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!

For better pain control, add a benzo? (Part 1 - Trauma)

If a patient is in pain, should we also be treating their anxiety more aggressively? Some medical practitioners feel strongly that we should be.  In part 1, I'll discuss the evidence for using "benzos" (e.g. midazolam, lorazepam) for traumatic pain. The (forthcoming) part 2 will discuss using benzos to treat the pain of cardiac ischemia. 

Bourbon, for example, can treat the anxiety of MI.
Source: Not the NEJM

Trauma, pain, and benzos
Many paramedics believe that they could control traumatic pain better, and reduce morphine or fentanyl dosing, if they were allowed to add a benzodiazepine, like midazolam or Ativan. Different reasons are offered for this approach, such as the role of anxiety, the spasming of muscles in trauma, or the difficulty in controlling pain quickly with just opioids. An interesting new EMS study adds some evidence to this discussion.

The French authors of  "Does midazolam enhance pain control in prehospital management of traumatic severe pain?" enrolled patients who had a traumatic injury, and who described their pain as at least a "6" on a 10-point scale. 

All of the patients got morphine, and good doses too! The first dose was 0.1 mg/kg, and then repeat doses of 3 mg PRN every 3 minutes were administered, until the pain was down to a “3.” 

Half of these patients also received 0.04 mg/kg IV of midazolam at the same time as the initial dose of morphine, while the other half received a placebo injection.

So, did adding the benzo help? It appears not. Surprisingly, the patients who received midazolam had about the same pain relief as the placebo group. 

Unsurprisingly, they also had much higher rates of sedation: 44%, versus only 7% for the placebo group. They also found a strong trend for more hypoxia in the benzo group: 13% versus 2% for placebo. Lastly, there was no difference in the total doses of morphine given.

So, unless you're looking to "snow" more patients, this isn't a good approach!


How does this agree with other studies?

Pretty well. For example, an ED study done with kids with fractured arms also looked at morphine ± midazolam for pain control. Similar to the present study, they found no advantage in pain control, but more "drowsiness." (In the graph, "VAS" means pain level.)

The Bottom Line
When I interviewed medics for a study I did a few years ago, I was surprised to hear that many medics, from both rural and urban locations across New England, felt strongly about giving benzos for acute traumatic pain.  Here's a sample quote from one of the subjects:

Ref.

Despite having personally worked as a medic at a few of the places I visited, I was surprised to hear this perspective. Adding benzos for pain control is not common (or usually even permitted) in the emergency departments where these medics trained. 

Unless we are trying to sedate a patient, severe pain is probably best controlled with opioids only.