Adenosine triphosphate-sensitive
potassium channels are important regulators of arterial vascular smooth muscle tone and are implicated in the pathophysiology of
catecholamine tachyphylaxis in
septic shock. The present study was designed as a prospective, randomized, double-blinded, clinical pilot study to determine whether different doses of
glibenclamide have any effects on
norepinephrine requirements, cardiopulmonary hemodynamics, and global
oxygen transport in patients with
septic shock. We enrolled 30 patients with
septic shock requiring invasive hemodynamic monitoring and
norepinephrine infusion of 0.5 microg.kg-1.min-1 or greater to maintain MAP between 65 and 75 mmHg. In addition to standard
therapy, patients were randomized to receive either 10, 20, or 30 mg of enteral
glibenclamide. Systemic hemodynamics, global
oxygen transport including arterial
lactate concentrations, gas
exchange, plasma glucose concentrations, and
electrolytes were determined at baseline and after 3, 6, and 12 h after administration of the study drug.
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, global
oxygen transport, gas exchange, or
electrolytes. These data suggest that oral
glibenclamide in doses from 10 to 30 mg fails to counteract arterial
hypotension and thus to reduce
norepinephrine requirements in
catecholamine-dependent human
septic shock.