Adjuncts to Peripheral Nerve Blocks Mark Mudarth, MD

Objectives Review the evolution of Regional Anesthesia Recap common peripheral nerve block (PNB) adjuncts Discuss the findings of “Investigating the Efficacy of Dexmedetomidine as an Adjuvant to Local Anesthesia in Brachial Plexus Block” Discuss impact on current practice

Regional Anesthesia: How did we get here? Intravenous Regional Anesthesia Bier Block, 1908 Anatomical Approach Interscalene, early 1900s Brachial Plexus Nerve Stimulation Popularized in the 1980s Ultrasound Guided Single shot and perineural catheters Highest rates of success and greatest safety

Facilitation of block quality and duration Despite improvements in safety, there exist risks associated with PNBs Nerve damage Local Anesthetic Systemic Toxicity (LAST) Diaphragm dysfunction Pneumothorax Therefore, numerous adjuvants have been evaluated to provide the following Faster onset Slowed absorption Prolonged analgesic duration These adjuncts, with a diverse range of mechanisms of action, have been studied with various results Opioid receptor agonists Buprenorphine Morphine Fentanyl Vasoactive agents Epinephrine Alpha – 2 agonists Clonidine Dexmedetomidine Anti-Inflammatory agents Dexamethasone

Common adjuncts Opioid Receptor Agonists Buprenorphine, Morphine, Fentanyl Study data shows prolonged analgesic duration but at the risk of known opioid-induced side effects Pruritus, nausea, and vomiting Additionally there are in vitro studies that have shown opioids to have some neurotoxic potential Vasoactive adjuncts – Epinephrine Believed to prolong duration by decreasing LA absorption May decrease the likelihood of LAST Can help detect an intravascular injection Data shows minimal change in duration of analgesia when used with ropivacaine Shown to compromise endoneural blood flow

Common adjuncts Vasoactive adjuncts – Clonidine Provides block prolongation via hyperpolarization of cation channels on the nerve Significant side effect profile that includes: Hypotension Bradycardia Syncope Inconsistent results in studies make it hard to determine its role Vasoactive adjuncts – Dexmedetomidine An alpha-2 agonist with 7x the affinity of clonidine, causes prolonged blockade via a hyperpolarization activated cation current Preventing the nerve from returning to resting membrane potential Side effects again include hypotension and bradycardia Possibly neuroprotective, based on rat studies

Common adjuncts - Dexamethasone Shown to prolong block duration, although mechanism not fully elucidate Has been shown to improve PONV There is concern for neurotoxic potential, especially in vitro Perineural Intravascular Suppressed excitability of nociceptive C fibers Some vasoconstrictive properties reducing LA uptake Local inflammatory mediator suppression Peripheral and central anti-inflammatory effects, inhibiting the production of prostaglandins, leukotrienes, and proinflammatory cytokines Decreased neuropeptide immune response in injured tissue

A meta-analysis of RCTs comparing dexmedetomidine’s (Dex) ability to prolong block duration and shorten onset time when used as an adjunct versus local anesthetic alone Additionally, the authors hoped to gain a better insight into the adverse event profile of Dex Primary outcomes: Onset and Duration of sensory and motor blockade Secondary outcomes: Duration of Analgesia Adverse Events Overall post-op pain at 24 hours follow-up Post-op analgesic consumption

Study construction Data Management and Extraction Assessment of Methodological Quality and Risk of Bias Statistical Analysis and Measurement of Treatment Effect Assessment of Heterogeneity Assessment of Publication Bias

Results: Sensory Block Onset and Duration

Results: Motor Block Onset and Duration

Results: Analgesia, Analgesic Consumption, and Pain @24 hours Unfortunately, given the varied choices of consumable analgesics, an estimated effect on Total Analgesic Consumption could not be constructed Only 3 studies allowed for statistical pooling regarding pain at 24 hours, and there was no significant difference found with the addition of dexmedetomidine

Adverse Events: Hypotension & Bradycardia

Results: In Summary

Where do we go from here? Is there utility in extending the duration of our blocks? Williams et al published that each additional hour of analgesia reduced pain scores by .03 units In regards to Dexmedetomidine, there may be benefit to its use to help prolong block duration in the diabetic population, especially given its efficacy noted with Ropivacaine In the non-diabetic population, especially those at risk for PONV, dexamethasone can be an appropriate adjunct for prolonging analgesic duration

Questions? References: Abdallah et al, Intravenous dexamethasone and perineural dexamethasone similarly prolong the duration of analgesia after supraclavicular brachial plexus block: a randomized, triple-arm, double-blind, placebo-controlled trial. Reg Anesth Pain Med. 2015 Mar- Apr;40(2):125-32. Bailard et al, Additives to local anesthetics for peripheral nerve blocks: Evidence, limitations, and recommendations. Am J Health Syst Pharm. 2014 Mar 1;71(5):373-85. Brattwall et al, Upper extremity nerve block: how can benefit, duration, and safety be improved? An update. F1000Res. 2016 May 18;5. pii: F1000 Faculty Rev-907 Hussain et al, Investigating the Efficacy of Dexmedetomidine as an Adjuvant to Local Anesthesia in Brachial Plexus Block: A Systematic Review and Meta-Analysis of 18 Randomized Controlled Trials. Reg Anesth Pain Med. 2017 Mar/Apr;42(2):184-196. Kirksey et al, Local Anesthetic Peripheral Nerve Block Adjuvants for Prolongation of Analgesia: A Systematic Qualitative Review. PLoS One. 2015 Sep 10;10(9):e0137312. Leurcharusmee et al, A Multicenter Randomized Comparison Between Intravenous and Perineural Dexamethasone for Ultrasound-Guided Infraclavicular Block. Reg Anesth Pain Med. 2016 May-Jun;41(3):328-33. Rosenfeld et al, Perineural versus intravenous dexamethasone as adjuncts to local anaesthetic brachial plexus block for shoulder surgery. Anaesthesia. 2016 Apr;71(4):380-8.