Dextrose 5% vs. Dexamethasone in Regional Anesthesia: A Comparative Review of Mechanisms and Clinical Efficacy in Peripheral Nerve Blocks

Abstract

Context: The inherent duration limitations of single-injection peripheral nerve blocks (PNBs) have driven the widespread investigation of perineural adjuvants to optimize postoperative analgesia. While perineural dexamethasone remains the most extensively studied agent for block prolongation, 5% dextrose in water (D5W), traditionally utilized for nerve hydrodissection and treating neurogenic inflammation, has emerged as a distinct physiological alternative. Evidence Acquisition: This narrative review evaluates the comparative pharmacology, efficacy, and safety of these two agents. Results: We contrast their divergent mechanisms of action: dexamethasone prolongs blockade via glucocorticoid receptor-mediated anti-inflammation and inhibition of potassium channel-mediated firing in nociceptive C-fibers, whereas D5W induces analgesia, in part, by blocking transient receptor potential vanilloid 1 (TRPV1) receptor. Clinical evidence consistently confirms that perineural dexamethasone significantly extends sensory and motor block duration and provides opioid-sparing benefits, although the magnitude of benefit over systemic administration remains debated. Conversely, D5W has demonstrated clinical utility in entrapment neuropathies and chronic pain conditions, with limited data suggesting a potential for earlier onset of axillary brachial plexus block and rapid functional improvement in select acute cases. The safety profiles represent a critical point of divergence; dexamethasone carries risks of transient hyperglycemia and theoretical concern regarding particulate neurotoxicity or crystal deposition, whereas D5W exhibits a benign safety profile favorable for diabetic patients and those with pre-existing neuropathy. Conclusions: From a clinical perspective, dexamethasone remains the preferred adjuvant for reliably prolonging perioperative PNBs, whereas D5W represents a non-steroidal, metabolically favorable option for perineural interventions in patients with chronic entrapment neuropathies or in whom steroid-related risks are a concern.