- Guest Post by Dr. Bob Twillman
Earlier this week, I got myself into some very hot water by tweeting a link to a story from MedPageToday. The article reported on a study presented at a meeting of the Society of Maternal-Fetal Medicine, investigating whether, in women who had had Cesarean deliveries (CDs), adding opioids to a post-partum regimen of ibuprofen plus acetaminophen provided additional pain relief. The headline on that article provoked me, and while, in no way did I intend my tweet to be an endorsement of the study’s findings, within the span of about three tweets, I felt like I was being perceived as a misogynist who thought women needed nothing for CD pain and should be expected to go right back to work in the fields the next day. Nothing could be further from the truth, and closer examination of the study in question makes me think it never should have seen the light of day.
The researchers conducted an open label trial in which women who had CDs were discharged from the hospital with a randomly selected pain regimen. One group received ibuprofen 600 mg every six hours plus acetaminophen 325 mg, one to two every four hours. The other group received the same dose of ibuprofen, but instead of single-agent acetaminophen, they were prescribed hydrocodone/acetaminophen 5/325, also one to two every four hours. Note that the only difference between the two regimens was 5 to 10 mg of hydrocodone every four hours. Two to four weeks later (mean = 15 and 17 days), the patients were asked to rate their pain on a visual analogue scale (VAS).
In analyzing the results, the authors note that the mean difference in VAS pain ratings was 4.89 mm on (presumably, since the authors didn’t specify) a 100 mm scale; that difference has a 95% confidence interval from -2.19 to 11.9—signifying no statistical difference between the groups. But wait—the authors determined that the treatments should be considered equivalent only if the confidence interval was between -10 and +10 mm. How they made this determination, and whether they did so before or after running the test, was not stated. So, even though the statistical test was non-significant, the authors concluded that there was, in fact, a significant difference, with the opioid group faring worse.
Closer examination of the data, however, reveals something more telling: the mean VAS score for the non-opioid group (two to four weeks post-partum) was 12.3, while the mean score for the opioid group was 15.9. In other words, using the common 0-10 scale used to rate pain, the average pain scores were 1.23 and 1.59. I have more pain than that when I get up in the morning! To say that one of these groups has significantly more pain than the other reminds me of one of my favorite aphorisms: “Twice nothing is still nothing!”
One wonders how much pain the authors would have found at 2-4 weeks post-partum if they had given the women placebos.
By waiting until two to four weeks post-partum to measure pain, the authors completely ignored the time frame when pain medications might be most helpful, i.e., while the surgical incision was healing. The important question is not how much pain a woman has after her CD incision has healed, but how much pain she has while it is healing—something the authors completely ignored.
The primary danger in publishing scientific nonsense like this is that someone will see the headline, read the abstract, and conclude that all women having CD can do without opioids. This study does not lend itself to that conclusion. In answer to the MedPageToday headline (Pain After C-Section: Are Opioids Really Necessary?), all we can really say is that this study doesn’t tell us the answer.
It is true that there are physiological reasons to expect that ibuprofen and acetaminophen could be helpful in reducing post-CD pain, but we need a much-better designed study to determine if opioids add significantly to those effects. Maybe opioids really aren’t necessary. I don’t know, because I’ve never had a CD, but that looks like a significant surgery to me, and if it was my significant other having the procedure, I’d recommend the opioids.
There is one more thing that will probably keep me in hot water, but it probably needs to be said: given the prevailing practice in this country of prescribing opioids after a CD, it is statistically unlikely that any of the women who tweeted back at me, attesting to the necessity of opioids, had actually used only ibuprofen and acetaminophen after their procedures. They only know their own experience and can attest to the fact that their opioid regimens reduced their pain, but they can’t tell us how much more or less pain they would have had with only ibuprofen and acetaminophen. Don’t misunderstand me—I am not advocating for avoiding opioids in this setting, but there is still an open question as to how much they really are needed—especially if state-of-the-art treatments like liposomal bupivacaine was used.
In the widespread zeal to reduce opioid prescribing, it is inevitable that unwitting researchers and reporters will conduct, and then report on, studies that purport to show that opioids produce no more pain relief than non-opioid pain medications. There may be elements of truth in those reports, but we need to keep everyone honest by examining the study’s methods closely and identifying possible sources of bias when we find them.
Dr. Fudin: To add icing on Dr. Twillman’s post, I recently experienced a situation where a young woman with preeclampsia (well-known to me) underwent an emergency CD. Post CD, she was denied opioids because “we try to avoid them in young woman due to potential for abuse and addiction”. In the meantime, her blood pressure was 178/105. I couldn’t believe that the doctor told me “naproxen doesn’t raise the blood pressure too much”. She knew I was a pharmacist which was even more infuriating. I asked her if she evaluated this patient for opioid addiction risk – she looked at me like I had three heads. Turns out there was no risk, and if anything, a negative risk! I made it crystal clear to the OB-GYN attending that she was dead wrong, that NSAIDs where clearly contraindicated in this situation, in favor of opioids, and if the end result was seizure, stroke, blindness, or death, she would be sure to see me in court! THANK YOU DR. TWILLMAN FOR CRITIQUING THIS MISGUIDED STUDY.
As always, comments are encouraged and welcome!!!
A clinical psychologist, Dr. Twillman is the former executive director of the Academy of Integrative Pain Management. He advocates widely for rational pain management policy that promotes the availability of comprehensive integrative pain care.