For women at risk for pain and depression in the months following a cesarean delivery, adding more pain medicine during the operation may help, according to a small study presented at the annual meeting of the Society for Obstetric Anesthesia and Perinatology (SOAP).
All of the 50 women included in the study were considered to be at risk for experiencing relatively high levels of pain immediately after the procedure, as well as pain and depression two months later.
But when half of the women received twice the dose of intrathecal morphine (300 mcg) during the operation, as well as 1 g of acetaminophen (equivalent to two extra-strength Tylenol) every six hours for 24 hours in the recovery room, they experienced significantly less pain on movement and at rest, and had lower pain scores overall, 24 hours after the operation (abstract 87).
“There does seem to be value in identifying patients who are likely to have increased pain requirements, and not treat all comers the same way,” said study author Robert Fish, MD, obstetric anesthesia fellow at Wake Forest University in Winston-Salem, N.C.
Dr. Fish and his team selected their subjects based on their responses to three questions: How much do you expect to hurt after this surgery? How anxious are you about this surgery? How much pain medicine will it take to treat your pain after surgery?
Will Polymorphisms Predict Practice?
In another study presented at the SOAP meeting, researchers found that pregnant women with two common polymorphisms responded differently to intravenous and intrathecal fentanyl during labor, providing more evidence that affirms the importance of customizing analgesia for certain patients (abstract 86).
Ruth Landau, MD, at the University of Washington, in Seattle, and Brendan Carvalho, MD, from Stanford University, in Stanford, Calif., found that 20% of women carried a specific allelic combination of two common polymorphisms of the OPRM1 and COMT genes known to affect response to opioids. These women were also less likely to respond to an intravenous dose of fentanyl (1.5 mcg/kg) given early in labor.
When women went on to receive an intrathecal dose of fentanyl (20 mcg), those who were A118 homozygous for the A118G polymorphism of the OPRM1 gene continued to report significantly higher pain scores for up to 25 minutes after receiving the intrathecal dose, compared with women carrying the minor allelic variant (G118). Specifically, the A118 group had an average pain score of 20, compared with 5 for the remaining women, a significant difference.
Furthermore, women with the G118 variant who were also Met158 homozygous for the Val158Met polymorphism of the COMT gene had significantly lower pain scores after the intrathecal dose than women who had a different allelic combination of these two polymorphisms.
In the future, women and their doctors likely will want to know their genetic makeup, to determine if they carry genetic variants that make them less likely to benefit from intravenous fentanyl, Dr. Landau predicted. Currently, many women hesitate to progress right to an epidural, but don’t realize that intravenous fentanyl will cross the placenta. If women carry these genetic variants, that’s an unnecessary exposure, she noted. “So these women should be offered an epidural right away.”
That time may be sooner than we realize, said Dr. Flood, who did not participate in the study. She has contributed to another preliminary study that suggested polymorphisms in the oxytocin receptor predict the speed of a woman’s labor.
It doesn’t cost much to analyze selected genes, said Dr. Flood, and if knowing that information could tell doctors that, for instance, a woman is naturally going to progress slowly through labor and won’t need a cesarean as a result, “I think people will get these tests. I think obstetricians are going to want to know.”
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Previous research showed that responses can predict a woman’s chances of experiencing severe pain following cesarean delivery. “These questions have become part of our standard preoperative questionnaire,” Dr. Fish said.
At 24 hours after the surgery, women who received the additional analgesia reported average pain scores on a visual analog scale (VAS) of 9.6 at rest, whereas those given the standard regimen had an average VAS score of 20.9. For movement-related pain, the added-analgesia group reported a score of 29.7; for controls, the score was 47.
The women who received multimodal analgesia were more likely to experience side effects. For instance, 56% of patients overall reported nausea or vomiting that required treatment, which was an issue for just 40% of the group that received only 150 mcg of intrathecal morphine. Furthermore, 64% of the study group experienced pruritus, compared with 56% of controls.
Previous research showed that women who have pain after cesarean delivery are at risk for pain and depression for months after the procedure, so a measure that controls immediate pain could, ideally, have a lasting benefit, Dr. Fish said. “What we hope to find is that when pain is better controlled acutely, patients will be less likely to have persistent pain or depression.”
These findings are encouraging, said Pamela Flood, MD, professor of clinical anesthesia at Columbia University College of Physicians and Surgeons, in New York City, who was not part of the study group. Dr. Flood said she is looking forward to seeing the two-month data. “Literally giving people Tylenol could actually reduce the risk of depression in two months,” she said. “That would be a huge public health benefit.”
It is possible that the morphine and additional acetaminophen have an additive or synergistic effect, said Dr. Flood, so doctors can get a bigger effect without a huge dose increase. “If you have 10-out-of-10 pain, and you brought it down to 8, that’s not a huge benefit. But if the morphine has brought the pain down to 5 in a high-risk patient, and the additional acetaminophen takes it down to 3, that would feel like an important improvement.”
For now, Dr. Fish and his team are continuing to enroll patients, collecting data gathered from the women two months after the procedure, to see if the immediate benefits of the multimodal analgesic approach last.
