Efficacy and safety of ketamine wound infiltration for postoperative pain management: A systematic review, meta-analysis and trial sequential analysis

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Background: Postoperative pain has a huge impact to the patients, families, healthcare practitioners, and healthcare delivery. Pain management with opioid-based analgesics and blind techniques have certain limitations, and ultrasound-based regional analgesia necessitates resources and experience, but ketamine wound infiltration is innovative with few side effects. However, its effectiveness is still uncertain. Methods: A thorough search was carried out across various databases including PubMed/Medline, Cochrane, Science Direct, CINHAL, and LILACS, with no limitations on date or language. Only randomized trials comparing the effectiveness of ketamine wound infiltration for managing postoperative pain were considered for inclusion. Two authors independently conducted data extraction, and the quality of evidence was assessed using GRADEpro software. Trial sequential analysis was utilized to ascertain the conclusiveness of the findings. Results: The review showed that the first analgesic request was higher in control group as compared to Ketamine SMD=1.68 (95% CI: 0.95 to 2.41). The TSA revealed that the cumulative Z-curve crosses both alpha-spending boundaries and reaches the required information size threshold, revealing strong power for current evidence. However, the quality of evidence was moderate. Conclusion: Despite available evidences, provision of firm conclusion is less optimal with current evidence as the included studies were unpowered with low to very low quality of evidences. Registration: This systematic review protocol was registered in Prospero (CRD42021268774).