Study Supports Etomidate for General Anesthesia in Older Patients

Kerry Dooley Young

August 17, 2022

Etomidate fared well against propofol in a test conducted in China involving patients aged 65 to 80 years who were scheduled for major abdominal surgery, suggesting etomidate may be another agent to consider for total IV anesthesia, researchers say.

In-hospital complications and 1-year mortality were comparable in the etomidate group, although there were slightly more cases of pneumonia and transient adrenocortical suppression, the randomized study found.

In a study published in JAMA Surgery, Zhihong Lu, MD, PhD, of China's Fourth Military Medical University, and co-authors conclude, "Results of this trial indicated that total intravenous anesthesia with etomidate for less than 4 hours is not inferior to propofol with respect to postoperative outcomes."

Most studies of etomidate have focused on its use to induce anesthesia in trauma, cardiac surgery, and for patients with critical illness, the authors write.

"Although etomidate may be advantageous for induction of anesthesia in patients at high risk for perioperative morbidity and mortality because of its hemodynamic stability, concerns regarding relative adrenal insufficiency and its potential impact on outcomes may lead many anesthesiologists and anesthesia practitioners to instead favor propofol in this setting," Lu and co-authors write.

"However, there is limited evidence regarding outcomes of etomidate in high-risk patients, especially when used for anesthesia maintenance," they write.

The trial was designed to examine the use of etomidate as general anesthesia in older patients undergoing elective surgery and to assess the effect of etomidate infusion on adrenal suppression and postoperative complications in this population, Lu and co-authors write.

The main hypothesis of the investigators was that there would be no increase in in-hospital morbidity after abdominal surgery with the use of etomidate for older patients in comparison with propofol. Thus, it could be regarded as noninferior. To test this, Lu and colleagues set as a primary endpoint a composite of major in-hospital postoperative complications.

The EPIC (Etomidate vs Propofol for In-hospital Complications) study was conducted between 2017 and 2020 at 22 hospitals in China. The primary endpoint occurred in 90 of 967 patients (9.3%) in the etomidate group and 83 of 950 patients (8.7%) in the propofol group, which met the noninferiority criterion, the authors write.

In an invited commentary on the study, Jason M. Johanning, MD, of the University of Nebraska, writes that the EPIC trial "provides a solid basis for etomidate as another agent to consider for total IV anesthesia.

"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," Johanning writes.

"In contrast, etomidate maintains cardiovascular stability with administration," Johanning writes. "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."

Johanning says "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%)," he writes. "Etomidate produced more episodes of hypertension (10.3% vs 3.8%) and less episodes of hypotension (2.4% vs 10.5%)."

Johanning stresses a caveat that the EPIC trial was conducted in normal-risk patients of older age, which limits its applicability.

"The trial did not enroll patients with frailty or serious comorbidities nor evaluate patients for specific geriatric outcomes, such as postoperative delirium," he said.

In an interview with Medscape, Roderic G. Eckenhoff, MD, of the University of Pennsylvania, noted this point as well about the patients in the EPIC trial.

"They were older, but their comorbidities were few," Eckenhoff said. "They were not a real sick or unstable group of patients, and those are the patients we would use etomidate in."

A former vice chair for scientific activities of the American Society of Anesthesiologists' ad hoc committee on perioperative brain health initiative, Eckenhoff said etomidate is used in the US "mainly for induction and usually for induction in very sick, unstable people, people for whom you don't want to suppress their heart rate or blood pressure."

Eckenhoff said he would not expect a call for greater use of etomidate on the basis of the EPIC study. While the study was well done, it lacked diversity, inasmuch as all patients were of Han Chinese nationality. Thus, it is hard to say how older patients in the US who are facing elective surgery would react if given etomidate for anesthesia, he said.

JAMA Surg. Published online August 10, 2022. Full text, Commentary

Kerry Dooley Young is a freelance journalist based in Miami Beach, Florida. She is the core topic leader on patient safety issues for the Association of Health Care Journalists. Follow her on Twitter at @kdooleyyoung.

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