High-dose intravenous isosorbide-dinitrate is safer and better than Bi-PAP ventilation combined with conventional treatment for severe pulmonary edema

J Am Coll Cardiol. 2000 Sep;36(3):832-7. doi: 10.1016/s0735-1097(00)00785-3.


Objective: To determine the feasibility, safety and efficacy of bilevel positive airway ventilation (BiPAP) in the treatment of severe pulmonary edema compared to high dose nitrate therapy.

Background: Although noninvasive ventilation is increasingly used in the treatment of pulmonary edema, its efficacy has not been compared prospectively with newer treatment modalities.

Methods: We enrolled 40 consecutive patients with severe pulmonary edema (oxygen saturation <90% on room air prior to treatment). All patients received oxygen at a rate of 10 liter/min, intravenous (IV) furosemide 80 mg and IV morphine 3 mg. Thereafter patients were randomly allocated to receive 1) repeated boluses of IV isosorbide-dinitrate (ISDN) 4 mg every 4 min (n = 20), and 2) BiPAP ventilation and standard dose nitrate therapy (n = 20). Treatment was administered until oxygen saturation increased above 96% or systolic blood pressure decreased to below 110 mm Hg or by more than 30%. Patients whose conditions deteriorated despite therapy were intubated and mechanically ventilated. All treatment was delivered by mobile intensive care units prior to hospital arrival.

Results: Patients treated by BiPAP had significantly more adverse events. Two BiPAP treated patients died versus zero in the high dose ISDN group. Sixteen BiPAP treated patients (80%) required intubation and mechanical ventilation compared to four (20%) in the high dose ISDN group (p = 0.0004). Myocardial infarction (MI) occurred in 11 (55%) and 2 (10%) patients, respectively (p = 0.006). The combined primary end point (death, mechanical ventilation or MI) was observed in 17 (85%) versus 5 (25%) patients, respectively (p = 0.0003). After 1 h of treatment, oxygen saturation increased to 96 +/- 4% in the high dose ISDN group as compared to 89 +/- 7% in the BiPAP group (p = 0.017). Due to the significant deterioration observed in patients enrolled in the BiPAP arm, the study was prematurely terminated by the safety committee.

Conclusions: High dose ISDN is safer and better than BiPAP ventilation combined with conventional therapy in patients with severe pulmonary edema.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Injections, Intravenous
  • Isosorbide Dinitrate / administration & dosage*
  • Isosorbide Dinitrate / adverse effects
  • Isosorbide Dinitrate / therapeutic use
  • Male
  • Oxygen / blood
  • Positive-Pressure Respiration / adverse effects
  • Positive-Pressure Respiration / methods*
  • Pulmonary Edema / blood
  • Pulmonary Edema / drug therapy
  • Pulmonary Edema / therapy*
  • Treatment Outcome
  • Vasodilator Agents / administration & dosage*
  • Vasodilator Agents / adverse effects
  • Vasodilator Agents / therapeutic use


  • Vasodilator Agents
  • Isosorbide Dinitrate
  • Oxygen