Quick Delirium Literature Update

I regularly run  quick medical literature searches on PubMed as a check on how to improve my current practice as a consulting psychiatrist in a large academic medical center. I’m frequently called to consult on difficult delirium cases. My recommendations often include instructions to simplify a patient’s medication regimen, which can include anticholinergic and sedative hypnotic medications. Pharmacologic prevention and treatment of delirium in the general hospital and in the intensive care unit often entail managing the agitation of patients with antipsychotics as well, which is supported by current reviews, though larger and better-quality studies are needed [1,2].

Many patients have medical conditions that militate against using antipsychotics, including but not limited to prolonged cardiac conduction, often approximated by the QTc interval. Occasionally I’ll suggest considering Dexmedetomidine as an alternative anesthetic agent, which is not a psychotropic drug but one with which intensivists are likely to be familiar [3].

It’s not unusual to find hospitalists who are unfamiliar with standard screening tools for delirium, like the Confusion Assessment Method (CAM). Others include the Delirium Observation Screening Scale (DOSS), which nurses adopted for use at our hospital [4].

Ideally, we’d like to prevent delirium, preferably using nonpharmacologic multicomponent methods, some of which can be replicated in smaller community hospitals. One limitation might be coming up with the twenty or so volunteers needed to implement many of the interventions [5-7].

We also need a comprehensive change in culture and policy with respect to our approach to training medical professionals and prioritizing the prevention of delirium in hospitals [8]. O’Hanlon and colleagues had a nice list of a dozen points for improving care. It might even be a nice idea for a Dirty Dozen.

12 point plan for improved delirium care from O'Hanlon, S., et al., Improving delirium care through early intervention: from bench to bedside to boardroom. Journal of Neurology, Neurosurgery & Psychiatry, 2013.

12 point plan for improved delirium care from O’Hanlon, S., et al., Improving delirium care through early intervention: from bench to bedside to boardroom. Journal of Neurology, Neurosurgery & Psychiatry, 2013.


1. Teslyar, P., V. M. Stock, et al. (2013). “Prophylaxis with Antipsychotic Medication Reduces the Risk of Post-Operative Delirium in Elderly Patients: A Meta-Analysis.” Psychosomatics 54(2): 124-131.

Background Delirium commonly occurs in hospitalized elderly patients, resulting in increased morbidity and mortality. Although evidence for treatment of delirium exists, evidence supporting pharmacologic prevention of delirium in high risk patients is limited. Objective This review examined whether delirium in at-risk patients can be prevented with antipsychotic prophylaxis in the inpatient setting. Data sources A systematic literature review of articles from January 1950 to April 2012 was conducted in PubMed, PsychInfo, and Cochrane Controlled Trials and databases. Study selection Five studies (1491 participants) met our inclusion criteria for analysis. Medication administered included haloperidol (three studies), risperidone (one study), and olanzapine (1 study). All five studies examined older post-surgical patients, spanning five different countries. Data extraction Only RCTs of antipsychotic medication used to prevent delirium were included. Key words used in the search were: “delirium,” “encephalopathy,” “ICU psychosis,” “prevention,” and “prophylaxis.” Studies had to include a validated method of diagnosing delirium. Data analysis was performed using the Metan command in Stata (Stata Corp LP, College Station, TX). Results The pooled relative risk of the five studies resulted in a 50% reduction in the relative risk of delirium among those receiving antipsychotic medication compared with placebo (RR(95% CI): 0.51 (0.33–0.79; heterogeneity, p < 0.01, random effects model). Examination of the funnel plot did not indicate publication bias. Conclusions Although few studies have examined prophylactic use of antipsychotics, this analysis suggests that perioperative use of prophylactic antipsychotics may effectively reduce the overall risk of postoperative delirium in elderly patients.

2. Meagher, D. J., L. McLoughlin, et al. “What Do We Really Know About the Treatment of Delirium With Antipsychotics? Ten Key Issues for Delirium Pharmacotherapy.” The American Journal of Geriatric Psychiatry(0).

Despite the significant burden of delirium among hospitalized adults, no pharmacologic intervention is approved for delirium treatment. Antipsychotic agents are the best studied but there are uncertainties as to how these agents can be optimally applied in everyday practice. We searched Medline and PubMed databases for publications from 1980 to April 2012 to identify studies of delirium treatment with antipsychotic agents. Studies of primary prevention using pharmacotherapy were not included. We identified 28 prospective studies that met our inclusion criteria, of which 15 were comparison studies (11 randomized), 2 of which were placebo-controlled. The quality of comparison studies was assessed using the Jadad scale. The DRS (N = 12) and DRS-R98 (N = 9) were the most commonly used instruments for measuring responsiveness. These studies suggest that around 75% of delirious patients who receive short-term treatment with low-dose antipsychotics experience clinical response. Response rates appear quite consistent across different patient groups and treatment settings. Studies do not suggest significant differences in efficacy for haloperidol versus atypical agents, but report higher rates of extrapyramidal side effects with haloperidol. Comorbid dementia may be associated with reduced response rates but this requires further study. The available evidence does not indicate major differences in response rates between clinical subtypes of delirium. The extent to which therapeutic effects can be explained by alleviation of specific symptoms (e.g. sleep or behavioral disturbances) versus a syndromal effect that encompasses both cognitive and noncognitive symptoms of delirium is not known. Future research needs to explore the relationship between therapeutic effects and changes in pathophysiological markers of delirium. Less than half of reports were rated as reasonable quality evidence on the Jadad scale, highlighting the need for future studies of better quality design, and in particular incorporating placebo-controlled work.

3. Mo, Y. and A. E. Zimmermann (2013). “Role of Dexmedetomidine for the Prevention and Treatment of Delirium in Intensive Care Unit Patients (June).” The Annals of Pharmacotherapy.

OBJECTIVE: To review recent clinical studies regarding the role of dexmedetomidine for prevention and treatment of delirium in intensive care unit (ICU) patients.DATA SOURCES: MEDLINE and PubMed searches (1988-Feburary 2013) were conducted, using the key words delirium, dexmedetomidine, Precedex, agitation, α-2 agonists, critical care, and intensive care. References from relevant articles were reviewed for additional information.STUDY SELECTION AND DATA EXTRACTION: Clinical trials comparing dexmedetomidine with other sedatives/analgesics or with antipsychotics for delirium were selected. Studies that evaluated the use of dexmedetomidine for sedation for more than 6 hours were included in this review.DATA SYNTHESIS: Dexmedetomidine is a highly selective α-2 receptor agonist that provides sedation, anxiolysis, and modest analgesia with minimal respiratory depression. Its mechanism of action is unique compared with that of traditional sedatives because it does not act on γ-aminobutyric acid receptors. In addition, dexmedetomidine lacks anticholinergic activity and promotes a natural sleep pattern. These pharmacologic characteristics may explain the possible anti delirium effects of dexmedetomidine. Eight clinical trials, including 5 double-blind randomized trials, were reviewed to evaluate the impact of dexmede to midine on ICU delirium.CONCLUSIONS: Currently available evidence suggests that dexmedetomidine is a promising agent, not only for prevention but also for treatment of ICU-associated delirium. However, larger, well-designed trials are warranted to define the role of dexmedetomidine in preventing and treating delirium in the ICU.

4. Young, R. S., K. Hinami, et al. (2012). “Hospitalists’ lack of knowledge of the Confusion Assessment Method: a barrier to systematic validated delirium surveillance.” Hosp Pract (1995) 40(4): 56-63.

INTRODUCTION: Delirium is frequently missed by inpatient health care providers despite the existence of a highly sensitive and specific assessment for delirium, the Confusion Assessment Method (CAM). The CAM, due to its test characteristics and ease of use, is an ideal physician instrument for systematic inpatient delirium screening; however, little is known about hospitalists’ knowledge of the CAM. METHODS: A short survey with items assessing respondents’ perceptions of delirium detection, familiarity and proficiency with the CAM, and knowledge of the CAM algorithm was administered at a regional hospital medicine conference. Participants included a group of hospital medicine providers comprised of physicians (79.9%), nurse practitioners (7.2%), and physician assistants (12.9%). Results in the form of counts, percentages, and distributions of Likert scale responses and multiple-choice questions were reported. RESULTS: Of 157 surveys distributed, 94% (n = 147) were returned. Approximately 3 of 4 of providers (77%) reported encountering delirium at least once per week, with 45% reporting encountering delirium more than once per week. Yet, 82% had never used or heard of the CAM; only 3 respondents felt proficient with its use. Of the knowledge items, 4 respondents were able to correctly indicate the 4 clinical features of the CAM. Only 1 respondent was able to answer all knowledge items correctly. The respondents also agreed that nurses have an important role in delirium detection (65%), delirium diagnosis is often delayed (68%), and reported that not knowing patients’ baseline cognitive status (53%) and having difficulty separating delirium from dementia or psychiatric illnesses (25%) were important challenges to delirium diagnosis. CONCLUSION: Hospital medicine providers who responded to the survey reported encountering delirium often in their clinical practice; however, they also reported poor familiarity with and demonstrated poor knowledge of the CAM. These results suggest a potential barrier to systematic inpatient delirium screening and support increased delirium education and the use of validated delirium assessments among hospitalists.

5. Reston, J. T. and K. M. Schoelles (2013). “In-facility delirium prevention programs as a patient safety strategy: a systematic review.” Ann Intern Med 158(5 Pt 2): 375-380.

Delirium, an acute decline in attention and cognition, occurs among hospitalized patients at rates estimated to range from 14% to 56% and increases the risk for morbidity and mortality. The purpose of this systematic review was to evaluate the effectiveness and safety of in-facility multicomponent delirium prevention programs. A search of 6 databases (including MEDLINE, EMBASE, and CINAHL) was conducted through September 2012. Randomized, controlled trials; controlled clinical trials; interrupted time series; and controlled before-after studies with a prospective postintervention portion were eligible for inclusion. The evidence from 19 studies that met the inclusion criteria suggests that most multicomponent interventions are effective in preventing onset of delirium in at-risk patients in a hospital setting. Evidence was insufficient to determine the benefit of such programs in other care settings. Future comparative effectiveness studies with standardized protocols are needed to identify which components in multicomponent interventions are most effective for delirium prevention.

6. Zhang, H., Y. Lu, et al. (2013). “Strategies for prevention of postoperative delirium: a systematic review and meta-analysis of randomized trials.” Crit Care 17(2): R47.

INTRODUCTION: The ideal measures to prevent postoperative delirium remain unestablished. We conducted this systematic review and meta-analysis to clarify the significance of potential interventions. METHODS: The PRISMA statement guidelines were followed. Two researchers searched MEDLINE, EMBASE, CINAHL and the Cochrane Library for articles published in English before August 2012. Additional sources included reference lists from reviews and related articles from ‘Google Scholar’. Randomized clinical trials (RCTs) on interventions seeking to prevent postoperative delirium in adult patients were included. Data extraction and methodological quality assessment were performed using predefined data fields and scoring system. Meta-analysis was accomplished for studies that used similar strategies. The primary outcome measure was the incidence of postoperative delirium. We further tested whether interventions effective in preventing postoperative delirium shortened the length of hospital stay. RESULTS: We identified 38 RCTs with interventions ranging from perioperative managements to pharmacological, psychological or multicomponent interventions. Meta-analysis showed dexmedetomidine sedation was associated with less delirium compared to sedation produced by other drugs (two RCTs with 415 patients, pooled risk ratio (RR) = 0.39; 95% confidence interval (CI) = 0.16 to 0.95). Both typical (three RCTs with 965 patients, RR = 0.71; 95% CI = 0.54 to 0.93) and atypical antipsychotics (three RCTs with 627 patients, RR = 0.36; 95% CI = 0.26 to 0.50) decreased delirium occurrence when compared to placebos. Multicomponent interventions (two RCTs with 325 patients, RR = 0.71; 95% CI = 0.58 to 0.86) were effective in preventing delirium. No difference in the incidences of delirium was found between: neuraxial and general anesthesia (four RCTs with 511 patients, RR = 0.99; 95% CI = 0.65 to 1.50); epidural and intravenous analgesia (three RCTs with 167 patients, RR = 0.93; 95% CI = 0.61 to 1.43) or acetylcholinesterase inhibitors and placebo (four RCTs with 242 patients, RR = 0.95; 95% CI = 0.63 to 1.44). Effective prevention of postoperative delirium did not shorten the length of hospital stay (10 RCTs with 1,636 patients, pooled SMD (standard mean difference) = -0.06; 95% CI = -0.16 to 0.04). CONCLUSIONS: The included studies showed great inconsistencies in definition, incidence, severity and duration of postoperative delirium. Meta-analysis supported dexmedetomidine sedation, multicomponent interventions and antipsychotics were useful in preventing postoperative delirium.

7. Zaubler, T. S., et al. (2013). “Quality Improvement and Cost Savings with Multicomponent Delirium Interventions: Replication of the Hospital Elder Life Program in a Community Hospital.” Psychosomatics 54(3): 219-226.
Delirium is a common problem associated with increased morbidity, mortality, and healthcare costs in the hospitalized elderly, yet there is little research outside of academic medical centers exploring methods to prevent its onset. The authors adapted the Hospital Elder Life Program (HELP) for use in a community hospital and assessed its impact on delirium rate, length of stay (LOS) and healthcare costs in elderly patients. Delirium episodes and duration, total patient-days with delirium and LOS were assessed in 595 patients 70 years of age or older admitted to a general medical floor at a community hospital. Pre-intervention outcomes were assessed on the medical floor for 4 months. Interventions adapted from HELP occurred over 9 months and included daily visits, therapeutic activities, and assistance with feeding, hydration, sleep, and vision/hearing impairment. Delirium was assessed on a daily basis with the Confusion Assessment Method (CAM). The rate of episodes of delirium decreased from 20% in the pre-intervention group to 12% in the intervention group, a relative 40% reduction (P = 0.019). Total patients days with delirium decreased from 8% in the usual care group to 6% in the intervention group (P = 0.005). LOS among all patients enrolled in the intervention group decreased by 2 days (P < 0.001). Interventions resulted in $841,000 cost savings over 9 months. HELP can be successfully adapted for implementation in a community hospital setting to decrease delirium episodes, total patient-days with delirium and LOS, and generate substantial cost savings.

8. O’Hanlon, S., N. O’Regan, et al. (2013). “Improving delirium care through early intervention: from bench to bedside to boardroom.” Journal of Neurology, Neurosurgery & Psychiatry.

Delirium is a complex neuropsychiatric syndrome that impacts adversely upon patient outcomes and healthcare outcomes. Delirium occurs in approximately one in five hospitalised patients and is especially common in the elderly and patients who are highly morbid and/or have pre-existing cognitive impairment. However, efforts to improve management of delirium are hindered by gaps in our knowledge and issues that reflect a disparity between existing knowledge and real-world practice. This review focuses on evidence that can assist in prevention, earlier detection and more timely and effective pharmacological and non-pharmacological management of emergent cases and their aftermath. It points towards a new approach to delirium care, encompassing laboratory and clinical aspects and health services realignment supported by health managers prioritising delirium on the healthcare change agenda. Key areas for future research and service organisation are outlined in a plan for improved delirium care across the range of healthcare settings and patient populations in which it occurs.

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