Morphine for Chest Pain Increases ACS Death Risk

by Neil Osterweil, Senior Associate Editor, 番茄社区 May 6, 2005

DURHAM, N.C., May 6-Morphine to relieve severe chest pain associated with the non-ST-segment elevation acute coronary syndrome may increase the risk of death by nearly 50%, report Duke investigators. They recommend nitroglycerin as first choice.

In a national study of more than 57,000 patients with non-ST-segment elevation acute coronary syndrome at 443 hospitals, those patients given morphine to treat chest pain were also at 34% greater risk for other poor outcomes, such as MI, cardiogenic shock, and congestive heart failure, adds the Duke team.

Action Points

Morphine, according to this study, appears to be contraindicated in patients who present with non-ST-segment elevation acute coronary syndrome. Chest pain in these patients should be managed with full-dose nitroglycerin, with morphine as a treatment of last resort, the investigators recommend in accord with ACC/AHA guidelines.
Understand that this study, although limited by its retrospective, non-randomized design, draws on a large database, suggesting that the findings of negative outcomes with morphine use in the study population may be significant. However, a prospective, randomized clinical trial is needed to validate these findings with certainty.

The worse outcomes occurred when morphine was used either alone or in combination with nitroglycerin, and persisted even when the data were adjusted for severity of disease and other factors at baseline, cardiologist Trip Meine, M.D., and colleagues reported in a fast-track paper in the American Heart Journal.

"The results of this analysis raise serious concerns about the safety of the routine use of morphine in this group of heart patients," said Dr. Meine. He recommended full-dose nitroglycerin as the pain-relief measure of first choice in these patients, and morphine only after everything else has failed.

"Nitroglycerin has a physiological effect that may, at least temporarily, influence the underlying ischemia," said Dr. Meine. "Morphine, on the other hand, doesn't do anything about what is actually causing the pain. It just masks it, and may, in fact, make the underlying disease worse."

Morphine has been used for nearly a century to relieve chest pain associated with heart attack, but it may exacerbate existing heart function problems by its suppressive effects on respiration, blood pressure, and heart rate, said the Duke investigators.

Current American College of Cardiology/American Heart Association guidelines for the management of patients with non-ST-segment elevation ACS (which includes patients with unstable angina and those with non-ST-segment-elevation MI) list IV morphine as an option for patients with suspected ACS who don't get relief, or who have recurrent pain, after receiving nitroglycerin.

But that recommendation is based more on custom than on science, said the Duke team, which is why the investigators decided to examine the validity of the practice systematically.

They reviewed records on 57,039 patients presenting with non-ST-segment elevation acute coronary syndrome (NTSE ACS) at 443 U.S. hospitals. The records were drawn from the CRUSADE database, which is part of a cardiac care quality initiative underwritten by pharmaceutical companies.

In all, 17,003 patients received morphine within 24 hours. Patients who received any morphine had a higher adjusted risk of death, with an odds ratio of 1.48, (95% CI 1.33-1.64). In addition, those who got morphine had a greater risk of dying in hospital, with an OR of 1.41, (95% CI 1.26-1.57). The link between morphine and increased risk of death held up across all subgroups studied.

The researchers suggest several possible explanations for the increased risk of worse outcomes seen in morphine-treated patients. Morphine use could indicate suboptimal care, for example. But the researchers in fact found that patients who got morphine were more likely to also get evidence-based therapies, to be under a cardiologist's care, and to undergo an invasive procedure.

A more likely explanation, they suggest, is that morphine can actually be bad for the heart in patients with NTSE ACS. They point to evidence showing that morphine causes respiratory depression, hypotension and bradycardia, which can in turn lead to decreased oxygen delivery to the myocardium and other harmful effects.

The investigators acknowledge that there could be unmeasured treatment biases in the study data, and that they didn't have data on the dosing and timing of drug administration.

"Given the adverse outcomes associated with IV morphine use in this analysis, a prospective, randomized clinical trial is needed to determine whether morphine should be administered to patients with chest pain and acute coronary syndromes," they write.

Primary Source

American Heart Journal

Am Heart J. 2005;149.