• Luc Martinez, Evan Ekman, and Nardine Nakhla.
• Former employee of the Department of General Medicine, University of Paris VI, Paris, France. Electronic address: luc.martinez@orange.fr.
• Clin Ther. 2019 Dec 1; 41 (12): 2612-2628.

PurposeOpioids have long been used to treat acute postsurgical and postprocedural pain; however, opioid-related adverse events (AEs) contribute to poor patient outcomes. In addition, perisurgical exposure to opioids can potentially increase the risk for opioid-use disorder. NSAIDs reduce pain and inflammation by a mechanism different from that of opioid analgesics and may be useful in reducing the need for opioid drugs as part of a multimodal analgesia strategy. We conducted this review to assess the effectiveness and tolerability of adjunctive conventional NSAIDs given systemically in the perioperative setting in terms of opioid-sparing effects observed postoperatively.MethodsClinical trials published since 2000 that have assessed the opioid-sparing effects of conventional, nonselective NSAIDs were identified by a literature search using the PubMed search engine. Search terms were identified for the treatment of interest, the timing of the intervention, and the drugs of interest (NSAIDs). Data from studies that assessed opioid consumption outcomes with systemic NSAID administration were included in the review; data from studies in which NSAIDs were administered topically or via periarticular injection, local infiltration, or regional block were excluded.FindingsUpon full-text review of the search results, 32 studies were chosen for inclusion in this literature review. These studies included those that assessed diclofenac, ketorolac, ibuprofen, ketoprofen, dexketoprofen, flurbiprofen, lornoxicam, tenoxicam, meloxicam, and piroxicam. In studies in which NSAIDs were associated with opioid-sparing effects within the setting of patient-controlled analgesia, opioid use was reduced by 17%-∼50% with diclofenac, 9%-66% with ketorolac, 22%-46% with ibuprofen, 34%-66% with ketoprofen, 36%-50% with dexketoprofen, 38%-41% with tenoxicam, 36%-54% with lornoxicam, and ∼50% with flurbiprofen. No opioid-sparing effect was noted with meloxicam (1 study). The majority of studies that reported on pain-score changes revealed either pain reductions with NSAIDs versus placebo or similar pain scores between groups, indicating that NSAIDs did not compromise pain control. Although many studies found no difference in the prevalence of AEs in NSAID-treated patients compared with controls, several studies noted lower rates of nausea, vomiting, sedation, and pruritus with NSAIDs versus placebo. Conversely, NSAID-related AEs were few overall but included gastrointestinal bleeding, injection site reactions, transient oliguric renal failure, and dizziness. No surgery-related bleeding complications were observed.ImplicationsNSAIDs have the potential to play an important role in reducing postoperative opioid requirements. Reducing the amount of opioids used could be expected to reduce opioid-related side effects and contribute to reversing the opioid epidemic.Copyright © 2019 Elsevier Inc. All rights reserved.

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