Evaluation of Etomidate Use and Association with Mortality Compared with Ketamine among Critically Ill Patients summary

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Hey there, critical care pharmacists! Welcome to today’s literature briefing. I’m here to discuss a paper from the *American Journal of Respiratory and Critical Care Medicine* titled “Evaluation of Etomidate Use and Association with Mortality Compared with Ketamine among Critically Ill Patients.” This important work was led by Wunsch and colleagues, and you can find it with P. M. I. D. three, nine, one, seven, three, one, seven, three.

So, let's dive into the study overview. This was a retrospective observational cohort study that utilized propensity score matching to assess outcomes. The population included critically ill adults who received invasive mechanical ventilation, or I. M. V., in I. C. U.s across the Premier Healthcare Database between two thousand eight and two thousand twenty-one. They looked at a massive cohort of one million, six hundred eighty-nine thousand, nine hundred forty-five patients, and for the primary analysis, they established twenty-two thousand, two hundred seventy-three matched pairs. The core intervention under scrutiny was the receipt of etomidate on the day of I. M. V. initiation, compared with ketamine. The main outcome of interest was hospital mortality, and they also explored whether subsequent corticosteroid use modified any observed associations.

Now, for the key findings. First off, etomidate use on the day of I. M. V. initiation was quite common, with nearly half, or forty-three point seven percent, of patients receiving it. In the propensity score-matched analysis, etomidate was associated with a higher hospital mortality compared to ketamine. We’re talking twenty-one point six percent mortality with etomidate versus eighteen point seven percent with ketamine. This translates to an absolute risk difference of two point eight percent, with a ninety-five percent confidence interval ranging from two point one percent to three point six percent. The adjusted odds ratio for mortality with etomidate was one point two eight, with a ninety-five percent confidence interval of one point two one to one point three four. You know, these findings were notably consistent across all subgroups and sensitivity analyses, which really strengthens the results. And here's something crucial for us: the increased mortality risk associated with etomidate was *not* attenuated by the administration of corticosteroids in the days following intubation.

To put these results in context, there's some interesting related research. A systematic review and meta-analysis from two thousand twenty-five, which you can find with P. M. I. D. four, zero, two, three, nine, one, zero, four, found no significant difference in thirty-day survival between etomidate and ketamine, but they *did* link etomidate to adrenal insufficiency and ketamine to increased vasopressor needs. Another meta-analysis of randomized controlled trials, P. M. I. D. three, seven, one, two, seven, zero, two, zero, actually showed etomidate increased mortality versus other agents, with a risk ratio of one point one six. And on the flip side, a Bayesian meta-analysis, P. M. I. D. three, eight, three, six, eight, three, two, six, found ketamine was associated with a moderate probability, specifically eighty-three point two percent, of improved survival in critically ill patients. So, while etomidate has historically been favored for its hemodynamic stability, the risk of adrenal suppression, as you know, has always been a concern.

From a clinical implications perspective, I think this study really reinforces the need for us, as critical care pharmacists, to carefully weigh the risks. We need to consider the potential for etomidate-related adrenal suppression and the increased mortality risk identified here, against ketamine’s hemodynamic effects during rapid sequence intubation in critically ill patients. These data suggest that considering alternative induction agents beyond etomidate may actually improve hospital survival outcomes. And remember, the study clearly showed that giving corticosteroids after intubation did *not* mitigate etomidate’s mortality risk, which is a key takeaway. So, continued close monitoring for both adrenal insufficiency and hemodynamic instability remains absolutely essential, regardless of your induction agent choice.

Of course, like any study, this one has its limitations. Being an observational design, it cannot definitively prove causality, and there's always the potential for unmeasured confounding variables, such as detailed illness severity scores, that weren't captured in the database. Also, the information on the precise timing and doses of corticosteroids and vasopressors was somewhat limited. However, the study's strengths are significant: its very large I. C. U. cohort from the Premier Healthcare Database, the use of propensity score matching to balance known confounders, and the consistent findings across numerous sensitivity and subgroup analyses.

So, in conclusion, this large I. C. U. cohort study demonstrates that the use of etomidate on the day of invasive mechanical ventilation initiation is common and was associated with a higher odds of hospital mortality compared with ketamine. Furthermore, this association was independent of subsequent treatment with corticosteroids. That wraps up today’s update—thanks for listening, and I’ll catch you next time with more specialty pharmacy insights.