Morphine for MI - Benefit and risk

Should we be using morphine to treat chest pain? It seems like an odd question - we're supposed to treat pain, right? - but there some interesting wrinkles to this issue when it comes to heart problems; i.e. acute coronary syndrome (ACS).

At the outset, let me emphasize that the Sponsor Hospital Council guidelines suggest that morphine be used, up to 0.1 mg/kg IV, if chest pain of suspected cardiac origin is not relieved with 3 tabs/sprays of nitroglycerin. That hasn't changed!

The benefit of morphine in ACS
Angina and infarction hurt, and morphine can treat that. There are other supposed benefits (reducing ischemia, reducing "stress," blood pressure reduction), but these are mostly theoretical, and often can be accomplished with other agents.

For example!  (Source)

Okay, perhaps not bourbon, but there are others.

The risk of morphine in ACS
Of course, morphine causes (infrequently) respiratory depression, hypotension, or depressed mental status. These are true for any patient, not just those with ACS, and are generally avoidable with careful administration.

The patient with ACS may face specific risks with morphine though, leading to worse outcomes with their ischemia. This is a controversial area, and there is little good evidence. Nonetheless, breathless headlines like this came out after publication of a study in 2005 (PDF link).

"News" link

This study did not prove a cause & effect relationship with morphine - the study design could only show an association - but people have proposed 3 ways that morphine could potentially harm cardiac patients; 1) direct harm to the myocardum, 2) the side effects of orphine harm the myocardium, and 3) the "masking" of ischemic pain, such that it delays definitive therapy, such as angiography/angioplasty.

1. Does morphine directly harm the myocardium in ACS?
Some people are concerned that morphine, during an episode of ACS, may directly harm the ischemic heart. The authors of the "morphine increases death risk" study remark on the discussion section that "in animal studies, morphine has been demonstrated quite conclusively to actually increase myocardial infarction size." 

They cite, as "quite conclusive," a study from 1982, where rats where given a subcutaneous dose of morphine at 3 mg/kg. (That would be 210 mg for an adult human!) They then performed open-heart surgery, and tied-off a coronary artery - just blocked it off. When they looked at the hearts 2 days later, the rats who had morphine had MIs that involved 10% more myocardium than the morphine-free rats.

Rat open-heart surgery, w/ ligation of LAD. source

On the other hand, North Carolina researchers studied rats who underwent a limited period of coronary occlusion, and found that the morphine pre-treated rats had smaller infarct extent.

So it's an open question whether any of these animal studies represent great (or even mediocre) evidence that can guide our clinical management. It's not conclusive, that much is clear.

2. Do the adverse effects of morphine (hypotension, hypoxia) cause harm in ACS?
Perhaps morphine doesn't have a direct toxic effect on the myocardium, but the known adverse effects can certainly cause problems. Generally, though, these are not common if morphine is administered cautiously, and in practice hypotension or hypoxia are rare.

One study that has been cited as demonstrating the potential for hypotension in MI patients was conducted 1969. In The effect of morphine on blood pressure and cardiac output in patients with AMI the authors gave 15 mg morphine, intramuscularly, to 10 patients with an MI. They found a "slight tendency to development of orthostatic hypotension."

So if you give 15 mg IM of morphine, you might want to be ready to give them some fluids, or just not have them stand, but this doesn't seem persuasive as a severe adverse effect.

 3. Does morphine "mask" the ischemic pain, rather than treat it?
 This is really the most interesting question - should we avoid using opiod medications that could "mask" recurrent or continuing ischemic pain, so that we can make better decisions about further interventions?  I.e., does morphine delay angiography?

Spoiler alert: We have no idea. There is no evidence here, only opinion. 



Chest pain today = abdominal pain 50 years ago?
An analogy with abdominal pain is appealing. In the past physicians relied on the severity and evolution of abdominal pain to aid them in the decision to pursue surgery. If a patient's pain was "masked," the physicians had few means to understand the evolution of the disease. Nowadays, given the accuracy of blood tests and CT scans, most clinicians feel they may safely treat the abdominal pain prior to full evaluation of the patient.

A number of people would argue that we are still at the "pre-CT scan" point now for ACS. The argument is that, absent angiography, we have few means to establish the need for invasive treatment. Like the surgeons of ye olden days, we may be led to a "false sense of security" after morphine reduces the pain.

This is an important question since, in the UA/ACS patient, we use "recurrent ischemic pain" as one factor determining how urgently the patient is taken to angiography. Dr. Stephan Smith, of Dr. Smiths ECG Blog points out one case, for example, where he believes that the heavy-handed use of opiods contributed to a delay in angiography. 
  
But how much do we depend on the character or presence of recurrent/refractory pain, as opposed to other factors? We have the ability to check troponins, perform sequential (or even continuous) ECGs, and we can look "directly" at the myocardium with a bedside echo. We are not dependent on the unimpaired report of symptoms - technology has provided a few tools!

Two patients
Let's consider two extremes, two different patient presentations.

First, how should we consider a patient who adamantly denies any chest pain/pressure (or back pain, shoulder aches, or jaw discomfort...), but has an ECG that looks like this:
 

True story. Yeah, it was an RCA.

This patient was in serious denial, but after intensive interviewing (the Geneva conventions were observed!) he admitted to "chest congestion" that improved with NTG, and consented to cath.

Second, how should we proceed with a patient who describes "crushing" chest pain, with left arm radiation, an sensation of doom, etc., and looks like this...

... but whose ECG looks like this?

Stop looking, it's normal.

Yes, pain means something, but so do the troponins, the echo, and of course the ECG. 

In the end, it's worth pointing out that Dr Smith's "missed MI"  had an initial ECG that actually showed a STEMI, albeit an uncommon (but not rare) pattern. 


Bottom line: Still a recommended therapy!
This post contains more opinion than I usually like to write. There just isn't the level of evidence to help us. I think my observations are pretty mainstream, however. Talking with my colleagues, most of them tend to agree with the use of morphine in this situation. One emergency physician remarked "That's what morphine is for - to mask pain."

Despite the hypothesis-generating evidence provide by the CRUSADE trial, there is little other evidence that suggests that morphine is harmful, or that analgesia must be deferred while patients are in pain. Despite the inflammatory press coverage of the CRUSADE results, the AHA continues to recommend the use of morphine in ACS.


But hold the bourbon!


 

Why do paramedics not want to treat pain in kids?

Forgive me for my provocative title.

Of course, most paramedics do want to treat pain in kids. It's been shown, however, that EMS (like many areas of medicine) doesn't do a great job treating it. Why is that?

Quantitative versus qualitative research

Studying many questions in EMS is relatively straightforward, as you can always look at the numbers.

Does prehospital CPAP prevent intubations? Just count how many people get tubed in the ED! Does use of a CPR-machine save lives? Well, count up how many patients get ROSC!

These sorts of studies, where we look at numerical comparisons, rates, and statistical differences are all quantitative - these rely on obtaining and comparing numbers. To answer this question (about what keeps medics from providing analgesia to pediatric patients), however, EMS researchers in Rochester NY used a qualitative method. 

So this study didn't involve measuring or testing, and collecting a bunch of numbers. Instead, the authors went out and, essentially, listened to what paramedics had to say on this topic!

PubMed link

How they did they do the study?
Getting a paramedic to open up and share their experiences is not exactly the hardest thing in the world...

Pictured: A whole book about medics talking.

 Far from just writing down a bunch of "war stories," however, the authors followed a few steps to ensure they obtained useful and credible information. 

They recruited medics from a variety of agencies in western NY state, with differing levels of experience, and varying levels of comfort dealing with kids. They also brought in a paramedic to actually conduct the interviews, figuring that this would be less intimidating than a physician or PhD. They also tried to figure out a useful way to guide the interviews, designing a set of provocative questions, but also planned to let the medics talk freely and widely on the topic.

So what did the medics say?

Some surprising things!

Now, this sort of research isn't designed to produce statistics or predictions, but I want to highlight some of the results that were felt by the authors to be new and significant, as well as direct quotations from the interviews.

The authors found that "the majority [of medics] viewed relieving pain as unimportant and not part of their job."

They also saw that the medics, in general, "were also concerned that the patients might have an unknown allergy to morphine ... [and had] a similar concern for causing respiratory depression"

Lastly, they found that paramedics "reported receiving generally no response or a negative response from hospital pediatric ED staff."

There are a number of other results and quotations in the article, but I think that these 3 selections convey the general point. Analgesia for pediatric patients is seen as fraught with risks, and is not emphasized as a priority.

As the medics see it, there are few ways to win, and many ways to lose!

Given the inconsistent support from supervisors and ED staff, there is every incentive to shove the issue off, and let the ED handle analgesia.

So, what can be done?

Paramedics are known for their aggressive attitudes in the field, and they don't shy away from challenges. Drilling needles into bone, cardioverting VT with a pulse, or even giving tPA in the ambulance - medics get into the field so that they can tackle the tough problems, not avoid them!

So it's not too hard to figure out where the medics acquired these perceptions about pediatric analgesia. They got these ideas from their supervisors, from their EMS educators, from their rotations in the ED, and in discussions with ED nurses and medical control doctors every day. I agree wholeheartedly with the authors when they conclude that

... the onus of responsibility to change the belief structure regarding pediatric pain management lies not with the paramedic, but with physicians, hospital staff, and paramedic supervisors.

The Bottom Line...

Medics, like all of us, like to engage in a modest amount of medically-appropriate bragging.

"Modest bragging" source

Whether it's sinking a tight ET tube, reversing a bad CHF with aggressive CPAP and nitro, or cardioverting VT in a patient's living room - it's all good material for illustrating your medical prowess. So why not with analgesia?

Perhaps in the future, we'll have quotations from medics that read a little different from those in this study. So, if medical control physicians all do our job right, we'll hear medics bragging about how many mg/kg of morphine they gave, or how quickly they medicated the kid with a femur fracture!

With that in mind, I made my own EMS meme. If we do our jobs right, maybe this will be less of a joke, and more of a reality in the future.

I can getz artsy on Cheezburger!

Prehospital Analgesia - Recent Research

Enough cardiology - time to come back to a topic that's a lot closer to my heart.

Given the relative safety of morphine, the reversibility, the low cost, as well as the immediate and clinically-apparent benefit, I've always been interested about the hand-wringing and strong feelings that surrounds the use of this medication. Frankly, I'm more worried about giving Lasix to someone who turns out to have pneumonia, or overdosing an atrial fib patient on diltiazem.

I wanted to review some recent results in the literature, highlighting a few aspects. While giving any medication requires thought and attention from the paramedic, I think some of the results should make paramedics feel more comfortable with breaking out the box o' narcs.

Should have a lock on it. Two locks, really.

How much morphine can we give?

The first paper, while not that recent, points out safety and effectiveness of the aggressive use of morphine. Is there an ideal morphine dose for prehospital treatment of severe acute pain? describes a study done in a French EMS system. That system uses physicians in place of paramedics, but I'm not sure that matters so much for this topic.

They randomized patients to 2 different IV morphine dosing strategies:

Group A - Start @ 0.05 mg/kg, then 0.025 mg/kg every 5 min.

Group B - Start @ 0.1 mg/kg, then 0.05 mg/kg every 5 min.

Pretty strong doses; a 220 lb guy in Group B would get an initial bolus of 10 mg of morphine. The endpoint was getting the pain score below a 3/10, and Group B appeared to get there quicker (no surprise).

The interesting part was the rate of adverse events:

Basically no difference. An extra 3 patients in group B vomited, and one person had their sat drop to 92% - nobody got intubated or became hypotensive. Pretty safe, and very effective.

Great, but that was a study setting. What about in the "real world?"

In a follow-up study that was published last year, they looked at the "real-world" use of morphine and sufentanil in the same EMS system. It was a prospective trial, but just observational. Patients got at an average initial dose of morphine of 0.083 mg/kg, but not so many titration doses. Again, they found that this kind of dose was very safe, as can be seen in their Table 3.

Looking at the Greater Bridgeport Sponsor Hospital protocols, with a max of 0.1 mg/kg of morphine (before talking to med control), you can feel pretty confident giving an initial bolus of 5 mg in adults!

Well, morphine is going out of style. How about fentanyl?

If you read a recent post by RogueMedic, you know that fentanyl is supposed to be pretty strong, so we might expect that it has a high rate of hypoxia and hypotension. In fact, though, it appears to be just as safe as morphine.  

(Well, not always - there is one way that fentanyl can cause respiratory failure that you may not have prepared for:)

Fentanyl patch stuck in the left bronchus: Reference

The study Fentanyl in the out-of-hospital setting: variables associated with hypotension and hypoxia looked at the experience of an aeromedical service. They used relatively high doses of fentanyl, and medics could give up to 5 µg/kg total every hour. For those of you who don't have experience with this drug, that's about equivalent to 0.5 mg'kg of morphine every hour, or 35 mg for a "average" weight patient. The researchers checked the vital signs before and after drug administration to catch any problems with hypotension or hypoxemia. 

They gave plenty of opioid: The average inital dose was 1.1 µg/kg,while the average total amount given during transport was 3 µg/kg (or 0.3 mg/kg of morphine-equivalents).

Hypotension? Not so much. 

Systolic blood pressures did not, on average, change after giving fentanyl. There were some people, about 5% of all the patients, who had hypotension after getting fentanyl, but about half of those patients were hypotensive before they got the drug as well. 

On the other hand, some hypotensive patients (about 50%) had their blood pressure increase after fentanyl! Go figure...

As for hypoxia, none of the non-intubated patients became hypoxic, 0%. 

So, what can I do with this information on my next shift?

Most importantly, remember that morphine is a pretty safe drug. Looking over the doses they were giving in these studies - pretty aggressive. Now, there is always a risk of some rare event happening, and your patient drops their pressure to 70 and stops breathing. But rare events can happen with any of the drugs in your kit, not just the narcs. The rare patient will have an anaphylactic reaction to aspirin, but it is still a good idea to give it (assuming you've asked about drug allergies).

 

Pain control - Recent controversies and research

Second post, and I wanted to go over recent issues in one of my favorite topics, prehospital analgesia. I found a couple discussions in EMS forums that piqued my interest. If you don't want to stick around for the conclusion, I'll give it to you here now; you can feel safe in using the SHCGB protocols to treat pain, and using them aggressively.

You can give morphine to patients with abdominal pain, you can give it to pregnant patients - no worries. 

You can also feel extremely comfortable with the protocol dosing. Giving 2-5mg IV of morphine, to a total of 0.1 mg/kg, is a very conservative dosing strategy.

Opiods in pregnancy
One discussion I found over at JEMS Connect involved pain management for a pregnant female who had sustained an isolated femur fracture in an MVC. A number of folks, as well as the OP, expressed some concern about the effect of opiods on the fetus, and felt accordingly hesitant about giving morphine or other meds in that situation. One of the quotations stood out to me - "I am normally a huge advocate of pain management in EMS but the risks (harming the fetus) don't seem to outweigh the benefits (not being in pain) when all things are considered."

I'm sympathetic - after all, primum non nocere! You would think that there would be more written on the topic, but Rosen's, the 18 pound bible of EM, says only that "The short-term use of opiates appears to be safe in pregnancy," but doesn't give us any evidence to support that.

Opiods in abdominal pain
Another forum posting, this time over at CTFIRE-EMS, was a discussion trying to elicit people's feelings about giving analgesia as a medic in general. One of the more interesting points was about giving analgesia to a patient with abdominal pain, with one poster believing that "most if not all surgeons would prefer to examine the abdomen before pain meds are given." Other posters weighed in with different opinions (Clashing opinions in a paramedic forum? Unheard of!),  and the observation that protocols in CT are evolving.

Our protocols
And what do the SHCGB protocols recommend? The language is clear:

"Patients in severe pain (7-10/10), in whom a narcotic analgesic will have a beneficial effect on outcome should be considered as candidates for pain management."

No exceptions for abdominal pain, pregnancy, young or old age - go for it!

In the second part (coming up!) I'll go over some recent research about prehospital narcotics, and I'll review some of the other protocols out there. I think it'll really drive home why you can feel safe using our protocol aggressively.