title: Single versus multiple doses of acetazolamide for metabolic alkalosis in critically ill medical patients: a randomized, double-blind trial.
abstract: OBJECTIVE
  To compare two dosing regimens of acetazolamide for the reversal of metabolic alkalosis in mechanically ventilated patients with asthma or chronic obstructive pulmonary disease.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled trial.
  
  
  METHODS
  A 35-bed medical intensive care unit in a tertiary care teaching hospital.
  
  
  METHODS
  Forty mechanically ventilated patients with a metabolic alkalosis (arterial pH > or = 7.48 and serum bicarbonate concentration > or = 26 mEq/L) resistant to fluid or potassium therapy (serum potassium concentration, > or = 4 mEq/L) not receiving acetazolamide or sodium bicarbonate in the previous 72 hrs.
  
  
  METHODS
  Stratified by previous diuretic use and randomized to receive intravenous administration of acetazolamide, one dose of 500 mg or 250 mg every 6 hrs for a total of four doses.
  
  
  RESULTS
  Serum bicarbonate and potassium concentrations were drawn every 6 hrs for 72 hrs, arterial blood gases were drawn every 12 hrs for 72 hrs, and both urine chloride and pH were drawn at hours 0, 6, 12, 18, 24, 48, and 72. By using generalized estimating equation techniques, no difference was found between the two dosing regimens at any point over the study period for serum bicarbonate, serum potassium, or urine chloride end points. Results did not differ between diuretic- and nondiuretic-treated patients. Serum bicarbonate concentrations remained significantly decreased in both treatment groups 72 hrs after administration of the first acetazolamide dose (31.8 +/- 4.9-25.3 +/- 3.8 mEq/L, p < .0001 [250 mg x 4]; 31.9 +/- 25.4-25.4 +/- 3.6 mEq/L, p < .0001 [500 mg x 1]).
  
  
  CONCLUSIONS
  We conclude that a single 500-mg dose of acetazolamide reverses nonchloride responsive metabolic alkaloses in medical intensive care unit patients as effectively as multiple doses of 250 mg. Studies to examine the prolonged duration of action of acetazolamide observed in this study as well as the effect of acetazolamide on clinical end points, such as duration of mechanical ventilation, are warranted.
authors.affiliation: Department of Pharmacy Services, Henry Ford Health System, Detroit, MI, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Mazur
authors.forename: J W
authors.initials: JW
authors.lastname: Devlin
authors.forename: M J
authors.initials: MJ
authors.lastname: Peters
authors.forename: M A
authors.initials: MA
authors.lastname: Jankowski
authors.forename: M C
authors.initials: MC
authors.lastname: Iannuzzi
authors.forename: B J
authors.initials: BJ
authors.lastname: Zarowitz
mesh_terms: D000086:Acetazolamide / Q000008:administration & dosage*; D000471:Alkalosis / Q000188:drug therapy* / Q000209:etiology; D001249:Asthma / Q000150:complications; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage*; D016638:Critical Illness; D004232:Diuretics / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000150:complications; D008297:Male; D008875:Middle Aged; D012121:Respiration, Artificial; D018709:Statistics, Nonparametric
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D004232:Diuretics; D000086:Acetazolamide