Dose-Dependent Association of Gabapentinoids with Pulmonary Complications After Total Hip and Knee Arthroplasties

Abstract

Background: Gabapentinoids are commonly prescribed in perioperative multimodal analgesia protocols. Despite widespread use, the optimal dose to reduce opioid consumption while minimizing risks is unknown. We assessed dose-dependent effects of gabapentinoids on opioid consumption and postoperative pulmonary complications following total hip or knee arthroplasty (THA or TKA). We hypothesized that use of a gabapentinoid on the day of THA or TKA is associated with an increased risk of postoperative pulmonary complications in a dose-response fashion compared with the risk for patients who did not receive the drug. Methods: Using the Premier Database, we identified adults who underwent elective primary THA or TKA from 2009 to 2014. The exposure was receipt of a gabapentinoid (gabapentin or pregabalin) on the day of surgery. Gabapentin dose was categorized into 5 groups: none, 1 to 350, 351 to 700, 701 to 1,050, and >1,050 mg per day. Pregabalin dose was categorized into 4 groups: none, 1 to 110, 111 to 250, and >250 mg per day. The primary outcome was a composite of postoperative pulmonary complications, defined as respiratory failure, pneumonia, reintubation, pulmonary edema, noninvasive ventilation, or invasive mechanical ventilation. Results: Of 858,306 patients who underwent THA or TKA, 11.0% received gabapentin and 10.2% received pregabalin. The mean age (and standard deviation) of the patients was 65.6 ± 10.7 years, 39.6% were male, 78.2% were Caucasian, and 55.2% were covered by Medicare. In multilevel regression analysis, receipt of gabapentinoid at any dose on the day of surgery was associated with increased odds of postoperative pulmonary complications. Compared with no exposure to the drug being used by the particular group, all dose ranges of gabapentin and pregabalin were associated with greater odds of postoperative pulmonary complications (odds ratio, 95% confidence interval = 1.51, 1.40 to 1.63, for >1,050 mg of gabapentin and 1.81, 1.57 to 2.09, for >250 mg of pregabalin). We found no clinically meaningful associations between exposure to either gabapentin or pregabalin and perioperative opioid consumption or the length of the hospital stay. Conclusions: Exposure to gabapentinoids at any dose on the day of THA or TKA was associated with increased odds of postoperative pulmonary complications in a dose-response fashion, with minimal effects on perioperative opioid consumption. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Perioperative Pain Management and Opioid Stewardship: A Practical Guide

“…A third retrospective analysis found preoperative gabapentin exposure was associated with a 47% increase in odds of experiencing a postoperative respiratory event, though the vast majority of the studied population were administered doses exceeding 300 mg [190,191]. Gabapentinoids exhibit dose-dependent propensity to increase postoperative pulmonary complications, though combination with other multimodal agents may negate this risk, and the absolute risk of adverse events with perioperative gabapentinoids appears low [177,192,193]. Hence, adverse event risks of gabapentinoids can be substantially mitigated by using conservative doses (i.e., 300 mg gabapentin preoperatively), avoiding postoperative use in patients experiencing or at risk for sedation or dizziness, and/or avoiding entirely in high-risk patients.…”

Association of Gabapentinoids With the Risk of Opioid-Related Adverse Events in Surgical Patients in the United States

“…4,5,24 It also highlights the importance of the overall benefit-risk assessment when considering adjuvant use of gabapentinoids, which have been shown to be associated with a decrease in postoperative pain and opioid consumption, although not consistently. 2,4,25 A 2020 observational study 21 found no association between gabapentinoids and reduced opioid consumption either on the day of or the day after total knee or hip arthroplasty. A randomized clinical trial that observed patients after discharge 25 found that perioperative gabapentin had no effect on postoperative pain resolution, although it had some effect on promoting opioid cessation after surgery.…”

Long-acting liposomal bupivacaine and postoperative opioid use after Peyronie’s disease surgery: a pilot study

“…Using this protocol, the authors found a significant decrease in postoperative pain coupled with lower oral opioid consumption when compared with a historical opioidbased regimen. There are new concerns regarding potential adverse perioperative effects with gabapentinoids including pulmonary complications (30,31). At our institution, colleagues in anesthesia have expressed similar concerns.…”