PMID- 38078559 OWN - NLM STAT- MEDLINE DCOM- 20231216 LR - 20240109 IS - 1469-493X (Electronic) IS - 1361-6137 (Linking) VI - 12 IP - 12 DP - 2023 Dec 11 TI - Diclofenac for acute postoperative pain in children. PG - CD015087 LID - 10.1002/14651858.CD015087.pub2 [doi] LID - CD015087 AB - BACKGROUND: Many children undergo various surgeries, which often lead to acute postoperative pain. This pain influences recovery and quality of life. Non-steroidal anti-inflammatory drugs (NSAIDs), specifically cyclo-oxygenase (COX) inhibitors such as diclofenac, can be used to treat pain and reduce inflammation. There is uncertainty regarding diclofenac's benefits and harms compared to placebo or other drugs for postoperative pain. OBJECTIVES: To assess the efficacy and safety of diclofenac (any dose) for acute postoperative pain management in children compared with placebo, other active comparators, or diclofenac administered by different routes (e.g. oral, rectal, etc.) or strategies (e.g. 'as needed' versus 'as scheduled'). SEARCH METHODS: We used standard, extensive Cochrane search methods. We searched CENTRAL, MEDLINE, and trial registries on 11 April 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in children under 18 years of age undergoing surgery that compared diclofenac (delivered in any dose and route) to placebo or any active pharmacological intervention. We included RCTs comparing different administration routes of diclofenac and different strategies. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our primary outcomes were: pain relief (PR) reported by the child, defined as the proportion of children reporting 50% or better postoperative pain relief; pain intensity (PI) reported by the child; adverse events (AEs); and serious adverse events (SAEs). We presented results using risk ratios (RR), mean differences (MD), and standardised mean differences (SMD), with the associated confidence intervals (CI). MAIN RESULTS: We included 32 RCTs with 2250 children. All surgeries were done using general anaesthesia. Most studies (27) included children above age three. Only two studies had an overall low risk of bias; 30 had an unclear or high risk of bias in one or several domains. Diclofenac versus placebo (three studies) None of the included studies reported on PR or PI. We are very uncertain about the benefits and harms of diclofenac versus placebo on nausea/vomiting (RR 0.83, 95% CI 0.38 to 1.80; 2 studies, 100 children) and any reported bleeding (RR 3.00, 95% CI 0.34 to 26.45; 2 studies, 100 children), both very low-certainty evidence. None of the included studies reported SAEs. Diclofenac versus opioids (seven studies) We are very uncertain if diclofenac reduces PI at 2 to 24 hours postoperatively compared to opioids (median pain intensity 0.3 (interquartile range (IQR) 0.0 to 2.5) for diclofenac versus median 0.7 (IQR 0.1 to 2.4) in the opioid group; 1 study, 50 children; very low-certainty evidence). None of the included studies reported on PR or PI for other time points. Diclofenac probably results in less nausea/vomiting compared to opioids (41.0% in opioids, 31.0% in diclofenac; RR 0.75, 95% CI 0.58 to 0.96; 7 studies, 463 participants), and probably increases any reported bleeding (5.4% in opioids, 16.5% in diclofenac; RR 3.06, 95% CI 1.31 to 7.13; 2 studies, 222 participants), both moderate-certainty evidence. None of the included studies reported SAEs. Diclofenac versus paracetamol (10 studies) None of the included studies assessed child-reported PR. Compared to paracetamol, we are very uncertain if diclofenac: reduces PI at 0 to 2 hours postoperatively (SMD -0.45, 95% CI -0.74 to -0.15; 2 studies, 180 children); reduces PI at 2 to 24 hours postoperatively (SMD -0.64, 95% CI -0.89 to -0.39; 3 studies, 300 children); reduces nausea/vomiting (RR 0.47, 95% CI 0.25 to 0.87; 5 studies, 348 children); reduces bleeding events (RR 0.57, 95% CI 0.12 to 2.62; 5 studies, 332 participants); or reduces SAEs (RR 0.50, 95% CI 0.05 to 5.22; 1 study, 60 children). The evidence certainty was very low for all outcomes. Diclofenac versus bupivacaine (five studies) None of the included studies reported on PR or PI. Compared to bupivacaine, we are very uncertain about the effect of diclofenac on nausea/vomiting (RR 1.28, 95% CI 0.58 to 2.78; 3 studies, 128 children) and SAEs (RR 4.52, 95% CI 0.23 to 88.38; 1 study, 38 children), both very low-certainty evidence. Diclofenac versus active pharmacological comparator (10 studies) We are very uncertain about the benefits and harms of diclofenac versus any other active pharmacological comparator (dexamethasone, pranoprofen, fluorometholone, oxybuprocaine, flurbiprofen, lignocaine), and for different routes and delivery of diclofenac, due to few and small studies, no reporting of key outcomes, and very low-certainty evidence for the reported outcomes. We are unable to draw any meaningful conclusions from the numerical results. AUTHORS' CONCLUSIONS: We remain uncertain about the efficacy of diclofenac compared to placebo, active comparators, or by different routes of administration, for postoperative pain management in children. This is largely due to authors not reporting on clinically important outcomes; unclear reporting of the trials; or poor trial conduct reducing our confidence in the results. We remain uncertain about diclofenac's safety compared to placebo or active comparators, except for the comparison of diclofenac with opioids: diclofenac probably results in less nausea and vomiting compared with opioids, but more bleeding events. For healthcare providers managing postoperative pain, diclofenac is a COX inhibitor option, along with other pharmacological and non-pharmacological approaches. Healthcare providers should weigh the benefits and risks based on what is known of their respective pharmacological effects, rather than known efficacy. For surgical interventions in which bleeding or nausea and vomiting are a concern postoperatively, the risks of adverse events using opioids or diclofenac for managing pain should be considered. CI - Copyright (c) 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. FAU - Ringsten, Martin AU - Ringsten M AD - Department of Health Sciences, Lund University, Skane University Hospital, Lund, Sweden. AD - Cochrane Sweden, Lund University, Skane University Hospital, Lund, Sweden. FAU - Kredo, Tamara AU - Kredo T AD - Health Systems Research Unit, South African Medical Research Council, Cape Town, South Africa. FAU - Ebrahim, Sumayyah AU - Ebrahim S AD - Health Systems Research Unit, South African Medical Research Council, Cape Town, South Africa. AD - Department of Surgery, School of Clinical Medicine, University of KwaZulu-Natal, Durban, South Africa. FAU - Hohlfeld, Ameer AU - Hohlfeld A AD - Health Systems Research Unit, South African Medical Research Council, Cape Town, South Africa. FAU - Bruschettini, Matteo AU - Bruschettini M AD - Cochrane Sweden, Lund University, Skane University Hospital, Lund, Sweden. AD - Department of Clinical Sciences Lund, Paediatrics, Lund University, Skane University Hospital, Lund, Sweden. LA - eng PT - Journal Article PT - Review PT - Systematic Review DEP - 20231211 PL - England TA - Cochrane Database Syst Rev JT - The Cochrane database of systematic reviews JID - 100909747 RN - 144O8QL0L1 (Diclofenac) RN - 362O9ITL9D (Acetaminophen) RN - 0 (Analgesics, Opioid) RN - Y8335394RO (Bupivacaine) SB - IM UOF - doi: 10.1002/14651858.CD015087 MH - Humans MH - Child MH - Adolescent MH - *Diclofenac/therapeutic use MH - *Acetaminophen/therapeutic use MH - Pain, Postoperative/drug therapy MH - Nausea/chemically induced MH - Vomiting/chemically induced MH - Analgesics, Opioid/therapeutic use MH - Bupivacaine PMC - PMC10712214 COIS- MR: previous employment as a physiotherapist in primary care in a university hospital setting, managing children with postoperative pain. TK: consultant to the national department of health in South Africa - no funds are received for this work. TK is employed by the South African Medical Research Council. TK is partly supported by the Research, Evidence and Development Initiative (READ-It) (https://www.evidence4health.org/). READ-It (project number 300342-104) is funded by UK aid from the UK government; however, the views expressed do not necessarily reflect the UK government's official policies. TK is a medical officer in the Infectious Diseases Clinic at Tygerberg Hospital, Stellenbosch University, Stellenbosch, South Africa. AH: none known. AH has previously been a practising clinician (physiotherapist), with no history of managing postoperative pain in children. SE: none known. SE is a lecturer at the School of Clinical Medicine at the University of KwaZulu-Natal (UKZN). MB: none known. MB has previously been a practising clinician (paediatrician), managing children with postoperative pain. MB is an Associate Editor with the Cochrane Neonatal Group but took no part in editorial acceptance or review of this manuscript. EDAT- 2023/12/11 12:41 MHDA- 2023/12/17 09:43 PMCR- 2024/12/11 CRDT- 2023/12/11 08:07 PHST- 2024/12/11 00:00 [pmc-release] PHST- 2023/12/17 09:43 [medline] PHST- 2023/12/11 12:41 [pubmed] PHST- 2023/12/11 08:07 [entrez] AID - CD015087.pub2 [pii] AID - 10.1002/14651858.CD015087.pub2 [doi] PST - epublish SO - Cochrane Database Syst Rev. 2023 Dec 11;12(12):CD015087. doi: 10.1002/14651858.CD015087.pub2.