Local Anesthetic Peripheral Nerve Block Adjuvants for Prolongation of Analgesia: A Systematic Qualitative Review

<div><p>Background</p><p>The use of peripheral nerve blocks for anesthesia and postoperative analgesia has increased significantly in recent years. Adjuvants are frequently added to local anesthetics to prolong analgesia following peripheral nerve blockade. Numerous randomized controlled trials and meta-analyses have examined the pros and cons of the use of various individual adjuvants.</p><p>Objectives</p><p>To systematically review adjuvant-related randomized controlled trials and meta-analyses and provide clinical recommendations for the use of adjuvants in peripheral nerve blocks.</p><p>Methods</p><p>Randomized controlled trials and meta-analyses that were published between 1990 and 2014 were included in the initial bibliographic search, which was conducted using Medline/PubMed, Cochrane Central Register of Controlled Trials, and EMBASE. Only studies that were published in English and listed block analgesic duration as an outcome were included. Trials that had already been published in the identified meta-analyses and included adjuvants not in widespread use and published without an Investigational New Drug application or equivalent status were excluded.</p><p>Results</p><p>Sixty one novel clinical trials and meta-analyses were identified and included in this review. The clinical trials reported analgesic duration data for the following adjuvants: buprenorphine (6), morphine (6), fentanyl (10), epinephrine (3), clonidine (7), dexmedetomidine (7), dexamethasone (7), tramadol (8), and magnesium (4). Studies of perineural buprenorphine, clonidine, dexamethasone, dexmedetomidine, and magnesium most consistently demonstrated prolongation of peripheral nerve blocks.</p><p>Conclusions</p><p>Buprenorphine, clonidine, dexamethasone, magnesium, and dexmedetomidine are promising agents for use in prolongation of local anesthetic peripheral nerve blocks, and further studies of safety and efficacy are merited. However, caution is recommended with use of any perineural adjuvant, as none have Food and Drug Administration approval, and concerns for side effects and potential toxicity persist.</p></div

PRISMA flowchart.

<p>Details regarding records that were identified, screened, and assessed for eligibility are provided, according to the PRISMA guidelines.</p

Clinical findings for most extensively studied agents not covered by recent meta-analyses.

<p>Abbreviations: SCB = supraclavicular block; ISB = interscalene block; PN = perineural; IM = intramuscular; IV = intravenous; BP = blood pressure; HR = heart rate; saph = saphenous; POD = postoperative day; SQ = subcutaneous; GI = gastrointestinal; TAP = transversus abdominis plane; epi = epinephrine; PONV = postoperative nausea and vomiting; pts: patients.</p><p>*Time to first analgesic;</p><p>**Time to first reported pain;</p><p>***Time to pinprick or restoration of sensation.</p><p>Clinical findings for most extensively studied agents not covered by recent meta-analyses.</p

Summary of meta-analyses analyzing adjuvants for analgesia/block duration.

<p>Abbreviations: LA = local anesthetic; OR = odds ratio</p><p>Summary of meta-analyses analyzing adjuvants for analgesia/block duration.</p

Summary of findings and recommendations.

<p>¹Attestation: Referenced in textbooks and/or multiple (>5) peer-reviewed research publications; Harm: Not Food and Drug Administration (FDA)-approved and balance of evidence suggests harm with perineural use; FDA: FDA-approved for regional anesthesia; IND: Investigational New Drug status (or international equivalent) granted or waived for in at least one reviewed study.</p><p>²a: Studies with Jadad score III+ or higher/total number of studies; b: % of studies with positive results; c: clinical significance of positive results (extent of prolongation of analgesia or sensory block).</p><p>³Agency for HealthCare Research and Quality Levels of Evidence and Grades of Recommendations: Grade A: based directly on Level 1 evidence; Level 1a: evidence from meta-analysis of clinical trials; Level 1b: evidence from at least 1 randomized controlled trial.</p><p>Abbreviations: PNB = peripheral nerve block; PONV = postoperative nausea and vomiting; ISB = interscalene block; FNB = femoral nerve block; GI = gastrointestinal.</p><p>Summary of findings and recommendations.</p