Intravenous midazolam-droperidol combination, droperidol or olanzapine monotherapy for methamphetamine-related acute agitation: subgroup analysis of a randomized controlled trial.
OBJECTIVE
To examine the efficacy and safety of (1) midazolam-droperidol versus droperidol and (2) midazolam-droperidol versus olanzapine for methamphetamine-related acute agitation.


METHODS
A multi-centre, randomized, double-blind, controlled, clinical trial was conducted in two Australian emergency departments, between October 2014 and September 2015.


METHODS
Three hundred and sixty-one patients, aged 18-65 years, requiring intravenous medication sedation for acute agitation, were enrolled into this study. We report the results of a subgroup of 92 methamphetamine-affected patients.
Patients were assigned randomly to receive either an intravenous bolus of midazolam 5 mg-droperidol 5 mg combined, droperidol 10 mg or olanzapine 10 mg. Two additional doses were administered, if required: midazolam 5 mg, droperidol 5 mg or olanzapine 5 mg, respectively.


METHODS
The primary outcome was the proportion of patients sedated adequately at 10 minutes. Odds ratios with 95% confidence intervals (ORs, 95% CI) were estimated.


RESULTS
The baseline characteristics of patients in the three groups were similar. At 10 minutes, significantly more patients in the midazolam-droperidol group [29 of 34 (85.3%)] were sedated adequately compared with the droperidol group [14 of 30 (46.7%), OR = 6.63, 95% CI = 2.02-21.78] or with the olanzapine group [14 of 28 (50.0%), OR 5.80, 95% CI = 1.74-19.33]. The number of patients who experienced an adverse event (AE) in the midazolam-droperidol, droperidol and olanzapine groups was seven of 34, two of 30 and six of 28, respectively. The most common AE was oxygen desaturation.


CONCLUSIONS
A midazolam-droperidol combination appears to provide more rapid sedation of patients with methamphetamine-related acute agitation than droperidol or olanzapine alone.
Centre for Medicine Use and Safety, Monash University, Parkville, Australia.
Celene Y L
http://orcid.org/0000-0001-8359-0605
CYL
Yap
Emergency Department, Austin Health, Heidelberg, Australia.
David McD
DM
Taylor
Emergency Department, Royal Melbourne Hospital, Parkville, Australia.
Jonathan C
JC
Knott
Pharmacy Department, Austin Health, Heidelberg, Australia.
Simone E
SE
Taylor
Emergency Department, St Vincent's Hospital, Fitzroy, Australia.
Georgina A
GA
Phillips
Emergency Department, St Vincent's Hospital, Fitzroy, Australia.
Jonathan
J
Karro
Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong.
Esther W
EW
Chan
Centre for Medicine Use and Safety, Monash University, Parkville, Australia.|Pharmacy Department, Ballarat Health Services, Ballarat, Central, Australia.
David C M
DCM
Kong
St Vincent's Hospital and The University of Melbourne, Fitzroy, Australia.
David J
DJ
Castle
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D017109:Akathisia, Drug-Induced / Q000188:drug therapy*; D001315:Australia; D001569:Benzodiazepines / Q000008:administration & dosage / Q000627:therapeutic use*; D065127:Dopamine D2 Receptor Antagonists / Q000627:therapeutic use; D004311:Double-Blind Method; D004329:Droperidol / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use; D007275:Injections, Intravenous; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D008874:Midazolam / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D000077152:Olanzapine; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
D001569:Benzodiazepines; D065127:Dopamine D2 Receptor Antagonists; D004329:Droperidol; D006993:Hypnotics and Sedatives; D008694:Methamphetamine; D008874:Midazolam; D000077152:Olanzapine; D017367:Selective Serotonin Reuptake Inhibitors
Droperidol; emergency care; methamphetamine; midazolam; olanzapine; psychomotor agitation; sedation