A meta-analysis of randomized controlled trials shows that gabapentin provides additional analgesia benefit in the regional anesthesia setting across a range of surgical procedures.
According to the study authors, however, providers should consider limiting gabapentin to a one-time preoperative dose to maximize analgesic efficacy and modify its potential side-effect profile.
“In the setting of regional anesthesia, the administration of gabapentin is shown to decrease opioid consumption and improve pain scores, but one dose seems to be all that’s required,” said Jean-Pierre P. Ouanes, DO, MS, director of regional anesthesia and assistant professor of anesthesiology and critical care medicine at Johns Hopkins Bayview Medical Center, in Baltimore. “A single preoperative dose shows a similar effect to multiple doses administered postoperatively.”
According to Dr. Ouanes, gabapentin has helped to limit opioid usage in multimodal analgesia, which remains a central tenet in enhanced recovery after surgery (ERAS) pathways. Although gabapentin has emerged as a “useful perioperative tool,” data regarding its efficacy are limited, specifically in the setting of regional analgesia and other multimodal pain regimens.
For this meta-analysis, Dr. Ouanes and his colleagues searched Medline, Embase and CINAHL (Cumulative Index to Nursing and Allied Health Literature) research databases for randomized controlled trials involving adult patients who underwent general anesthesia with regional anesthesia, defined as either neuraxial or peripheral nerve blockade. The intervention was preoperative oral gabapentin administration greater than 30 minutes prior to surgical incision, and predefined outcomes were postoperative pain at rest at 12 hours, pain at rest at 24 hours and opioid consumption within the first 24 hours of surgery. All analyses were evaluated using the Cochrane Risk of Bias rubric, and predetermined subgroup analyses were performed based on regional technique, procedure type and gabapentin dosing schedule.
Pain and Opioid Use Down
As Dr. Ouanes reported at the 2017 annual Spring meeting of the American Society of Regional Anesthesia and Pain Medicine (abstract 3608), the researchers included 24 trials (N=2,278 patients) in the meta-analysis.
Administration of gabapentin resulted in a statistically significant reduction in pain at rest at 12 hours (standardized mean difference [SMD], –48; 95% CI, –0.81 to –0.14; P=0.006), pain at rest at 24 hours (SMD, –31; 95% CI, –0.61 to 0.00; P<0.05) and morphine equivalent requirement at 24 hours (SMD, –44; 95% CI, –0.81 to –0.08; P<0.02) compared with the control in the setting of concomitant regional analgesia.
“When the 24 trials were analyzed, we found that all pain scores at 12 hours and 24 hours and opioid consumption in the first 24 hours were reduced in patients that received gabapentin in the setting of regional anesthesia,” Dr. Ouanes said.
Subgroup studies of neuraxial or peripheral nerve blockade as well as orthopedic or abdominal procedures yielded similar results, the authors noted. Further subgroup analysis of trials involving only one-time preoperative administration of gabapentin showed similar efficacy when compared with patients who received multiple postoperative doses. An examination of side effects found preoperative gabapentin to be associated with higher rates of sedation and lower rates of pruritus than in the control group, and the drug was not associated with dizziness, nausea or vomiting.
“We think that this analysis is a starting point for future studies to determine whether we can reduce the side-effect profile by limiting the amount of gabapentin,” Dr. Ouanes said.
Furthermore, Michael Grant, MD, the senior author and assistant professor of anesthesiology and critical care medicine at Johns Hopkins Hospital, in Baltimore, previously was published on the efficacy of preoperative gabapentin for the prevention of postoperative nausea and vomiting following general anesthesia.
“Gabapentin has been repeatedly shown to benefit patients in the acute surgical setting as each of these meta-analyses suggests that gabapentin may be associated with improved patient outcome,” Dr. Grant said. “However, the potential for significant postoperative sedation, an inherently dose-dependent phenomenon, may require careful consideration of both dosage and the schedule of the medication. Interestingly, one may gain substantial benefit without excessive sedation through a single preoperative administration.”
Despite this advantage, John F. Butterworth IV, MD, professor and chair of anesthesiology at Virginia Commonwealth University School of Medicine, in Richmond, wondered whether it would be possible to analyze these data for serious adverse events associated with gabapentin, given its potential drawbacks.
“Clinical trials are rarely powered for serious adverse events,” said Dr. Butterworth, who noted that important adverse events sometimes only come to light after drug approval. “The drug [metoclopramide] is no longer on our formularies because it had a one-in-10,000 risk of liver failure. It was seen occasionally, but it was sporadic, so no one thought it was associated with the drug. When the drug hit the market, however, transplant surgeons had a heyday for liver failure, and it was subsequently withdrawn.”
He added, “Same with beta blockers. We’ve shown conclusively that they reduce the incidence of heart attacks, but it wasn’t until data emerged from a bigger trial that we discovered they killed a few more people in the process.”