title: Methylene blue administration in septic shock: a clinical trial.
abstract: OBJECTIVE
  A release of nitric oxide has been incriminated in the cardiovascular alterations of septic shock. Since guanylate cyclase is the target enzyme in the endothelium-dependent relaxation mediated by nitric oxide, we studied the acute effects of methylene blue, a potent inhibitor of guanylate cyclase in patients with septic shock.
  
  
  METHODS
  Prospective clinical trial.
  
  
  METHODS
  Medical-surgical intensive care unit in a university hospital.
  
  
  METHODS
  Fourteen patients with severe septic shock requiring adrenergic therapy.
  
  
  METHODS
  Short-term intravenous infusion of methylene blue.
  
  
  RESULTS
  Hemodynamic measurements were obtained at baseline, and 30, 60, and 90 mins after the infusion of 2 mg/kg of methylene blue. Methylene blue administration was followed by a progressive increase in mean arterial pressure (from 61.1 +/- 7.6 to 71.7 +/- 12.0 mm Hg at 60 mins, p < .01). Pulmonary arterial pressure, cardiac filling pressures, cardiac output oxygen delivery, and oxygen consumption were not significantly affected. Left ventricular stroke work increased from 42.5 +/- 17.9 to 48.9 +/- 14.5 g.m after 60 mins (p < .05). Arterial lactate concentration decreased from 3.4 +/- 1.4 to 2.7 +/- 1.3 mmol/L (p < .05). Since these effects were transient, a second dose of methylene blue was administered 90 mins later to six patients and was followed by a similar response. No adverse effect was observed.
  
  
  CONCLUSIONS
  In septic shock patients, the administration of methylene blue results in a transient and reproducible increase in arterial pressure, associated with an improvement in cardiac function, but does not increase cellular oxygen availability. The significant reduction in blood lactate concentration is probably related to the reductor effect of methylene blue, rather than to an improvement in tissue oxygenation.
authors.affiliation: Department of Intensive Care, Erasme University Hospital, Brussels, Belgium.
authors.forename: J C
authors.initials: JC
authors.lastname: Preiser
authors.forename: P
authors.initials: P
authors.lastname: Lejeune
authors.forename: A
authors.initials: A
authors.lastname: Roman
authors.forename: E
authors.initials: E
authors.lastname: Carlier
authors.forename: D
authors.initials: D
authors.lastname: De Backer
authors.forename: M
authors.initials: M
authors.lastname: Leeman
authors.forename: R J
authors.initials: RJ
authors.lastname: Kahn
authors.forename: J L
authors.initials: JL
authors.lastname: Vincent
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006801:Humans; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008297:Male; D008751:Methylene Blue / Q000627:therapeutic use*; D008875:Middle Aged; D019001:Nitric Oxide Synthase; D010100:Oxygen / Q000097:blood; D011446:Prospective Studies; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D007773:Lactates; D019344:Lactic Acid; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006162:Guanylate Cyclase; D010100:Oxygen; D008751:Methylene Blue