S010: PARADOXICAL CARDIOVASCULAR SAFETY SIGNALS WITH KETAMINE VERSUS ETOMIDATE FOR ANESTHESIA INDUCTION: A PHARMACOVIGILANCE ANALYSIS OF FDA ADVERSE EVENT REPORTS
Carlos Ojeda, OMSI; Jadyn Krokosky, OMSI; Samatha Turner, OMSI; Alexander Uhlman, OMSI; Amena Payami, DO
Orlando College of Osteopathic Medicine
Background: Ketamine and Etomidate represent fundamentally different approaches to anesthesia induction, with traditional teaching emphasizing Etomidate's hemodynamic stability and Ketamine's sympathomimetic properties. Ketamine is a dissociative medication used to prevent pain during surgery and other medical procedures. Etomidate is an intravenous anesthetic agent approved for induction of general and short-term anesthesia. However, real-world comparative safety data remain limited. We conducted a comprehensive pharmacovigilance analysis to characterize the cardiovascular and systemic safety profiles of these agents in clinical practice.
Methods: We analyzed the FDA Adverse Event Reporting System (FAERS) database from 2015 Q1 through 2025 Q3 (43 quarters), restricting analysis to anesthesia-related indications only. Adverse events were classified using Medical Dictionary for Regulatory Activities (MedDRA) terminology. Disproportionality analysis was performed using six complementary metrics: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (IC), Multi-item Gamma Poisson Shrinkage (EBGM), chi-squared test, and linear regression. Signals were considered significant when the ROR >2 and the lower bound of the 95% confidence interval was >1.
Results: We identified 97 unique adverse events for Etomidate (446 total reports) and 325 unique adverse events for Ketamine (3,867 total reports) meeting minimum frequency thresholds. Despite a lower total number of reports, Etomidate demonstrated substantially stronger disproportionality signals as 58.8% of its adverse events met the ROR significance threshold, compared with 0.9% for Ketamine (median ROR: 2.89 vs 0.86).
A paradoxical cardiovascular pattern was elucidated. Minor hemodynamic instability was significantly associated with Ketamine: tachycardia (ROR 4.16 [95% CI 2.56-6.76]), bradycardia (ROR 5.44 [3.68-8.05]), and hypotension (ROR 1.49 [1.35-1.66]). Conversely, Etomidate demonstrated signals for severe cardiovascular events: cardiac arrest (ROR 3.15 [2.26-4.40]) and hypertension (ROR 9.37 [5.04-17.44]).
Ketamine showed a substantial disproportionality signal for anaphylaxis (ROR 4.98 [4.58-5.41], 561 reports) compared to Etomidate (ROR 0.32 [0.23-0.44], 38 reports). Etomidate-specific signals included adrenal suppression (ROR 37.76 [13.96-102.13]), malignant hyperthermia (ROR 13.00 [8.17-20.70]), and dystonia (ROR 72.03 [33.11-156.76]).
Conclusions: This pharmacovigilance analysis reveals a paradoxical cardiovascular safety pattern: Ketamine associates with more frequent minor hemodynamic perturbations while Etomidate demonstrates signals for severe cardiovascular events including cardiac arrest. The substantial anaphylaxis signal with Ketamine and adrenal suppression signal with Etomidate confirm and quantify known risks. These real-world safety signals suggest greater complexity in the cardiovascular effects of both agents than previously recognized, emphasizing the need for individualized selection based on patient-specific risk factors rather than categorical assumptions about hemodynamic stability.