In this episode, I’ll discuss the mortality rate for critically ill patients when ketamine vs etomidate is used as an induction agent for intubation.
Out of the available induction agents for intubation, ketamine is considered to have the best cardiovascular risk profile, as it typically has a neutral to slightly positive effect on heart rate and blood pressure. This may be particularly relevant in critically ill patients, as hemodynamic compromise is a common factor in many critical illnesses such as septic shock or acute respiratory failure.
In order to assess whether this favorable side effect profile translates into a clinically relevant effect on mortality, a group of authors published a meta-analysis in the journal Critical Care examining mortality in critically ill patients that received ketamine vs other induction agents.
The article search strategy was for any randomized controlled trial or matched observational study that compared ketamine against any control in critically ill patients as an induction agent. 7 RCTs and one propensity-matched study were identified, all of which compared ketamine against etomidate.
The primary outcome was mortality at the longest follow-up available. The relative risk and the 95% credible interval were used to estimate the probability of mortality reduction. Using this analysis, the authors determined that the probability that ketamine reduced mortality was 83.2%. A sub group analysis was then performed which excluded studies with a high risk of bias, and this analysis confirmed the overall finding.
Several secondary outcomes were analyzed including SOFA score, ventilator-free days at day 28, vasopressor-free days at day 28, post-induction MAP, and first-attempt intubation success. None of these outcomes were different between groups.
The authors concluded:
This meta-analysis showed a moderate probability that induction with ketamine is associated with a reduced risk of mortality.
To evaluate this study it is important to note the different approach used to determine the significance of the primary outcome. The author used a Bayesian analysis for mortality which gives a probabilistic characterization of the potential magnitude and direction of the treatment effect. This is different from a traditional analysis that uses a dichotomous yes or no approach based on whether the 95% confidence interval excludes 1 or not. If the latter method were to be used, ketamine would not be considered to reduce mortality compared to etomidate. The authors justified using the Bayesian analysis becuase they felt “…the high severity and considerable heterogeneity in critically ill patients make it challenging to detect a statistically significant mortality difference attributable to a specific intervention.”
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