RANDOMISED
TRIAL OF HIGH-DOSE ISOSORBIDE DINITRATE PLUS LOW-DOSE FUROSEMIDE VERSUS
HIGH-DOSE FUROSEMIDE PLUS LOW-DOSE ISOSORBIDE DINITRATE IN SEVERE PULMONARY
EDEMA.
Cotter
G, et al. Lancet 1998 Feb 7;351(9100):389-93.
BACKGROUND:
Nitrates and furosemide, commonly administered in the treatment of pulmonary
oedema, have not been compared in a prospective clinical trial. We compared the
efficacy and safety of these drugs in a randomised trial of patients with
severe pulmonary oedema and oxygen saturation below 90%.
METHODS:
Patients presenting to mobile emergency units with signs of congestive heart
failure were treated with oxygen 10 L/min, intravenous furosemide 40 mg, and
morphine 3 mg bolus. 110 patients were randomly assigned either to group A, who
received isosorbide dinitrate (3 mg bolus administered intravenously every 5
min; n=56) or to group B, who received furosemide (80 mg bolus administered
intravenously every 15 min, as well as isosorbide dinitrate 1 mg/h, increased
every 10 min by 1 mg/h; n=54). Six patients were withdrawn on the basis of
chest radiography results. Treatment was continued until oxygen saturation was
above 96% or mean arterial blood pressure had decreased by 30% or to below 90
mm Hg. The main endpoints were death, need for mechanical ventilation, and
myocardial infarction. The analyses were by intention to treat.
FINDINGS:
Mechanical ventilation was required in seven (13%) of 52 group-A patients and
21 (40%) of 52 group-B patients (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 13 (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 controlling severe
pulmonary oedema. This treatment regimen is more effective than high-dose
furosemide with low-dose isosorbide nitrate in terms of need for mechanical
ventilation and frequency of myocardial infarction.
INTRAVENOUS
NITRATES IN THE PREHOSPITAL MANAGEMENT OF ACUTE PULMONARY EDEMA.
Bertini
G, et al. Ann Emerg Med 1997 Oct;30(4):493-9.
STUDY
OBJECTIVE: We sought to assess the effect of nitrates on prehospital mortality
among patients with acute pulmonary edema (APE).
METHODS:
The study involved a retrospective evaluation of the records of prehospital
outcome in 640 patients with APE rescued by the mobile CCU (MCCU) of Florence,
Italy, between January 1980 and December 1991. The MCCU serves an urban
environment with a population of 400,000 in a 102-sq km area. In the years 1980
through 1983, patients were treated with oxygen, morphine, furosemide, digoxin,
nitrates, aminophylline, or dopamine, according to the attending physician's
judgment. From 1984 through 1991, new guidelines for the use of intravenous
nitrates, based on differential treatment according to blood pressure, were in
use.
RESULTS:
Overall prehospital mortality rate for APE in all patients was 7.8% (50 of of
640 patients). Mortality after 1984 was significantly lower than before (5.3%
versus 13%, P < .01). Nitrates were effective in reducing mortality, even in
hypotensive patients. Multivariate analysis showed that outcome was
significantly affected by two clinical features (dyspnea and low blood
pressure), treatment with nitrates, and calendar period effects (before/after
1984).
CONCLUSION:
Our findings suggest that the use of intravenous nitrates improves short-term
prognosis in APE.
COMMENCTS:
Note that the first study used high dose nitroglycerine, and it showed
benefits. Many doctors & nurses are afraid to increase the rate once IV
nitroglycerine infusion has been started, usually at 30 microgram/hr.
Remember that we give patients 1200 micrograms of sublingual nitroglycerine all
the time. The Lancet study above used 3 milligram boluses.