Results
During the study period, 2342 unique patient encounters with active anti-agitation medication orders in the ED were identified and 232 encounters met the inclusion criteria. Of those excluded, 605 encounters had alcohol involvement. The study included 152 patient encounters for 128 patients aged 18 to 64 years of whom 16 patients had > 1 encounter with a mean (SD) 2.5 (1.1) visits. The study included 80 patient encounters for 72 patients aged ≥ 65 years of whom 7 patients had > 1 encounter with a mean (SD) 2.1 (0.3) visits. The mean age was 45.5 years in the younger cohort and 72.2 years in the older cohort. For data analysis and characterization of the ED population, each patient encounter was treated as a unique patient.
Baseline characteristics significantly differed between the 2 groups (Table 1). 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). Diagnoses in the younger cohort included 1 each for hyperglycemia, urinary tract infection, and hyponatremia. Diagnoses in the older cohort included 4 for urinary tract infections, 4 for sepsis, 2 for encephalopathy, 2, for hyperglycemia, 1 gastrointestinal bleed, 1 thyrotoxicosis, and 1 respiratory failure.
Endpoints
The primary outcome of anti-agitation medication selection significantly differed between the younger cohort and older cohort (P = .02). All medication combinations ordered are shown in the eAppendix based on patient age and the percentage of patients in the age cohort that received that medication combination. Lorazepam monotherapy was the most common anti-agitation medication regimen ordered: 43.4% in patients aged 18 to 64 years and 41.3% in patients aged ≥ 65 years. Second-generation antipsychotic use was low.
Only 10.5% of patients aged 18 to 64 years and 8.8% of patients aged ≥ 65 years received a medication combination including a second-generation antipsychotic. Intramuscular administration (41.4%) was most common followed by intravenous (37.5%), oral (19.8%), and oral disintegrating tablets (1.3%). The median (IQR) number of anti-agitation medications ordered by a prescriber was 6 (3-11) and 18 of 28 prescribers did not prescribe second-generation antipsychotics.
Medication doses ordered did not significantly differ except lorazepam monotherapy, as patients aged ≥ 65 received a lower dose (P = .007) (Table 2). Given the limited data within 1 hour, the first set of vital signs available after medication administration was used for analysis of safety outcomes. Vital signs were documented within 1 hour after medication administration for only 28.3% of patients aged 18 to 64 years and 42.5% of patients aged ≥ 65 years. The median (IQR) time to documentation for vital signs after medication administration was 96 minutes (56-177) for patients aged 18 to 64 years and 64 minutes (25-121) for patients aged ≥ 65 years. Electrocardiogram measurement after medication administration only occurred in 7.9% of patients aged 18 to 64 years and 5% of patients aged ≥ 65 years.
Fourteen patients (7.9%) aged 18 to 64 years and 17 patients (15.0%) aged ≥ 65 years experienced an adverse outcome (P = .09) (Table 3). Most patients who had an adverse safety outcome experienced new oxygen desaturation < 95%. Of those patients, only a small proportion required new supplemental oxygen or intubation. The 2 patients intubated had ongoing medical issues complicating their course in the ED. New QTc prolongation was only documented in haloperidol-containing regimens.
The proportion of patients requiring additional anti-agitation medication doses within 3 hours following initial administration was similar between the 2 groups. The mean (SD) amount of time to administration of subsequent dose was 55 minutes (30) in the younger cohort and 64 minutes (36) in the older cohort. Patient disposition from the ED, significantly differed based on age (P < .001) (Table 4). Patients aged 18 to 64 years were more frequently admitted to the psychiatry unit, while patients aged ≥ 65 years were primarily admitted to the hospital. One patient in the younger cohort died due to hyponatremia.