Randomized, double-blind, placebo-controlled crossover pilot study of a potassium channel blocker in patients with septic shock

Stephen Warrillow, Moritoki Egi, Rinaldo Bellomo

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50 Citations (Scopus)

Abstract

Background: Marked potassium efflux prevents calcium entry into vascular smooth muscle cells and may be responsible for the "vasoplegia" of septic shock. Blockade of adenosine triphosphate (ATP)-sensitive potassium channels restores vascular tone in animal studies of septic shock. The effect of such potassium channel blockade has not been previously studied in humans. Objective: To test whether the administration of an ATP-sensitive potassium (KATP) channel blocker restores norepinephrine responsiveness in patients with septic shock. Design: Randomized, double-blind, placebo-controlled crossover pilot study. Setting: Intensive care unit of a university hospital. Patients: Ten patients with septic shock requiring invasive hemodynamic monitoring and infusion of norepinephrine to maintain adequate mean arterial pressure. Intervention: In addition to standard therapy, patients were randomized to initially receive either the KATP channel blocker glibenclamide (20 mg) or placebo. Then, after 24 hrs, each patient crossed over to receive the alternative therapy. Measurements and Main Results: After the administration of the KATP channel blocker glibenclamide, median norepinephrine requirements decreased from 13 to 4 μg/min compared with a change from 19 to 7 μg/min after placebo. The two changes represented a decrease of 78.9% and 71.1% in dose, respectively (p = .57, not significant). There were also no significant changes in heart rate, mean arterial blood pressure, and lactate concentration when comparing the study drug with placebo. Glibenclamide, however, induced a significant decrease in median blood glucose concentration (5.4 [inter-quartile range, 4.5-7.0] vs. 7.0 mmol/L [5.2-9.3], p < .0001) compared with placebo and increased the need for parenteral glucose administration. Conclusions: The KATP channel blocker glibenclamide failed to achieve a greater reduction in norepinephrine dose than placebo in septic shock patients, although it caused a reduced glucose concentration. Our observations suggest that, in such patients, blockade of KATP channels does not have a potent effect on vasomotor tone.

Original languageEnglish
Pages (from-to)980-985
Number of pages6
JournalCritical Care Medicine
Volume34
Issue number4
DOIs
Publication statusPublished - 1 Apr 2006
Externally publishedYes

Keywords

  • Adenosine triphosphate-sensitive potassium channel
  • Glibenclamide
  • Norepinephrine
  • Sepsis
  • Septic shock
  • Sulfonylurea

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