Use of Morphine for MI Questioned

NEW ORLEANS — Use of intravenous morphine in patients with acute coronary syndromes is a long-standing common practice—and the focus of new safety questions.

Data from the CRUSADE national quality-improvement registry indicate nearly 30% of patients hospitalized with non-ST segment elevation acute coronary syndrome (NSTE ACS) receive intravenous morphine within the first 24 hours of presentation.

Patients who received morphine had increased rates of mortality and other in-hospital adverse outcomes than did those who did not, even after controlling for differences in patient, hospital, and physician characteristics, Trip J. Meine, M.D., reported at the annual scientific sessions of the American Heart Association.

Morphine has been used for management of refractory chest pain in patients with MI since at least 1912. The practice has never been the subject of a randomized trial, nor even—until CRUSADE—a large observational study. Yet it enjoys a class I-C recommendation in the AHA/American College of Cardiology guidelines, noted Dr. Meine of the Duke Clinical Research Institute, Durham, N.C.

He reported that of 57,039 patients who presented with NSTE ACS in 2001-2003 to more than 400 U.S. hospitals participating in CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines), 30% received intravenous morphine within the first 24 hours.

“That was the first surprise. It's a really common practice,” he observed.

Morphine-treated patients presented with more high-risk features, such as ST-segment depression and positive biomarkers, than patients who didn't get morphine.

Perhaps for this reason, morphine recipients also were more likely to get evidence-based medications in accord with ACC/AHA guidelines, including ?-blockers, aspirin, and glycoprotein IIb/IIIa inhibitors. They also got speedier care and were more likely to undergo diagnostic cardiac catheterization and coronary revascularization, all of which indicates morphine use is not a marker for overall suboptimal care.

Morphine-treated patients had worse unadjusted in-hospital outcomes. Moreover, after extensive statistical adjustment for patient risk level, use of evidence-based therapies, and hospital and physician characteristics, they still had a 48% increased relative risk of death and a 34% increased risk of reinfarction, compared with patients who didn't get morphine.

Could morphine merely be a marker for more refractory ongoing chest pain and a particularly severe acute presentation? To examine this possibility, investigators looked at the more than 13,000 patients who got another agent widely prescribed for chest pain—intravenous nitroglycerin—but not morphine.

Like the morphine-treated patients, those on intravenous nitroglycerin presented with more high-risk characteristics and were more likely to receive evidence-based therapies than were patients on neither therapy. Yet their in-hospital combined death or reinfarction rate was only 6.5%, compared with 9.6% in the morphine group. After controlling for patient risk level and other relevant factors, morphine-treated patients still had a 40% greater risk of the combined end point than did those given intravenous nitroglycerin.

Clinical outcomes in the subset of CRUSADE participants who got both agents were worse than in those who received intravenous nitroglycerin alone.

It's worth noting, Dr. Meine continued, that nitroglycerin reduces ventricular wall tension and myocardial oxygen demand, both potentially beneficial effects on ischemic myocardium. In contrast, morphine has many side effects that reduce myocardial oxygen delivery and are thus potentially harmful to ischemic myocardium, including respiratory depression, bradycardia, and hypotension.

“I think it's important to bring up the question of whether morphine itself is a deleterious medication,” Dr. Meine said. “Clearly, a randomized controlled trial is warranted. … My gut feeling is morphine is probably often reached for much earlier than it needs to be, before trying maximum-dose IV nitroglycerin.”

NEW ORLEANS — Use of intravenous morphine in patients with acute coronary syndromes is a long-standing common practice—and the focus of new safety questions.

Data from the CRUSADE national quality-improvement registry indicate nearly 30% of patients hospitalized with non-ST segment elevation acute coronary syndrome (NSTE ACS) receive intravenous morphine within the first 24 hours of presentation.

Patients who received morphine had increased rates of mortality and other in-hospital adverse outcomes than did those who did not, even after controlling for differences in patient, hospital, and physician characteristics, Trip J. Meine, M.D., reported at the annual scientific sessions of the American Heart Association.

Morphine has been used for management of refractory chest pain in patients with MI since at least 1912. The practice has never been the subject of a randomized trial, nor even—until CRUSADE—a large observational study. Yet it enjoys a class I-C recommendation in the AHA/American College of Cardiology guidelines, noted Dr. Meine of the Duke Clinical Research Institute, Durham, N.C.

He reported that of 57,039 patients who presented with NSTE ACS in 2001-2003 to more than 400 U.S. hospitals participating in CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines), 30% received intravenous morphine within the first 24 hours.

“That was the first surprise. It's a really common practice,” he observed.

Morphine-treated patients presented with more high-risk features, such as ST-segment depression and positive biomarkers, than patients who didn't get morphine.

Perhaps for this reason, morphine recipients also were more likely to get evidence-based medications in accord with ACC/AHA guidelines, including ?-blockers, aspirin, and glycoprotein IIb/IIIa inhibitors. They also got speedier care and were more likely to undergo diagnostic cardiac catheterization and coronary revascularization, all of which indicates morphine use is not a marker for overall suboptimal care.

Morphine-treated patients had worse unadjusted in-hospital outcomes. Moreover, after extensive statistical adjustment for patient risk level, use of evidence-based therapies, and hospital and physician characteristics, they still had a 48% increased relative risk of death and a 34% increased risk of reinfarction, compared with patients who didn't get morphine.

Could morphine merely be a marker for more refractory ongoing chest pain and a particularly severe acute presentation? To examine this possibility, investigators looked at the more than 13,000 patients who got another agent widely prescribed for chest pain—intravenous nitroglycerin—but not morphine.

Like the morphine-treated patients, those on intravenous nitroglycerin presented with more high-risk characteristics and were more likely to receive evidence-based therapies than were patients on neither therapy. Yet their in-hospital combined death or reinfarction rate was only 6.5%, compared with 9.6% in the morphine group. After controlling for patient risk level and other relevant factors, morphine-treated patients still had a 40% greater risk of the combined end point than did those given intravenous nitroglycerin.

Clinical outcomes in the subset of CRUSADE participants who got both agents were worse than in those who received intravenous nitroglycerin alone.

It's worth noting, Dr. Meine continued, that nitroglycerin reduces ventricular wall tension and myocardial oxygen demand, both potentially beneficial effects on ischemic myocardium. In contrast, morphine has many side effects that reduce myocardial oxygen delivery and are thus potentially harmful to ischemic myocardium, including respiratory depression, bradycardia, and hypotension.

“I think it's important to bring up the question of whether morphine itself is a deleterious medication,” Dr. Meine said. “Clearly, a randomized controlled trial is warranted. … My gut feeling is morphine is probably often reached for much earlier than it needs to be, before trying maximum-dose IV nitroglycerin.”

NEW ORLEANS — Use of intravenous morphine in patients with acute coronary syndromes is a long-standing common practice—and the focus of new safety questions.

Data from the CRUSADE national quality-improvement registry indicate nearly 30% of patients hospitalized with non-ST segment elevation acute coronary syndrome (NSTE ACS) receive intravenous morphine within the first 24 hours of presentation.

Patients who received morphine had increased rates of mortality and other in-hospital adverse outcomes than did those who did not, even after controlling for differences in patient, hospital, and physician characteristics, Trip J. Meine, M.D., reported at the annual scientific sessions of the American Heart Association.

Morphine has been used for management of refractory chest pain in patients with MI since at least 1912. The practice has never been the subject of a randomized trial, nor even—until CRUSADE—a large observational study. Yet it enjoys a class I-C recommendation in the AHA/American College of Cardiology guidelines, noted Dr. Meine of the Duke Clinical Research Institute, Durham, N.C.

He reported that of 57,039 patients who presented with NSTE ACS in 2001-2003 to more than 400 U.S. hospitals participating in CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines), 30% received intravenous morphine within the first 24 hours.

“That was the first surprise. It's a really common practice,” he observed.

Morphine-treated patients presented with more high-risk features, such as ST-segment depression and positive biomarkers, than patients who didn't get morphine.

Perhaps for this reason, morphine recipients also were more likely to get evidence-based medications in accord with ACC/AHA guidelines, including ?-blockers, aspirin, and glycoprotein IIb/IIIa inhibitors. They also got speedier care and were more likely to undergo diagnostic cardiac catheterization and coronary revascularization, all of which indicates morphine use is not a marker for overall suboptimal care.

Morphine-treated patients had worse unadjusted in-hospital outcomes. Moreover, after extensive statistical adjustment for patient risk level, use of evidence-based therapies, and hospital and physician characteristics, they still had a 48% increased relative risk of death and a 34% increased risk of reinfarction, compared with patients who didn't get morphine.

Could morphine merely be a marker for more refractory ongoing chest pain and a particularly severe acute presentation? To examine this possibility, investigators looked at the more than 13,000 patients who got another agent widely prescribed for chest pain—intravenous nitroglycerin—but not morphine.

Like the morphine-treated patients, those on intravenous nitroglycerin presented with more high-risk characteristics and were more likely to receive evidence-based therapies than were patients on neither therapy. Yet their in-hospital combined death or reinfarction rate was only 6.5%, compared with 9.6% in the morphine group. After controlling for patient risk level and other relevant factors, morphine-treated patients still had a 40% greater risk of the combined end point than did those given intravenous nitroglycerin.

Clinical outcomes in the subset of CRUSADE participants who got both agents were worse than in those who received intravenous nitroglycerin alone.

It's worth noting, Dr. Meine continued, that nitroglycerin reduces ventricular wall tension and myocardial oxygen demand, both potentially beneficial effects on ischemic myocardium. In contrast, morphine has many side effects that reduce myocardial oxygen delivery and are thus potentially harmful to ischemic myocardium, including respiratory depression, bradycardia, and hypotension.

“I think it's important to bring up the question of whether morphine itself is a deleterious medication,” Dr. Meine said. “Clearly, a randomized controlled trial is warranted. … My gut feeling is morphine is probably often reached for much earlier than it needs to be, before trying maximum-dose IV nitroglycerin.”