Association of perioperative gabapentinoids with persistent opioid requirements following below knee amputation - A nationwide claims-based retrospective cohort study.

BACKGROUND

Gabapentin and pregabalin (gabapentinoids) are commonly used in enhanced recovery protocols to reduce postoperative pain and opioid requirements. Below knee amputation (BKA) patients experience intense nociceptive and neuropathic pain post-BKA, increasing their risk of chronic pain and long-term opioid dependence, while multimodal analgesia including gabapentinoids is considered protective against these outcomes. We evaluated the role of gabapentinoids in reducing long-term opioid requirements post-BKA.

METHODS

A nationwide claims database was searched for opioid-naïve patients who had BKA between January-2010 and April-2022. We evaluated the association between newly prescribed perioperative gabapentinoid claims and continued opioid claims at three and six months post-BKA using multivariable regression modelling. We also explored this association using sensitivity analysis based on gabapentinoid type (gabapentin vs. pregabalin), claim timing (preoperative vs. postoperative), and post-BKA analgesics claims as acute pain control indicators.

RESULTS

The matched cohort included 27,264 opioid-naïve BKA patients; 3338 had gabapentinoids claims in the 30 days pre- and/or post-BKA, while 23,926 did not. After multivariable adjustment, patients with gabapentinoid claims had higher odds of continued opioid claims at three and six months, with ratios (OR)[95% confidence interval] of 3.07[2.76, 3.42](p < 0.0001) and 2.44[2.17, 2.75](p < 0.0001), respectively. Three-month sensitivity analysis based on gabapentinoid type maintained a strong association; gabapentin and pregabalin OR = 3.08[2.45, 3.87](p < 0.0001) and 3.47[3.07, 3.94](p < 0.0001), respectively. Similarly, both pre-BKA and post-BKA gabapentinoids maintained an association; OR = 3.26[2.92, 3.63](p < 0.0001) and 5.32[3.72, 7.59](p < 0.0001), respectively. Finally, postoperative pain severity, estimated by analgesics claims, only marginally explained this association, OR = 1.34[1.23, 1.47](p < 0.0001).

CONCLUSIONS

Perioperative gabapentinoid appears to be associated with a higher odds of persistent opioid claims in opioid-naïve BKA patients. While novel and requiring randomized trial confirmation, these findings may undermine gabapentinoids protective and opioid-sparing effects, and merit reexamining their use in multimodal perioperative pathways and pain regimens.