Washington University Emergency Medicine Journal Club – April 16th, 2026
Dr. Brian Cohn
Hello all,
This month’s journal club will be looking at the management of agitation in elderly patients with delirium. We will look at pharmacologic and non-pharmacologic treatment options. The PGY-1 paper will be appraised using the meta-analysis form. The PGY-2, 3, and 4 papers will be appraised using the Therapy form.
Vignette
You’re working an evening shift in the emergency department when EMS brings in an 82-year-old male with a history of Alzheimer’s dementia and recurrent UTIs from a skilled nursing facility for “acute confusion and agitation.” According to staff, the patient was at his baseline—confused but conversational—earlier that morning. Over the past several hours, he became increasingly disoriented, began yelling at staff, and attempted to climb out of bed multiple times, prompting transfer to the ED.
On arrival, the patient is visibly agitated. He is yelling incoherently, intermittently trying to get off the stretcher, and swatting at staff who attempt to examine him. His vital signs show a temperature of 38.3°C, heart rate of 108, blood pressure of 146/82, respiratory rate of 22, and oxygen saturation of 96% on room air.
The nurse asks if you would like to order some versed to help “calm him down.” At the same time, your attending suggests starting with non-pharmacologic measures and identifying the underlying cause, while also mentioning that medications may still be necessary if the patient becomes a danger to himself or staff.
As the patient continues to thrash and attempts to remove his IV, security is called to the bedside. The team looks to you for guidance—should you proceed with pharmacologic sedation, and if so, which agent is safest and most effective in this elderly patient? You pause for a moment, realizing that while treating agitation is urgent, the underlying issue may be delirium—and the best approach may not be as straightforward as simply giving an antipsychotic. You begin to wonder: what does the evidence say about managing agitation and delirium in elderly patients?
PICO Question
Population: Elderly patients (≥65 years) with acute delirium and/or agitation in the
hospital or ICU
Intervention: Pharmacologic treatment (e.g., antipsychotics, benzodiazepines,
dexmedetomidine
Comparison: Placebo, usual care, or non-pharmacologic management
Outcome: Duration of delirium, mortality, need for additional sedation/restraints,
adverse events (e.g., QT prolongation, oversedation)
Article 1: Casey MF, Elder NM, Fenn A, et al. Comparative safety of medications for
severe agitation: A Geriatric Emergency Department Guidelines 2.0 systematic
review. J Am Geriatr Soc. 2025;73(9):2893–2904. [Answer Key].
Article 2: Andersen-Ranberg NC, Poulsen LM, Perner A, et al. Haloperidol for the
treatment of delirium in ICU patients. N Engl J Med. 2022;387(26):2425–2435.
[Answer Key].
Article 3: Godet T, Louis C, Rieu B, et al. Dexmedetomidine for treatment of
hyperactive delirium in non-intubated ICU patients: the 4D randomized clinical trial.
Intensive Care Med. 2025;51(12):2305–2317. [Answer Key].
Article 4: Inouye SK, Bogardus ST Jr, Charpentier PA, et al. A multicomponent
intervention to prevent delirium in hospitalized older patients. N Engl J Med.
1999;340(9):669–676. [Answer Key].
Bottom Line
Delirium is relatively common among hospitalized patients, with an increasing risk seen with advancing age (Bugiani 2021). Delirium is seen in around 10 to 15% of elderly patients in the ED alone, and its presence in the ED has been associated with higher 30-day mortality and increased need for readmission within 30 days (Kennedy 2014). We sought to evaluate evidence related to the treatment and prevention of delirium among elderly patients in the ED, with a specific focus on the management of hyperactive delirium and agitation in this population, including both pharmacologic and non-pharmacologic treatment options.
A quasi-experimental trial of a multicomponent, nonpharmacologic delirium-prevention strategy in hospitalized older adults randomized patients to usual care or intervention. Patients in the intervention arm were treated using components of the Elder Life Program, targeting six modifiable delirium risk factors—cognitive impairment, sleep deprivation, immobility, visual impairment, hearing impairment, and dehydration—using standardized, nonpharmacologic protocols (e.g., orientation and cognitive activities, sleep hygiene, early mobilization, vision and hearing aids, hydration). The intervention achieved high adherence (~87%), with modest cost per case prevented, and demonstrated a significant reduction in the incidence of delirium compared with usual care (9.9% vs 15.0%; OR 0.60, 95% CI 0.39–0.92), along with fewer total delirium days and episodes.. While the absence of randomization introduces risk of selection bias, and lack of blinding raises concern for performance and observer bias, this was a relatively benign and common-sense intervention whose merits like outweighs these concerns.
In a large, multicenter, double-blind randomized controlled trial of ICU patients with delirium, haloperidol did not significantly improve the primary outcome of days alive and out of the hospital at 90 days compared with placebo (mean difference 2.9 days, 95% CI −1.2 to 7.0). Secondary outcomes, including duration of delirium, mechanical ventilation–free days, and hospital length of stay, were also similar. Although 90-day mortality was lower in the haloperidol group (36.3% vs 43.3%; absolute difference −6.9%), this was not the primary endpoint and lacks a clear mechanistic explanation. Limitations include potential selection bias due to exclusion of patients previously receiving antipsychotics and geographic enrollment imbalance, which may affect generalizability.
A systematic review of pharmacologic management for severe agitation in older adults from 2025 found that adverse events were common (16.8% overall) and varied substantially by agent, with the highest rates observed with midazolam (53%) and the lowest with quetiapine (5%) and ziprasidone (0%). Compared with haloperidol, midazolam significantly increased the risk of any adverse event (OR 5.25, 95% CI 2.64–10.45) and respiratory complications (OR 10.69, 95% CI 2.96–38.60), while quetiapine was associated with fewer adverse events (OR 0.27, 95% CI 0.08–0.97). Treatment failure requiring redosing was also more common with midazolam. However, conclusions are limited by the predominance of small, high-risk-of-bias observational studies, lack of heterogeneity assessment, and potential publication bias, reducing confidence in comparative safety estimates.
A randomized controlled trial evaluating dexmedetomidine for hyperactive delirium in non-intubated ICU patients demonstrated improvement in a composite primary outcome of agitation duration, delirium duration, and need for intubation (median difference −30.9 points, 95% CI −49.4 to −12.4), driven primarily by reduced agitation (1.0 vs 2.0 hours). Dexmedetomidine also reduced the need for haloperidol and rescue sedatives but did not significantly impact delirium resolution, intubation rates, or 30-day mortality. Limitations include early trial termination for perceived benefit, reliance on a composite outcome with unequal component effects, and modest sample size, which may overestimate treatment effects and limit interpretability.
Overall, these studies suggest that pharmacologic strategies for agitation and delirium offer limited benefit on primary clinical outcomes such as mortality, length of stay, or delirium resolution, with some signals of harm—particularly with benzodiazepines—while certain agents like dexmedetomidine may improve agitation-related endpoints without clear impact on harder outcomes. Demedetomidine use in the ED may be more limited than in the ICU, but does show promise for agitation in patients not responding to redirection and antipsychotic therapy. In contrast, nonpharmacologic, multicomponent interventions demonstrate more consistent benefit in preventing delirium and reducing its burden, but again may not be feasible in the emergency department. Instead, common sense approaches to preventing delirium in elderly patients in ED should be implemented, including use of appropriate lighting for time of day; reducing unnecessary monitoring equipment, lines, and tubes; and reducing unnecessary nighttime sleep interruptions for boarding patients. Interpretation across these studies is limited by methodological concerns, including high risk of bias in observational data, reliance on composite or secondary outcomes, and early trial termination, underscoring the need for rigorous trials focused on patient-centered endpoints.