Post-operative pain affects millions of patients worldwide and the post-operative period has high rates of morbidity and mortality. Some of this morbidity may be related to analgesics. The aim of this review was to provide an update of current knowledge of adverse events (AE) associated with the most common perioperative non-opioid analgesics: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCCs), gabapentinoids and their combinations. The review is based on data from systematic reviews with meta-analyses of analgesic efficacy and/or adverse effects of perioperative non-opioid analgesics, and randomised trials and cohort/retrospective studies. Generally, data on AE are sparse and related to the immediate post-operative period. For paracetamol, the incidence of AEs appears trivial. Data are inconclusive regarding an association of NSAIDs with mortality, cardiovascular events, surgical bleeding and renal impairment. Anastomotic leakage may be associated with NSAID usage. No firm evidence exists for an association of NSAIDs with impaired bone healing. Single-dose GCCs were not significantly related to increased infection rates or delayed wound healing. Gabapentinoid treatment was associated with increased sedation, dizziness and visual disturbances, but the clinical relevance needs clarification. Importantly, data on AEs of combinations of the above analgesics are sparse and inconclusive. Despite the potential adverse events associated with the most commonly applied non-opioid analgesics, including their combinations, reporting of such events is sparse and confined to the immediate perioperative period. Knowledge of benefit and harm related to multimodal pain treatment is deficient and needs clarification in large trials with prolonged observation.
OBJECTIVES: To update a previous report on the comparative benefits and harms of oral non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, over-the-counter supplements (chondroitin and glucosamine), and topical agents (NSAIDs and rubefacients, including capsaicin) for osteoarthritis.
DATA SOURCES: Ovid MEDLINE (1996–January 2011), the Cochrane Database (through fourth quarter 2010), and reference lists.
REVIEW METHODS: We included randomized trials, cohort studies, case-control studies, and systematic reviews that met predefined inclusion criteria. For each study, investigators abstracted details about the study population, study design, data analysis, followup, and results, and they assessed quality using predefined criteria. We assessed the overall strength of each body of evidence using predefined criteria, which included the type and number of studies; risk of bias; consistency; and precision of estimates. Meta-analyses were not performed, though pooled estimates from previously published studies were reported.
RESULTS: A total of 273 studies were included. Overall, we found no clear differences in efficacy for pain relief associated with different NSAIDs. Celecoxib was associated with a lower risk of ulcer complications (RR 0.23, 95% CI 0.07 to 0.76) compared to nonselective NSAIDs. Coprescribing of proton pump inhibitors, misoprostol, and H2-antagonists reduce the risk of endoscopically detected gastroduodenal ulcers compared to placebo in persons prescribed NSAIDs. Celecoxib and most nonselective, nonaspirin NSAIDs appeared to be associated with an increased risk of serious cardiovascular (CV) harms. There was no clear association between longer duration of NSAID use or higher doses and increased risk of serious CV harms. There were no clear differences between glucosamine or chondroitin and oral NSAIDs for pain or function, though evidence from a systematic review of higher-quality trials suggests that glucosamine had some very small benefits over placebo for pain. Head-to-head trials showed no difference between topical and oral NSAIDs for efficacy in patients with localized osteoarthritis, lower risk of gastrointestinal (GI) adverse events, and higher risk of dermatological adverse events, but serious GI and CV harms were not evaluated. No head-to-head trials compared topical salicylates or capsaicin to oral NSAIDs.
CONCLUSIONS: Each of the analgesics evaluated in this report was associated with a unique set of risks and benefits. Choosing the optimal analgesic for an individual with osteoarthritis requires careful consideration and thorough discussion of the relevant tradeoffs.
Post-operative pain affects millions of patients worldwide and the post-operative period has high rates of morbidity and mortality. Some of this morbidity may be related to analgesics. The aim of this review was to provide an update of current knowledge of adverse events (AE) associated with the most common perioperative non-opioid analgesics: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCCs), gabapentinoids and their combinations. The review is based on data from systematic reviews with meta-analyses of analgesic efficacy and/or adverse effects of perioperative non-opioid analgesics, and randomised trials and cohort/retrospective studies. Generally, data on AE are sparse and related to the immediate post-operative period. For paracetamol, the incidence of AEs appears trivial. Data are inconclusive regarding an association of NSAIDs with mortality, cardiovascular events, surgical bleeding and renal impairment. Anastomotic leakage may be associated with NSAID usage. No firm evidence exists for an association of NSAIDs with impaired bone healing. Single-dose GCCs were not significantly related to increased infection rates or delayed wound healing. Gabapentinoid treatment was associated with increased sedation, dizziness and visual disturbances, but the clinical relevance needs clarification. Importantly, data on AEs of combinations of the above analgesics are sparse and inconclusive. Despite the potential adverse events associated with the most commonly applied non-opioid analgesics, including their combinations, reporting of such events is sparse and confined to the immediate perioperative period. Knowledge of benefit and harm related to multimodal pain treatment is deficient and needs clarification in large trials with prolonged observation.
