Decreased adrenal reserve after etomidate use in moderate and severe traumatic brain injuries: clinical implications

Introduction

Etomidate is frequently used as an anesthetic induction agent for the intubation of head trauma patients. The clinical impacts of its effects on adrenal function are still debated. Therefore, the primary objective of this study was to determine the length and the importance of relative adrenal insufficiency (RAI) induced by etomidate in moderate and severe head trauma patients. The secondary objective was to determine etomidate's impacts on mortality and morbidity.

Methods

This was a prospective cohort study. Eligible participants were intubated moderate to severe head trauma victims aged ≥16 years, admitted to a tertiary neurosurgical reference center between August 2003 and November 2004. The induction agent was chosen by the physician, without any interference by the research team. ACTH stimulation tests (250 μg) were performed on each participant 24, 48 and 168 hours after intubation. Responses to these tests were compared between patients having received etomidate and those having received other induction agents. RAI was defined as an increase in cortisol levels <248.4 nmol/l (9 μg/dl), measured 30 and 60 minutes after the ACTH test. Logistic and linear regression models were used to compare the two groups of patients on outcomes while taking confounding variables into account.

Results

Of the 94 patients eligible for this study, 40 (43%) gave consent for the ACTH test. Fifteen patients received etomidate and 25 received other induction agents. At 24 hours, there were no differences in the risk of RAI between groups (OR: 1.8, 95% CI: 0.2–14.3, P = 0.59). However, at 24 hours, subjects who had received etomidate presented a significantly lower response to ACTH (adjusted mean: 299.7 nmol/l, 95% CI: 214.7–384.8 versus 503.8 nmol/l, 95% CI: 441.8–565.7, P = 0.002). At 48 and 168 hours, this difference disappeared. For all eligible patients (n = 94), there was a nonsignificant trend to an increased risk in mortality in the etomidate group (adjusted OR: 4.8, 95% CI: 0.6–35.9, P = 0.13). Etomidate was also associated with an increased risk of pneumonia (adjusted OR: 3.0, 95% CI: 1.0–8.7). The adjusted length of stay in the ICU was not different between groups. At discharge, the adjusted motor Functional Independence Measure (FIM) score was significantly lower for subjects in the etomidate group (32 versus 56, P = 0.002), but the adjusted cognitive FIM score was not significantly different in the etomidate group (35 versus 46, P = 0.15).

Conclusion

These results suggest that etomidate decreases the adrenal reserve up to 24 hours after a single dose used for the intubation of traumatic brain injury victims. A larger randomized controlled trial is needed to further assess etomidate's impacts on morbidity and mortality.