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 3.072.76, 3.42(p < 0.0001) and 2.442.17, 2.75(p < 0.0001), respectively. Three-month sensitivity analysis based on gabapentinoid type maintained a strong association; gabapentin and pregabalin OR = 3.082.45, 3.87(p < 0.0001) and 3.473.07, 3.94(p < 0.0001), respectively. Similarly, both pre-BKA and post-BKA gabapentinoids maintained an association; OR = 3.262.92, 3.63(p < 0.0001) and 5.323.72, 7.59(p < 0.0001), respectively. Finally, postoperative pain severity, estimated by analgesics claims, only marginally explained this association, OR = 1.341.23, 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.