Evaluation of concurrent vancomycin and pentobarbital use and the achievement of therapeutic vancomycin trough concentrations in a Neurosciences Intensive Care Unit

Purpose : Vancomycin is frequently utilized for empiric coverage or treatment of severe gram positive bacterial infections, while pentobarbital is indicated for barbiturate coma in the Neuro ICU.  Pentobarbital is known to affect the metabolism of hepatically metabolized medications, but little is known about its effects on renal drug clearance. Anecdotal observations have shown that there is potential for reduced renal clearance and risk of supratherapeutic vancomycin drug exposure with concomitant administration. The purpose of this study was to evaluate a correlation between concurrent exposure of vancomycin and pentobarbital and risk of supra-therapeutic serum vancomycin trough concentrations.

Methods :  This retrospective case-control chart review study was approved by the Colorado Multiple Investigational Review Board. Adult patients receiving concomitant vancomycin and pentobarbital administration in the Neuro ICU at the University of Colorado Hospital between January 2000 and May 2012 were evaluated and compared to matched control patients receiving vancomycin without concomitant pentobarbital. Vancomycin and pentobarbital doses, frequency, duration and drug levels were evaluated between groups.  The primary objective was evaluated by comparing the incidence of supratherapeutic vancomycin trough concentrations (> 20 mcg/ml) between groups.  Additionally, vancomycin total daily dose and weight based dose were compared between groups. The Fisher Exact test and Mann Whitney U test were used for categorical and continuous data analysis, respectively.  A p value < 0.05 was considered significant. 

Results:   A total of 26 patients were evaluated; 13 in the pentobarbital plus vancomycin group and 13 in the vancomycin control group. All data has been collected and is in the process of being analyzed. Results are pending and will be available for the poster symposium at ACCP Annual Meeting in October 2012.

Conclusion: The results of this study will clarify if a therapeutic drug interaction exists between vancomycin and pentobarbital resulting in the requirement for lower vancomycin doses.