Critical Care, Critical Care Alert

Critical Care Alert: Etomidate Use Is Associated with Less Hypotension Than Ketamine for Emergency Department Sepsis Intubations: A NEAR Cohort Study

Critical Care Alert

Mohr NM, Pape SG, Runde D, Kaji AH, Walls RM, Brown CA. Etomidate Use Is Associated with Less Hypotension Than Ketamine for Emergency Department Sepsis Intubations: A NEAR Cohort Study. Acad Emerg Med. June 30, 2020.

The objectives of this study were 1) to describe the current use of etomidate and other induction agents in patients with sepsis and 2) to compare adverse events between etomidate and ketamine in sepsis.

Intubation in the critically ill patient is not uncommonly associated with adverse events, especially in septic patients. Mitigation of peri-intubation risk begins with initial stabilization prior to intubation followed by responsible choice of induction agent (if one is to be used). When considering intubating septic vs non-septic patients, the question of etomidate vs ketamine arises. Etomidate is thought to be hemodynamically stable at the cost of adrenal suppression (via inhibition of  11 ꞵ-hydroxylase). Historically, there was concern that adrenal suppression in already critical patients would worsen outcomes - enter ketamine.  Ketamine is thought to be a hemodynamically stable agent but without interference with the adrenal pathway. More recent reports have suggested that specifically in critically ill patients who are catecholamine-depleted on presentation, ketamine may result in higher than expected rates of negative cardiovascular effects, including hypotension.

Multicenter observational cohort study


Inclusion Criteria:

  • Septic and non-septic patients
  • Intubated using induction agents
  • Intubated in EDs in the National Emergency Airway Registry (NEAR)

Exclusion Criteria: none listed

Primary Outcome
Choice of induction agent for sepsis intubations + comparison between sepsis and non-sepsis cases. Induction options: etomidate, ketamine, midazolam, propofol, no medication

Secondary Outcomes

Evaluated only amongst sepsis intubations.

  • First pass intubation success rates
  • Rates of adverse events including:
    • cardiac arrest
    • dental trauma airway injury
    • post-intubation hypotension
    • use of vasopressor medications
    • desaturation during intubation
    • equipment failure
    • medication error
    • pharyngeal laceration
    • pneumothorax
    • ET tube cuff failure
    • emesis

Key Results
Of the 12,722 intubations performed, 531 (4.2%) were performed for sepsis.

Primary Outcomes: 363 (71%)  of cases used etomidate, 140 (27%) ketamine, 2% other medications. Etomidate used less frequently in sepsis vs non-sepsis cases (71% vs 85%, OR=0.4, 95%CI= 0.4 to 0.6). Ketamine was used more frequently in sepsis vs non-sepsis cases (27% vs 12 %, OR 2.8, 95%CI= 2.3 to 3.5).

Secondary Outcomes (adverse events)

Among sepsis intubation, there were higher rates of post procedure hypotension in patient sedated with ketamine vs etomidate (74% vs 50%, OR=2.9, 95% CI 1.9 to 4.5)

In a separate sensitivity analysis with a propensity-adjusted cohort study, Ketamine was independently associated with higher incidence of post-intubation hypotension. (aOR=2.7, 95% CI 1.1 to 6.7)

Patients intubated for sepsis had greater risk of peri-intubation adverse events than those without sepsis (23% vs 12%, OR=2.3, 95% CI 1.8 to 2.8) and included increased rates of hypotension and need for vasopressor support.

Among sepsis intubation, there was similar first pass intubation success rates (89% vs 84%, OR=2.0, 95% CI = 0.8 to 1.3) between ketamine and etomidate.


  • Large sample size


  • Observational study
  • Did not evaluate long-term outcomes
  • Inclusion of only large, academic  medical centers

EM Take-Aways
Intubating the critically ill septic patient is a high-risk procedure. Overall, these patients are more prone to adverse outcomes when compared to critically ill, non-septic patients. This observational study reported higher levels of procedural hypotension with the use of ketamine when compared to etomidate when intubating septic patients. The short-term and long term clinical outcomes of ketamine induced hypotension are not clear. Awareness of the potential for hypotension will provide opportunity to be prepared - availability of push-dose pressor agents to augment induction induced hypotension should be quickly accessible.

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