Inhibition of potassium channels in critical illness.
OBJECTIVE
The development of refractory arterial hypotension represents a significant problem in the treatment of critically ill patients, especially during sepsis. Increased activation of ATP-sensitive potassium channels in vascular smooth muscle cells is critically implicated in the pathophysiology of sepsis-induced vasodilation and vascular hyporesponsiveness to catecholamines. Pharmacological blockade of ATP-sensitive potassium channels has been proposed as a goal-directed therapeutic approach to stabilize hemodynamics in septic patients.


RESULTS
In different animal models of sepsis, ATP-sensitive potassium channel inhibition with intravenously infused sulfonylureas effectively reversed sepsis-induced systemic vasodilation and hypotension. Two recent clinical trials, however, failed to demonstrate beneficial effects of enterally administered glibenclamide on norepinephrine requirements and blood pressure in septic shock patients. Relevant problems related to ATP-sensitive potassium channel blockade with sulfonylureas in human septic shock include the route of administration (enteral versus intravenous) and the dose itself (benefit-risk relationship). In addition, significant adverse events may result from unspecific inhibition of nonvascular ATP-sensitive potassium channels.


CONCLUSIONS
Inhibition of ATP-sensitive potassium channels remains an attractive option to treat excessive vasodilation in the presence of systemic inflammation. Before this knowledge can be translated into clinical practice, however, future research is needed to define the role of ATP-sensitive potassium channels in critical illness and their specific inhibition in different tissues in more detail.
Lange
Matthias
M
Department of Anesthesiology and Intensive Care, University of Muenster, Muenster, Germany. lange-m@anit.uni-muenster.de
Morelli
Andrea
A
Westphal
Martin
M
D000818:Animals; D016638:Critical Illness; D006801:Humans; D054086:KATP Channels / Q000037:antagonists & inhibitors* / Q000502:physiology; D026902:Potassium Channel Blockers / Q000627:therapeutic use*; D018805:Sepsis / Q000188:drug therapy*
D054086:KATP Channels; D026902:Potassium Channel Blockers