Gabapentin as Post-Op Painkiller Gets a Cold Shower

SAN FRANCISCO — Gabapentin failed to outperform placebo as an analgesic for pain after major surgery, according to a study presented here.

No clinically significant benefit was seen for the active drug in terms of length of hospital stay, opioid use, patient-reported acute pain, or quality of life, reported Ben Gibbison, MBBS, of the University of Bristol in England.

Several measures actually seemed to favor placebo, he said during a late-breaking abstract session at the American Society of Anesthesiologists annual meeting. Trends toward less severe pain, when assessed 4 months after surgery, and better quality of life were seen in the placebo group.

Gibbison said he had no explanation for those findings. But overall, he said, it’s clear that gabapentin was not helpful in the context of this trial, which was focused on invasive major body-cavity procedures.

The GAP Study was also supposed to provide data on cost-effectiveness. But since gabapentin was not clinically effective, there was nothing beyond the obvious for Gibbison to say about it.

As most clinicians know, gabapentin is now widely used as a painkiller in a variety of settings, often as an alternative to opioids. While evidence backs up some of those applications, its effectiveness in the immediate post-operative period after major surgery is less clear. Gibbison noted that well over 100 randomized trials have been conducted in surgical patients, but, he said, “most are small… and highly heterogeneous.” Few had as many as 200 patients, for example. And none had examined duration of hospital stay, an important patient-centered outcome insofar as lingering severe pain can delay discharge.

In light of this evidence gap, the U.K. National Institute for Health and Care Excellence declined in 2020 guidance to endorse gabapentin for acute post-surgical pain, instead calling for more research.

GAP randomized 1,196 patients 1:1 to receive gabapentin or placebo for 3 days, starting immediately before surgery. The first gabapentin dose was 600 mg, then it was given at 300 mg twice daily on days 1 and 2 after surgery. Gibbison explained that dosing beyond day 2 was considered unnecessary since research has shown that pain following major body-cavity surgery rarely lasts that long.

Investigators had hoped to enroll 500 patients each for three types of surgery: cardiac, other thoracic, and abdominal. But the COVID-19 pandemic intervened and the researchers ended up settling for about 340 per surgery type, which reduced the study’s power from 90% to 80% for detecting a difference in length of stay, the primary outcome.

Median patient age was about 68, and roughly two-thirds were men. Most were overweight but not obese.

It seemed unlikely that the larger enrollment would have made a difference. With the data collected, the gabapentin group’s median stay was 5.94 days, versus 6.15 with placebo. That worked out to a hazard ratio of 1.07 (P=0.26). This minor difference was the same with all three surgery types.

Opioid use did appear to favor gabapentin for non-cardiac thoracic and abdominal procedures over the first few post-operative days, being roughly 30% lower at several time points. But Gibbison said this was “a classic example of a statistically significant difference not being clinically significant.” Similar differences were seen with patient-reported acute pain, but again, Gibbison said, these were not clinically important, representing less than one point on the standard 10-point scale.

Meanwhile, the longer-term evaluations of chronic pain and quality of life, which trended against gabapentin, also indicated that the differences were relatively small in clinical terms. Adverse event rates did not differ at all, recorded for about one-third of patients in both treatment groups.

Study limitations included its restriction to major body-cavity surgeries, meaning that the study is not relevant to joint replacements (when painkillers are often required for much longer than 2 days) or any kind of ambulatory procedure, and the inflexible dosing protocol.

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