All Pharmacy Pearls

Introduction

    sequence intubation in emergency departments in the United

    States.

  • Favorable characteristics include reliably good intubating

    • conditions, a rapid onset and offset of activity, non-renal

    elimination, and maintenance of the cardiorespiratory drive

  • Unfortunately, etomidate causes relative adrenal insufficiency in

    • up to 90% of patients after a single dose for up to 48 hours

  • Serious safety concerns first surfaced in the early 1980’s when

    • continuous infusions were associated with increased mortality in

    trauma patients.

    Etomidate

    Mechanism of

    Action

    Short-acting hypnotic, which appears to have

    gamma-aminobutyric acid (GABA)-like effects.

    Unlike the barbiturates, etomidate reduces

    subcortical inhibition at the onset of hypnosis

    while inducing neocortical sleep.

    Dose

  • 3 mg/kg IV (range 0.2 to 0.6 mg/kg)

    • Adverse

    Effects

    Injection site pain (20%)

Clinical Detail

PropertyEtomidate
Mechanism of ActionShort-acting hypnotic, which appears to have gamma-aminobutyric acid (GABA)–like effects.
Unlike the barbiturates, etomidate reduces subcortical inhibition at the onset of hypnosis while inducing neocortical sleep.
Dose0.3 mg/kg IV (range 0.2 to 0.6 mg/kg)
Adverse EffectsInjection site pain (20%)
Nausea, Vomiting
Myoclonus (32%)
KineticsOnset ~20 seconds
Duration 4 to 10 minutes
Routes IV only
Renal Excretion 75%
AdministrationIV push followed by paralytics and flush

Evidence

Author, YearDesignSample SizeEtomidate + Comparator RegimenOutcome (Comparator vs Etomidate)
McPhee C, 2013Retrospective cohort studyn=2014Not publishedNo difference in ICU and hospital mortality, shock, duration of mechanical ventilation, ICU or hospital length of stay, or vasopressor use
Chan CM, 2012Meta-analysisn=1,623Etomidate (mostly 0.3 mg/kg)
Vs
comparator		↑ All-cause mortality RR 1.20 (95% CI 1.02-1.42)
↑ Adrenal insufficiency RR 1.33 (95% CI 1.22–1.46)
Tekwani K, 2010RCTn=122Etomidate 0.3 mg/kg
vs
midazolam 0.1 mg/kg		No significant differences in median hospital LOS (9.5 vs 7.3 days), ICU LOS (4.2 vs 3.1 days), In-hospital mortality (26% vs 43%) or ventilator days
Jabre P, 2009RCTn=469Etomidate 0.3 mg/kg
vs
Ketamine 2 mg/kg		No difference in SOFA score, 28 day mortality, Vent free days, vasopressor support, or GCS
Cuthbertson, 2009a-priori sub-study of the CORTICUS trialn=499Not published↑ non-responders to corticotropin with etomidate
↑ 28-day mortality in univariate analysis (P = 0.02) with etomidate
Hydrocortisone administration did not change the mortality of patients receiving etomidate (45 vs. 40%)
den Brinker, 2008Retrospectiven=29Etomidate 0.29 mg/kg x 1Mean cortisol levels were 3.2 times lower in case of etomidate use
Mean ACTH levels were 4.1 times higher in etomidate use

Conclusions

  • Etomidate offers favorable rapid sequence intubation conditions in septic shock with rapid onset and offset and relative hemodynamic stability, but a single induction dose causes relative adrenal insufficiency in up to 90% of patients for up to 48 hours.
  • In sepsis, this adrenal suppression has been associated with signals of harm: a meta-analysis (Chan 2012) linked etomidate to increased all-cause mortality and adrenal insufficiency, and a CORTICUS substudy (Cuthbertson 2009) found more corticotropin non-responders and higher 28-day mortality.
  • When etomidate was compared head-to-head with ketamine for RSI in acutely ill patients (Jabre 2009), there was no difference in 28-day mortality, SOFA score, vasopressor support, ventilator-free days, or GCS — making ketamine a reasonable alternative induction agent in this population.
  • On balance, the adrenal-suppression concern with single-dose etomidate in septic shock supports considering an alternative such as ketamine for RSI, while individualizing the choice to the patient and clinical setting.

References

Etomidate: pharmacokinetics. (2018). In Micromedex [Electronic version]. Greenwood Village, CO: Truven Health Analytics. Retrieved November 6, 2018, from http://www.micromedexsolutions.com/

McPhee C, et al. Single-dose etomidate is not associated with increased mortality in ICU patients with sepsis: analysis of a large electronic ICU database. Crit Care Med 2013; 41: 774-83.

den Brinker M, et al. One single dose of etomidate negatively influences adrenocortical performance for at least 24h in children with meningococcal sepsis. Intensive Care Med. 2008 Jan;34(1):163-8.

Tekwani KL, et al. A comparison of the effects of etomidate and midazolam on hospital length of stay in patients with suspected sepsis: a prospective, randomized study. Ann Emerg Med. 2010 Nov;56(5):481-9.

Jabre P, et al. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. Lancet. 2009 Jul 25;374(9686):293-300.

Cuthbertson BH, et al. The effects of etomidate on adrenal responsiveness and mortality in patients with septic shock. Intensive Care Med. 2009 Nov;35(11):1868-76.

Chan CM, et al. Etomidate is associated with mortality and adrenal insufficiency in sepsis: a meta-analysis.

Tags:etomidate RSI septic shock adrenal suppression

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Etomidate for RSI in Septic Shock Patients.pdf