Adjuncts to local anesthetic wound infiltration for postoperative analgesia: a systematic review

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) (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=103851).