Expanding Options for Total Intravenous Anesthesia—The Etomidate vs Propofol for In-Hospital Complications Trial

Jason M. Johanning

JAMA Surg. Published online August 10, 2022. doi:10.1001/jamasurg.2022.3339

Using a randomized clinical trial design, the authors compared the ability of etomidate to provide total intravenous (IV) anesthesia with propofol.¹ Propofol is the most common IV anesthesia medication used for general anesthesia in combination with analgesia and neuromuscular blockade. But propofol is far from perfect with an adverse effect profile having significant effect on cardiovascular parameters, including reduced blood pressure and elevated heart rate. In contrast, etomidate maintains cardiovascular stability with administration. Yet, etomidate has adverse effects, too, which until the current trial were considered possibilities as conflicting evidence suggested significant effect on cortisol and aldosterone levels and potential lung effect with increased risk of pneumonia based on single-dose administration.

The noninferiority Etomidate vs Propofol for In-Hospital Complications (EPIC) trial is unique in focusing solely on older persons between the ages of 65 to 80 years who underwent major abdominal surgery where one would expect significant physiologic stress. Composite of major in-hospital postoperative complications was the primary end point with multiple secondary end points consisting of plasma cortisol, aldosterone, adrenocorticotropic hormone levels, and 6- and 12-month mortality.² The trial was well designed, resulting in randomization with equivalent groups along all measures with a predominance of patients who classified as American Society of Anesthesiology 2 patients. The primary outcome of in-hospital complications occurred in 9.3% of the etomidate group and 8.7% of the propofol group resulting in noninferiority. No difference was noted for 6-month and 1-year mortality. Yet the crux of the trial lies in the results of blood pressure, plasma, and pneumonia. Pulmonary complications were present in significantly more patients taking etomidate than propofol (2.0% vs 0.5%). Etomidate produced more episodes of hypertension (10.3% vs 3.8%) and less episodes of hypotension (2.4% vs 10.5%). And alterations in cortisol, aldosterone, and adrenocorticotropic hormone were present in both arms at the end of surgery through postoperative day 3.

The EPIC trial provides a solid basis for etomidate as another agent to consider for total IV anesthesia. The caveat is the trial was performed in and the results should be applied to normal-risk patients of older age. The trial did not enroll patients with frailty or serious comorbidities nor evaluate patients for specific geriatric outcomes, such as postoperative delirium.³ Although the trial was not designed for addressing inherent patient-risk profiles, one could envision that based on a patient-specific factors, an optimal IV agent could be selected, which provides an opportunity for future studies, to identify the ideal total IV anesthesia regimen for this challenging population.