By Samuel Nadler, MD, PhD
Critical Care, Pulmonary Medicine, The Polyclinic Madison Center, Seattle; Clinical Instructor, University of Washington, Seattle
SYNOPSIS: In a single-center, open label study, ketamine for emergency intubation compared to etomidate was associated with lower seven-day mortality, although 28-day mortality was similar.
SOURCE: Matchett G, Gasanova I, Riccio CA, et al. Etomidate versus ketamine for emergency endotracheal intubation: A randomized clinical trial. Intensive Care Med 2022;48:78-91.
Emergency endotracheal intubation often requires the use of sedative medications with rapid onset and minimal hemodynamic effects. Commonly used medications include propofol, etomidate, and ketamine, although the optimal agent for each intubation has not been established. This study compared etomidate and ketamine for emergency endotracheal intubation in a prospective, randomized, but open-label design. Inclusion criteria included adult patients 18 years and older in need of emergency endotracheal intubation. Notably, the airway team responsible for intubations was permitted to screen out patients for whom a specific agent was considered most appropriate. Exclusion criteria included women who were pregnant, patients intubated without sedative agents, and those requiring awake intubation. Patients were randomized to either intravenous etomidate (0.2 mg/kg to 0.3 mg/kg) or ketamine (1 mg/kg to 2 mg/kg). The primary endpoint was seven-day mortality, and secondary endpoints included 28-day mortality, duration of mechanical ventilation, intensive care unit (ICU) length of stay, vasopressor use, severity of illness score, and an assessment of new-onset adrenal insufficiency.
A total of 801 patients were enrolled in the study, with 791 patients included in the analysis. The mean age in the etomidate and ketamine groups were 55.8 and 55.4 years, respectively. Women comprised 38.6% and 38% of each group, respectively. Black patients represented 33.6% and 30.9% of patients in each group, respectively, and Hispanic patients accounted for 35.6% and 35.2% in each group, respectively. The reason for intubation was more commonly shock in the etomidate group (47.7%), while acute respiratory failure was more common in the ketamine group (48.4%). The primary outcome of seven-day survival was higher in the ketamine group compared with etomidate (85.1% vs. 77.3%; P = 0.005). There were no statistically significant differences in any of the secondary outcomes, including 28-day mortality, vasopressor use, duration of mechanical ventilation, diagnosis of adrenal insufficiency, or ICU length of stay. Of the numerous exploratory outcomes, the only statistically significant difference was a higher proportion of post-induction cardiovascular compromise with ketamine compared with etomidate (25.1% vs. 17.4%, difference -7.6%; 95% confidence interval [CI], -13% to -2%).
Commentary
This study adds to a growing evidence base of the risks and benefits associated with induction agents for emergency endotracheal intubation. A few details of the study deserve further mention. First, this study employed a high-volume airway team that used advanced practices tailored to intubations in the ICU setting. As stated in this paper, many institutions do not have similar teams; as such, this limits the generalizability of this study. Rather than selection of sedative medication, the support of a dedicated airway team may have the greatest impact on outcomes. Second, the primary outcome was seven-day survival. While this may focus on outcomes more immediate to the agents used for intubation, these differences are lost by day 28. Third, the improved outcome at day 7 was not accompanied by other clinically significant improvements, such as decreased vasopressor need, duration of mechanical ventilation, or ICU length of stay. Showing improvements in these other outcomes would be more consistent with overall benefit.
This study can be viewed in the context of other studies comparing etomidate and ketamine. Previously, the KETASED study group published a randomized controlled study of 655 patients receiving either etomidate or ketamine for intubation.1 While this study confirmed that the use of etomidate was associated with adrenal suppression, it did not show statistically significant differences in overall probability of 28-day survival, vasopressor need, or use of mechanical ventilation. Notably, that study had a lower percentage of sepsis patients than the current study, and the reason for intubation was more commonly altered mental status rather than shock or respiratory failure. In contrast, a recent publication by the NEAR investigators raised concerns that ketamine was more likely to cause hemodynamic instability compared with etomidate.2 While the current study did not report a significant difference in the proportion of patients receiving vasopressor infusions or the duration of vasopressors, it did demonstrate a higher proportion of patients who became hypotensive immediately after intubation.
Overall, this trial aligns with other studies showing similar outcomes for etomidate and ketamine when used for emergency intubation. Although reported seven-day survival was higher in the ketamine group, this did not translate into other important outcomes, and this isolated finding should be viewed with caution.
REFERENCES
- Jabre P, Combes A, Lapostolle F, et al. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: A multicentre randomized controlled trial. Lancet 2009;374:293-300.
- April MD, Arana A, Schauer SG, et al. Ketamine versus etomidate and peri-intubation hypotension: A National Emergency Airway Registry study. Acad Emerg Med 2020;27:1106-1115.
In a single-center, open label study, ketamine for emergency intubation compared to etomidate was associated with lower seven-day mortality, although 28-day mortality was similar.
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