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Thursday, June 26, 2014

For better pain control, add a benzo? (Part 2 - Chest pain)

In my last post, I reviewed a recent study that demonstrated that adding a benzodiazapine (or "benzo") to morphine didn't seem to help in treating traumatic pain, and may increase the rate of side effects. But what about atraumatic pain? Specifically, what about chest pain?

Well, at least chest pain from suspected cardiac ischemia...

You can probably skip the ECG in this case.
So, could adding Ativan or Versed help when treating chest pain?

Background
There are some good reasons to think that controlling anxiety, and not just pain, would help in the treatment of patients with acute coronary syndrome, and especially STEMIs. For example, anxiety during an MI can cause an increased heart rate, and thus worsen oxygen demand, and so potentially worsen the cardiac ischemia. 

So, if we give beta-blockers to address this issue, why not treat the problem right at the root?  

A review from 2003 looked over the basic science, a few small clinical trials, and also the side effect profile of using diazepam or similar agents in acute or subacute ACS. The conclusion was pretty enthusiastic about using benzos, describing the potential risk-benefit ratio as very favorable.
"In conclusion, the authors disagree on whether the chief benefit of adding
benzodiazepines is tasting great, or in being less filling."
The studies they reviewed, however, were small, had conflicting results, and didn't apply to EMS very well. Fortunately, our Swedish friends stepped up to the plate, and conducted a randomized prehospital trial to answer this question.
 
The Study
Methods
The authors of Anxiolytics in patients suffering a suspected acutecoronary syndrome: multi-centre randomised controlled trial inEmergency Medical Service studied if adding midazolam (Versed) to standard analgesia (morphine) could help patients with chest pain. The study included EMS systems from across the Swedish region of Västra, including 500 prehospital personnel, 60 ambulances and one EMS boat.

"Squad 51 responding 11:33. KMG365"
The “usual” dose of morphine was 5 mg, while midazolam was given in 0.5 mg boluses until a total of 1-2 mg had been given. The primary outcome was the pain level at 15 minutes after the decision to give analgesia. 

Results 
After looking at the 1763 patients enrolled in the trial, they found.... no difference. Even when they looked at the subset of 599 patients who turned out to have real ACS diagnosed in the hospital, there was no benefit to adding a benzo for pain relief. 



The addition of midazolam seemed to reduce the heart rate and blood pressure to a statistically significant degree, but the clinical effect was pretty minimal.

Unfortunately, the benzo-getting patients more often became drowsy (or “dozy,” per the authors' language), much like in the trauma patients in my prior post.

Limitations
Yes, the study could have been done better. Many potential patients were not enrolled, and we don't know if they were different from the enrolled folks. Many of the secondary endpoints were vaguely defined, and not based on the patients' self-report. For example, the degree of anxiety, unlike pain, was judged by EMS personnel.

Lastly, while the trial was randomized, the EMS personal were not blinded to the study drug. In other words, EMS knew who got midazolam, and who didn't. This could have introduced some bias in the results (although I would expect it only would have made the midazolam group report better pain relief).

The Bottom Line
This trial may have had some shortcomings, but it did not suggest a clinically significant role for benzos in treating chest pain of suspected cardiac origin. So, we don't have to figure out a way to add a "B" into MONA!


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