title: Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high-dose furosemide plus low-dose isosorbide dinitrate in severe pulmonary oedema.
abstract: BACKGROUND
  Nitrates and furosemide, commonly administered in the treatment of pulmonary oedema, have not been compared in a prospective clinical trial. We compared the efficacy and safety of these drugs in a randomised trial of patients with severe pulmonary oedema and oxygen saturation below 90%.
  
  
  METHODS
  Patients presenting to mobile emergency units with signs of congestive heart failure were treated with oxygen 10 L/min, intravenous furosemide 40 mg, and morphine 3 mg bolus. 110 patients were randomly assigned either to group A, who received isosorbide dinitrate (3 mg bolus administered intravenously every 5 min; n=56) or to group B, who received furosemide (80 mg bolus administered intravenously every 15 min, as well as isosorbide dinitrate 1 mg/h, increased every 10 min by 1 mg/h; n=54). Six patients were withdrawn on the basis of chest radiography results. Treatment was continued until oxygen saturation was above 96% or mean arterial blood pressure had decreased by 30% or to below 90 mm Hg. The main endpoints were death, need for mechanical ventilation, and myocardial infarction. The analyses were by intention to treat.
  
  
  RESULTS
  Mechanical ventilation was required in seven (13%) of 52 group-A patients and 21 (40%) of 52 group-B patients (p=0.0041). Myocardial infarction occurred in nine (17%) and 19 (37%) patients, respectively (p=0.047). One patient in group A and three in group B died (p=0.61). One or more of these endpoints occurred in 13 (25%) and 24 (46%) patients, respectively (p=0.041).
  
  
  CONCLUSIONS
  High-dose isosorbide dinitrate, given as repeated intravenous boluses after low-dose intravenous furosemide, is safe and effective in controlling severe pulmonary oedema. This treatment regimen is more effective than high-dose furosemide with low-dose isosorbide nitrate in terms of need for mechanical ventilation and frequency of myocardial infarction.
authors.affiliation: Assaf Harofeh Medical Center, Zerifin, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Cotter
authors.forename: E
authors.initials: E
authors.lastname: Metzkor
authors.forename: E
authors.initials: E
authors.lastname: Kaluski
authors.forename: Z
authors.initials: Z
authors.lastname: Faigenberg
authors.forename: R
authors.initials: R
authors.lastname: Miller
authors.forename: A
authors.initials: A
authors.lastname: Simovitz
authors.forename: O
authors.initials: O
authors.lastname: Shaham
authors.forename: D
authors.initials: D
authors.lastname: Marghitay
authors.forename: M
authors.initials: M
authors.lastname: Koren
authors.forename: A
authors.initials: A
authors.lastname: Blatt
authors.forename: Y
authors.initials: Y
authors.lastname: Moshkovitz
authors.forename: R
authors.initials: R
authors.lastname: Zaidenstein
authors.forename: A
authors.initials: A
authors.lastname: Golik
mesh_terms: D000208:Acute Disease; D000368:Aged; D004232:Diuretics / Q000008:administration & dosage* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005665:Furosemide / Q000008:administration & dosage* / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D015994:Incidence; D007275:Injections, Intravenous; D007548:Isosorbide Dinitrate / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D009203:Myocardial Infarction / Q000453:epidemiology; D011446:Prospective Studies; D011654:Pulmonary Edema / Q000188:drug therapy* / Q000628:therapy; D012121:Respiration, Artificial; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D004232:Diuretics; D014665:Vasodilator Agents; D005665:Furosemide; D007548:Isosorbide Dinitrate