Randomized Double‐blind Trial of Intramuscular Droperidol, Ziprasidone, and Lorazepam for Acute Undifferentiated Agitation in the Emergency Department

Abstract

Background The optimal agent to treat acute agitation in the emergency department (ED) has not been determined. The objective of this study was to compare the effectiveness and safety of intramuscular droperidol, ziprasidone, and lorazepam for acute agitation in the ED. Methods This was a randomized, double‐blind trial of ED patients with acute agitation requiring parenteral sedation. The study was conducted under exception from informed consent (21 CFR 50.24) from July 2004 to March 2005. Patients were randomized to receive 5 mg of droperidol, 10 mg of ziprasidone, 20 mg of ziprasidone, or 2 mg of lorazepam intramuscularly. We recorded Altered Mental Status Scale (AMSS) scores, nasal end‐tidal carbon dioxide (ETCO2), and pulse oximetry (SpO2) at 0, 15, 30, 45, 60, 90, and 120 minutes as well as QTc durations and dysrhythmias. Respiratory depression was defined as a change in ETCO2 consistent with respiratory depression or SpO2 < 90%. The primary outcome was the proportion of patients adequately sedated (AMSS ≤ 0) at 15 minutes. Results We enrolled 115 patients. Baseline AMSS scores were similar between groups. For the primary outcome, adequate sedation at 15 minutes, droperidol administration was effective in 16 of 25 (64%) patients, compared to seven of 28 (25%) for 10 mg of ziprasidone, 11 of 31 (35%) for 20 mg of ziprasidone, and nine of 31 (29%) for lorazepam. Pairwise comparisons revealed that droperidol was more effective that the other medications, with 39% (95% confidence interval [CI] = 3% to 54%) more compared to 20 mg of ziprasidone and 33% (95% CI = 8% to 58%) more compared to lorazepam. There was no significant difference between groups in need of additional rescue sedation. Numerically, respiratory depression was lower with droperidol (3/25 [12%]) compared to 10 mg of ziprasidone (10/28 [36%]), 20 mg of ziprasidone (12/31 [39%]), or lorazepam (15/31 [48%]). One patient receiving 20 mg of ziprasidone required intubation to manage an acute subdural hematoma. No patients had ventricular dysrhythmias. QTc durations were similar in all groups. Conclusions Droperidol was more effective than lorazepam or either dose of ziprasidone for the treatment of acute agitation in the ED and caused fewer episodes of respiratory depression.

Antipsychotic Drugs or Benzodiazepines for Rapid Tranquilization in Mental Health Facilities or Emergency Department Settings

“…Thirteen relevant reports were identified: 5 SRs, [13][14][15][16][17] 3 RCTs, [18][19][20] 4 observational studies, [21][22][23][24] and 1 clinical practice guideline. 1 Two of the 5 SRs had broader inclusion criteria than the present review.…”

“…All 3 RCTs directly compared 2 or more therapies. [18][19][20] Two RCTs involved a single study centre 19,20 and 1 involved multiple centres within Hong Kong. 18 All 4 observational studies compared 2 or more therapies.…”

“…16,17 Among the RCTs, 1 each was from China, 18 Lebanon, 19 and the US. 20 Three observational studies were from the US [21][22][23] and 1 was from Mexico. 24 The joint BAP/ NAPICU guidelines are from the UK.…”

“…Age of patients enrolled ranged from 18 to 75 years, 18 18 to 65 years, 19 or 18 years and older with no upper limit. 20 Two trials took place in the emergency department 18,20 and 1 in a psychiatric hospital. 19 Etiology of aggression and/or agitation was mainly psychiatric illness in 2 trials 18,19 and mixed but mainly alcohol intoxication in 1 trial.…”

“…19 Etiology of aggression and/or agitation was mainly psychiatric illness in 2 trials 18,19 and mixed but mainly alcohol intoxication in 1 trial. 20 All 4 of the observational studies took place in an emergency department setting. [21][22][23][24] Etiology of aggression and/or agitation was schizophrenia in 1 study, 24 while the 3 other studies focused on aggression and/or agitation mainly due to alcohol intoxication, with 10% to 17% due to psychiatric illness.…”