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A new study compared opioids and over-the-counter painkillers in ERs. Opioids didn't do so well.

The study challenges some big assumptions about acute pain treatment in emergency settings.

German Lopez, Vox, Nov 9, 2017

For years, doctors have deployed opioids in emergency room settings as a standard response to severe acute pain. A new study, however, is questioning that practice in some cases.

The study, published in the Journal of the American Medical Association this month by researchers at Albany Medical College and Albert Einstein College of Medicine in New York, looked at four alternative approaches to acute pain in an emergency department: three treatments with opioids and one with over-the-counter, non-opioid painkillers. The researchers concluded that “there were no statistically significant or clinically important differences in pain reduction at 2 hours” between the opioid treatments and the non-opioid variant.

In other words, the kind of pain studied - acute shoulder, arm, hip, or leg pain in an emergency room setting - was treated equally well with non-opioids as it was with opioids. That’s promising, given that opioids generally carry greater risks in terms of addiction, misuse, and overdose - as the nation’s opioid epidemic has shown.

Now, the study does not say that opioids have no place in pain care. Andrew Chang, the lead author of the study, told me he’s worried that in the response to the opioid crisis, we may overcorrect and limit opioids too much. “I do also worry that we might be swinging the pendulum too far in the other direction,” he wrote in an email, “and I hope we don’t end up creating arbitrary regulatory restrictions that prevent patients who appropriately need opioids from receiving opioids.”

But his research demonstrates that it may be possible to cut back on the amount of opioids used in at least some acute pain care settings without inflicting harm. As policymakers and health care providers respond to the opioid epidemic, that’s good to know.

What the study found

The study looked at more than 400 patients going to the Montefiore Medical Center in Bronx, New York, for acute extremity pain from bone fractures, dislocated shoulders, sprained ankles, and other injuries or conditions.

The patients were then randomly divided into four groups, with each group getting a different combination of drugs to treat their pain. The non-opioid group got 400 mg of ibuprofen and 1,000 mg of acetaminophen, which are often sold over the counter as Advil and Tylenol, respectively. The opioid groups got 5 mg of oxycodone and 325 mg of acetaminophen, 5 mg of hydrocodone and 300 mg of acetaminophen, or 30 mg of codeine and 300 mg of acetaminophen.

On a scale of zero to 10, the patients in the study reported, on average, an initial pain score of 8.7, with no significant differences between the groups. One and two hours later, they reported their pain scores after getting their assigned medication.

Across all groups, patients’ pain scores fell over the two hours: by 4.3 in the ibuprofen and acetaminophen group, 4.4 in the oxycodone and acetaminophen group, 3.5 in the hydrocodone and acetaminophen group, and 3.9 in the codeine and acetaminophen group. The reductions were statistically equivalent across all four groups.

“Some (not all) physicians reflexively think fractures require opioids, but this study lends evidence that opioids are not always necessary even in the presence of fractures,” Chang told me, cautioning that there are likely exceptions for worse and more complicated injuries.

The study was a randomized clinical trial, which is considered the gold standard for medical research. When I asked Stanford drug policy expert Keith Humphreys, who was not involved in the research, what he thought of it, he said that it was a “[g]ood study in a good journal.”

There were limitations in the study. For one, the findings only apply to this specific emergency room setting and over two hours. The researchers also explicitly excluded chronic conditions, such as sickle cell disease, because they wanted to focus on acute pain. More research will be needed to see not just if the study’s findings can be replicated, but also if they apply to other settings, other conditions, or over greater periods of time.

Another big caveat: Even if future studies produce similar findings, that does not mean that everyone will be able to use non-opioids for acute pain. As Chang told me, “[I]t’s important to recognize that the lack of a difference in our study among the four groups is on average, and that any individual patient might receive better pain relief with a particular analgesic.” In short, just because something might be generally true does not mean it can apply to every single individual.

For example, patients who require more pain relief may benefit from a higher dose of opioids than what was provided in the study. Chang’s study used a fairly high dose of ibuprofen and acetaminophen; anything higher could risk serious health problems, since ibuprofen can be hard on the kidneys, among other side effects. But the doses used in the opioid groups, while common in ER settings, weren’t close to the maximum safe dose, so they could be scaled up with fewer potential health risks than the ibuprofen-acetaminophen combination.

Kidney donors or people with kidney disease would also likely benefit more from the opioids. Any loss in kidney function makes ibuprofen inadvisable, so it might be better for these types of patients to get opioids regardless of what the study found.

And for patients in end-of-life care, it’s possible that opioids are simply better because the risk of addiction is, frankly, not a very big concern for someone who is terminally ill. So it might be better to use what can be more easily scaled up to higher doses.

Other caveats may apply, depending on the kinds of conditions and circumstances that a patient is going to the hospital with.

The study also did not measure adverse effects. The researchers pointed to another that did: A “similar [emergency department]-based study lasting 90 minutes had an incidence of adverse events of 1.6% in the codeine group, 3.3% in the nonopioid group, and 16.9% in the oxycodone group, with lightheadedness accounting for 70% of adverse events in the oxycodone group.” But since that study used higher doses for opioids than Chang’s research, the findings aren’t comparable to what Chang and his colleagues found.

So the study isn’t the final word. Still, it gives promising insight in a crucial area of public health.

We can pull back on opioids without doing harm

This research falls under the shadow of the opioid epidemic. The current overdose crisis has over time changed to involve all kinds of opioids - painkillers, heroin, and fentanyl. But it originally began with the overprescription of opioid painkillers, which allowed the supply of the prescription drugs to explode. That led opioids to proliferate, landing in the hands of not just patients but also teens rummaging through their parents’ medicine cabinets, other family members, friends of patients, and the black market. (More on the opioid epidemic’s causes and evolution in Vox’s explainer.)

The crisis has led policymakers and health care providers to look at cutting back on prescription opioids. But this comes with a challenge: Policymakers and health care providers also want to make sure that the drugs are available to patients who truly need them.

The study shows that this really might be possible, at least in the kind of emergency room setting that the researchers looked at. If nothing else, it should lead some doctors to rethink the default mode they might have when it comes to acute pain - to always reach for the opioid.

As Chang told me, “If we can administer a combination of non-opioids to patients while they are in the [emergency department] and show them (as well as the treating physician) that it provides comparable pain relief to opioids, then the patient will likely be more accepting of a non-opioid upon discharge, and the physician may feel less pressure to prescribe an opioid.”

Several weeks ago, I underwent surgery for a minor heart condition. (Don’t worry; I’m not going to die - yet, anyway.) In my hospital room, I reported my pain score after the procedure as a six out of 10, and I was vocally resistant to getting opioids. The nurses gave me opioids anyway. I turned out fine, as most people who get opioids in these settings do. But Chang’s study suggests I could have been just as fine if I got a high dose of ibuprofen and acetaminophen instead. Yet there seemed to be a bias in favor of the opioids.

In general, this is what the response to the opioid epidemic has been about: weakening that bias in favor of opioids for treating pain - while ensuring that patients who truly need opioids can still get them.

This applies to chronic pain as well. The evidence for opioids treating chronic pain is very weak (despite their effectiveness for acute pain), while the evidence that opioids cause harm in the long term is very strong. And a recent study found that doctors can wean some chronic pain patients off opioids and actually improve their pain outcomes. More research is needed in this area, but the current evidence suggests that the risks of opioids might not be worth the gains, if there actually are any, for most chronic pain patients.

As with acute pain, that does not mean opioids will never be useful in chronic pain cases. When prescribed carefully on a schedule that works to diminish the excessive buildup of tolerance, they can work for some people. Stanford pain specialist Sean Mackey previously told me that opioids should not be a first-line treatment due to the risks, and alternatives should be tried first - but they can work for some chronic pain patients, and keeping them from such patients can cause unnecessary harm and suffering.

So opioid policy, as with many public health issues, is a balancing act. But studies like Chang’s and other research suggest that it is possible to moderate our opioid use and not inflict unnecessary harm on patients. That could be a crucial step in confronting the ongoing drug epidemic and preventing more crises like it in the future.

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