Poor outcomes when morphine used in AMI

[OzMedic]

I knew the evidence was poor supporting it's use but this article came as a bit of a shock. Sorry I have not been able to locate the links to the original study as yet (feel free to add them if you are familiar with their location). Any comments?

Morphine for chest pain increases death risk

While patients hospitalized for a heart attack have long been treated with morphine to relieve chest pain, an analysis by researchers from the Duke Clinical Research Institute has shown that these patients have almost a 50 percent higher risk of dying.

The researchers call for a randomized clinical trial to confirm their analysis. Meanwhile, they advise cardiologists to begin treatment with sufficient doses of nitroglycerin to relieve pain before resorting to morphine.

In their analysis of the clinical data and outcomes of more than 57,000 high-risk heart attack patients -- 29.8 percent of whom received morphine within the first 24 hours of hospitalization -- the researchers found that those who received morphine had a 6.8 percent death rate, compared to 3.8 percent for those receiving nitroglycerin. The increase in mortality persisted even after adjustment for the patients' baseline clinical risk.

The results of the Duke were published as a fast-track article 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 Duke cardiologist Trip Meine, M.D., the study's lead author. "Since randomized clinical trials evaluating the safety or effectiveness of morphine for these patients have not been conducted, official guidelines for its use are based solely on expert conjecture. Given the adverse outcomes associated with morphine use found in our analysis, a randomized clinical trial is in order."

Morphine was first used to relieve the chest pain associated with heart attacks in 1912 and has been used regularly ever since. Nitroglycerin has been used for more than 130 years for the relief of chest pain, also known as unstable angina. It works by relaxing blood vessels and allowing blood flow to increase.

"Nitroglycerin has a physiological effect that may, at least temporarily, influence the underlying ischemia," Meine said. "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 the well-known and potentially harmful side effects of depressing respiration, reducing blood pressure and slowing heart rate," he continued. "These side effects could explain the worse outcomes in patients whose heart function has already been compromised by disease."

For their analysis, the researchers consulted the nationwide quality improvement initiative named CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology and AHA Guidelines) The registry continually collects data from more than 400 hospitals on outcomes and on the use of proven drugs and procedures used to restore blood flow to the heart.

From this registry, the researchers identified 57,039 high-risk patients with non-ST-segment elevation myocardial infarction (non-STEMI), a categorization of heart attack based on electrocardiogram (ECG) readings. These patients typically arrive at emergency rooms with chest pain, but often will not have telltale signs of a heart attack on the initial ECG. They might be diagnosed with a heart attack only when the results of the blood tests are reported a few hours later.

The researchers found that patients who were given morphine had 48 percent higher risk of dying and 34 percent higher risk of suffering another heart attack while in the hospital.

"This increase in mortality was present in every subgroup of patients we studied," Meine said. "What we found interesting was that patients given morphine were more likely to receive evidence-based medicine, were more likely to be treated by a cardiologist and were more likely to receive an invasive cardiac procedure."

Meine recommended that physicians with hospitalized heart attack patients should begin with nitroglycerin therapy to control pain.

"Our recommendation is that patients should receive the full dose of nitroglycerin," he said. "Based on our analysis, morphine should be the last resort after else has been tried."

While patients with acute STEMI are at higher risk of dying within 30 days of their hospital stay, patients with non-STEMI actually have a higher risk of dying six months and one year after initial hospital presentation. It is estimated that about 1.3 million Americans are hospitalized each year with non-STEMI.

CRUSADE continuously gathers data from participating U.S. hospitals on treatments for patients with non-STEMI and provides quarterly feedback to hospitals with the ultimate goal of improving adherence to the ACC/AHA treatment guidelines and patient outcomes.

[WelshMedic]

This article makes interesting reading, but leaves me with more questions than it actually answered.

1) How was it carrried out? Was it a retrospective literature review?

2) Is it not the case that those receiving opiates are, by definition, sicker and therefore more likely to die? This issue wasn't addressed in the article

3) Is it Morphine specific? How do the synthetic opiates such as fentanyl fare?

Anybody any answers?

WM

[BushyFromOz]

If the reasoning behind the higher mortality is indeed the cardio vascular effects of morphine sulfate, i wonder then if similar data could be collected on the use of fentanyl instead?

Or do we simply allow them to stay in pain, even with GTN and O2?

[BushyFromOz]

2) Is it not the case that those receiving opiates are, by definition, sicker and therefore more likely to die? This issue wasn't addressed in the article

3) Is it Morphine specific? How do the synthetic opiates such as fentanyl fare?

Should have paid more attention, sorry for re-stating your previous post welsh

[WelshMedic]

No worries cobber!

WM (a pommie, of course)

[Ridryder 911]

Faulty, and shotty study. Not enough scientific data and details to warrant a concern and changes to occur. Not specific enough to describe if those patients had enough damage that mortality would had been high already or not.

Interesting since all other literature is describing we are not giving enough Morphine dosages. NTG is good, but it only works to a point. It is not an analgesic and we only want and can dilate vessels to a point, then it can become dangerous.

R/r 911

[chbare]

Ridryder911, I agree with your assessment as well. The evidence and conclusions are pretty vague and lack specific details. This seems similar to a study that concluded patients taken into the hospital by ambulance were more prone to death, so EMS care caused people to die. :roll:

Take care,

chbare.

[ERDoc]

I'm not sure why this is making news now. It was published in June of 2005. Below is a link to the abstract with a link to the full article. You will have to register to read the full article, but registration is free. CRUSADE is one of the largest databases on ACS in the world. Most of what we know and what we use to determine care comes from what is in this database. It is very similar to the trauama registry. It's a great source for data collection and analysis. Nothing shoddy about it. Morphine was shown to be associated with an increased risk in a subgroups, controlling for many factors. Sound EBM at work here.

http://www.ahjonline.com/article/PIIS00028...001493/abstract

A study was published in 2000 that showed pts with fentanyl also had increased mortality compared to morphine (pubmed.com is your friend).

http://www.ncbi.nlm.nih.gov/entrez/query.f...l=pubmed_docsum

[WelshMedic]

Hi Doc,

The latter study you mention looked at the combination of Fentanyl with Droperidol. This WAS a commonly used preparation in the treatment of ACS here in Europe a few years ago. It was marketed under the name Thalamonal.The thinking was that you could relieve pain and anxiety at the same time with this product. I personally never thought very highly of it. Then some research was published to suggest that the droperidol component led to ECG changes that could precipitate ventricular arrythmia's (can't remember exactly what the problem was, sorry).

The drug was taken out of our protocols in 2001 and was replaced by fentanyl and low dose midazolam, if required.

I only read the astract, but I do wonder whether the neuroleptic component in this study was the cause of the problems, as opposed to fentanyl.

Take Care

Welsh Medic

[ERDoc]

Hi Doc,

The latter study you mention looked at the combination of Fentanyl with Droperidol. This WAS a commonly used preparation in the treatment of ACS here in Europe a few years ago. It was marketed under the name Thalamonal.The thinking was that you could relieve pain and anxiety at the same time with this product. I personally never thought very highly of it. Then some research was published to suggest that the droperidol component led to ECG changes that could precipitate ventricular arrythmia's (can't remember exactly what the problem was, sorry).

The drug was taken out of our protocols in 2001 and was replaced by fentanyl and low dose midazolam, if required.

I only read the astract, but I do wonder whether the neuroleptic component in this study was the cause of the problems, as opposed to fentanyl.

Take Care

Welsh Medic

It could be. Droperidol can cause QT prolongation (though how clinically significant it is is up for debate) and it received (an unwarranted) FDA black box warning. I will admit that I didn't do a very detailed search, so there may be more literature out there on fentanyl.