Glibenclamide dose response in patients with septic shock

Introduction

(K+ATP) channels are implicated in the pathophysiology of catecholamine tachyphylaxis in septic shock. This prospective, randomized, double-blinded, clinical study was designed to determine whether different doses of glibenclamide have any effects on norepinephrine requirements and cardiopulmonary hemodynamics in patients with septic shock.

Methods

We enrolled 30 patients with septic shock requiring invasive hemodynamic monitoring and norepinephrine infusion ≥ 0.5 μg/kg/min to maintain MAP between 65 and 75 mmHg. Patients were randomized to receive either 10, 20, or 30 mg enteral glibenclamide. Systemic hemodynamics, global oxygen transport, arterial lactate concentrations, gas exchange, and plasma glucose concentrations were determined at baseline, and following 3, 6 and 12 hours after administration of the study drug.

Results

Glibenclamide decreased plasma glucose concentrations in a dose-dependent manner, but failed to reduce norepinephrine requirements. None of the doses had any effects on cardiopulmonary hemodynamics. See Table 1.

Table 1 Plasma glucose concentration (mg/dl)

Conclusion

Oral glibenclamide is an ineffective adjunct in the treatment of catecholamine-dependent human septic shock.