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.

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background The Opioid Safety Initiative decreased high-dose prescriptions across the Veterans Health Administration. This study sought to examine the impact of this intervention (i.e., the Opioid Safety Initiative) on pain scores and opioid prescriptions in patients undergoing total knee arthroplasty. Methods This was an ecological study of group-level data among 700 to 850 patients per month over 72 consecutive months (January 2010 to December 2015). The authors examined characteristics of cohorts treated before versus after rollout of the Opioid Safety Initiative (October 2013). Each month, the authors aggregated at the group-level the differences between mean postoperative and preoperative pain scores for each patient (averaged over 6-month periods), and measured proportions of patients (per 1,000) with opioid (and nonopioid) prescriptions for more than 3 months in 6-month periods, preoperatively and postoperatively. The authors compared postintervention trends versus trends forecasted based on preintervention measures. Results After the Opioid Safety Initiative, patients were slightly older and sicker, but had lower mortality rates (postintervention n = 28,509 vs. preintervention n = 31,547). Postoperative pain scores were slightly higher and the decrease in opioid use was statistically significant, i.e., 871 (95% CI, 474 to 1,268) fewer patients with chronic postoperative prescriptions. In time series analyses, mean postoperative minus preoperative pain scores had increased from 0.65 to 0.81, by 0.16 points (95% CI, 0.05 to 0.27). Proportions of patients with chronic postoperative and chronic preoperative opioid prescriptions had declined by 20% (n = 3,355 vs. expected n = 4,226) and by 13% (n = 5,861 vs. expected n = 6,724), respectively. Nonopioid analgesia had increased. Sensitivity analyses confirmed all findings. Conclusions A system-wide initiative combining guideline dissemination with audit and feedback was effective in significantly decreasing opioid prescriptions in populations undergoing total knee arthroplasty, while minimally impacting pain scores.

Objective: The aim of this study was to determine the association between gabapentinoids on the day of surgery and adverse postoperative outcomes in patients undergoing colorectal surgery in the United States. Background: Gabapentinoids, gabapentin and pregabalin, are recommended in multimodal analgesia protocols for acute postoperative pain management after colorectal surgery. However, current literature focuses on the efficacy in reducing opioid consumption, but provides limited information about adverse risks. Methods: This was a retrospective study including 175,787 patients undergoing elective colorectal surgery using the Premier database between 2009 and 2014. Multilevel regression models measured associations of receipt of gabapentinoids with naloxone use after surgery, non-invasive ventilation (NIV), invasive ventilation (IMV), hospital length of stay (LOS), and parental morphine equivalents (PMEs) on the day of surgery and on the day before discharge. Results: Overall, 4677 (2.7%) patients received gabapentinoids on the day of surgery, with use doubling (1.7% in 2009 to 4.3% in 2014). Compared with patients who were unexposed to ganapentinoids, gabapentinoid exposure was associated with lower PMEs on the day of surgery [−2.7 mg; 95% confidence interval (CI), −5.2 to −0.0 mg], and with higher odds of NIV [odds ratio (OR) 1.22, 95% CI, 1.00–1.49] and receipt of naloxone (OR 1.58, 95% CI, 1.11–2.26). There was no difference between the groups with respect to IMV or PMEs on the day before discharge. Conclusions: Although use of gabapentinoids on the day of surgery was associated with slightly lower PMEs on the day of surgery, it was associated with higher odds of NIV and naloxone use after surgery.

The chief technology officer, Jay Song, of the California Highway Patrol and Adam Fried of Waze (Google) assisted in providing data and data support; David Bychkov, PhD, assisted with data collection and partnerships; and Cheng Zheng assisted with data analysis.