Clinical Evaluation of Non-Opioid Multimodal Analgesia in Orthopedic Surgery

Opioid-based analgesia has long been the default approach to pain after orthopedic surgery, but the recognized costs of routine opioid use, including nausea, delayed mobilization, and persistent postoperative opioid consumption, have driven a shift toward multimodal regimens in which opioids are reserved as rescue therapy rather than scheduled as first-line treatment. This review evaluates the clinical trial evidence for the principal non-opioid components of these regimens across elective orthopedic surgery, including scheduled acetaminophen and NSAID therapy, gabapentinoids, peripheral nerve blockade, and periarticular local infiltration including liposomal bupivacaine formulations. Regional anesthesia and peripheral nerve blockade remain the most consistently effective non-opioid intervention, while gabapentinoids show modest opioid-sparing benefit that must be weighed against sedation and fall risk in older patients, and newer local anesthetic formulations have not shown clear superiority over standard bupivacaine when combined with a nerve block. Practical pathway design also requires attention to rebound pain as peripheral blocks resolve and to adjuncts such as perineural dexamethasone that extend block duration without opioid exposure. We conclude that a procedure-specific, layered combination of these agents can deliver adequate analgesia with minimal or no opioid use across most elective orthopedic procedures, though outcome auditing at the institutional level remains necessary to confirm that trial-level benefits translate into routine practice.