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Three Part Question

In [patients diagnosed with acute coronary syndrome] does [giving an opiate for analgesia] lead to [increased morbidity or mortality]

Clinical Scenario

You are the RMO in A&E and are seeing a gentleman with suspected cardiac chest pain. He is still in significant pain despite taking his GTN spray and you decide to give him some morphine. Soon after, his blood pressure drop to 70/40, and you need to give naloxone to reverse the effect of the opiate. Fortunately, his blood pressure comes up again, but the episode has left you with concerns. You wonder if giving an opiate is the best thing to do for analgesia in these patients.

Search Strategy

OVID Medline 1966 - 2006 Week 2
OVID Embase 1980 - 2006 Week 10
{exp Myocardial Infarction/ or exp Coronary Thrombosis/ or exp Angina, Unstable/ or (myocard$ adj (infarct$ or ischaem$ or ischem$)).mp. or (acute coronary syndrome or ACS or MI or AMI).mp.} AND {(opiates or morphine or diamorphine).mp}

Search Outcome

2681 papers were identified, of which only one was relevant. This is shown below:

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Meine et al. June 2005 USA	Patients presenting with non ST-elevation acute coronary syndrome (NSTEACS) at 443 hospitals across the USA from January 2001 to June 2003 (n=57,039). Two comparisons were made: 1. Patients receiving morphine versus those who did not. 2. Patients receiving morphine versus those who received IV nitroglycerin.	Non-randomized, retrospective, observational study	In-hospital mortality of patients given morphine vs patients not given morphine	Patients treated with morphine had a higher adjusted risk of death (odds ratio 1.48, 95% CI 1.33-1.64) than patients not treated with morphine.	Non randomized. Thus patients in each group may not have been matched (e.g. those given morphine may have had other factors contributing to increased mortality rate). No mention of effects of morphine on outcomes other than patient morbidity (e.g. did patients given morphine who did not die suffer other side effects such as a higher incidence of renal failure).
			In-hospital mortality of patients given morphine vs patients given IV nitroglycerin	Patients treated with morphine had a higher adjusted risk of death (odds ratio 1.50, 95% CI 1.26-1.78) than those who received IV nitroglycerin.

Comment(s)

Opiates such as morphine or diamorphine have long been used in the management of patients presenting with cardiac chest pain. This is a reflection of just how severe the pain from cardiac ischemia can be. Although nitrates, administered either sublingually or intravenously, can be an effective alternative, many clinicians will choose to use an opiate (either as an alternative or in addition to the nitrate) due to its high efficacy and speed in reducing the pain. The depressive effects of opiates on the cardiorespiratory system are well recognized, and it thus surprising that more research has not been conducted into their safety when given for cardiac chest pain. The CRUSADE initiative is the one major study that has looked into this, and the results give cause for concern. According to the study, there is a clear price to pay for using opiates as analgesia in the setting of NSTEACS, that price being an increase in mortality rate. Given a choice between severe pain which could be relieved by an alternative means, or an opiate which may increase their chance of death, the majority of patients would surely opt for the former. Of course this is but one study. Moreover, the study suffers from the weaknesses mentioned above. The lack of randomization in particular means that it is difficult to tell whether other factors may have been involved in causing the different mortality rates. But in any event, the analysis has raised sufficient concerns to reinforce the view that a prospective, randomized trial needs to be conducted in this important area.

Clinical Bottom Line

The limited available evidence suggests that giving an opiate as an analgesic for cardiac chest pain may increase the chance of in-hospital mortality for your patient. Clinicians should seriously consider whether they really need to give an opiate or if other alternatives are possible.

References

1. Meine TJ, Roe MT, Chen AY, Patel MR, Washam JB, Ohman EM, Peacock WF, Pollack CV Jr, Gibler WB, Peterson ED; CRUSADE Investigators. Association of intravenous morphine use and outcomes in acute coronary syndromes: results from the CRUSADE Quality Improvement Initiative. American heart journal 2005 Jun;149(6):1043-9