Friday, July 8, 2005

CRUSADE: Increased Risk of Death with IV Morphine Use?
By Julie McKeel

Intravenous morphine is commonly used to treat patients coming to the hospital with symptoms of chest pain or heart attack (or acute coronary syndrome, ACS). However, the use of IV morphine may actually increase death rates for these patients, according to a new study published in the June 2005 issue of the American Heart Journal.

Trip Meine, MD

The recent findings continue to fuel the debate. Even the reviewers for this study couldn’t agree on the interpretation of the findings, according to Meine. "Either they've always thought that morphine was harmful and that no one would listen to them, or they felt remarkably strongly that morphine is an easy-to-use, safe drug and we're idiots for suggesting otherwise," Meine told theheart.org.

The current ACC/AHA guidelines list morphine as the primary treatment option for patients with unstable angina whose pain is not relieved by nitroglycerine. Morphine, in this scenario, is listed in the guidelines as a class 1C, which means that while it is the primary treatment option, there is no clinical evidence to support its safety or efficiency for ACS patients.

This new analysis was based on data for more than 57,000 patients from the CRUSADE* study admitted to one of 443 U.S. hospitals between January 2001 and June 2003. Of these, 29.8% (17,003 patients) received morphine within the first 24 hours. When compared with CRUSADE patients who did not receive any morphine, morphine-treated patients were more likely to die, have a heart attack, or both. In addition, this increased risk occurred for morphine-treated patients who also received nitroglycerine.

Meine and his colleagues explored possible explanations for the increased risk of death. One such explanation, write the authors, is that morphine blunts the severity of the chest pain without improving underlying condition. At the same time, morphine's side effects including hypotension, slower heart beat, and respiratory depression might result in harmful outcomes in these patients.

While the authors agree that a randomized clinical trial is needed to determine the true effects of morphine, they acknowledge that such a trial is unlikely. One of the editorialists, Dr. Freek WA Verheugt (of the Heart Center in Nijmegen, the Netherlands) agrees that this type of trial would be impossible, given the lack of a "proper alternative" to morphine.

"Most physicians will tell you the reason they use morphine is because they can't get the person chest-pain free,” Meine told theheart.org. In the absence of a trial, concerns about morphine may affect how clinicians deal with ACS patients. "If I can't get a patient chest-pain free with nitroglycerine, there's a reason. Just because their chest pain goes away with morphine doesn't mean the pathophysiologic process causing the chest pain went away, so I think you need to be hypervigilant in those patients, to look for ECG changes, BP changes, or heart-rate changes to tip you off that the patient is still having ischemia. Just because you make them fall asleep doesn't mean you've made their ischemia go away."

In a perfect world, according to Meine, a trial could be set up in which one group of patients receives IV nitroglycerine with morphine added until the patient is chest-pain free while a second group receives increased doses of nitroglycerine until the patient is chest-pain free, with both groups of patients being sent to the cath lab if their chest pain doesn't go away. "That would get at whether these are people who are getting morphine in place of therapeutic doses of nitroglycerine or whether these are people who are a sicker patient population who need to be cared for more aggressively," Meine told theheart.org.

The new information about morphine risks is being considered during the current debate about revisions to the ACC/AHA guidelines. The authors conclude that the cumulative body of evidence pointing to the potential risks of morphine use for ACS patients may lead to a reevaluation of morphine as a class 1C option.

Study authors include the DCRI’s Dr. Trip Meine, Dr Matthew Roe, Anita Y. Chen, Dr. Manesh Patel, Jeffrey B. Washam, Dr. Eric Peterson, and Dr. Magnus Ohman, as well as Dr. Frank Peacock (Cleveland Clinic), Dr. Charles Pollack (Pennsylvania Hospital, Philadelphia), and Dr. Brian Gibler (University of Cincinnati School of Medicine, Cincinnati, Ohio) for the CRUSADE Investigators.

* CRUSADE: Can Rapid risk stratification of Unstable angina patients Suppress ADverse Event outcomes with early implementation of the ACC/AHA guidelines?