Etomidate for RSI in Septic Shock Patients

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 Overview

Parameter	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	0.3 mg/kg IV (range 0.2 to 0.6 mg/kg)
Adverse Effects	Injection site pain (20%) Nausea, Vomiting Myoclonus (32%)
Kinetics	Onset ~20 seconds Duration 4 to 10 minutes Routes IV only Renal Excretion 75%
Administration	IV push followed by paralytics and flush

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.

Author, Year	Design	Sample Size	Etomidate + Comparator Regimen	Outcome (Comparator vs Etomidate)
McPhee C, 2013	Retrospective cohort study	n=2014	Not published	No difference in ICU and hospital mortality, shock, duration of mechanical ventilation, ICU or hospital length of stay, or vasopressor use
Chan CM, 2012	Meta-analysis	n=1,623	Etomidate (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, 2010	RCT	n=122	Etomidate 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, 2009	RCT	n=469	Etomidate 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, 2009	a-priori sub-study of the CORTICUS trial	n=499	Not 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, 2008	Retrospective	n=29	Etomidate 0.29 mg/kg x 1	Mean cortisol levels were 3.2 times lower in case of etomidate use Mean ACTH levels were 4.1 times higher in etomidate use

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.

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.