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BackgroundHip and knee arthroplasty are a fundamental part of modern orthopaedic practice. These procedures often require extensive postoperative analgesia, including opiate painkillers that are frequently associated with adverse side effects and risk of abuse. This review, therefore, investigated how postoperative administration of nonopioid coanalgesics (e.g., parecoxib, pregabalin) can affect postoperative pain scores and opioid use.MethodsA systematic search of OVID, Embase, Medline, and PubMed was conducted, and studies were filtered to trials of patients undergoing arthroplasty who received nonopioid analgesia. Several meta-analyses were conducted to investigate the effects of various medications and classes at multiple postoperative time points on pain scores and opioid use. Standardized mean differences were conducted for analyses involving more than one measure of pain. There were 28 analyses included in the final review.ResultsOn average, nonsteroidal anti-inflammatory drugs (NSAIDs) and gabapentinoids reduced between 9.30 and 10.89 mg, respectively of intravenous morphine in a 24-hour period. Reductions were also observed at various time points for NSAIDs, gabapentinoids, parecoxib, and pregabalin. Nonopioid coanalgesia improved pain at rest for various time points, including NSAIDs at postoperative day (POD) 1 and PODs 3 and 5. Parecoxib and corticosteroids were protective at POD 3. Pain during movement was significantly reduced by NSAIDs at 6 hours, POD 1, 2, and 3, with parecoxib demonstrating similar benefits at POD 1 and POD 2 to 3.ConclusionsThis review found that postoperative administration of nonopioid coanalgesia may alleviate the need for opioids and have modest protective effects on postoperative pain. The effects of these analgesics, however, may be clinically nonmeaningful for reducing pain. These results may further implicate a need to implement nonopioid coanalgesia in postoperative patient care. Future research may include an updated investigation of this research question as more medication granular research becomes available.

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ObjectiveTo identify which drugs are effective at preventing delirium after surgery in adults over 60 years of age and estimate the effects on morbidity and mortality.DesignSystematic review and network meta-analysis.Data sourcesEmbase, Medline, and Cochrane Library up to 4 March 2024.Eligibility criteriaRandomised controlled trials with administration of one or more drugs for the prevention of delirium after surgery requiring general or regional anaesthesia that recruited participants at least 60 years old and used a validated delirium assessment tool to measure the outcome. Surgery under local anaesthesia only, preoperative mechanical ventilation, and studies of interventions to treat delirium were excluded.Data extraction and synthesisAssessors masked to each other's decisions screened studies, extracted data, and assessed risk of bias and quality of evidence in duplicate by using the Cochrane risk of bias tool version 2 and the CINeMA tool. Bayesian arm based network meta-analysis was used to compare interventions.Results158 trials were identified with 41 084 participants comparing 52 drug interventions. Seventeen trials were rated as being at high risk of bias. The overall risk of delirium after surgery was 14.5% (n=5957). Dexmedetomidine (odds ratio 0.46, 95% credible interval 0.36 to 0.57), corticosteroids (0.53, 0.31 to 0.87), melatonin receptor agonists (0.54, 0.34 to 0.85), parecoxib (0.34, 0.16 to 0.74), olanzapine (0.27, 0.07 to 0.94), and intranasal insulin (0.13, 0.04 to 0.34) were the most effective interventions at preventing delirium in trials not at high risk of bias. Only corticosteroids reduced the severity of delirium (mean difference -2.42 (95% credible interval -4.72 to -0.12) Memorial Delirium Assessment Scale points). Most interventions had no effect on length of stay, mortality, cognition, or quality of life. Hypotension and bradycardia were more common with dexmedetomidine, but postoperative nausea and vomiting were reduced. Postoperative infection rates were not increased by corticosteroids.ConclusionsDexmedetomidine is effective in the prevention of postoperative delirium. This finding remains after exclusion of studies at high risk of bias. Corticosteroids, melatonin receptor agonists, parecoxib, intranasal insulin, and olanzapine have potential benefit, although evidence is of moderate to very low quality. Evidence synthesis in this area is complicated by inadequate trial registration practices and incomplete adoption of core outcome sets.Systematic review registrationPROSPERO CRD42023488337.

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Complex regional pain syndrome (CRPS) is a debilitating chronic pain condition that may develop after fractures, surgery, or soft tissue trauma. It is characterized by pain disproportionate to the initial injury, often accompanied by sensory, motor, autonomic, and trophic changes. Despite extensive research, pathophysiology remains unclear, and treatment approaches are varied, with inconsistent supporting evidence. Given its complexity and the potential for chronic disability, identifying effective therapies remains a clinical priority. This review systematically evaluated the analgesic efficacy of pharmacological and non-pharmacological therapies for CRPS, based on randomized controlled trials (RCTs) published between 2003 and 2025. The protocol was developed previously and registered in PROSPERO (CRD420251026503). A structured literature search using a PICO (Population, Intervention, Comparator, Outcome) framework was conducted across MEDLINE, PubMed, and the Cochrane Library. Search terms included "Complex Regional Pain Syndrome," its earlier term "Reflex Sympathetic Dystrophy," and intervention-specific keywords. Included were English-language RCTs in adults with clinically diagnosed CRPS (type I or II), assessing pain reduction as the primary outcome and function, quality of life, and pain medication use as secondary outcomes. Two reviewers independently screened and extracted studies. Risk of bias was assessed using the Cochrane Risk of Bias (ROB) 2. Publication bias was evaluated using funnel plots of standard errors and effect sizes. In total, 45 RCTs met the inclusion criteria and included 2,125 patients. Among pharmacological interventions, bisphosphonates showed consistent and significant pain reduction over six months. Intravenous ketamine demonstrated strong short-term analgesia, though findings were limited by small samples, variable protocols, and lack of long-term data. Combinations of local anesthetics and other medications (e.g., lidocaine with citalopram or parecoxib) were especially effective in acute CRPS. Steroid treatments (oral or regional) offered short-term pain relief and functional improvement, particularly in early or post-stroke CRPS. Non-pharmacological therapies also showed promise in reducing CRPS pain. Mirror therapy (MT) and graded motor imagery (GMI) consistently improved pain and motor function, especially when applied early. Pain exposure physical therapy (PEPT) improved range of motion but had a limited impact on overall functional outcomes. Neuromodulation methods, including spinal cord stimulation (SCS), dorsal root ganglion (DRG) stimulation, and transcutaneous electrical nerve stimulation (TENS), provided durable pain relief in select patients but were technically complex and associated with complications, particularly with SCS. In conclusion, CRPS remains a complex and difficult-to-treat condition, with substantial variability in treatment response. RCT evidence supports the use of bisphosphonates, ketamine, and early use of mirror or motor imagery therapies. Neuromodulation via electrical stimulation may benefit select cases but carries procedural risks. Physiotherapeutic strategies offer low-cost, low-risk benefits, especially when started early or combined with pharmacotherapy. However, many studies were limited by small size, short follow-up, or methodological flaws. There is an urgent need for large, high-quality, and mechanistically informed RCTs to guide long-term CRPS management.

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