• Tetsu Ohnuma, Karthik Raghunathan, Alan R Ellis, John Whittle, Srinivas Pyati, William E Bryan, Marc J Pepin, Raquel R Bartz, and Vijay Krishnamoorthy.
• Patient Safety Center of Inquiry, Durham VA Medical Center, Durham, North Carolina.
• Pain Med. 2020 Oct 1; 21 (10): 2385-2393.

ObjectiveMultimodal analgesia has gained popularity in total hip arthroplasty (THA) and total knee arthroplasty (TKA), but large multicenter studies evaluating specific analgesic combinations are lacking.DesignA retrospective study using the Premier Healthcare Database (2009-2014).SubjectsAdults who underwent elective primary THA or TKA.MethodsWe categorized day-of-surgery analgesic exposure using eight mutually exclusive categories: acetaminophen (Ac), nonsteroidal anti-inflammatory drugs (Ns), gabapentinoids (Ga; gabapentin or pregabalin), Ac+Ns, Ac+Ga, Ns+Ga, Ac+Ns+Ga, and none of the three drugs. Multilevel models measured associations of the analgesic categories with a composite of postoperative pulmonary complications (PPCs).ResultsAmong 863,139 patients, 75.2% received at least one of the three drugs. In multilevel models, compared with none of the three drugs, Ga use was associated with increased odds of PPCs when used alone (adjusted odds ratio [aOR] = 1.35, 95% confidence interval [CI] = 1.27 to 1.44), combined with Ac (aOR = 1.16, 95% CI = 1.08 to 1.26), or combined with Ns (aOR = 1.28, 95% CI = 1.21 to 1.34). In contrast, the Ac+Ns pair was associated with decreased odds of PPCs (OR = 0.86, 95% CI = 0.83 to 0.90) and lower opioid consumption. Ac+Ns+Ga was not associated with PPCs, whereas it was associated with the lowest opioid consumption on the day of surgery.ConclusionsGabapentinoids, alone and in single combination with either acetaminophen or nonsteroidal anti-inflammatory drugs, were associated with higher PPCs, whereas the Ac+Ns pair was associated with fewer PPCs and an opioid-sparing effect. Ac+Ns+Ga was not associated with PPCs, whereas it was associated with the lowest opioid consumption on the day of surgery.© The Author(s) 2020. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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