Adjunct Medications for Single-Injection Pediatric Regional Blocks: Implications for Peripheral Nerve Blocks

Single-injection peripheral nerve blocks (PNBs) provide excellent perioperative analgesia in children but are limited by finite duration. Pediatric populations were excluded from the major adult adjunct reviews. This narrative review synthesizes the evidence for adjuncts added to local anesthetics for single-injection PNBs and caudal blocks in patients aged 0 to 18 years, including dexamethasone, dexmedetomidine, clonidine, conventional opioids, buprenorphine, magnesium sulfate, midazolam, ketamine, neostigmine, tramadol, nalbuphine, and epinephrine.

Across 58 studies, dexmedetomidine (0.5 to 1 mcg/kg) and dexamethasone (0.1 mg/kg perineural) were the best-supported agents, each roughly doubling analgesic duration with acceptable safety. Two network meta-analyses ranked neostigmine highest for caudal duration, but its postoperative nausea and vomiting burden limits use. Clonidine has the longest safety record. Ketamine and midazolam show robust caudal efficacy but unresolved neurotoxicity concerns. Nalbuphine and buprenorphine are promising but under-studied. Tramadol carries pediatric regulatory restrictions, while epinephrine and conventional opioids add little. Dexmedetomidine and dexamethasone are the preferred adjuncts in pediatric regional anesthesia. Adult evidence should not be extrapolated directly given developmental pharmacology and pediatric-specific safety considerations. Prospective trials in true pediatric PNBs and pediatric rebound-pain studies remain the critical evidence gaps.