Prolonging Peripheral Nerve Blocks in Adults: A Narrative Review of Adjunct Medications for Single-Injection...

Single-injection peripheral nerve blocks (PNBs) are a cornerstone of multimodal perioperative analgesia. However, the duration of commonly used long-acting local anesthetics is finite; many patients experience abrupt and sometimes severe "rebound pain" as the block resolves. This phenomenon is particularly prominent after painful orthopedic procedures and may increase early opioid consumption and reduce patient satisfaction.

To review the effectiveness and safety of pharmacologic adjuncts used to prolong adult single-injection PNBs and to provide practical, clinically oriented recommendations for their use.

Narrative review.

I conducted a focused narrative review of randomized controlled trials, observational studies, and systematic reviews or meta-analyses evaluating adjunct medications administered with single-injection PNBs in adults. The agents considered were dexamethasone, dexmedetomidine, clonidine, morphine, fentanyl, buprenorphine, magnesium sulfate, midazolam, and ketamine. The outcomes of interest were sensory block duration and analgesia, postoperative opioid consumption, rebound pain, and adverse events.

Dexamethasone, given intravenously or perineurally, consistently prolongs analgesia by approximately 6-8 hours and reduces early opioid use. Buprenorphine, administered perineurally, often extends analgesia to 24-48 hours but increases postoperative nausea. Dexmedetomidine modestly prolongs a block's duration and improves a block's quality, but is associated with dose-dependent bradycardia, hypotension, and sedation. Clonidine yields smaller gains in a block's duration with similar hemodynamic and sedative concerns to dexmedetomidine. Magnesium sulfate and midazolam produce modest and more variable benefits. Ketamine has inconsistent effects on a block's duration but may help mitigate hyperalgesia in select patients. Conventional opioids (morphine, fentanyl) provide little incremental benefit as perineural adjuncts; they also increase opioid-typical adverse effects.

This is a narrative rather than a systematic review; heterogeneity among studies in block type, local anesthetic formulation, dosing, and outcome definitions precludes pooled quantitative estimates.

Dexamethasone and buprenorphine have the strongest and most consistent evidence for clinically meaningful prolongation of single-injection PNBs in adults and may be considered first-line adjuncts in appropriate patients. Dexmedetomidine, clonidine, magnesium, midazolam, and ketamine may be useful in some situations when their specific benefit-risk profiles are acceptable. Conventional opioids offer little advantage as perineural adjuncts and are not recommended for routine use. Evidence-based selection of adjuncts within a multimodal analgesic strategy can improve postoperative analgesia, reduce opioid exposure, and potentially attenuate rebound pain.