Older patients who received anesthesia with etomidate had no higher risk of major complications after elective abdominal surgery compared to propofol, a randomized trial found.
Among 1,917 such patients, rates of major in-hospital morbidity were 9.3% with etomidate versus 8.7% with propofol in an intention-to-treat analysis. The risk difference of 0.6% (95% CI -1.6% to 2.7%) easily met the prespecified margin of non-inferiority of 3%, according to Lize Xiong, MD, PhD, of the Shanghai Fourth People’s Hospital in China, and colleagues.
However, etomidate did lead to transient adrenal suppression, as evidenced by lower mean cortisol levels at the end of surgery (4.8 vs 6.1 μg/dL, P<0.001), the investigators wrote in JAMA Surgery.
Additionally, the etomidate group had lower aldosterone levels relative to propofol:
- At the end of surgery: 0.13 vs 0.15 ng/dL
- Post-operative day one: 0.14 vs 0.16 ng/dL
Etomidate may be a better option for anesthesia induction among those at high risk for perioperative morbidity and mortality due to hemodynamic stability, but there have been concerns surrounding its impact on relative adrenal insufficiency, Xiong’s group noted. This is the first study to evaluate the impact of etomidate on adrenal suppression and complications among older patients after surgery.
“Propofol is the most common IV [intravenous] anesthesia medication used for general anesthesia in combination with analgesia and neuromuscular blockade,” Jason Johanning, MD, MS, of the University of Nebraska Medical Center in Omaha, stated in an accompanying editorial. “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.”
For this single-blind trial, called EPIC, Xiong and colleagues enrolled patients age 65-80 scheduled for abdominal surgery with total intravenous anesthesia, randomizing 967 to receive etomidate (mean age 70.3, 60% men) and 950 to propofol (mean age 70.6; 56% men). Surgeries were performed in 22 Chinese hospitals from August 2017 to November 2020.
Mean BMI among participants was 23. Nearly three-quarters had an American Society of Anesthesiologists physical status class of 2. More underwent gastrointestinal surgery (59-60%) than hepatobiliary surgery (40-41%) with an average duration of 2 hours. Average anesthesia duration was about 2.5 hours.
General anesthesia was administered via a target-controlled titrated infusion, with target plasma concentrations during surgery set at 0.5-0.8 μg/mL for etomidate induction and 0.2-0.4 μg/mL for maintenance. For both induction and maintenance, the target plasma concentration for propofol was 2-4 μg/mL. Additionally, both groups also received sufentanil (Dsuvia) and cisatracurium (Nimbex). Patients could also receive nicardipine or norepinephrine to control blood pressure, if needed.
More etomidate patients developed pneumonia (2.0% vs 0.3%). Pulmonary complications were the only significantly greater in-hospital complication among the etomidate group (19% vs 5%). A prior study, however, found no link between etomidate and pneumonia, leading Xiong and colleagues to write, “Collective evidence supports cautious use of etomidate infusion in patients at risk for pulmonary complications.”
Etomidate patients experienced more hypertension (3.8% vs 10.3%), but less hypotension (10.5% vs 2.4%) and consistently higher diastolic blood pressure, except at 120 minutes after incision.
No significant difference in mortality was seen at 6 months (2.2% with etomidate vs 3.0% with propofol) and 1 year after surgery (3.3% vs 3.9%).
Nor were there any significance differences in postoperative nausea/vomiting scores of 3 or higher or pain up to 3 days later.
“The EPIC trial provides a solid basis for etomidate as another agent to consider for total IV anesthesia,” Johanning wrote. “The caveat is the trial was performed in and the results should be applied to normal-risk patients of older age.”
Xiong’s group acknowledged limitations to the data. Findings may not be generalizable to surgeries lasting up to 4 hours or to patients outside of China. Also, frequency and duration of events related to abnormal blood pressure were not evaluated, the researchers stated.
This study was supported by the National Natural Science Foundation of China.
Study authors and the editorialist declared they had no relevant financial interests.