Date: June3, 2023 Reference: Kotani et al. Etomidate as an induction agent for endotracheal intubation in critically ill patients: A meta-analysis of randomized trials. Journal of Critical Care April 2023 Guest Skeptic: Dr. Amber Gombash is an emergency physician in Concord, NC. Case: You have a critically ill patient that you are preparing to intubate and wonder if the use of etomidate as your induction agent increases mortality. Missy Carter Background: Intubation is something we have a covered a few times on the SGEM. There was an episode with Physician Assistant (PA) Chip Lange on the use of POCUS to confirm tube placement (SGEM#249). This got some feedback from our friend Scott Weingart over at EMcrit. Our usual go to guest skeptic for airway has been paramedic and PA Missy Carter (SGEM#247, SGEM#271 and SGEM#396). One aspect that has not been well covered on the SGEM is the choice of induction agent when intubating patients. There was an episode 10 years ago looking at the use of etomidate in septic patients (SGEM#44). It was a SRMA reporting an associated increase in adrenal insufficiency and all-cause mortality with the use of etomidate to intubate septic patients. A more recent SGEM episode looked at an unblinded single centre randomized trial comparing etomidate vs ketamine in adult patients requiring emergency endotracheal intubation (SGEM#356). The primary outcome was an 8% absolute increase in all-cause mortality at seven days for patients allocated to the etomidate group. This outcome was no longer statistically different at 28 days. There were multiple issues with this trial including a lack of masking (blinding), selection bias and the primary outcome measure of all-cause mortality at 7 days. Etomidate is often used as the induction agent in critically ill patients due to its fast onset and hemodynamically neutral nature. However, it is hypothesized that etomidate may increase the risk of organ dysfunction and death by the suppression of cortisol production through inhibition of 11-beta-hydroxylase. This goes back to at least 2009 the Ketased study. That trial found that in a critical care setting there was an increase adrenal insufficiency in the group receiving etomidate. There are now multiple randomized trials studying the effect of etomidate as an induction agent on adrenal function and mortality. These studies have reported mixed results—with some finding a statistically significant increase in mortality. There was a SRMA in 2021 that reported an associated increase in adrenal suppression and mortality with etomidate. However, this review combined high-level studies (five randomized controlled trials) with low-level studies (nine post hoc and 15 retrospective studies). Clinical Question: Does etomidate used as an induction agent cause an increased mortality in critically ill adults? Reference: Kotani et al. Etomidate as an induction agent for endotracheal intubation in critically ill patients: A meta-analysis of randomized trials. Journal of Critical Care April 2023 Population: Critically ill adults undergoing emergency endotracheal intubation for critical illness Exclusions: Pediatric patients < 15 years old, etomidate as an infusion (rather than induction/bolus dose), non-randomized trials, systemic reviews, commentaries/editorials and literature reviews, studies not addressing the review question Intervention: Etomidate Comparison: Any other induction agent Ketamine (4 studies), midazolam (4 studies), thiopental (1 study), ketamine + midazolam (1 study), ketamine + propofol admixture (1 study) Outcome: Primary Outcome: Mortality at the main timepoint defined by trial authors Timepoint: Intensive care unit (1 study), Hospital (5 studies), 24 hours (1 study), 7 days (1 study), 28 days (2 studies), 30 days (1 study) Secondary Outcome: Development of adrenal insufficiency