RANDOMIZED TRIAL OF HIGH-DOSE ISOSORBIDE DINITRATE PLUS LOW-DOSE FUROSEMIDE VERSUS HIGH-DOSE FUROSEMIDE PLUS LOW-DOSE ISOSORBIDE DINITRATE IN SEVERE PULMONARY-EDEMA

Background Nitrates and furosemide, commonly administered in the treat ment of pulmonary oedema, have not been compared in a prospective clin ical trial. We compared the efficacy and safety of these drugs in a ra ndomised trial of patients with severe pulmonary oedema and oxygen sat uration below 90%., Methods Patients presenting to mobile emergency un its with signs of congestive heart failure were treated with oxygen 10 L/min, intravenous furosemide 40 mg, and morphine 3 mg bolus. 110 pat ients were randomly assigned either to group A, who received isosorbid e dinitrate (3 mg bolus administered intravenously every 5 min; n=56) or to group B, who received furosemide (80 mg bolus administered intra venously every 15 min, as well as isosorbide dinitrate 1 mg/h, increas ed every 10 min by 1 mg/h; n=54). Six patients were withdrawn on the b asis of chest radiography results. Treatment was continued until oxyge n saturation was above 96% or mean arterial blood pressure had decreas ed by 30% or to below 90 mm Hg. The main endpoints were death, need fo r mechanical ventilation, and myocardial infarction. The analyses were by intention to treat. Findings Mechanical ventilation was required i n seven (13%) of 52 group-A patients and 21 (40%) of 52 group-B patien ts (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 1 3 (25%) and 24 (46%) patients, respectively (p=0.041). Interpretation High-dose isosorbide dinitrate, given as repeated intravenous boluses after low-dose intravenous furosemide, is safe and effective in contro lling severe pulmonary oedema, This treatment regimen is more effectiv e than high-dose furosemide with low-dose isosorbide nitrate in terms of need for mechanical ventilation and frequency of myocardial infarct ion.