Evidence-based Synthesis Program Department of Veterans Affairs

Health Services Research & Development Service Evidence-based Synthesis Program 

Delirium: Screening, Prevention, 

and Diagnosis – A Systematic Review 

of the Evidence

Department of Veterans Affairs

Health Services Research & Development Service

September 2011

Prepared for:

Department of Veterans Affairs

Veterans Health Administration

Health Services Research & Development Service

Washington, DC 20420

Prepared by:

Evidence-based Synthesis Program (ESP) Center

Minneapolis VA Medical Center

Minneapolis, MN

Timothy J. Wilt, MD, MPH, Director

Investigators:

Principal Investigator: 

Rebecca Rossom, MD, MSCR

Co-Investigators:

Pauline Anderson, RN 

Nancy Greer, PhD

Research Associates:

Roderick MacDonald, MS

Indulis Rutks, BS

James Tacklind, BS
i

Delirium: Screening, Prevention, and Diagnosis – 

A Systematic Review of the Evidence Evidence-based Synthesis Program

PREFACE

Health Services Research & Development Service’s (HSR&D’s) Evidence-based Synthesis 

Program (ESP) was established to provide timely and accurate syntheses of targeted healthcare 

topics of particular importance to Veterans Affairs (VA) managers and policymakers, as they 

work to improve the health and healthcare of Veterans. The ESP disseminates these reports 

throughout VA.

HSR&D provides funding for four ESP Centers and each Center has an active VA affiliation. The 

ESP Centers generate evidence syntheses on important clinical practice topics, and these reports 

help:

• develop clinical policies informed by evidence,

• guide the implementation of effective services to improve patient outcomes and to 

support VA clinical practice guidelines and performance measures, and 

• set the direction for future research to address gaps in clinical knowledge.

In 2009, the ESP Coordinating Center was created to expand the capacity of HSR&D Central 

Office and the four ESP sites by developing and maintaining program processes. In addition, 

the Center established a Steering Committee comprised of HSR&D field-based investigators, 

VA Patient Care Services, Office of Quality and Performance, and Veterans Integrated Service 

Networks (VISN) Clinical Management Officers. The Steering Committee provides program 

oversight, guides strategic planning, coordinates dissemination activities, and develops 

collaborations with VA leadership to identify new ESP topics of importance to Veterans and the 

VA healthcare system.

Comments on this evidence report are welcome and can be sent to Nicole Floyd, ESP 

Coordinating Center Program Manager, at nicole.floyd@va.gov.

Recommended citation: Greer N, Rossom R, Anderson P, MacDonald R, Tacklind J, Rutks 

I, Wilt TJ. Delirium: Screening, Prevention, and Diagnosis - A Systematic Review of the 

Evidence. VA-ESP Project #09-009; 2011.

This report is based on research conducted by the Evidence-based Synthesis 

Program (ESP) Center located at the Minneapolis VA Medical Center, 

Minneapolis, MN funded by the Department of Veterans Affairs, Veterans Health 

Administration, Office of Research and Development, Health Services Research 

and Development. The findings and conclusions in this document are those of 

the author(s) who are responsible for its contents; the findings and conclusions 

do not necessarily represent the views of the Department of Veterans Affairs 

or the United States government. Therefore, no statement in this article should 

be construed as an official position of the Department of Veterans Affairs. No 

investigators have any affiliations or financial involvement (e.g., employment, 

consultancies, honoraria, stock ownership or options, expert testimony, grants or 

patents received or pending, or royalties) that conflict with material presented in 

the report.
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Delirium: Screening, Prevention, and Diagnosis – 

A Systematic Review of the Evidence Evidence-based Synthesis Program

EXECUTIVE SUMMARY

BACKGROUND

Delirium is a common syndrome in hospitalized or institutionalized adults. It is characterized 

by the acute onset of altered mental status, hallmarked by difficulty sustaining attention and 

a fluctuating course. Delirium frequently causes patients, families, and health care providers 

considerable distress. The incidence varies widely based on patient population, setting, and 

intensity of diagnostic ascertainment with reported values of 10% to over 80%. Delirium is 

associated with multiple serious outcomes including increased morbidity, length of hospital 

stay, healthcare costs, institutionalization, and mortality.1,2,3 In surgical settings, older adults 

and those with multiple medical conditions are at increased risk for postoperative delirium.4

Delirium may be under-recognized by healthcare providers and it can be difficult to resolve.5,6

Several brief “bedside” questionnaires and checklists exist that can help detect delirium earlier 

and among those with milder symptoms. Additionally, efforts to prevent the development of 

delirium in those at risk have been advocated.3,6 Medications (including sedatives, narcotics, and 

anticholinergic drugs), diseases and intercurrent illnesses (e.g., stroke, infection, shock, anemia), 

surgical procedures (especially orthopedic and cardiac surgery), and environmental factors 

(e.g., use of a bladder catheter, pain, and emotional stress) are all associated with delirium.3,7

Therefore, identifying and implementing effective strategies to prevent and detect delirium could 

improve clinical outcomes and resource utilization. Suggested strategies to prevent delirium 

include avoidance of psychoactive medications, pharmacologic interventions to decrease risk, 

and single- or multi-component non-pharmacologic interventions (including use of music, 

mobilization, fluid and nutrition management, and orientation and cognitive stimulation).4,6,7

This review was undertaken to evaluate the effectiveness of screening for delirium, the 

effectiveness and harms of strategies to prevent delirium, and the comparative diagnostic 

accuracy of tools used to detect delirium. Specifically, we addressed the following key questions:

1. What is the effectiveness of screening for delirium in adult inpatients? 

a. Do these results vary by medical unit, age, gender or comorbid conditions? 

b. Does screening for delirium improve clinical outcomes? 

2. What are the effectiveness and harms of delirium prevention strategies in acute elderly 

inpatients? 

a. Do these results vary by medical unit, age, gender or comorbid conditions?

3. What is the comparative diagnostic accuracy of the tools used to detect delirium:

a. In elderly medical and surgical inpatients?

b. In elderly medical or surgical intensive care unit (ICU) inpatients?
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Delirium: Screening, Prevention, and Diagnosis – 

A Systematic Review of the Evidence Evidence-based Synthesis Program

METHODS

We searched MEDLINE, CINAHL, and PsycINFO from 1950 to November 2010 using standard 

search terms (Appendix A). We limited the search to peer-reviewed articles involving human 

subjects and published in the English language. Additional citations were identified from 

reference lists and Technical Expert Panel members. Titles and abstracts were reviewed by 

physicians, nurses, and research assistants trained in the critical analysis of literature. Full text 

versions of potentially relevant articles were similarly reviewed. Study characteristics, patient 

characteristics, and outcomes were extracted and evidence and outcomes tables, organized 

by key question, were created under the supervision of the Principal Investigator, a geriatric 

psychiatrist. 

We assessed study quality of randomized trials of prevention strategies (Key Question 2) 

according to the following criteria: 1) adequate allocation concealment, 2) blinding of key study 

personnel, 3) analysis by intention-to-treat, and 4) reporting of number of withdrawals/dropouts 

by group assignment. Study quality of studies reported for Key Question 3 (studies of diagnostic 

accuracy) was assessed using the method described in the Rationale Clinical Examination series.8

DATA SYNTHESIS

We constructed evidence tables showing the study characteristics and results for all included 

studies. We critically analyzed studies to compare their characteristics, methods, and findings. 

Pooled analyses were performed, where feasible, for studies of prevention strategies. All other 

data were narratively summarized.

PEER REVIEW

A draft version of this report was reviewed by technical experts, as well as VA clinical leadership. 

Reviewer comments were addressed and our responses incorporated in the final report. 

RESULTS

For the screening question, we identified 1,889 abstracts and excluded 1,778. We reviewed the 

full text of 111 references and none met inclusion criteria. For prevention, we identified 1,175 

abstracts and excluded 947. Of 228 full text articles reviewed, 31 met eligibility criteria. We 

added 8 references from hand-searching for a total of 39 included references. For diagnostic 

accuracy in intensive care units, we identified 76 abstracts and excluded 40 of those. Of 36 full 

text articles reviewed, 15 met inclusion criteria.

KEY QUESTION #1. What is the effectiveness of screening for delirium in adult 

inpatients? 

1a. Do these results vary by medical unit, age, gender or comorbid conditions? 

1b. Does screening for delirium improve clinical outcomes?

We identified no randomized controlled trials of screening for delirium in hospitalized patients. 

There is no direct evidence that screening for delirium is beneficial or harmful. However, while 
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Delirium: Screening, Prevention, and Diagnosis – 

A Systematic Review of the Evidence Evidence-based Synthesis Program

potentially beneficial, universal screening may also pose harms, such as misclassification, 

subsequent treatment of non-delirious patients, or failure to accurately identify or intervene 

on delirious patients. Additionally, we found no evidence from recent systematic reviews that 

pharmacologic and non-pharmacologic treatments improve outcomes for patients with screendetected delirium. Therefore, we conclude that the evidence is insufficient about the net benefit 

of delirium screening among all hospitalized patients or subgroups of patients as defined by age, 

gender, comorbidities or admission to intensive care units.

KEY QUESTION #2. What are the effectiveness and harms of delirium prevention 

strategies in acute elderly inpatients? 

2a. Do these results vary by medical unit, age, gender or comorbid conditions?

We identified randomized and non-randomized trials of pharmacologic and non-pharmacologic 

strategies for prevention of delirium. Studies using pharmacologic interventions to prevent 

delirium were few in number, small in size, and examined different categories of prevention 

medications often in unique patient populations and settings. Moderate level evidence from 

two studies of atypical antipsychotics and low level evidence from one study each of analgesia 

via fascia iliaca compartmental block (pre- and post-operative), lighter anesthesia, or postoperative sedation with dexmedetomidine suggests that these pharmacological approaches 

may reduce the incidence of delirium following orthopedic or cardiac surgery. There was no 

difference in delirium incidence associated with the use of cholinesterase inhibitors, statins, a 

benzodiazepine/opioid protocol, or regional versus general anesthesia and the evidence for using 

typical antipsychotics is mixed. Multi-component strategies varied greatly but often included 

staff education plus additional components such as geriatric consultation, individual care 

planning, focused prevention of infection, improving mobility, frequent orientation, bowel and 

bladder care regimens, insomnia protocols, adequate pain management, minimizing psychoactive 

or sedating medications, and maintaining adequate hydration and nutrition. Strategies were 

generally successful in preventing delirium but intervention variability and lack of assessment 

of individual intervention components made it difficult to determine which components may be 

effective. Limited evidence suggests that staff education alone or music therapy may be effective 

strategies. In one small study, bright light therapy was found to be not effective for delirium 

prevention. Harms were infrequent and mild.

None of the included studies were stratified by medical unit, age, gender, or comorbid conditions 

although two studies enrolled only men. There is insufficient evidence to determine whether 

the effects of different preventive strategies vary by medical unit, age, gender, or comorbid 

conditions. 

KEY QUESTION #3. What is the comparative diagnostic accuracy of the tools 

used to detect delirium:

3a. In elderly medical and surgical inpatients?

3b. In elderly ICU inpatients?

A systematic review of the comparative effectiveness of bedside instruments concluded that the 

Confusion Assessment Method (CAM) was a suitable tool for medical and surgical inpatients, 

many of whom were evaluated in geriatric units. Using Diagnostic and Statistical Manual of 
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Delirium: Screening, Prevention, and Diagnosis – 

A Systematic Review of the Evidence Evidence-based Synthesis Program

Mental Disorders (DSM) criteria performed by a specialist physician as a reference standard, 

the pooled sensitivity and specificity of the CAM were 86% and 93%, respectively. The pooled 

likelihood ratio for a positive test was 9.6 (95%CI 5.8 to 16.0). The pooled likelihood ratio for 

a negative test was 0.16 (95%CI 0.09 to 0.29). However, there was considerable heterogeneity 

in the 12 studies. The ease of administration (completion in less than 5 minutes) was also 

considered although it was noted that administrators should be trained for optimal use and that 

the CAM was originally developed for use in conjunction with a formal cognitive assessment. 

The accuracy of bedside instruments delivered by individuals without training as stand-alone 

tools for delirium screening is not known.

Fewer studies have evaluated the diagnostic accuracy of tools to detect delirium for elderly 

intensive care unit (ICU) inpatients. The CAM-ICU, a version of the CAM adapted for use in 

the ICU, appears to have high specificity but the sensitivity is less consistent (ranging from 64 

to 100%) indicating that some patients with delirium will not be identified using the CAM-ICU 

alone. Other tools have been evaluated in only one or two studies.

FUTURE RESEARCH

The highest future research need is to conduct a large multicenter pragmatic randomized trial to 

evaluate the clinical effectiveness and harms of screening for delirium in a broad spectrum of 

patients admitted to hospitals. More research is needed to verify the findings that pharmacologic 

and non-pharmacologic strategies can prevent delirium, particularly in larger and more 

diverse populations, and with reports stratified by age, medical unit, and comorbid conditions. 

Additionally, more research is needed to identify which components of the multi-component 

non-pharmacologic strategies may be most successful in delirium prevention. Finally, continued 

evaluation of diagnostic tools (especially bed side tools in stand-alone settings administered by 

clinical personnel) is warranted especially across a wide range of populations and settings.