Each year, about 2.6% of emergency department (ED) visits involve agitation.1 ED clinicians are especially prone to workplace violence and assault, facing the challenge of caring for patients while maintaining safety. A 2013 prospective study found an average of 4.15 violent events per employee in 9 months; nurses and patient care assistants were most frequently affected.2 A 2022 survey from the American College of Emergency Physicians found 55% of respondents reported being physically assaulted in the ED and 79% of respondents reported witnessing another assault. Most of these assaults (98%) were committed by the patients.3 Appropriate management of patients experiencing acute agitation is critical for the safety of all parties involved.
The initial approach to acute agitation management involves nonpharmacologic measures in an attempt to avoid coercive actions, such as physical restraints. Reducing environmental stimulation and verbal de-escalation are effective and help the patients with agitation regain control over their behavior.4
When these measures fail, however, pharmacologic therapy is often administered to ensure safety. The goal of pharmacologic therapy is to calm the patient without causing sedation.5 This allows the patient to continue participating in their care and allows the care team to accurately assess them, which is critical in determining the underlying etiology of agitation. Historically, haloperidol has commonly been used to manage acute agitation. It is frequently administered with lorazepam and diphenhydramine to reduce the incidence of haloperidol’s extrapyramidal adverse effects. However, there are several potential concerns with this method, including oversedation, QTc prolongation, potential drug interactions, and polypharmacy.5,6
The American Association of Emergency Psychiatry Project BETA Psychopharmacology Workgroup published a Consensus Statement in 2012 regarding the psychopharmacology of agitation.5 When considering medication for agitation management, clinicians must first determine a provisional diagnosis outlining the most probable etiology of the patient’s behavior, such as delirium, intoxication, or a psychiatric disorder. Apart from alcohol intoxication, benzodiazepines (BZDs) or second-generation antipsychotics as monotherapy are generally preferred over haloperidol for acute agitation.5 Second-generation antipsychotics have demonstrated to be as effective as haloperidol but are thought to be safer options. Quetiapine is not recommended for use in the ED due to the risk of orthostatic hypotension, as patients are often volume depleted.5The Veterans Affairs Southern Nevada Healthcare System (VASNHS) serves veterans in the Las Vegas area. Among the nearly 220,000 veterans in Nevada, about 100,000 veterans are aged ≥ 65 years.7 The 2012 consensus statement on psychopharmacology for agitation offers no specific age-related guidance. However, there are safety concerns in older adults both with antipsychotics and BZDs, even with acute use. The US Food and Drug Administration (FDA) issued a boxed warning for all antipsychotics due to increased mortality in older adult patients with dementia-related psychosis.8 The 2023 American Geriatrics Society Beers Criteria provides guidance on pharmacological therapy for adults aged ≥ 65 years and recommends avoiding antipsychotics and BZDs.9 In addition to the FDA boxed warning, data suggest increased mortality with antipsychotic use independent of dementia. With BZDs, changes in pharmacodynamics make older adults more prone to adverse effects, including cognitive impairment, delirium, falls, and fractures. A retrospective chart review evaluated risperidone use in the ED and found that adults aged ≥ 65 years experienced higher rates of hypotension, even though this age group received about half the dose of risperidone compared with younger patients.10 For this patient population, the general approach in treating acute agitation has been to avoid the use of medications, but prescribe lower doses when necessary.11
With limited research on acute agitation management in older adults, the purpose of this study was to compare current prescribing practices of anti-agitation medications between adults aged 18 to 64 years and adults aged ≥ 65 years in the VASNHS ED. This study was also conducted to better understand the anti-agitation prescribing practices at VASNHS, as no order sets or protocols existed at the time of the study to guide medication selection in agitation management. To our knowledge, this is the first observational study evaluating pharmacologic acute agitation management in the ED based on age.
Methods
This study was a retrospective chart review of patients aged ≥ 18 years who presented to the VASNHS ED and received medication for acute agitation. Patients were identified through active orders for a formulary agitation medication from August 1, 2019, to July 31, 2022. Formulary medication options included intravenous, oral, and intramuscular routes for haloperidol, droperidol, lorazepam, olanzapine, or ziprasidone. Veterans were excluded if they presented with alcohol intoxication, alcohol or BZD withdrawal, if the medication administration was unrelated to agitation, or whether the medication was not administered. While alcohol and/or BZDs can contribute to acute agitation, these patients were excluded due to a clear indication for BZD therapy and the challenge in a retrospective chart review to determine whether patients received medication for agitation vs other withdrawal-related symptoms.
Endpoints
The primary endpoint was the medication selection between 2 age groups: 18 to 64 years and ≥ 65 years. The secondary endpoints included ordered medication dose by regimen, additional anti-agitation medication use within 3 hours of initial medication administration, and disposition. Safety outcomes included incidence of newly occurring oxygen desaturation < 95%, supplemental oxygen requirement, intubation, QTc prolongation, and hypotension with systolic blood pressure < 90 mm Hg within 1 hour of medication administration. Data collected included patient demographics, substance use, conditions contributing to altered mental status, active psychotropic medication prescriptions, medication adherence, agitation medication prescriber, and doses. Adherence to psychotropic medication in the past 6 months was defined as ≥ 80% of days covered with medication and based on fill history. This was only calculated for applicable patients and did not include patients with only as-needed medications, such as hydroxyzine for anxiety.
Statistical Analysis
Statistical analyses were performed using IBM SPSS. Baseline characteristics were analyzed using descriptive statistics. χ2 and Fisher exact tests were used to analyze categorical data. A student t test was used for continuous variables and a 2-sided P value of < .05 was considered statistically significant.