PMID- 34125958 OWN - NLM STAT- MEDLINE DCOM- 20210803 LR - 20220716 IS - 1469-493X (Electronic) IS - 1361-6137 (Linking) VI - 6 IP - 6 DP - 2021 Jun 14 TI - Pre-emptive and preventive NSAIDs for postoperative pain in adults undergoing all types of surgery. PG - CD012978 LID - 10.1002/14651858.CD012978.pub2 [doi] LID - CD012978 AB - BACKGROUND: Postoperative pain is a common consequence of surgery and can have many negative perioperative effects. It has been suggested that the administration of analgesia before a painful stimulus may improve pain control. We defined pre-emptive nonsteroidal anti-inflammatories (NSAIDs) as those given before surgery but not continued afterwards and preventive NSAIDs as those given before surgery and continued afterwards. These were compared to a control group given the NSAIDs after surgery instead of before surgery. OBJECTIVES: To assess the efficacy of preventive and pre-emptive NSAIDs for reducing postoperative pain in adults undergoing all types of surgery. SEARCH METHODS: We searched the following electronic databases: CENTRAL, MEDLINE, Embase, AMED and CINAHL (up to June 2020). In addition, we searched for unpublished studies in three clinical trial databases, conference proceedings, grey literature databases, and reference lists of retrieved articles. We did not apply any restrictions on language or date of publication. SELECTION CRITERIA: We included parallel-group randomized controlled trials (RCTs) only. We included adult participants undergoing any type of surgery. We defined pre-emptive NSAIDs as those given before surgery but not continued afterwards and preventive NSAIDs as those given before surgery and continued afterwards. These were compared to a control group given the NSAIDs after surgery instead of before surgery. We included studies that gave the medication by any route but not given on the skin. DATA COLLECTION AND ANALYSIS: We used the standard methods expected by Cochrane, as well as a novel publication bias test developed by our research group. We used GRADE to assess the certainty of the evidence for each outcome. Outcomes included acute postoperative pain (minimal clinically important difference (MCID): 1.5 on a 0-10 scale), adverse events of NSAIDs, nausea and vomiting, 24-hour morphine consumption (MCID: 10 mg reduction), time to analgesic request (MCID: one hour), pruritus, sedation, patient satisfaction, chronic pain and time to first bowel movement (MCID: 12 hours). MAIN RESULTS: We included 71 RCTs. Seven studies are awaiting classification. We included 45 studies that evaluated pre-emptive NSAIDs and 26 studies that evaluated preventive NSAIDs. We considered only four studies to be at low risk of bias for most domains. The operations and NSAIDs used varied, although most studies were conducted in abdominal, orthopaedic and dental surgery. Most studies were conducted in secondary care and in low-risk participants. Common exclusions were participants on analgesic medications prior to surgery and those with chronic pain. Pre-emptive NSAIDs compared to post-incision NSAIDs For pre-emptive NSAIDs, there is probably a decrease in early acute postoperative pain (MD -0.69, 95% CI -0.97 to -0.41; studies = 36; participants = 2032; I(2) = 96%; moderate-certainty evidence). None of the included studies that reported on acute postoperative pain reported adverse events as an outcome. There may be little or no difference between the groups in short-term (RR 1.00, 95% CI 0.34 to 2.94; studies = 2; participants = 100; I(2) = 0%; low-certainty evidence) or long-term nausea and vomiting (RR 0.85, 95% CI 0.52 to 1.38; studies = 5; participants = 228; I(2) = 29%; low-certainty evidence). There may be a reduction in late acute postoperative pain (MD -0.22, 95% CI -0.44 to 0.00; studies = 28; participants = 1645; I(2) = 97%; low-certainty evidence). There may be a reduction in 24-hour morphine consumption with pre-emptive NSAIDs (MD -5.62 mg, 95% CI -9.00 mg to -2.24 mg; studies = 16; participants = 854; I(2) = 99%; low-certainty evidence) and an increase in the time to analgesic request (MD 17.04 minutes, 95% CI 3.77 minutes to 30.31 minutes; studies = 18; participants = 975; I(2) = 95%; low-certainty evidence). There may be little or no difference in opioid adverse events such as pruritus (RR 0.40, 95% CI 0.09 to 1.76; studies = 4; participants = 254; I(2) = 0%; low-certainty evidence) or sedation (RR 0.51, 95% CI 0.16 to 1.68; studies = 4; participants = 281; I(2) = 0%; low-certainty evidence), although the number of included studies for these outcomes was small. No study reported patient satisfaction, chronic pain or time to first bowel movement for pre-emptive NSAIDs. Preventive NSAIDs compared to post-incision NSAIDs For preventive NSAIDs, there may be little or no difference in early acute postoperative pain (MD -0.14, 95% CI -0.39 to 0.12; studies = 18; participants = 1140; I(2) = 75%; low-certainty evidence). One study reported adverse events from NSAIDs (reoperation for bleeding) although the events were low which did not allow any meaningful conclusions to be drawn (RR 1.95; 95% CI 0.18 to 20.68). There may be little or no difference in rates of short-term (RR 1.26, 95% CI 0.49 to 3.30; studies = 1; participants = 76; low-certainty evidence) or long-term (RR 0.85, 95% CI 0.52 to 1.38; studies = 5; participants = 456; I(2) = 29%; low-certainty evidence) nausea and vomiting. There may be a reduction in late acute postoperative pain (MD -0.33, 95% CI -0.59 to -0.07; studies = 21; participants = 1441; I(2) = 81%; low-certainty evidence). There is probably a reduction in 24-hour morphine consumption (MD -1.93 mg, 95% CI -3.55 mg to -0.32 mg; studies = 16; participants = 1323; I(2) = 49%; moderate-certainty evidence). It is uncertain if there is any difference in time to analgesic request (MD 8.51 minutes, 95% CI -31.24 minutes to 48.27 minutes; studies = 8; participants = 410; I(2) = 98%; very low-certainty evidence). As with pre-emptive NSAIDs, there may be little or no difference in other opioid adverse events such as pruritus (RR 0.56, 95% CI 0.09 to 3.35; studies = 3; participants = 211; I(2) = 0%; low-certainty evidence) and sedation (RR 0.84, 95% CI 0.44 to 1.63; studies = 5; participants = 497; I(2) = 0%; low-certainty evidence). There is probably little or no difference in patient satisfaction (MD -0.42; 95% CI -1.09 to 0.25; studies = 1; participants = 72; moderate-certainty evidence). No study reported on chronic pain. There is probably little or no difference in time to first bowel movement (MD 0.00; 95% CI -15.99 to 15.99; studies = 1; participants = 76; moderate-certainty evidence). AUTHORS' CONCLUSIONS: There was some evidence that pre-emptive and preventive NSAIDs reduce both pain and morphine consumption, although this was not universal for all pain and morphine consumption outcomes. Any differences found were not clinically significant, although we cannot exclude this in more painful operations. Moreover, without any evidence of reductions in opioid adverse effects, the clinical significance of these results is questionable although few studies reported these outcomes. Only one study reported clinically significant adverse events from NSAIDs administered before surgery and, therefore, we have very few data to assess the safety of either pre-emptive or preventive NSAIDs. Therefore, future research should aim to adhere to the highest methodology and be adequately powered to assess serious adverse events of NSAIDs and reductions in opioid adverse events. CI - Copyright (c) 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. FAU - Doleman, Brett AU - Doleman B AD - Department of Surgery and Anaesthesia, Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, University of Nottingham, Derby, UK. FAU - Leonardi-Bee, Jo AU - Leonardi-Bee J AD - Centre for Evidence Based Healthcare, Division of Epidemiology and Public Health, Clinical Sciences Building Phase 2, University of Nottingham, Nottingham, UK. FAU - Heinink, Thomas P AU - Heinink TP AD - Department of Anaesthesia, Frimley Health NHS Foundation Trust, Frimley Park Hospital, Frimley, UK. FAU - Boyd-Carson, Hannah AU - Boyd-Carson H AD - Department of Surgery, Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, University of Nottingham, Derby, UK. FAU - Carrick, Laura AU - Carrick L AD - Department of Anaesthesia and Intensive care, Royal Derby Hospital, Derby, UK. FAU - Mandalia, Rahil AU - Mandalia R AD - Department of Anaesthesia, University Hospitals of Leicester, Leicester, UK. FAU - Lund, Jon N AU - Lund JN AD - Division of Health Sciences, School of Medicine, University of Nottingham, Derby, UK. FAU - Williams, John P AU - Williams JP AD - Department of Surgery and Anaesthesia, Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, University of Nottingham, Derby, UK. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20210614 PL - England TA - Cochrane Database Syst Rev JT - The Cochrane database of systematic reviews JID - 100909747 RN - 0 (Analgesics, Opioid) RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Cyclooxygenase 2 Inhibitors) RN - 76I7G6D29C (Morphine) SB - IM UOF - doi: 10.1002/14651858.CD012978 MH - Acute Pain/*prevention & control MH - Adult MH - Analgesics, Opioid/administration & dosage/adverse effects MH - Anti-Inflammatory Agents, Non-Steroidal/adverse effects/*therapeutic use MH - Bias MH - Confidence Intervals MH - Cyclooxygenase 2 Inhibitors/adverse effects/therapeutic use MH - Humans MH - Morphine/administration & dosage/adverse effects MH - Pain, Postoperative/*prevention & control MH - Patient Satisfaction/statistics & numerical data MH - Postoperative Hemorrhage/surgery MH - Postoperative Nausea and Vomiting/epidemiology MH - Pruritus/chemically induced MH - Randomized Controlled Trials as Topic MH - Reoperation MH - Surgical Procedures, Operative/*adverse effects PMC - PMC8203105 COIS- Brett Doleman: has received a grant from Association of Anaesthetists of Great Britain and Ireland (AAGBI) for a randomized controlled trial of pre-emptive paracetamol (ongoing) and has previously undertaken a meta-analysis of pre-emptive paracetamol (Doleman 2015b). John P Williams: has received a grant from AAGBI for a randomized controlled trial of pre-emptive paracetamol (ongoing) and has previously undertaken a meta-analysis of pre-emptive paracetamol (Doleman 2015b). Jon Lund: has received a grant from AAGBI for a randomized controlled trial of pre-emptive paracetamol (ongoing) and has previously undertaken a meta-analysis of pre-emptive paracetamol (Doleman 2015b). Jo Leonardi-Bee: no declarations of interest in relation to this review Thomas Heinink: no declarations of interest Hannah Boyd-Carson: no declarations of interest Laura Carrick: no declarations of interest Rahil Mandalia: no declarations of interest EDAT- 2021/06/15 06:00 MHDA- 2021/08/04 06:00 PMCR- 2022/06/14 CRDT- 2021/06/14 17:30 PHST- 2021/06/14 17:30 [entrez] PHST- 2021/06/15 06:00 [pubmed] PHST- 2021/08/04 06:00 [medline] PHST- 2022/06/14 00:00 [pmc-release] AID - CD012978.pub2 [pii] AID - 10.1002/14651858.CD012978.pub2 [doi] PST - epublish SO - Cochrane Database Syst Rev. 2021 Jun 14;6(6):CD012978. doi: 10.1002/14651858.CD012978.pub2.