• 
• 

Three Part Question

In [patients with acute left ventricular failure] is [frusemide better than nitrates] at [reducing symptoms and avoiding the need for intubation]?

Clinical Scenario

An 80-year old man is brought into the Emergency Department in the early hours of the morning with acute shortness of breath. He is pale, clammy and very distressed. You diagnose acute left ventricular failure. You have heard that frusemide may increase vascular resistance and wonder whether nitrates should be used instead.

Search Strategy

Medline 1966-09/00 using the OVID interface.
([exp heart failure, congestive OR exp ventricular dysfunction, left OR left ventricular failure.mp OR exp pulmonary edema OR pulmonary edema.mp OR pulmonary oedema.mp] AND [nitrate$.mp OR exp nitroglycerin OR nitroglycerin.mp OR gtn.mp OR glyceryl trinitrate.mp OR exp isosorbide dinitrate OR isosorbide dinitrate.mp OR isosorbide mononitrate.mp] AND [exp furosemide OR furosemide.mp OR frusemide.mp OR exp bumetanide OR bumetanide.mp OR exp diuretics OR loop diuretic$.mp]) LIMIT to human AND english.

Search Outcome

116 papers found of which 112 were irrelevant or of insufficient quality. The remaining 4 papers are shown in the table.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Nelson GI et al, 1983	28 men with radiographic and haemodynamic evidence of left ventricular failure following acute myocardial infarction Frusemide (1 mg/kg) vs Isosorbide dinitrate (50 - 200 micrograms/kg/h)	PRCT	Left heart filling pressure	Fell with both	Small numbers
			Cardiac output	Fell with frusemide, maintained with isosorbide
			Systematic blood pressure	Transiently rose with frusemide, fell with isosorbide
Verma SP et al, 1987	48 men with transmural myocardial infarction and a pulmonary artery wedge pressure over 20 mm Hg within 18h of admission to CCU Frusemide (12) vs isosorbide dinitrate (ISDN) (12) vs hydralazine (12) vs prenalterol (12)	PRCT	Pulmonary artery wedge pressure	Frusemide and ISDN reduced PAWP more than hydralazine and prenalterol	Small numbers
			Cardiac index	Hydralazine and prenalterol increase cardiac index by increasing heart rate
Cotter G et al, 1998, Israel.	110 patients with acute severe pulmonary oedema. All treated with oxygen at 10 l/min and frusemide 40 mg. Isosorbide dinitrate 3mg every 5 min (56) vs frusemide 80mg every 15 min and isosorbide dinitrate 1mg/h (54).	PRCT	Need for mechanical ventilation	7/52 vs 21/52 (P=0.0041)	Important group of patients were excluded
Beltrame JF et al, 1998, Australia.	59 consecutive patients with acute pulmonary oedema. iv morphine / frusemide (32) vs iv nitroglycerin / N-acetylcysteine (37)	PRCT	Change in PaO2 and FIO2 over the first 60 minutes.	No significant difference	Small numbers
			Need for mechanical ventilatory assistance	No significant difference

Comment(s)

There are still no large trials looking directly at this question. The majority of this work was carried out on patients with recent myocardial infarction.

Clinical Bottom Line

Nitrates have some benefit as the first-line pharmacological treatment of acute pulmonary oedema.

References

1. Nelson GI, Silke B, Ahuja RC et al. Haemodynamic advantages of isosorbide dinitrate over frusemide in acute heart failure following myocardial infarction Lancet 1983;1(8327):730-33.
2. Verma SP, Silke B, Hussain M et al. First-line treatment of left ventricular failure complicating acute myocardial infarction: a randomised evaluation of immediate effects of diuretic, venodilator, arteriodilator, and positive inotropic J Cardiovasc Pharmacol 1987;10:38-46.
3. 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.
4. Beltrame JF, Zeitz CJ, Unger SA et al. Nitrate therapy is an alternative to furosemide/morphine therapy in the management of acute cardiogenic pulmonary edema J Cardiac Failure 1998;4:271-9.