High-Dose Isosorbide Dinitrate Plus Low-Dose Furosemide Versus High-Dose Furosemide Plus Low-Dose Isosorbide Dinitrate in Severe Pulmonary Edema - Isosorbide Dinitrate Plus Low-Dose Furosemide Versus High-Dose Furosemide Plus Low-Dose Isosorbide Dinitrate in Severe Pulmonary Edema

Description:

The goal of this randomized trial was to compare high-dose furosemide to high-dose isosorbide among patients with severe pulmonary edema.

Hypothesis:

Patients with severe pulmonary edema may require less ventilatory support with the use of high-dose nitrates in addition to furosemide.

Study Design

Study Design:

Patients Screened: 446
Patients Enrolled: 110
Mean Follow Up: 24 hours
Mean Patient Age: Mean age 74 years
Female: 48
Mean Ejection Fraction: 42.3 ± 11.0% in Group A, and 42.7 ± 13.0% in Group B

Patient Populations:

  • Presence of pulmonary edema (confirmed on chest X-ray)
  • Oxygen saturation <90% prior to supplemental oxygen administration

Exclusions:

  • Prior treatment with greater than 40 mg of oral nitrate daily
  • Isosorbide mononitrate use more than twice daily
  • Isosorbide trinitrate use more than three times per day
  • Use of greater than 80 mg of furosemide per day
  • Blood pressure less than 110/70 mm Hg
  • History of allergic reaction to study drugs

Primary Endpoints:

  • In-hospital death
  • Need for mechanical ventilation within 12 hours (determined by oxygen saturation <80% for more than 20 minutes; progressive deterioration of oxygen saturation to below 80%; progressive dyspnea, apnea, or severe arrhythmias)
  • Myocardial infarction within 24 hours (determined by Q waves on ECG, increase in creatine phosphokinase above upper limit of normal, or MB fraction >6%)
  • Severe bradyarrhythmias or tachyarrhythmias
  • Excessive reduction in mean blood pressure (30% below baseline or below 90 mm Hg)

Secondary Endpoints:

Changes in heart rate, respiratory rate, and oxygen saturation within one hour of treatment

Drug/Procedures Used:

  • Group A: 3 mg bolus of isosorbide dinitrate every five minutes
  • Group B: 80 mg bolus of furosemide every 15 minutes and isosorbide dinitrate 1 mg/h (increased by 1 mg/h every 10 minutes)
Treatment was continued until oxygenation was ≥96% or mean arterial blood pressure was <90 mm Hg or decreased by 30%. All medications were given intravenously.

Concomitant Medications:

Both groups received oxygen at 10 l/min, 40 mg furosemide, and 3 mg morphine at presentation.

Principal Findings:

  • The criteria for mechanical ventilation were less often met in patients randomized to Group A (13% vs. 40%, p=0.004).
  • Myocardial infarction occurred less often in Group A (17% vs. 37%, p=0.047).
  • There was no significant difference in the mortality between the two groups (p=0.61).

Interpretation:

Among patients with severe pulmonary edema with blood pressure ≥110/70, treatment with sequential boluses of isosorbide dinitrate was less often associated with myocardial infarction and less often met criteria for mechanical ventilation compared to sequential boluses of furosemide.

References:

Cotter G, Metzkor E, Kaluski E, et al. Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high-dose furosemide plus low-dose isosorbide dinitrate in severe pulmonary oedema. Lancet 1998;351:389-93.

Clinical Topics: Heart Failure and Cardiomyopathies, Statins, Acute Heart Failure

Keywords: Isosorbide Dinitrate, Pulmonary Edema, Myocardial Infarction, X-Rays, Arterial Pressure, Nitrates, Respiration, Artificial, Diuretics, Heart Failure, Oxygen, Furosemide, Vasodilator Agents


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