title: Glibenclamide dose response in patients with septic shock: effects on norepinephrine requirements, cardiopulmonary performance, and global oxygen transport.
abstract: 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.
authors.affiliation: Department of Anesthesiology and Intensive Care, University of Rome, La Sapienza, Rome, Italy. andrea.morelli@uniroma1.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Morelli
authors.forename: Matthias
authors.initials: M
authors.lastname: Lange
authors.forename: Christian
authors.initials: C
authors.lastname: Ertmer
authors.forename: Katrin
authors.initials: K
authors.lastname: Broeking
authors.forename: Hugo
authors.initials: H
authors.lastname: Van Aken
authors.forename: Alessandra
authors.initials: A
authors.lastname: Orecchioni
authors.forename: Monica
authors.initials: M
authors.lastname: Rocco
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bachetoni
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Traber
authors.forename: Giovanni
authors.initials: G
authors.lastname: Landoni
authors.forename: Paolo
authors.initials: P
authors.lastname: Pietropaoli
authors.forename: Martin
authors.initials: M
authors.lastname: Westphal
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000368:Aged; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D002395:Catecholamines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005905:Glyburide / Q000008:administration & dosage*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007022:Hypotension; D019344:Lactic Acid / Q000097:blood; D008168:Lung / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000503:physiopathology; D009638:Norepinephrine / Q000008:administration & dosage*; D010100:Oxygen / Q000378:metabolism; D010865:Pilot Projects; D015221:Potassium Channels / Q000378:metabolism; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage*; D014882:Water-Electrolyte Balance / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D002395:Catecholamines; D007004:Hypoglycemic Agents; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D010100:Oxygen; D005905:Glyburide; D009638:Norepinephrine