Evaluation of Anti-Agitation Medication Prescribing Patterns by Age in the Emergency Department
Background: Acute agitation frequently occurs in the emergency department. Appropriate management is critical for the safety of all parties involved. Benzodiazepines and antipsychotics are commonly used for agitation, but safety concerns exist with these medications in older adults, even with acute use. The purpose of this study was to compare prescribing practices of anti-agitation medications between adults aged 18 to 64 years and those aged ≥ 65 years.
Methods: This study was a retrospective chart review of patients who presented to the Veteran Affairs Southern Nevada Healthcare System emergency department and received haloperidol, droperidol, lorazepam, olanzapine, or ziprasidone from August 1, 2019, to July 31, 2022. Veterans were excluded if they had alcohol intoxication, alcohol withdrawal, benzodiazepine withdrawal, or medication administration unrelated to agitation. Safety outcomes included oxygen saturation < 95%, supplemental oxygen use, intubation, QTc prolongation, and new hypotension within 1 hour of medication administration.
Results: For the 232 patients who met inclusion criteria, baseline characteristics differed significantly. When comparing patients aged 18 to 64 years and those aged ≥ 65 years, the younger cohort had higher rates of substance use disorder diagnosis (55.3% vs 27.5%, P < .001), positive urine drug screen (69.7% vs 22.5%, P < .001), and 72-hour legal hold (59.9% vs 32.5%, P < .001), and lower rates of cognitive impairment or dementia (0.7% vs 48.8%, P < .001), and altered mental status-related diagnosis (2.0% vs 18.8%, P < .001). Anti-agitation medication selection significantly differed based on age (P = .02). Other than lorazepam (P = .007), no significant differences were noted in the dose ordered. No significant differences were observed for safety outcomes or additional anti-agitation doses.
Conclusions: Anti-agitation prescribing practices may differ between adults aged 18 to 64 years and those aged ≥ 65 years. The findings of this study also suggest that the most common agitation etiologies may differ based on patient age. Additional higher-quality studies are needed to further explore acute agitation in older adults.
Discussion
The most likely causes of acute agitation significantly differed between patients aged 18 to 64 years and patients aged ≥ 65 years. Patients in the younger cohort were more likely to present with a history of substance use disorder or a positive urine drug screen for illicit substances. They were also more likely to have a 72-hour legal hold initiated, suggesting higher rates of suicidal and/or homicidal ideations. Patients in the older cohort were likely to present with a history of cognitive impairment or be diagnosed with a condition contributing to an altered mental status. To our knowledge, this is the first study that has assessed characteristics of patients experiencing acute agitation in the ED based on age and demonstrated significant differences in potential contributing factors to acute agitation. These findings may have important implications in helping guide the selection of empiric regimens, especially when the cause of agitation cannot immediately be elucidated.
Lorazepam monotherapy, haloperidol monotherapy, and a combination of haloperidol, lorazepam, and diphenhydramine were the 3 most frequently prescribed regimens for acute agitation. There was low second-generation antipsychotic use. Outside of the VASNHS formulary, there were no policies or restrictions that would have prevented clinicians from ordering a particular anti-agitation medication during the study period.
Since the end of the period assessed in this study, VASNHS clinicians have been educated on the guidelines for anti-agitation medication regimens to encourage higher use of second-generation antipsychotics when appropriate. Training has been developed to prevent unnecessary delays when using these products. Barriers to second-generation antipsychotic use at VASNHS have also been identified and addressed. Previously, second-generation antipsychotics and the sterile water required for medication reconstitution were not overridable in Pyxis machines, often resulting in delays in administering these medications to acutely agitated patients. As of February 2023, olanzapine, ziprasidone, and sterile water are overridable, making them more accessible in situations when medication is urgently needed. Clinicians also expressed concern regarding a lack of familiarity with reconstituting and administering intramuscular second-generation antipsychotics.
While the general guidance has been to use lower doses of anti-agitation medications in patients aged ≥ 65 years, no significant differences were seen in doses ordered other than for lorazepam. In our study, however, there were no significant differences in adverse safety outcomes, though a higher proportion of patients in the older cohort experienced new respiratory-related outcomes after medication administration. Given the retrospective nature of this study and limited documentation of vital signs after medication administration, we cannot conclude the adverse safety outcomes were directly related to the anti-agitation medications. Most patients in both groups did not require additional doses of anti-agitation medications. The results of this study have been used to guide the development of an order set for anti-agitation medications.