EM Lit Review: Etomidate versus Ketamine for Induction of RSI in Sepsis

By University of Virginia Health System emergency physician Joshua Easter, MD, MSc

Study: Etomidate Use Is Associated With Less Hypotension Than Ketamine for Emergency Department Sepsis Intubations: A NEAR Cohort Study. Nicholas M. Mohr, Stephen G. Pape, Dan Runde, Amy H. Kaji, Ron M. Walls, Calvin A. Brown Society for Academic Emergency Medicine, June 2020.

Case: A 67 year old female presents to your ED in respiratory distress. She has had cough and fever for the past 4 days and developed trouble breathing last night. She has a temperature of 39o C, heart rate of 120, blood pressure of 95/60, and oxygen saturation of 93% on 15L via non-rebreather mask. She is tired appearing, retracting, speaking in one word sentences, and has coarse breath sounds. Due to her respiratory distress and fatigue, you prepare to intubate. The nurse asks you what medications you want to administer for rapid sequence intubation.

Review and Analysis: Emergency physicians most commonly administer etomidate for induction of rapid sequence intubation, but recently ketamine is being utilized more commonly, particularly in the setting of sepsis and trauma. Etomidate provides reliable sedation and has reasonably stable hemodynamics. Several studies suggest it may cause adrenal suppression, which may be problematic for septic patients. Other studies have refuted these results. Ketamine does not cause adrenal suppression and classically is considered to be hemodynamically stable, with a catecholamine induced increase in heart rate and blood pressure. However, recent studies suggest that critically ill patients may lack sufficient catecholamines to induce this response. When these patients receive ketamine for intubation, the positive pressure of intubation coupled with hypovolemia may lead to hypotension. A prior randomized control trial of ketamine and etomidate in a diverse group of patients found no difference in the incidence of hypotension between agents, but only included 76 patients with sepsis (Jabre et al., Lancet, 2009).

Mohr et al. performed an observational study of 531 septic and 12,191 non-septic patients >14 years of age undergoing ED intubation in the National Emergency Airway Registry (NEAR) database (Mohr et al., Acad Emerg Med, 2020). Data on induction agent and peri-intubation adverse events, including hypoxemia and hypotension were prospectively collected for all intubations at 25 EDs. The authors attempted to control for clustering by hospital as well confounding by indication through calculation of a propensity score to account for variables that may have prompted clinicians to choose ketamine or etomidate, e.g., baseline oxygen saturation, pre-intubation vasopressor requirement, airway difficulty, etc.

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Septic patients were more likely to receive ketamine (OR=2.8, 95% CI=2.3-3.5) than non-septic patients. Ketamine utilization varied greatly by hospital, from 0% to 92% of all intubations for septic patients. Intubated patients with sepsis experienced more adverse events than non-septic patients (OR=2.3, 95% CI=1.8-2.8). Nearly half of intubated septic patients experienced hypotension with a median systolic blood pressure of 72 mm Hg (IQR 60-84), and 39% required intervention for this hypotension. Patients receiving ketamine were more likely to have hypotension and require treatment for their low blood pressure compared to etomidate (Table). In the propensity analysis, patients receiving ketamine were more likely to experience hypotension but not necessarily require vasopressors compared to patietns receiving etomidate.

This study demonstrates that septic patients are at high risk for adverse events during intubation. Patients receiving ketamine had a higher frequency of hypotension compared to etomidate. While this study did not assess long-term outcomes, prior studies have shown a single episode of hypotension is associated with increased mortality for patients with sepsis. This study also did not assess the impact of a single dose of etomidate on adrenal suppression. Given these limitations, definitive conclusions about the overall superiority of etomidate or ketamine cannot be made. However, this is the largest study to date of ketamine for sepsis patients and demonstrates that ketamine does not universally provide hemodynamic support. 

Given the patient’s tenuous hemodynamic status, you decide to administer etomidate, as it is associated with less frequent hypotension than ketamine for septic patients. You intubate the patient without any adverse events. You administer antibiotics, fluids, and admit the patient to the ICU for treatment of pneumonia, sepsis, and respiratory failure.


About the VACEP EM Lit Review: Every month, VACEP members will share their readings of the latest medical literature. Submit yours to us by emailing Executive Director Sarah Marshall.

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