December 25, 2013
Etomidate for Anesthesia Induction Increases Mortality

Cleveland—Patients induced with the widely used anesthesia drug etomidate for surgery may be at much higher risk of mortality and cardiovascular events than those where propofol was used, according to a large study.

The report from the Cleveland Clinic was published recently in Anesthesia & Analgesia, official journal of the International Anesthesia Research Society.

“Because etomidate impairs adrenal function and blunts the cortisol release associated with surgical stimulus, we hypothesized that patients induced with etomidate suffer greater mortality and morbidity than comparable patients induced with propofol,” the authors note.

For the study, researchers reviewed electronic records for 31,148 ASA physical status III and IV patients who had noncardiac surgery at the Cleveland Clinic. For most of the patients, 28,532, anesthesia was induced with propofol. For the other 2,616, anesthesia was induced with etomidate.

A match was then made between 2,144 patients given etomidate and 5,233 patients given propofol, comparing 30-day postoperative mortality, length of hospital stay, cardiovascular and infectious morbidities, vasopressor requirement, and intraoperative hemodynamics.

The study found that patients given etomidate had 2.5 (98% confidence interval [CI], 1.9–3.4) times the odds of dying than those given propofol. Etomidate patients also had significantly greater odds of having cardiovascular morbidity (odds ratio [OR] [98% CI]: 1.5 [1.2–2.0]), and significantly longer hospital stay (hazard ratio [95% CI]: 0.82 [0.78–0.87]).

No difference was found in infectious morbidity or intraoperative vasopressor use.

The authors conclude that “etomidate was associated with a substantially increased risk for 30-day mortality, cardiovascular morbidity, and prolonged hospital stay.”

Even though the study showed only an association and not causal relationship, the researchers cautioned that “clinicians should use etomidate judiciously, considering that improved hemodynamic stability at induction may be accompanied by substantially worse longer-term outcomes.”

An accompanying editorial underscored those concerns.

“There is accumulating evidence for an association between mortality and etomidate use, both in critically ill patients and now in [non-critically ill] patients undergoing non-cardiac surgery,” write Drs. Matthieu Legrand and BenoĆ®t Plaud of Paris-Diderot University.

The results are “striking and troubling,” but the study is not the first to raise safety concerns over etomidate, according to the commentary, which notes that previous reports have suggested an increased risk of death in patients receiving etomidate in emergency situations or during critical illness, particularly sepsis.

While it remains unclear how etomidate—a drug with only short-lasting effects—can affect patient outcomes several weeks later, Legrand and Plaud suggest that it may represent a “butterfly effect,” with “very small differences in the initial state of a physical system [making] a significant difference to the state at some later time.”

U.S. Pharmacist Social Connect