Placebo CAM-ICU scorej Mean score. nonsignificant. randomized clinical trial. © 2017 American Medical Association. Delirium incidence was not the primary outcome for some of the perioperative intervention studies NS.82 RCT. Quality Category Study Design (Study Duration) (Intervention/Control) Intervention Control Outcome No. Number 12 (Reprinted) intensive care unit stay could not be determined. GI.

a concerted effort to reduce the use of and were more likely to require breakthrough treatment compared antipsychotics and focus on nonpharmacologic management may with participants receiving placebo. or nonlicensed professionals chotic drugs including oral risperidone. antipsychotics for the treatment of delirium. and need for multicomponent approaches. While such an approach has not been validated. 2017 Volume 318. with all prior evidence. graded re- superimposed on dementia found no benefit on delirium duration lationship. multimorbidity. ing delirium once its presence is confirmed.60. The literature search was restricted to the past 6 years. pharma- according to bispectral index monitoring can decrease the inci. which may decrease risk. tribute to heightened adverse effects and poorer long-term out- tipsychotics. safe and highly change in delirium duration. protocols—but with varying and limited results. However. bright light therapy. dence of delirium. ommendations can be made at this time. and intra. nificant decrease in delirium incidence among 19 studies and no Although promising approaches are emerging. comes.89 A recent clinical trial sponse to treatment. and hearing and Selected pharmacologic delirium treatment studies from the past 6 vision adaptations are effective and cost-effective and remain the years are summarized in Table 6. complexity.80 Other strategies.92 Primary prevention with multicomponent nonpharmacologic approaches such as reorientation. Moreover. however. hydration. The algorithm entails assessing delirium risk. has been recognized as increas- decreased hospitalization rates. include the use of volunteers. intramuscular ziprasidone. a combined or severity but did demonstrate significantly improved executive approach including interview and chart review is recommended. intravenous. these of antipsychotics in decreasing the duration or severity of delirium. such as current evidence Treatment against the use of antipsychotic medications in the treatment of de- Nonpharmacologic Approaches lirium because of lack of efficacy and increased risk of adverse events Few recent studies have examined nonpharmacologic approaches and poor outcomes. therapeutic Pharmacologic Treatment Approaches activities. further testing of the ingly important for tracking clinical course. 90 Other studies have traoperative EEG monitoring and bispectral monitoring are emerg- focused on specialized delirium rooms or improving sleep to treat ing strategies that identify delirium risk and help to adjust depth of delirium with use of earplugs. Number 12 1169 © 2017 American Medical Association. jama. There was no sig. cologic strategies. opment of effective treatments have been hindered by multiple muscular haloperidol100 and concluded that the current evidence challenges. to enhance feasibility and reduce costs of implementation. but this finding will need to be replicated in larger thesizes recent evidence gleaned from this comprehensive review studies. including tight control of glucose lev. Downloaded From: http://jamanetwork. Most studies do not show benefit cornerstone of delirium management . prognosis. detailed suggested algorithm is presented in the Figure. and oral. instituting delirium prevention measures.86. drug interactions). severity. in a randomized clinical trial of atypical anti. systematic review examined antipsy. Devel- quel. have shown varying degrees of benefit. approaches can be labor intensive. However. 3D-CAM. and melatonin. a be effective in reducing delirium incidence in patients with mild cog. such as that mea- and found that it was feasible. in appropriate cases. similar to the initiative by the Centers for Medi- psychotic drugs in palliative care settings. For complete capture of delirium episodes. and streamlined approaches A recent comprehensive. More research is needed to receptor agonist (ramelteon). oral olanzapine. The same meta-analysis also found minimal evi.99 Only a few lim.60 establish safe and effective pharmacologic treatment approaches. and treating delirium quality evidence suggests that adjusting the depth of anesthesia using both nonpharmacologic and. which syn- nitive impairment. been identified. Antipsychotics are often used for patients with Potential harm was demonstrated in 2 studies in which delirium and with severe agitation and safety risks but may con- more patients required institutionalization after treatment with an. nonpharmacologic management group also had better overall sur. or reduction in mortality.87 Moderate. participants receiving care & Medicaid Services to reduce the use of antipsychotics for oral risperidone or haloperidol had higher delirium symptom scores improved dementia care. All rights reserved. Delirium severity. One pilot study involving 143 nursing Advances in diagnosis have included the development of new home patients examined a modified Hospital Elder Life Program in brief screening tools (Short-CAM by a Hospital Pablo Tobon Uribe User on 09/28/2017 . early mobilization. diagnostic does not support the use of antipsychotics for treatment (or (Reprinted) JAMA September 26. oral sero. Several limitations of this review must be acknowledged. and re- intervention in a clinical trial will be needed. and sleep anesthesia. hospital or intensive care effective pharmacologic treatments for delirium have not yet length of stay. aides.91. Measures that capture both intensity and using daily therapeutic activities such as reminiscence activities for duration of an episode of delirium (such as the sum of all CAM-S cognitive stimulation in the postacute care setting for delirium scores) correlate best with clinical outcomes in a direct. heightened risk of adverse effects (ie. for the treatment of delirium. els and blood transfusions for delirium prevention in the periopera. One study showed that dexmedetomidine may To assist clinicians with the evaluation and treatment of delirium. nutrition. In- function and decreased length of stay. Participants in the placebo/ improve delirium care.88 it is based on the best available evidence from prior studies and in- corporates relevant recent evidence. ited studies have considered pharmacologic approaches other than dence to support the use of medications to prevent delirium. vention) of delirium in hospitalized older adults. Delirium Prevention for the Surgical Patient Most perioperative measures involving the use of different types of Discussion sedation or anesthesia have not effectively reduced the incidence of delirium (Table 5). including the multifactorial contributors. sleep strategies. Therefore. evaluating and manag- tive setting. and 4AT) to the long-term care setting for prevention and treatment of delirium improve delirium identification. based on meta-analysis. melatonin. Advances in Diagnosis and Treatment of Delirium Review Clinical Review & Education this time (Table 5). vival compared with those in the haloperidol group. and no definitive rec- including cholinesterase inhibitors. with high satisfaction rates and sured with the new CAM-S scoring.

Number 12 (Reprinted) Schrøder Pedersen Prospective cohort Cardiac surgery 240 (123/117) Standardized treatment with No standardized Delirium duration 3 (range. initial. 1-4) 3 et al.5-5 mg treatment protocol d 3 times daily ×1. Placebo Delirium symptom Haloperidol vs placebo: by a Hospital Pablo Tobon Uribe User on 09/28/2017 Agar et al.6) 2 observa-tional surgicald risperidone. and Clinical Review & Education Review (mean doses 4-7 d) atypical) 13/21 (61. oral (0. Studies with overall quality score less than 2 were also e The study had different loading. For participants older than 65 years. oral (1-20 from baseline by [olanzapine].009 score = more Risperidone vs placebo: 0. RCT.61 20 mg/d) to 20 mg/d) hyperactive delirium Boettger et al. oncology 84 (21 haloperidol/21 Haloperidol (5.95 2012 Case series Hospital. then 0. initial.7) 5 2013 (2009-2011) mg/d for 1-7 d) mg/d for 1-7 d DRS-R-98 (higher P = .3 mg) Delirium resolution 16/21 (76.56 h vs 33. Korean version of the Delirium Rating Scale–Revised-98 (DRS-R-98). 6 of 21 [28. with 1 point assigned for each of 6 dose of 0. Doses could be titrated by 0.59 score = more severe) JAMA September 26.25-4 mg/d) ≥50% reduction [risperidone].42c Kishi et al. 25% number of treatment responders reduction in the vs nonresponders. oral (2. up scores on day higher in haloperidol group.2) vs 14/21 (66. P = . Quality Category Study Design Duration) Control) Intervention Control Outcome No.5 mg. and maximum doses were bias = not enough information to make a clear judgment (high or unclear risk of bias on 1 or more domains). intensive care unit stay could not be determined. risk of bias.99 2017 RCT Inpatient hospice.25 to 0.2) [aripiprazole].5-mg loading dose with the first b The quality rating was based on the Cochrane risk of bias overall quality score.25 mg every 12 h. 1-5) d vs 1 (range. 1170 Table 6. 2017 Volume 318.48 U severe) higher in risperidone group. medical 52 (24/28) Quetiapine. oral P = .5-mg maintenance dose every 12 hours. participants older than 65 years.5 mg. jama. 21 olanzapine) Olanzapine (7. All rights reserved. and 13/18 (72. 4 of 21 [19%]. high halved.5-2 Delirium severity by 22. care (2008-2014) to 2 mg/d)e 3 (higher P = . up to intramuscular (5 mg. Last 6 Yearsa Overall Sources by Setting (Study Sample Size (Intervention/ Results. medical 80 (23 haloperidol/21 Haloperidol.97 2014 (2012) haloperidol. Delirium duration in 31.98 2013 Prospective Hospital. 6 (low risk of bias in all domains). and maximum doses for participants 65 years or younger and for excluded.3 mg) and adverse-effect 18/21 (85. Selected Delirium Treatment (Typical and Atypical Antipsychotics) Studies. 249 (81 haloperidol.7 (6. 21 aripiprazole. (olanzapine. randomized Adverse effects: extrapyramidal symptoms (haloperidol.93 RCT Cardiac surgery 53 (27/26) Morphine sulfate. risperidone. oral (0.94 Open-label.8%]). then P = .1 mg) profiles (typical vs 16/21 (76. less than 4 (high risk of bias on !2 domains).9 (6. a d Some studies were excluded if studies were conducted exclusively in the intensive care unit or the duration of Study duration not reported. 18 olanzapine.9) [olanzapine] P = . risperidone. 14/29 (48) vs DRS-R-98 from 15/29 (51) baseline to day 7) Maneeton et al. then titrated) (responder. 1 of 21 [4.2) vs 3 2015 matched (2000-2006) risperidone.24 U 6 hospital palliative risperidone/86 placebo) oral (0. Hospital.(%) Scoreb Atalan et al. © 2017 American Medical Association.5-1 mg No control group Delirium severity No significant differences in the 2 to start. Participants 65 years or younger received a 0.23 taper) Yoon et al.9) vs 21. up those with P = . cancerd 29 (intervention) Risperidone. oral (25-100 Haloperidol.6%]).96 RCT Hospital. Low risk of bias.5 mg) Risperidone (1.5 d. unclear risk of maximum dose of 4 mg.6) quetiapine) Olanzapine.5-10 Risperidone. with domains found to be at low risk of bias. oral (0.7) [risperidone]. Intervention vs Control. 12/18 (66.97 (25-200 mg/d) Downloaded From: http://jamanetwork.02 c Abbreviations: DRS-K. Haloperidol.2) mg/d) DRS-K [quetiapine] Quetiapine. oral Delirium severity 15/23 ( Advances in Diagnosis and Treatment of Delirium .9 h 4 2013 (2010-2012) intramuscular (5 mg. the loading. Aripiprazole (18. 18 mg/d) (0. sedation clinical trial. 82 Haloperidol.

depression). H2-receptor antagonists. pulmonary Family involvement. Increasingly. oral ( by a Hospital Pablo Tobon Uribe User on 09/28/2017 . only studies published in English were included.5 mg. sedative-hypnotics. and dedicated delirium wards/services. oral (2. magnetic resonance imaging. Studies based solely in the ICU were over. staff. therefore. not to exceed 3-5 mg in 24 h). maintain effective dose Vital signs embolism. and chlorpromazine. EKG. MRI. brain MRI Lumbar puncture d CBC indicates complete blood cell count.10 e b Common delirium risk factors include dementia or cognitive (Reprinted) JAMA September 26. Delirium is diagnosed in the presence of the following core features: (1) acute electroencephalogram. may repeat every 20-30 Use less harmful alternatives Maintain sleep-wake cycle min. nonpharmacologic strategies should be used for both should trigger a rapid evaluation.5-1 mg twice daily) Encourage adequate hydration Minimize Beers criteria medicationse and nutrition Haloperidol. stroke. low-level Due to risk of torsades de pointes. Delirium should be considered a life-threatening medical emergency until f proven otherwise. oral (3-5 mg at bedtime) Ramelteon. at lowest possible dose. g incorporating delirium pathways (standing order sets for evaluation and Reserve antipsychotic medications for use only when behaviors (ie. Suggested Algorithm for Delirium Evaluation and Treatmenta Patient admitted to the hospital Assess delirium riskb Patients at high risk for delirium Assess cognitive function Implement multicomponent. implementation of delirium screening tools into the hallucinations) pose a serious safety hazard to patient. urinalysis. lighting at night intravenous haloperidol should be Sleep protocols involving massage. there is risk of interrupting essential medical care. chest radiograph. Administer lowest effective doses Uninterrupted sleep time. liver function. thyroid function. EEG Neuroimaging: head CT. 2017 Volume 318. computed tomography. electrocardiogram. which limited jama. and presence of specific comorbidities anticholinergics. history of alcohol misuse. toxicology screen. Number 12 1171 © 2017 American Medical Association. herbal tea. avoid restraints and Management of severe agitationg and drug use) Mobilize to prevent deep venous tethers (Foley catheters) Start with a low dose of 1 of the drugs Physical examination thrombosis. it has not been validated. The Beers Criteria for Potentially Inappropriate Medication Use in Older Adults functional or mobility impairment. (2) inattention PLUS a Although the algorithm is evidence-based. oral (8 mg at bedtime) Evaluate and treat Perform additional clinical evaluation as appropriate Laboratory tests: CBC. This includes tricyclic antidepressants. (3) disorganized thinking OR (4) altered level of consciousness. or both or when electronic medical record.1 corticosteroids.25-0. warm milk Management of sleep-wake cycle Yes Potential contributing No factor identified? Melatonin. administered in monitored settings only. for many excluded. dehydration. Last. multiple coexisting medical illnesses. prevent aspiration for changes over time Maintain normal volume status Provide nutritional support A B Perform clinical evaluation Provide skin care Nonpharmacologic strategiesf Pharmacologic strategies History (including alcohol Prevent pressure sores Early mobility. agitation. oral or intravenous (0. meperidine. (Beers Criteria)34 can help identify medications that should be avoided or used sleep deprivation. diphenhydramine). Formal assessment to establish nonpharmacologic strategies baseline cognitive function to prevent delirium (see A ) Delirium present? No Exclude conditions other than delirium Identify any acute change Screen with a validated possibly causing change in mental status in mental status from baselinec delirium instrument Dementia (alone) Depression Acute psychosis Yes Mania Confirm delirium diagnosisd Identify and treat underlying Prevent complications Manage delirium symptoms Measure delirium severity causes and contributing factors Protect airway. the presence of an acute change in mental status Multicomponent. c thioridizine. orientation. EKG.5-5 mg twice daily) as needed Review medications Risperidone. and fluctuating mental status change from baseline. (eg. CT. More- additional years of evidence. treatment of delirium). many hospitals are delirium prevention and treatment. Ensure patient has eyeglasses and Seroquel. because they were considered outside the scope of this areas explored. B12 Other tests: arterial blood gas. visual or hearing impairment. urinary tract infection cognitive stimulation for about 2 d before tapering Search for occult infections. benzodiazepines.5-25 mg twice daily) metabolic abnormalities hearing aids or other assistive devices Olanzapine. soothing music. Downloaded From: http://jamanetwork. inclusion of recent systematic reviews allowed incorporation of many review and already covered in recent comprehensive reviews. All rights reserved. we found weak to insufficient evidence. advanced age (>70 years). and listed below. Advances in Diagnosis and Treatment of Delirium Review Clinical Review & Education Figure. EEG. antihistamines (eg. oral (12.

ARTICLE INFORMATION and the assistance of Eyal Kimchi.stratifyingrisk. 2017. adequately powered studies of pharmaco- ology of delirium. Fearing MA. (Dr Inouye). High- priority areas for future investigation are outlined in eTable 2 in the Conclusions Supplement. intellectual content: All authors.monitoringseverity. for the literature review in this study 1172 JAMA September 26. Brush M. analysis. Borson S. Kim JM. Robinson TN. R24AG054259 Cooney LM Jr. and Alexandra Classification of Mental and Behavioural Disorders: status indications for lumbar puncture in a Pletnikova.161(20):2467-2473. enhancing sleep. Levy Family Chair (Dr Inouye). BA.296 Role of the Funder/Sponsor: The funding sources of missed delirium in patients referred to palliative (16):2012-2022. Hatala R. Thorpe KE. Brenner LA. or 5. Balkin S. at 10. J Am Geriatr Soc. A short portable mental status 3UL1TR001102 from the National Center for 2000. completed and submitted the ICMJE Form for 77(8):903-910. MD.7(10):1166. care in a comprehensive cancer center. The Rational Clinical Examination: does this adult interpretation of the data. Geneva. mdm608@northwestern. Hustey FM. and decision to submit Statistical Manual of Mental Disorders. the Johns Hopkins University School accuracy of the data analysis. Additional Contributions: We gratefully acknowledge 6.102 and fluid biomarkers are being studied to enhance clinical risk strati- Similartobiomarkerstudiesinotherfields.23(8):2427-2433. in. search. Inouye SK. We are access to all of the data in the study and take Siegal AP. 2013. (9920):911-922. Williams A. and by the ratings. or Mary McGrae McDermott. (Department of Neurology.standardizationofassayplat. Mion LC. I perform a lumbar puncture and analyze the results Milton and Shirley F. Rafanan AL. 2014. Tran ZV. Inouye SK. Straus © 2017 American Medical Association. J Am Geriatr Soc. Inouye SK. de la Cruz M.282(2): approval of the manuscript. Wong JG. fication and diagnosis. review. 5th ed. Hospital. questionnaire for the assessment of organic brain Advancing Translational Sciences (Dr Fong). management. Support 14. disorder and thereby effectively treat this condition. and many brief delirium screening tools ing (eTable 1 in the Supplement). deficit in elderly patients. DC: American Psychiatric Society. which is com- ized clinical trials represent an important priority for the field. serious condition associated with increased nistic understanding of delirium.15(11):1021-1027. detection of delirium. associations between delirium and mortality according to delirium subtype and age: Conflict of Interest Disclosures: All authors have REFERENCES a prospective cohort study. Statistical analysis: Hshieh. combination approaches. The Mini-Cog: a cognitive “vital signs” Funding/Support: This work was supported in part measure for dementia screening in multi-lingual by grant K23AG043504 from the National 2. Westendorp RG. Kim SY. stratification of delirium. Clinical Review & Education Review Advances in Diagnosis and Treatment of Delirium our recommendations. Because inflammation is thought to morbidity and mortality in older patients as well as enormous soci- play an important role in the pathogenesis of delirium. World Health Organization. mon and a highly morbid condition among older adults. Clarifying confusion: the also grateful to Carrie Price.146(3):295-300. Nurses’ recognition of delirium and (10):433-441. Attia J. Helfand and Lynne Morishita. Given the complex and multifactorial eti.383 11. Horwitz RI. The frequency to diagnose bacterial meningitis? JAMA. proaches is documented to be effective. Prevention of delirium using nonpharmacologic ap- physiologically targeted approaches. Welch Confusion Assessment Method: a new method for responsibility for the integrity of the data and the Medical Library. 2015. Dokmak A. the manuscript for publication. Number 12 (Reprinted) jama. the results amination and laboratory testing. Inouye SK. boosting cognitive reserve. had no role in the design and conduct of the study. Meldon S. preparation. 15. Ann Intern Med. Acad Emerg Med. The ICD-10 Retrospective analysis: are fever and altered mental the assistance of Asha Albuquerque. Inouye. Motor subtypes of postoperative delirium Obtained funding: Inouye.23 grants P01AG031720 (Dr Inouye).org in older adults. and Care Cancer. MD. Cook DJ. Massachusetts General World Health Organization. and its symptoms: comparison of nurse and researcher 13. Washington. Alessi CA. Vitaliano P. recognition and risk stratification. Palmer R. 1999. analysis. Submissions: We encourage authors to submit papers for consideration as a Review. Delirium is a common. American Psychiatric Association. Disclosure of Potential Conflicts of Interest and 1. Wei LA. 12. treatment. grant emergency department patients. for her assistance with the literature 941-948. Scanlan J. 1993. Fan J. High-quality. Diagnostic and patient have acute meningitis? JAMA. Along with thorough clinical ex- cluding interleukins and C-reactive protein. Pfeiffer E. et al. Pharmacologic prevention and treatment of forms across laboratories and validation across different clinical popu. Yennu S. Inouye. These persons received no extra Acquisition.101 inflammatory etal costs. Sternberg EJ. innovative approaches are greatly needed to break logic treatment are a priority to identify approaches that are effec- the escalating cycle of brain dysfunction that is the hallmark of the tive and safe. Raeburn CD. Switzerland: Accepted for Publication: August 9. How do K07AG041835 (Dr Inouye) from the NIA. Holroyd-Leduc J. Advances in the pathophysiologic understanding of delirium will be critical to advance the diagnosis and treatment of delirium. Arch Surg. 1990. the Roberts Fund (Dr Oh). Prevalence and documentation of impaired mental status in elderly elderly. 175-181. R01AG044518 (Dr Inouye). ment of delirium remains the cornerstone of delirium prevention and Innovative treatment approaches may include identifying patho. with delirium. Institutes of Health/National Institute on Aging (NIA) (Dr Oh).andprovidingmecha. MD. 4. Author Contributions: Drs Oh and Inouye had full review of an earlier draft of this manuscript. Differential Supervision: Oh. and nonpharmacologic manage- lations will facilitate incorporation of biomarkers into clinical practice. additional tools such as imaging arenotalwaysconsistentandnotyetreadyforclinicalapplication. 2006. 2015.livingston@jamanetwork. 2017 Volume 318. adequately powered random. for his critical 7. Please contact Edward Livingston. 1975. Although several studies have shown have been developed in the past 5 years to allow improvement in the association of elevated levels of inflammatory biomarker levels. Downloaded From: http://jamanetwork. Future high-quality. Arch Intern Med. 2001. delirium remains controversial. Metersky ML. van Dyck CH. and using multipronged vention and treatment of delirium remains controversial.56 Critical revision of the manuscript for important (5):823-830. Foreman MD. pro. dedicated to the memory of Joshua Bryan Inouye The Confusion Assessment Method: a systematic Drafting of the manuscript: All authors. MLS (William H. Moss M. Katz KH. This work is 8. Delirium in elderly people. PhD Diagnostic Criteria for Research. 9. technical. by a Hospital Pablo Tobon Uribe User on 09/28/2017 . 2008. Harvard Medical School).113(12): of Medicine). 2011. All rights reserved. review of current usage. 2000.50. whereas pharmacologic pre- viding neuroprotection. or material support: Oh. Hshieh. authors. collection. Lancet. BA. et al. at Edward. Psychosom Med. or interpretation of data: All compensation for their contributions. Saczynski JS. Int J Geriatr Psychiatry. Concept and design: All authors. none were reported. Advances in diagnosis can improve recognition and risk markers are widely studied for delirium risk stratification and monitor. Biomarkers are likely to play an increasing role in confirm- ingdiagnosis. Kim SW.

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