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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
jamanetwork.com/learning
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.
(eoh9@jhmi.edu).
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.

D
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.

jama.com (Reprinted) JAMA September 26, 2017 Volume 318, Number 12 1161

© 2017 American Medical Association. All rights reserved.

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ated in clinical trials. Furthermore. or Wernicke-Korsakoff syndrome (WKS). with delirium. and time course of conditions. Downloaded From: http://jamanetwork. older patients presenting with delirium and fever. such as hepatic or ure- Methods mic encephalopathy. memory impairment.7 Delirium includes both hypoactive and hyperactive forms. inappropriate or unsafe behavior.com/ by a Hospital Pablo Tobon Uribe User on 09/28/2017 .21 searching for possible causes. hallucinations or mispercep- tions).1. tal status change (such as vasculitis or herpes encephalitis) must line mental status and the acuity of any changes. depres. cycle. Depression Scale.6 Key diagnostic features. infections. prevention or treatment of delirium. such as the Informant Ques- diagnosis.7. plus tends to occur in later stages of dementia. disorientation. depres. inattention. while common in delirium. It is important not son for a missed diagnosis. This step is critical and ogy of delirium if the history suggests recent falls or examination requires obtaining the history from a knowledgeable informant. Tenth Revision from the and risk stratification of delirium. Because delirium can signify an acute Primary prevention of delirium with nonpharmacologic multi- medical emergency. and emotional lability.8 include an acute onset and fluctuating course outweigh the harms. ing with fever. safety risks. which has important prognostic implications.17 increased rating with a validated delirium instrument. prevention.16 Neglecting the baseline mental status assessment is a leading rea. sion. Once the baseline mental status is determined. component approaches has been shown to be effective and has targeted evaluation for electrolyte or metabolic derangements. and the condition is easily Key Points overlooked. The specific selection of tests should be based delirium. Other features sup. precipitating factors (eg.18 and higher rates of rehospitalization. Delirium and dementia commonly coexist. alcohol withdrawal de- lirium (delirium tremens). includ- Mini-Cog11 or the Short Portable Mental Status Questionnaire12 and ing accelerated rate of cognitive and functional decline. in. or alteration in language) Meaning Advances in screening and diagnosis of delirium can (CAM algorithm in eFigure 2 in the Supplement). Neuroimaging can be useful in identifying the etiol- changes typically occur over hours to days. length of hospital stay. reveals deteriorating mental status or focal neurologic findings. and is associated with higher rates of compli. delusions. 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. from the DSM-5 and the widely used Confusion Assessment For pharmacologic management of delirium. and psychosis (Table 1). cognitive changes (typically over months for dementia). (2) diagnosis or prevention or therapy. sion should also be ruled out in the interview with the patient and sion. therefore should not be overlooked in the evaluation. The presence of depres- ture unique to delirium that is less common with dementia.22 While many pharmacologic approaches have been evalu- on information obtained from the history and physical examination. metabolic derangement. lum. inattention. impaired level of consciousness. knowledge of the patient’s baseline is essential to make tionnaire on Cognitive Decline of the Elderly. prior diagno- in mental status from baseline may distinguish delirium from other sis of mild cognitive impairment or dementia. or psychosis. the presence of an underlying dementia. acute drug intoxication.20 can help establish the diagnosis. Number 12 (Reprinted) jama. the benefits do not Method (CAM).19 compared with dementia alone.23 cognitive impairment.15 or when a specific neurologic cause of acute men- The cornerstone of diagnosis is determining the patient’s base. As described above.10 encephalitis. signs suspicious for meningitis 14 or cations and mortality. All rights reserved. gained widespread acceptance as the most effective strategy for fection. For accurate differential administration of proxy-rated tools. and careful bedside observation of key features. at present there is no convincing. 2017.19 and death. 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. Examination of cerebrospinal fluid is not required for most Concepts were created for the topics of (1) delirium or confusion. perceptual disturbances (eg. family. using brief depression screening tools such as the Geriatric The next step is a careful physical and neurologic examination. improve recognition and risk stratification. derived nonpharmacologic multicomponent strategies is effective. Alteration in the level of consciousness is another fea. an acute change Interview with a caregiver for baseline mental status. the be excluded. thiamine supplementation for WKS) and Cochrane Library from January 1. through March 16. drugs).17 Conditions that may mimic delirium include dementia. delirium but also to recognize when delirium is superimposed on a preexist- is diagnosed by using brief cognitive screening tests such as the ing dementia. Some con- ditions presenting with symptoms of delirium. Embase. Search was conducted in Ovid MEDLINE. all patients presenting with delirium need rapid. or organ failure. and disturbance of cognition indicating disorganization of thought (eg. Delirium prevention with World Health Organization. headache. however. multiple comorbidities). 2017 Volume 318.1 Recognition is based on brief cognitive screening and Question What advances in diagnosis.com © 2017 American Medical Association. since the acute change might otherwise only to distinguish between delirium and dementia diagnostically be missed. institutionalization. using a combination of controlled vocabulary and keyword terms. and recommendations are to reserve treatment for patients with severe agitation that poses of symptoms. often bar puncture 13 should be strongly considered in patients present- goes unrecognized. (3) randomized trials 1162 JAMA September 26. and the have specific treatments (eg. older age. 2011.9. while implementation of nonpharmacologic delirium prevention strategies can portive of the delirium diagnosis include alterations in sleep-wake substantially improve outcomes among older patients. or both. The hypoactive form is more common among older persons. Clinical Review & Education Review Advances in Diagnosis and Treatment of Delirium Current Approach to Diagnosis and Treatment of Delirium Delirium remains a clinical diagnosis.

All rights reserved. clinical guidelines. Downloaded From: http://jamanetwork. many well-established delirium screening tools have been adapted or used in various clinical and research applica- Results tions. chomotor retardation. emergency department. The checklist has sensitivity of 72% and The CAM algorithm is based on the presence of 4 core features of specificity of 80%41. 5 were systematic reviews and meta. The presence analyses. drowsiness. which measures arousal.com (Reprinted) JAMA September 26. or stupor. and biomarker studies that were not also required. 4 attention treatment studies. 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. However.40 Other screening tools with more recent validation studies Screening Instruments include the Nursing Delirium Symptom checklist (Nu-DESC). and interrater reliability (κ = 0.8.28 Another screening tool is the 4A’s Test the current review and has been examined in comprehensive (4AT). or language. In addition to Definitive diagnosis of delirium should be conducted by randomized trials. many delirium. however. the following new information has become available. For instance. inappropriate behavior. and impaired conscious- 42 were cohort studies. The Modified Richmond Agitation and consciousness7) and has high sensitivity (94%-100%). sedation.30 reviews. such as hypervigilance. Advances in Diagnosis and Treatment of Delirium Review Clinical Review & Education Table 1.7% and specificity of 84. suggestive of cognitive impairment for which more detailed cogni- article quality was rated with the Cochrane Collaboration tool for tive testing is advised. experienced clinician and would entail cognitive test- to find other types of studies (eAppendix 1 in the Supplement). the overall search strategy was also designed a trained. including medical. 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.1%. specificity.com/ by a Hospital Pablo Tobon Uribe User on 09/28/2017 .24. Number 12 1163 © 2017 American Medical Association. we focused on studies in populations 65 years and older. which has been validated in various clinical settings.43 and the usefulness of the scale depends on the preva- screening tools are used to alert clinicians to the presence of pos.92). used in more than 4500 inappropriate communication.27 More recently. For 89. and (4) elderly adults. lence of decreased mental status in the population. search was limited to articles published in English. inattention (reduced ability to sustain attention and follow were retrieved for manual review. The 4AT provides a score range selected studies on pharmacologic prevention and treatment. 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. used delirium instrument worldwide. a positive screening test result should lead to further maximizing version. since this setting was considered outside the scope of in hospitalized patients. and either disorganized thinking or altered level of missing hypoactive delirium. and psy- original published studies to date and translated into 19 languages. Two hundred fifty-four full-text articles day. specificity Sedation Scale (mRASS).40 The Since 2011. level of consciousness. sensitivity. 2017 Volume 318. 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. such as problems articles were used for this review.42. orientation. and palliative care.26 have high ratings by the Standards for Reporting of Diagnostic Accuracy criteria. ICU 6 years.7 published in 1990. sible delirium. A total of 11 616 patients were represented in the provides a brief assessment (3 orientation items. with memory. the mRASS has a low sensitivity of 64% to of which have been developed in the past 6 years (Table 2). In settings with jama. inatten. These 70%. The 3-Minute Diagnostic Assessment (3D-CAM) cohort studies. (using the Cochrane highly sensitive search strategy for identify. The investigation for more definitive diagnosis of delirium. 2008 revision). The complete list of search strategies and a items. nursing home. and 55 were other categories including methodological of an underlying organic etiology or multiple etiologies is papers. the CAM7 is often used as a reference standard Clinical Diagnosis in studies of more newly developed delirium screening tools. ness. has been advocated as a screening tool for more than 20 delirium screening tools have been introduced.39 In recent years. 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. surgical. One hundred twenty-seven conversations). 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. (CAM-ICU). and (90%-95%). 3 symptom probes. disorganization of thought. continues to be the most widely includes assessment of disorientation.30 Both 3D-CAM and 4AT validation studies assessing risk of bias. overweighting of hyperactive or agitation symptoms and the risk of tion.and precision. limitations include the potential for delirium (acute onset and fluctuating course of symptoms. illusions or hallucinations. since delirium is more prevalent in older This tool is also brief and easy to administer and has a sensitivity of adults. of which 25 were clinical trials.25 In addition. which The CAM.

2 validation cohorts of assessment was completed using Diagnostic and Statistical Manual of Mental Disorders (DSM) IV or 5. possible delirium when score ≥4 89.4) 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. observer rating items.4) NR Possible delirium if (1) acute change in mental status 82 (90) 91 (69) κ = 0. of Screening Tool Setting No. 4 ORI. lThe sensitivity and specificity of 77. caregiver questionnaire 3D-CAM was validated with administration of all items. Informant Assessment of Geriatric Delirium scale. Number 12 (Reprinted) Clinical Review & Education Review Table 2. gInformation available at http://www. or Neelon and Champagne Confusion Scale. Some studies also comprehensive assessment system: acute change mental status from baseline.8 (7.m Hospital 239 (49) 82 (6. 4-7) 98 93 NR Software for objective 87 (dementia group) in delirium group. it will not yield a delirium diagnosis but only quantify the intensity of delirium. Delirium Rating Scale. Inter-RAI. PQI. intraclass correlation coefficient. fCAM-S is a tool to quantify the intensity of delirium.4l 63.65-1. Simple Query for Easy delirium screening tool does not apply. comparison of agreement between if any item in a section is answered incorrectly or endorsed as yes. SQeeC. specificity ranged from 66.79 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) 81.5) NR Maximum score = 10.9) <2 min Maximum score = 12. 10 (IQR. ICC = 0.4) NR Screening tool for acute care of confusion35 or was confused (subjectively or objectively) (2 PQI. 3D-CAM. cThere is a skip pattern option for which untrained nurses and geriatric psychiatrist calculated by each question. mental function varies over the determined the sensitivity and specificity of the screening tool for detecting delirium in individuals with course of the day. ORI.com .7 (71. patient Recovery sample.8%n Tool for informal caregivers 2-5 min (caregivers) and untrained nurses (7 ORI) Abbreviations: CAM.4% and 63.92 2 CQI. tool derived from the Short form.3%-92. 2017 Volume 318. NA. 7 (short form) NAf NA Long form. (2) validation study of a non-English version respectively.d Hospital 1219 (41) 77-80e Long form. dThe CAM-S is intended to be used in addition to the items. 3-Minute Diagnostic Assessment. DelApp31 Hospital 156 85 (delirium group <5 min Maximum score = 10. sensitivity and specificity in patients without dementia were 100% and 65.9) κ = 0.the4at. CAM-Severity Score. Maximum score: 19 (long form). Characteristics of Delirium Screening Tools (Last 6 Years)a Sensitivity Specificity Interrater Description (Cognitively (Cognitively Reliability (No. 6 ORI) RADAR36 Hospital.8) 7 s (average) Maximum score = 3. 6 (IQR. nComparison of agreement between cognitive impairment. Exclusion greater than 4 on the I-AGeD. CAM-S. possible delirium when score >4 77.5) 84. However.3 (8.g Hospital 234 (36) 84 (5. MOTYB. episode of disorganized speech.4) 67 (42.76 Screening tool and (2) mental function varies over the course of the day for acute care (4 ORI) MOTYB + signs Hospital 265 (51. not applicable. NR. Inter-Resident Assessment original CAM algorithm. IQR. possible delirium when score ≥1 73 (71.34-0.0% to 88.7% to of an existing delirium screening tool.com/ by a Hospital Pablo Tobon Uribe User on 09/28/2017 1164 JAMA September 26. then the rest of the PQI in that section and caregivers and geriatric psychiatrist ranged from 44% to 84% in agreement. and easily distracted.2% were derived from a cutoff score of DSM-derived criteria such as CAM. 4AT.88. interquartile range. kConstruction cohort N = 88. y Assessment Time Scoring Impaired). allowing administration of fewer questions (as few as 3). (% Male) Age. therefore. All rights reserved.5 90 64. 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. Months was validated in 2 different cohorts.4 (8.2 NR Caregiver-based questionnaire (10 CQI) Inter-RAI34. sustained attention counting task and is still in research phase. 10-10) in control group measurement of attention 75 (control group) (9 ORI. possible delirium when score ≥4 90 (94) 84 (91) NR Screening tool for delirium and cognitive impairment (5 PQI. I-AGeD. CAM (long form: 4 PQI. ICC = 0.2%. 4 A’s Test.0) (11 CQI) thinking OR (4) altered level of consciousness I-AGeD33 Hospital 88 (27)k 86. sensitivity and specificity as a Advances in Diagnosis and Treatment of Delirium questionnaire items. 2 ORI) © 2017 American Medical Association. (2) reference standard delirium cognitive impairment. 10 ORI)c CAM-S29. 193 (40) 80.8 (87. eCAM-S Instrument.9) 1-2 min (nurses).Downloaded From: http://jamanetwork.com. short form: 1 PQI.9%. Family-CAM. and those numbers are reported in parentheses. Recognizing Acute Delirium as Part of Your Routine. mean age was 77 years in the SAGES Study and 80 years in the Project of the Year Backwards. Sensitivity of 2 validation cohorts ranged from 70. %b Impaired). Confusion Assessment Method. 1 CQI. Mean (SD).65-0. or N = 59 and N = 33. j52 dyads (patient and caregiver).85 Screening tool for caregivers AND (2) inattention AND EITHER (3) disorganized (0. RADAR. hDelApp is a visual Evaluation of Consciousness. corresponding ORI can be skipped. the jama. NR Short form. 2 ORI) 4AT30. Maximum score = 18. CQI.1) 69 (27) NR Possible delirium if the patient failed MOTYB 93. ICC. iAll patients enrolled in the study had preexisting a Inclusion criteria: (1) study published during the defined search period. bSensitivity and specificity of the screening tool to detect delirium against 100%. Delirium assessment 10-15 min. FAM-CAM. median. criteria: (1) study of delirium in the critically ill (intensive care unit). 1 PQI)h FAM-CAM32 Homei 52 (33)j 82 (8) NR Possible delirium if (1) acute onset or fluctuation (88) (98) κ = 0. not reported. %b (95% CI) Question Items) 3D-CAM28 Hospital 201 (38) 84 (5.

risperidone. Standardized chart-based methods. orienting to surroundings.com (Reprinted) JAMA September 26. as well as cognitive function and Benzodiazepines should not be used as first-line treatment of delirium-associated agitation psychomotor activity. 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. or a combination of these mea. fluids. or both scores across the hospitalization. inOlderAdultsbestpracticestatement56 andabstractedclinicalpracticeguideline.com/ by a Hospital Pablo Tobon Uribe User on 09/28/2017 . a new scoring system based on either the short or long ver. none have yet been validated for clinical application. various larly episodes occurring during night shifts.46 The Delirium Obser. meta- been validated to show sensitivity of 74% and specificity of 83% in bolic. however. had the strongest association with a Adapted from American Geriatrics Society Expert Panel on Postoperative Delirium posthospital outcomes at 30 and 90 days. mental status change.geriatricscareonline.45 The DRS-R-98 has scale items cover. the combined method of interview plus chart pathogenesis of delirium. Since sensitivity and specificity determinations Because of its fluctuating nature and frequent hypoactive presen. neurodegenerative. preferably with nonopioid medications ing language.48 based on Biomarkers have assumed increasing importance. Therefore. In a recent review. since they may be identification of keywords (eg. provided for health care professionals nisms. 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. But Level of Evidence or Potential Risks Limit Strength of Recommendation sion of the CAM. others. This study demonstrated that episode severity measures are severely agitated. Inflammation is thought to play an important role in the panel. adequate oxygen. and neurotransmitter-based. monitoring re. interventions Includes mobility and walking. and nutrition sponse to treatment. Downloaded From: http://jamanetwork.org. since many cases of delirium will be missed. such as the sum of all CAM-S substantial harm to self.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). have been examined in the past comparison with a reference standard rating or clinical consensus 6 years. family members. American Geriatrics Society Clinical Practice Guidelines postoperative recovery room and ICU. and recent studies have focused on in- review48 is the recommended approach when complete and highly flammatory markers. hos. including length of stay. duration. however. disoriented/ useful for identifying patients at higher risk for developing delirium reoriented) by trained clinician abstractors.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. and evaluating pathophysiologic mecha. and cognition Medications to avoid Any medications associated with precipitating that are designed to capture gradations of symptom intensity. Number 12 1165 © 2017 American Medical Association. level of consciousness. 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.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. (eTable 1 in the Supplement). antihistamines. benzodiazepines. nisms. nurses. and death. quetiapine. can be used in combi. this may not be feasible in Biomarkers for Delirium many settings. Because delirium can be due to different etiologies. sleep hygiene. olanzapine. or threatening including both intensity and duration. routine use of the mRASS is not recommended out- Recommendation Description side of these settings. effective dose for shortest possible duration may be considered to treat delirious patients who sures. portance for tracking clinical course and recovery. cognitive change. Educational programs Ongoing. nursing home placement. avoiding physical (for prevention) restraints. Although numerous biomarkers have been studied. or ziprasidone) at the lowest tensity. motor symptoms. Pain management Should be optimized. high-dose opioids. Memorial Delirium Assessment Scale was designed for use in clini. for each screening tool can vary depending on the reference stan- tation. 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. thought processes. including interleukins and C-reactive protein50 sensitive detection of delirium is needed. encounters and need to be applied multiple times a day to improve the detection of delirium. particu. dard used. this approach may be valu. more standardization will improve the ability to cross- Interview-based methods are sometimes conducted during brief validate and to directly compare different screening tools.44 The delirium (eg. such as the Table 3. consensus diagnosis based on comprehensive assessment using information gathered from patients. vation Screening scale is a new nurse-based delirium measure47 that correlates strongly with DRS-R-98 scores. These methods have biomarkers. and yield clues to potential underlying pathophysiologic mecha- nation with interviews to maximize detection of delirium. including inflammatory. 2017 Volume 318. distressed. but validation studies have not yet been completed. Advances in Diagnosis and Treatment of Delirium Review Clinical Review & Education high prevalence of sedation and depressed sensorium. Refinement of Approaches for Definitive Diagnosis such as diagnosis or monitoring of delirium. Weak: Evidence in Favor of These Interventions. Pain management Injection of regional anesthetic at the time of surgery pital costs. the detection of delirium can be especially challenging. for the Prevention and Treatment of Postoperative Deliriuma able. tire hospital stay and compared 9 different measures reflecting in.23 Full guideline available at http://www. All rights reserved. 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. and Approaches to Maximize Detection of Delirium medical records.

with antipsychotics can prevent postoperative delirium. consultants. 0. These prevention strategies Introduce cognitively stimulating activities (eg. 2017 Volume 318. 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. 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. developed in accordance with Institute of Medicine stan. and hearing and vision fluids if necessary Seek advice regarding fluid balance in patients optimization by using hearing and vision aids as needed. 63 Prior to implementation of nonpharmacologic shown to be associated with a marked reduction in postop. with 1 study demonstrating an incremental net monetary Reduce noise at night benefit of £8180 (US $12 852 in 2014). but their success is dependent on adher- In 2014. findings suggestive of seizures results are not definitive.38 [95% CI.55 only 4. adequate hydration. cal adult patients 16 years and older.57. patient populations. cancer patients. In a recent Cochrane review medical evaluation of delirium etiology. 6 years are summarized in Table 5. Pharmacologic Approaches dards. whereas after implementation. 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. place. Clinical Review & Education Review Advances in Diagnosis and Treatment of Delirium Table 4. or treat.60]) among available and used by patients who need them hospitalized. approximately 20% of patients erative delirium53. non- your role ICU medical and surgical patients.com/ by a Hospital Pablo Tobon Uribe User on 09/28/2017 .com © 2017 American Medical Association.58). except in cases of alcohol or benzodiaz. or psychiatric caregivers. 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.54 and is currently under investigation in a large developed postoperative delirium. 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. Number 12 (Reprinted) jama. especially in patients with patients undergoing surgical hip fracture repair. regular ambulation Keep walking aids (canes.22 Sleep enhancement Avoid medical or nursing procedures during sleep if possible Multicomponent nonpharmacologic approaches are cost- Schedule medications to avoid disturbing sleep effective.51.23 The guide- lines. there was no clear benefit of ment for hypoactive delirium and avoidance of benzodiazepines antipsychotics as a group. education of health care professionals.25-0. approaches for delirium prevention have been examined in specific ment with medications that lower seizure threshold (eg. fective prevention strategies should be implemented together (typi- range-of-motion exercises cally 3 or more at a time) by a multidisciplinary team. person. Table 4 with comorbidities (heart failure. fluoro. Selected pharmacologic delirium prevention studies from the past logic prevention strategies. and avoiding high-risk medications for preventing delirium in hospitalized non-ICU medical and surgi- (Table 3). In 1 study of hospitalized patients with demen- quinolones.47 [95% CI. effective strategy for delirium prevention among hospitalized. consider parenteral reminiscence (for cognitive stimulation).9% of patients became delirious. and Ensure working hearing and visual aids are the risk of falls by 62% (odds ratio. specialized geriatric units. bispectral tia. and music therapy and psy- conditions. 0.52 In a recent innovation. sleep enhance- Facilitate regular visits from family. and terminal ill- Advances in Prevention and Treatment ness. New recommendations included avoidance of drug treat. All rights reserved. gaze deviation). these approaches resulted in noticeable decreases in delirium EEG monitoring and adjustment of anesthetic depth has been incidence.61. methodologic limitations preclude a definitive recommendation at 1166 JAMA September 26. non-ICU patients 65 years and older.60 Educating nursing aides and sive status epilepticus. therapeutic activities such as Fluid repletion Encourage patients to drink. how to implement delirium prevention strategies. however. ef- at all times Encourage all patients to engage in active. optimizing pain manage.60 Some studies suggest that prophylaxis for treatment of delirium. bupropion). Downloaded From: http://jamanetwork. delirium prevention approaches. focal dyscognitive seizures. plied in different settings. epine withdrawal. in long-term care.58 these approaches significantly reduced the risk of in- Vision and hearing Resolve reversible cause of the impairment cident delirium by 53% (odds ratio. orientation to time and place. the effect of these interventions on delirium incidence has been Development of systematic reviews and guidelines have served more limited. history of brain trauma or stroke.63 However. renal disease) provides details on these specific approaches to guide clinicians in Early mobilization Encourage early postoperative mobilization. clinical trial. 0.1 vention and treatment of postoperative delirium. friends ment.64-66 Geriatric consultative approaches have been ap- to facilitate application of more evidence-based approaches.38-0. calendars. but with a known history of seizures. signs. walkers) nearby Because delirium is usually precipitated by multiple factors. reminiscing) include early mobilization. Recent studies support the use of EEG in patients chotherapy have been examined for delirium prevention.59 Implement infection-control procedures This study took the novel approach of statistical modeling for Pain management Assess for pain.62 Multicomponent nonpharmacologic (eg. clocks therapeutic activities Reorient the patient to time. highlight the importance of multicomponent nonpharmaco. 0. 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. that examined prophylactic antipsychotics compared with control ment with nonopioids.

Delirium incidence 26/78 (33.68 RCT Cardiac surgery 101 (51/50) Risperidone. oral (3 mg/d) Placebo Delirium incidence 55/186 (29.5 mg/d) Placebo Delirium incidence 2/56 (3.com/ by a Hospital Pablo Tobon Uribe User on 09/28/2017 and diazepam (5 mg) Lurati et al.2-0.40 Hatta et al. Elective 119 (59/60) Haloperidol.5 mg/12 h among those with P = .001c Advances in Diagnosis and Treatment of Delirium in high-risk patients) patients Wang et al. Quality Category Study Design (Study Duration) (Intervention/Control) Intervention Control Outcome No. (0. Number 12 Review Clinical Review & Education 1167 .6) vs 10/52 (19.76 2016 Retrospective Hip fracture surgery 174 (78/96) Sugammadex. Last 6 Yearsa Overall jama.02d 72 de Jonghe et al.80 at induction and at initiation of cardiopulmonary bypass) Djaiani et al. medical 67 (33/34) Ramelteon.2) 5 2011 (2007-2008) P < .7 mg/d.4) vs 20/60 (33.5) 6 2014 (2008-2012) P = .38 Oh et al.4) 4 2012 (2009-2010) (1.67 Whitlock et al. All rights reserved.78 RCT Cardiac surgery 7507 (3755/3752) Methylprednisolone. intravenous No haloperidol Delirium incidence 25/59 (42.75 (0. intravenous Placebo Delirium incidence 35/229 (15.5) 4 (2012-2014) (2 mg/kg) intravenous P = . intravenous Neostigmine.73 RCT Hospital. Table 5.75 RCT Noncardiac surgery 385 (184/201) Sevoflurane Propofol Delirium incidence 21/184 (11.(%) Scoreb Antipsychotics (Typical and Atypical) Fukata et al.3) 5 2014 open-label. oral Placebo Delirium incidence 7/51 (13.3) vs 35/96 (36. Intervention vs Control.4) vs 29/205 (14. oral (0. 5 (2014-2015) (0.01g (continued) (Reprinted) JAMA September 26.69 PCT Hip fracture surgery 378 (173/205) Haloperidol.77 RCT Cardiac surgery 30 (15/15) Xenon Sevoflurane Delirium incidence 3/15 (20) vs 4/15 (27) 4 2013 (2011) P = .03 day 1) Melatonin or Ramelteon Al-Aama et al.4) vs 29/201 (14. medical 122 (61/61) Melatonin.01 mg/kg) Stoppe et al. oral No haloperidol Delirium incidence 73/173 (42.7) vs 17/50 (34) 6 2012 (2007-2010) (0.4) 6 2012 (2006-2010) P = .03 0.2-0. Selected Delirium Prevention Studies.3) P < .5) 6 2016 (2011-2014) (0.003 Perioperative Interventionse Ashraf et al. postoperative P = .6) vs 16/30 (43.03 postoperative day) subsyndromal delirium Vochteloo et al.4 μg/kg/h) 7/31 (22.6) vs 49/192 (25.1) 3 2011 (2008-2009) (1 mg/twice daily in lower-risk P < . GI/orthopedic (2.71 RCT Hospital.5 mg/d.4 μg/kg bolus. RCT Hip fracture surgery 378 (186/192) Melatonin.3) vs 53/228 (23. postoperative P = .31 prospective surgery days 1-3) (2007-2012) Hakim et al.05 mg/kg) + glycopyrrolate.79 RCT Cardiac surgery 183 (91/92) Dexmedetomidine Propofol Delirium incidence 16/91(17.7 μg/kg/h) Liu et al80 2016 RCT Orthopedic surgery 197 (99/98) Dexmedetomidine Placebo Delirium incidence In 65. intravenous © 2017 American Medical Association.70 RCT Noncardiac surgery 457 (229/228) Haloperidol. 2017 Volume 318.com Sources by Setting Sample Size Results.5) vs 29/92 (31. oral (8 mg/d) Placebo Delirium incidence 1/33 (3) vs 11/34 (32) 6 2014 (2011-2012) P = .67 Randomized. Placebo Delirium incidence 295/3755 (8) vs 289/3752 (8) 6 2015 (2007-2013) intravenous (250 mg P = . then (25-50 μg/kg/min) P = .to 75-year-olds.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.

Number 12 (Reprinted) intensive care unit stay could not be determined.3) vs 29/55 (52. 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 = . but the total number of individuals who Downloaded From: http://jamanetwork. with 1 point assigned for each and in individuals with normal cognition. In this study. 75 mg/12 h on 24/25 vs 21/25 postoperative days 1-5) P = .9) vs 11/143 (7.81 2017 RCT Cardiac surgery 285 (142/143) Dexmedetomidine Placebo Delirium incidence 7/142 (4. excluded. Whitlock et al78 [secondary outcome]).84 2014 (8 mg/d ×5 d) postoperative day 2 P = .04 e Abbreviations: CAM-ICU.3% (P < . Some studies were excluded if studies were conducted exclusively in the intensive care unit or the duration of f JAMA September 26.8% (P < .7) 6 (2014-2015) (0. oral (5 mg/d) Placebo Delirium presence 7/11 (64) vs placebo 9/14 (64) 6 al.01) for those c 75 years or older.5% bias = not enough information to make a clear judgment (high or unclear risk of bias on 1 or more domains). 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.01) for those aged 65 to 75 years and 37. high vs 90% (P < . Studies with overall quality score less than 2 were also Study duration not reported. P = .85 RCT Cardiac surgery 70 (35/35) Pregabalin.com/ by a Hospital Pablo Tobon Uribe User on 09/28/2017 from those of patients who received prophylaxis. (Lurati et al75 [tertiary end point]. Confusion Assessment Method for the Intensive Care Unit. Because of protocol violation. 2017 Volume 318. Delirium incidence was not the primary outcome for some of the perioperative intervention studies NS. and large study population. unclear risk of dexmedetomidine vs placebo (normal saline). d Numerator and denominators calculated after the prevalent delirium cases were subtracted (melatonin n = 5.7) on 5 al. jama.53 Marcantonio et RCT Hip fracture surgery 16 (7/9) Donepezil. less than 4 (high risk of bias on !2 domains). Patients with amnestic mild cognitive impairment: of 6 domains found to be at low risk of bias. Last 6 Yearsa (continued) Overall Sources by Setting Sample Size Results. nonsignificant. postoperative day 1: 5 2011 (2008-2009) on day 1. gastrointestinal. randomized clinical trial.8% (P < . (normal saline) 11. All rights reserved.6% vs 43.30 then 0. Patients with normal cognition: dexmedetomidine vs placebo risk of bias. Quality Category Study Design (Study Duration) (Intervention/Control) Intervention Control Outcome No.83 2011 (2007-2008) over time P = .94h Clinical Review & Education Review Papadopoulos et RCT Orthopedic surgeryf 106 (51/55) Ondansetron. stratified by age.7% vs 36. intravenous Placebo Delirium incidence 18/51 (35.6 μg/kg bolus. RCT. GI.01) for those aged 65 to 75 years and 16.4 μg/kg/h) Dighe et al. there were 26 patients in the high-risk group Denominator was number of interviews.9% vs 30. experienced delirium in each group are not reported. j Modified Finnish CAM-ICU score (highest 25 points). placebo n = 9).(%) Scoreb Li et al. Selected Delirium Prevention Studies. Intervention vs Control. but the delirium incidences in these patients were not significantly different i Study reports statistical significance on postoperative days 3 to 5.01) for those 75 years or older. © 2017 American Medical Association. intervention type. oral (150 mg/d Placebo CAM-ICU scorej Mean score. They were included because of the a study quality.07i Pesonen et al. Low risk of bias.com Advances in Diagnosis and Treatment of Delirium . 1168 Table 5. the patients received prophylactic haloperidol if they were determined to be at high risk based on h the Risk Model for Delirium score. 6 (low risk of bias in all domains). who did not receive haloperidol.82 RCT. more than 1 interview per patient. 22.

99 Only a few lim. The same meta-analysis also found minimal evi. One study showed that dexmedetomidine may To assist clinicians with the evaluation and treatment of delirium. nonpharmacologic management group also had better overall sur. In- function and decreased length of stay. 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.86. therapeutic Pharmacologic Treatment Approaches activities. 3D-CAM. and re- intervention in a clinical trial will be needed. Therefore. Number 12 1169 © 2017 American Medical Association. a be effective in reducing delirium incidence in patients with mild cog. and sleep anesthesia. or nonlicensed professionals chotic drugs including oral risperidone. The algorithm entails assessing delirium risk. and oral. 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). Several limitations of this review must be acknowledged. comes. and need for multicomponent approaches.com (Reprinted) JAMA September 26. oral sero. vention) of delirium in hospitalized older adults.60. heightened risk of adverse effects (ie. protocols—but with varying and limited results. include the use of volunteers. to enhance feasibility and reduce costs of implementation. these of antipsychotics in decreasing the duration or severity of delirium. 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 adaptations. tribute to heightened adverse effects and poorer long-term out- tipsychotics. diagnostic does not support the use of antipsychotics for treatment (or pre. Most studies do not show benefit cornerstone of delirium management . ing delirium once its presence is confirmed. however. and no definitive rec- including cholinesterase inhibitors. with all prior evidence. including the multifactorial contributors. antipsychotics for the treatment of delirium. prognosis. graded re- superimposed on dementia found no benefit on delirium duration lationship. and intra. early mobilization. Participants in the placebo/ improve delirium care. intramuscular ziprasidone. including tight control of glucose lev. hospital or intensive care effective pharmacologic treatments for delirium have not yet length of stay. with high satisfaction rates and sured with the new CAM-S scoring. 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. 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. 2017 Volume 318.60 establish safe and effective pharmacologic treatment approaches.87 Moderate. for the treatment of delirium. and streamlined approaches A recent comprehensive. For complete capture of delirium episodes. While such an approach has not been validated. els and blood transfusions for delirium prevention in the periopera. However. hydration. but this finding will need to be replicated in larger thesizes recent evidence gleaned from this comprehensive review studies. a combined or severity but did demonstrate significantly improved executive approach including interview and chart review is recommended. melatonin. and treating delirium quality evidence suggests that adjusting the depth of anesthesia using both nonpharmacologic and. Moreover. has been recognized as increas- decreased hospitalization rates. and 4AT) to the long-term care setting for prevention and treatment of delirium improve delirium identification. aides. been identified. safe and highly change in delirium duration. nificant decrease in delirium incidence among 19 studies and no Although promising approaches are emerging. More research is needed to receptor agonist (ramelteon).91. vival compared with those in the haloperidol group. similar to the initiative by the Centers for Medi- psychotic drugs in palliative care settings. severity. and melatonin. 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. complexity. such as that mea- and found that it was feasible. dence of delirium. oral olanzapine. Delirium severity. nutrition. participants receiving care & Medicaid Services to reduce the use of antipsychotics for oral risperidone or haloperidol had higher delirium symptom scores improved dementia care. sleep strategies. which syn- nitive impairment. detailed suggested algorithm is presented in the Figure. based on meta-analysis. Devel- quel. All rights reserved. instituting delirium prevention measures. which may decrease risk. 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. further testing of the ingly important for tracking clinical course. The literature search was restricted to the past 6 years. multimorbidity.80 Other strategies. jama. evaluating and manag- tive setting. pharma- according to bispectral index monitoring can decrease the inci. Downloaded From: http://jamanetwork. have shown varying degrees of benefit. However.com/ by a Hospital Pablo Tobon Uribe User on 09/28/2017 . in a randomized clinical trial of atypical anti. or reduction in mortality. approaches can be labor intensive. drug interactions). ited studies have considered pharmacologic approaches other than dence to support the use of medications to prevent delirium. intravenous. opment of effective treatments have been hindered by multiple muscular haloperidol100 and concluded that the current evidence challenges. There was no sig. Advances in Diagnosis and Treatment of Delirium Review Clinical Review & Education this time (Table 5). in appropriate cases. cologic strategies. bright light therapy.92 Primary prevention with multicomponent nonpharmacologic approaches such as reorientation.88 it is based on the best available evidence from prior studies and in- corporates relevant recent evidence.89 A recent clinical trial sponse to treatment. ommendations can be made at this time. systematic review examined antipsy. 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.

Placebo Delirium symptom Haloperidol vs placebo: 0.25 mg every 12 h.6) quetiapine) Olanzapine.5 mg. Quality Category Study Design Duration) Control) Intervention Control Outcome No. RCT. Doses could be titrated by 0. Haloperidol. then P = .5-10 Risperidone. high halved.9) [olanzapine] P = .98 2013 Prospective Hospital. oral (1-20 from baseline by [olanzapine].9 (6.93 RCT Cardiac surgery 53 (27/26) Morphine sulfate. Number 12 (Reprinted) Schrøder Pedersen Prospective cohort Cardiac surgery 240 (123/117) Standardized treatment with No standardized Delirium duration 3 (range. initial. up scores on day higher in haloperidol group. up to intramuscular (5 mg.56 h vs 33. 2017 Volume 318. Hospital. Participants 65 years or younger received a 0.42c Kishi et al.59 score = more severe) JAMA September 26.2) vs 14/21 (66. 82 Haloperidol. cancerd 29 (intervention) Risperidone. participants older than 65 years.2) mg/d) DRS-K [quetiapine] Quetiapine.25-4 mg/d) ≥50% reduction [risperidone]. oral P = . medical 80 (23 haloperidol/21 Haloperidol.7) [risperidone]. Aripiprazole (18. oncology 84 (21 haloperidol/21 Haloperidol (5. 14/29 (48) vs DRS-R-98 from 15/29 (51) baseline to day 7) Maneeton et al. 249 (81 haloperidol. unclear risk of maximum dose of 4 mg.5-2 Delirium severity by 22. initial.24 U 6 hospital palliative risperidone/86 placebo) oral (0. P = . up those with P = . medical 52 (24/28) Quetiapine.6) 2 observa-tional surgicald risperidone. 18 mg/d) (0. All rights reserved.5 mg.61 20 mg/d) to 20 mg/d) hyperactive delirium Boettger et al.95 2012 Case series Hospital.2) vs 3 2015 matched (2000-2006) risperidone. sedation clinical trial.9) vs 21. 21 olanzapine) Olanzapine (7. oral (0. Selected Delirium Treatment (Typical and Atypical Antipsychotics) Studies.1 mg) profiles (typical vs 16/21 (76. randomized Adverse effects: extrapyramidal symptoms (haloperidol.8%]).02 c Abbreviations: DRS-K. with 1 point assigned for each of 6 dose of 0. 12/18 (66. Low risk of bias. 25% number of treatment responders reduction in the vs nonresponders. 1-5) d vs 1 (range. a d Some studies were excluded if studies were conducted exclusively in the intensive care unit or the duration of Study duration not reported.97 2014 (2012) haloperidol. Intervention vs Control.5-1 mg No control group Delirium severity No significant differences in the 2 to start.com/ by a Hospital Pablo Tobon Uribe User on 09/28/2017 Agar et al. 18 olanzapine.com Advances in Diagnosis and Treatment of Delirium .7 (6.23 taper) Yoon et al.96 RCT Hospital.(%) Scoreb Atalan et al. © 2017 American Medical Association. Delirium duration in 31. For participants older than 65 years. risperidone.2) [aripiprazole]. 21 aripiprazole. 6 (low risk of bias in all domains). jama. oral (0. with domains found to be at low risk of bias. 1170 Table 6. Last 6 Yearsa Overall Sources by Setting (Study Sample Size (Intervention/ Results. less than 4 (high risk of bias on !2 domains).5 d.3 mg) Delirium resolution 16/21 (76. oral Delirium severity 15/23 (65. intensive care unit stay could not be determined. 1 of 21 [4. and maximum doses for participants 65 years or younger and for excluded.5-5 mg treatment protocol d 3 times daily ×1.5-mg loading dose with the first b The quality rating was based on the Cochrane risk of bias overall quality score.99 2017 RCT Inpatient hospice. oral (2. risk of bias.9 h 4 2013 (2010-2012) intramuscular (5 mg. (olanzapine. then titrated) (responder. care (2008-2014) to 2 mg/d)e 3 (higher P = . risperidone. Korean version of the Delirium Rating Scale–Revised-98 (DRS-R-98).5-mg maintenance dose every 12 hours. 6 of 21 [28.009 score = more Risperidone vs placebo: 0. the loading. Studies with overall quality score less than 2 were also e The study had different loading.5 mg) Risperidone (1.3 mg) and adverse-effect 18/21 (85. oral (25-100 Haloperidol. then 0.25 to 0. 4 of 21 [19%].97 (25-200 mg/d) Downloaded From: http://jamanetwork. and maximum doses were bias = not enough information to make a clear judgment (high or unclear risk of bias on 1 or more domains).94 Open-label.7) 5 2013 (2009-2011) mg/d for 1-7 d) mg/d for 1-7 d DRS-R-98 (higher P = . and Clinical Review & Education Review (mean doses 4-7 d) atypical) 13/21 (61. 1-4) 3 et al. oral (0.48 U severe) higher in risperidone group.6%]). and 13/18 (72.

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

and its symptoms: comparison of nurse and researcher 13. Alessi CA. serious condition associated with increased nistic understanding of delirium. Washington. mon and a highly morbid condition among older adults. Wong JG. Foreman MD. 9. Acad Emerg Med.com © 2017 American Medical Association. which is com- ized clinical trials represent an important priority for the field. Borson S.146(3):295-300.edu. van Dyck CH. Harvard Medical School). The frequency to diagnose bacterial meningitis? JAMA. and by the ratings. Delirium in elderly people. Fearing MA. and many brief delirium screening tools ing (eTable 1 in the Supplement). Kim SY. 1990. associations between delirium and mortality according to delirium subtype and age: Conflict of Interest Disclosures: All authors have REFERENCES a prospective cohort study. Administrative. 2017 Volume 318. 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A short portable mental status 3UL1TR001102 from the National Center for 2000. analysis. whereas pharmacologic pre- viding neuroprotection. the Roberts Fund (Dr Oh). Support 14.livingston@jamanetwork. Hospital. 2014. Rafanan AL. Inouye. Balkin S. R01AG044518 (Dr Inouye).23(8):2427-2433. (Dr Inouye). treatment. Along with thorough clinical ex- cluding interleukins and C-reactive protein. disorder and thereby effectively treat this condition. et al. analysis. Inouye SK. Diagnostic and patient have acute meningitis? JAMA. 12. technical. Geneva. Dokmak A.101 inflammatory etal costs. Attia J.stratifyingrisk.102 and fluid biomarkers are being studied to enhance clinical risk strati- Similartobiomarkerstudiesinotherfields. Meldon S. Helfand and Lynne Morishita. Prevention of delirium using nonpharmacologic ap- physiologically targeted approaches. mdm608@northwestern. the manuscript for publication. Submissions: We encourage authors to submit papers for consideration as a Review. Hshieh. Inouye SK. dedicated to the memory of Joshua Bryan Inouye The Confusion Assessment Method: a systematic Drafting of the manuscript: All authors. Hustey FM. or Mary McGrae McDermott. for her assistance with the literature 941-948. Given the complex and multifactorial eti. management. Metersky ML. none were reported. Pharmacologic prevention and treatment of forms across laboratories and validation across different clinical popu. Palmer R. 2011. Prevalence and documentation of impaired mental status in elderly elderly. Massachusetts General World Health Organization. Levy Family Chair (Dr Inouye). Brush M.standardizationofassayplat.296 Role of the Funder/Sponsor: The funding sources of missed delirium in patients referred to palliative (16):2012-2022. 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. (Department of Neurology. 2000. Concept and design: All authors. Fan J. completed and submitted the ICMJE Form for 77(8):903-910. Please contact Edward Livingston. MD. combination approaches. MD. The ICD-10 Retrospective analysis: are fever and altered mental the assistance of Asha Albuquerque. and nonpharmacologic manage- lations will facilitate incorporation of biomarkers into clinical practice. Int J Geriatr Psychiatry. and Care Cancer. or material support: Oh. Williams A. Katz KH. All rights reserved. delirium remains controversial. preparation. Kim SW. How do K07AG041835 (Dr Inouye) from the NIA. Lancet. Welch Confusion Assessment Method: a new method for responsibility for the integrity of the data and the Medical Library. 2017. 2015. Number 12 (Reprinted) jama. 2001. Clinical Review & Education Review Advances in Diagnosis and Treatment of Delirium our recommendations. Raeburn CD. or 5. adequately powered random. or interpretation of data: All compensation for their contributions. J Am Geriatr Soc.15(11):1021-1027. Nurses’ recognition of delirium and (10):433-441. boosting cognitive reserve. ment of delirium remains the cornerstone of delirium prevention and Innovative treatment approaches may include identifying patho. pro. stratification of delirium. 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. care in a comprehensive cancer center. proaches is documented to be effective. 2006.monitoringseverity. Institutes of Health/National Institute on Aging (NIA) (Dr Oh). These persons received no extra Acquisition. Switzerland: Accepted for Publication: August 9. Horwitz RI. Delirium is a common. Wei LA. 2008. 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. Author Contributions: Drs Oh and Inouye had full review of an earlier draft of this manuscript. Tran ZV.org in older adults. search. et al. detection of delirium. Yennu S. 1975. Biomarkers are likely to play an increasing role in confirm- ingdiagnosis.383 11. High- priority areas for future investigation are outlined in eTable 2 in the Conclusions Supplement. Arch Surg. review. Mion LC. review of current usage. 175-181. collection. fication and diagnosis. ARTICLE INFORMATION and the assistance of Eyal Kimchi.161(20):2467-2473. Straus SE. Future high-quality. at 10. (9920):911-922. I perform a lumbar puncture and analyze the results Milton and Shirley F. with delirium. Inouye SK. BA. for the literature review in this study 1172 JAMA September 26. enhancing sleep. DC: American Psychiatric Society. 2015. and Alexandra Classification of Mental and Behavioural Disorders: status indications for lumbar puncture in a Pletnikova. Saczynski JS. at Edward. World Health Organization. 3. deficit in elderly patients. J Am Geriatr Soc. Psychosom Med. in. adequately powered studies of pharmaco- ology of delirium. BA.56 Critical revision of the manuscript for important (5):823-830. Statistical analysis: Hshieh. grant emergency department patients. and decision to submit Statistical Manual of Mental Disorders. Pfeiffer E. The Rational Clinical Examination: does this adult interpretation of the data. Moss M. Differential Supervision: Oh. We are access to all of the data in the study and take Siegal AP. This work is 8. Inouye SK. 4. the results amination and laboratory testing. 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. recognition and risk stratification. Advances in the pathophysiologic understanding of delirium will be critical to advance the diagnosis and treatment of delirium.23 grants P01AG031720 (Dr Inouye).50. R24AG054259 Cooney LM Jr. Thorpe KE. and using multipronged vention and treatment of delirium remains controversial. Robinson TN. 5th ed. Additional Contributions: We gratefully acknowledge 6. Hatala R. Holroyd-Leduc J.282(2): approval of the manuscript. had no role in the design and conduct of the study. 1999. PhD Diagnostic Criteria for Research.

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