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Etomidate does not appear to harm outcome in severe sepsis

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – In a retrospective study of patients with severe sepsis or septic shock, those who received a single-dose of etomidate before rapid sequence intubation did not have worse outcomes relative to those who did not receive etomidate.

The use of etomidate to facilitate intubation, the study team found, did not increase mortality, the main outcome measure, or have an impact on secondary outcome measures, such as vasopressor use and time spent in the ICU or on a ventilator.

Dr. Dayton Dmello, of the division of pulmonary, critical care and sleep medicine, Saint Louis University Hospital in Missouri and colleagues report their observations in the December issue of the journal Chest.

They note in the article that etomidate is a “particularly attractive” option during rapid sequence intubation in cases of severe sepsis or septic shock for a variety of reasons, including the relative lack of adverse drug-induced hemodynamic consequences.

However, given that etomidate suppresses steroidogenesis and adrenal function, concerns have been raised regarding its safety in critically ill patients.

Dr. Dmello’s group concludes based on their study that “continued use of single-dose etomidate in critically ill patients during rapid sequence intubation appears reasonable, but necessitates a thorough understanding of its potential adverse pharmacodynamic effects on adrenal function.”

The study, conducted in a multidisciplinary ICU at St. Johns Mercy’s Medical Center in St. Louis, involved 224 consecutive patients with severe sepsis or septic shock who were intubated and mechanically ventilated. A total of 113 of the patients received a single-dose of etomidate; in the remaining 111 patients, intubation was performed without the use of etomidate.

The etomidate and nonetomidate groups were well-matched. The average age was similar (63 and 66 years, respectively) and they had similar Acute Physiology and Chronic Health Evaluation II (APACHE II) scores and probability of death on admission. The source of sepsis was also comparable between groups; the top three sources were pulmonary, abdominal and renal.

A similar number of patients in each group was tested for adrenal insufficiency within 72 hours of intubation (58% and 52%, respectively) and there were no marked differences in the number found to have relative adrenal insufficiency (24% and 22%, respectively).

According to the investigators, the relative risk of mortality with etomidate was 0.92 (P = 0.51). There was also no significant association of etomidate with mortality in multivariate analysis adjusted for age, sex, APACHE II score and corticosteroid use (odds ratio, 0.9; P = 0.78).

Etomidate did not increase vasopressor use (relative risk, 1.16; P = 0.31).

Patients who received etomidate spent an average of 14 days in the ICU and 11 days on a ventilator, compared to 12 days in the ICU and 8 days on a ventilator in those who did not receive etomidate; these differences, again, were not significant.

A significant increased risk for steroid use was found in the etomidate group (relative risk, 1.34; P = 0.003), but “with no difference in outcomes,” the authors note.

Dr. Dmello and colleagues say their data “should be interpreted cautiously and extrapolated with care.” The retrospective nature of the study, lack of randomization and blinding, and a limited sample sample size that was not powered to detect a statistical difference in outcomes are some of the limitations of the study, they point out.

For now, “informed clinical judgment should prevail when using etomidate in this controversial setting of clinical equipoise,” the clinicians conclude.

Chest 2010;138:1327-1332.