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CLINICAL STUDY

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

Ahuva Sharon, MD^a, Isaac Shpirer, MD^b, Edo Kaluski, MD, FACC , Yaron Moshkovitz, MD, Olga Milovanov, MD^a , Roman Polak, MD^a, Alex Blatt, MD , Avi Simovitz, EMS^||, Ori Shaham, EMS^||, Zvi Faigenberg, MD^||, Michael Metzger, David Stav, MD^b, Robert Yogev, MD^a, Ahuva Golik, MD^a, Rikardo Krakover, MD, Zvi Vered, MD, FACC and Gad Cotter, MD

^a Department of Medicine, Assaf-Harofeh Medical Center, Zerifin, Israel
^b Department of Pulmonology, Assaf-Harofeh Medical Center, Zerifin, Israel
The Cardiology Institute, Assaf-Harofeh Medical Center, Zerifin, Israel
Clinical Pharmacology Research Unit, Assaf-Harofeh Medical Center, Zerifin, Israel
^|| Magen-David-Adom (EMS Service), Zefirin, Israel

Manuscript received December 3, 1999; revised manuscript received March 15, 2000, accepted April 26, 2000.

Reprint requests and correspondence: Gad Cotter MD, The Cardiology Institute, Assaf-Harofeh Medical Center, 70300, Zerifin Israel
cotterg{at}hotmail.com

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.

Abbreviations and Acronyms   ANOVA = analysis of variance   BiPAP = bilevel positive pressure ventilation   CK = creatine phosphokinase   CPAP = continuous positive airway pressure   EPAP = expiratory positive airway pressure   IPAP = inspiratory positive airway pressure   ISDN = isosorbide dinitrate   LVEDP = left ventricular end diastolic pressure   MI = myocardial infarction

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