Emergency medical service/airway/brief research report
Etomidate Versus Midazolam for Out-of-Hospital Intubation: A Prospective, Randomized Trial

Presented as a poster at the American College of Emergency Physicians Research Forum, October 2003, Boston, MA.
https://doi.org/10.1016/j.annemergmed.2005.12.009Get rights and content

Study objective

The primary objective of this study is to compare the intubation success rates of etomidate and midazolam when used for sedative-facilitated intubation, without paralytics, in out-of-hospital adult patients.

Methods

This prospective, double-blind, randomized trial was conducted with 2 ground out-of-hospital advanced life support systems (ALS); all patients aged 18 or older who required out-of-hospital sedative-facilitated intubation were eligible for participation. The ambulances were stocked with blinded numbered syringes containing either 7 mg of midazolam or 20 mg of etomidate. No paralytics were used. If sedation was not achieved with the study drug, medics could request additional sedation from a medical command physician; only midazolam or diazepam were available outside of the study.

Results

One hundred ten patients were enrolled in the study; 55 patients received midazolam and 55 patients received etomidate. The 2 groups were similar with regard to age, sex, initial vital signs, and reasons for intubation or sedation. The overall intubation success rate was 76% (95% confidence interval [CI] 68% to 84%); 75% (41/55) for midazolam (95% CI 64% to 86%) and 76% (42/55) for etomidate (95% CI 65% to 87%). There was also no difference in incidence of hypotension, number of intubation attempts, or perceived difficulty of intubation. Additional sedation was requested almost equally for the 2 groups: 14 patients in the midazolam group and 12 patients in the etomidate group. A benzodiazepine was successful for rescue of a failed etomidate intubation 10 of 12 times (83%; 95% CI 62% to 100%). When used for rescue of failed midazolam intubations, benzodiazepines were effective in only 5 of 14 (36%, 95% CI 11% to 61%) attempts.

Conclusion

There were no observed differences between midazolam and etomidate in sedation-facilitated intubation success rates; we could not fully evaluate global outcomes of these agents or the sedative-facilitated intubation strategy itself.

Introduction

Sedation-facilitated intubation without paralytics is used by many emergency medical services (EMS) despite limited data to support the practice. The American College of Emergency Physicians’ recent policy statement on drug-assisted intubation in the out-of-hospital setting states that the practice of drug-assisted intubation “is an advanced airway procedure that should not be considered mandatory” for out-of-hospital EMS systems but is ambiguous about sedative-facilitated intubation (without paralytics), recommending that an out-of-hospital drug-assisted intubation program include “standardized drug-assisted intubation protocols, including the use of sedation and neuromuscular blockade.”1 At least 1 report noted limited success with etomidate-only assisted intubation,2 a provocative finding because etomidate is arguably safer than midazolam.3, 4 To our knowledge, this is the first study to compare the utility of etomidate and midazolam for sedative-facilitated intubation in a randomized, controlled, out-of-hospital trial.

Although retrospective series2, 5, 6, 7, 8 have compared etomidate and midazolam for out-of-hospital intubation, there have been no direct comparisons of the 2 drugs. Previous studies have suggested that to be as effective as etomidate for intubation, the doses of midazolam that must be used are more likely than etomidate to cause hypotension.3, 4 Because sedative-facilitated intubation is used by many out-of-hospital services5, 6, 7, 8 and is included as a component of the most recent published algorithm for out-of-hospital intubation,9 the question of which drug is most effective (has the highest success rate for intubation) and safest (has the least propensity to cause adverse effects) is of considerable importance.

The primary objective of this study was to compare the success rate of etomidate and midazolam for sedative-facilitated intubation in out-of-hospital adult patients. The secondary objectives were to compare the safety and perceived difficulty of intubation with the 2 drug regimens.

Section snippets

Study Design

The study began in October 2002 and continued for 32 months, until June 2005. The hospital pharmacy prepared numbered syringes (assigned by a random number table), each containing either 7 mg of midazolam (0.1 mg/kg × 70 kg) or 20 mg of etomidate (0.3 mg/kg × 70 kg). To further ensure blinding, the midazolam was mixed with normal saline solution to a volume equivalent to that in the etomidate syringe, and the syringe contents were concealed with labels such that only the syringe number was

Results

There were 115 patients entered into the study, and 110 completed it; 55 patients received midazolam and 55 patients were given etomidate. Five patients were excluded: 3 because of confusion about syringe numbers and data forms, which made it impossible to be certain what drug was administered (2 were successful); 1 because the intubation was attempted by an out-of-hospital physician rather than a medic (failed); and 1 because the patient woke up with naloxone before intubation was attempted.

Limitations

One limitation of our study is related to our regimen of drug dosing. First, by specifying a fixed dosage for both agents (7 mg of midazolam, 20 mg of etomidate), the effectiveness of 1 or both drugs might be suboptimal, and the adverse effect profile might be inaccurate as well. Moreover, the performance characteristics of any dosage regimen, even one that is weight based, could vary markedly, depending on the dosages used. Conversely, our data provide some evidence that in the case of

Discussion

This study, which directly compares the utility of etomidate and midazolam for sedative-facilitated intubation, demonstrates no important clinical differences between etomidate and midazolam used in the out-of-hospital setting for sedative-facilitated intubation. Our intubation success rate of 76% is low compared with the high success rates sometimes reported in the out-of-hospital sector, particularly when rapid sequence intubation is used, but is consistent with other series of

References (13)

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Supervising editor: Donald M. Yealy, MD

Author contributions: JJ, MH, JN conceived the study and designed the trial. JJ, GS, JM supervised the conduct of the trial and data collection. JR provided statistical advice on study design and analyzed the data and performed interim analysis. MC, JJ, GS, JN were responsible for paramedic teaching and field implementation. NP performed data collection and formatting (pre-hospital). SJ performed data collection and formatting (follow-up). JJ and MH drafted the manuscript. JJ takes responsibility for the paper as a whole.

Funding and support: The authors report this study did not receive any outside funding or support.

Reprints not available from the authors.

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