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Adjuncts to local anesthetic wound infiltration for postoperative analgesia: a systematic review
  1. Johnny Wei Bai,
  2. Dong An,
  3. Anahi Perlas and
  4. Vincent Chan
  1. Department of Anesthesiology and Pain Management, Toronto Western Hospital, Toronto, Ontario, Canada
  1. Correspondence to Dr Johnny Wei Bai, Department of Anesthesiology and Pain Management, Toronto Western Hospital, Toronto, ON M5T 2S8, Canada; jw.bai{at}


Local anesthetics (LAs) are commonly infiltrated into surgical wounds for postsurgical analgesia. While many adjuncts to LA agents have been studied, it is unclear which adjuncts are most effective for co-infiltration to improve and prolong analgesia. We performed a systematic review on adjuncts (excluding epinephrine) to local infiltrative anesthesia to determine their analgesic efficacy and opioid-sparing properties. Multiple databases were searched up to December 2019 for randomized controlled trials (RCTs) and two reviewers independently performed title/abstract screening and full-text review. Inclusion criteria were (1) adult surgical patients and (2) adjunct and LA agents infiltration into the surgical wound or subcutaneous tissue for postoperative analgesia. To focus on wound infiltration, studies on intra-articular, peri-tonsillar, or fascial plane infiltration were excluded. The primary outcome was reduction in postoperative opioid requirement. Secondary outcomes were time-to-first analgesic use, postoperative pain score, and any reported adverse effects. We screened 6670 citations, reviewed 126 full-text articles, and included 89 RCTs. Adjuncts included opioids, non-steroidal anti-inflammatory drugs, steroids, alpha-2 agonists, ketamine, magnesium, neosaxitoxin, and methylene blue. Alpha-2 agonists have the most evidence to support their use as adjuncts to LA infiltration. Fentanyl, ketorolac, dexamethasone, magnesium and several other agents show potential as adjuncts but require more evidence. Most studies support the safety of these agents. Our findings suggest benefits of several adjuncts to local infiltrative anesthesia for postoperative analgesia. Further well-powered RCTs are needed to compare various infiltration regimens and agents.

Protocol registration PROSPERO (CRD42018103851) (

  • anesthesia, local
  • pain, postoperative
  • pharmacology

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  • JWB and DA are joint first authors.

  • Twitter @PerlasAnahi

  • JWB and DA contributed equally.

  • Contributors JWB and DA contributed to the manuscript equally and are considered joint first authors. JWB and VC devised the protocol, performed title/abstract and full-text screening, and devised outcome extraction forms. DA and JWB extracted outcomes, and created and edited the tables and figures. AP provided expert guidance on systematic review methodology and helped with narrative synthesis. All authors wrote and edited the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests JWB and DA have no conflicts of interest to declare. AP has a research grant from Fisher and Paykel, ongoing, but unrelated to the topic of this article. VC previously received honorarium from Philips Healthcare which was not relevant to this systematic review, and he has no ongoing association.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as online supplementary information. All extracted and other study data available in online supplementary tables.