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1、Adjuvants for Peripheral Nerve Blockade: A Review of the Literature,Jonathan Weed, M.D.,Disclosures,None,Reasons to use adjuvants for nerve blocks,Increase duration of action Increase speed of onset Increase density or quality of the block Improve overall analgesic effect,Whats been tried?,Epinephri
2、ne Sodium bicarbonate -agonists (clonidine, dexmedetomidine) Opioids (fentanyl, sufentanil, morphine, buprenorphine, nalbuphine, tramadol) Steroids (dexamethasone, methylprednisolone) Midazolam,Neostigmine Verapamil Magnesium Ketamine NSAIDS (ketorolac) Lysine acetylsalicylate And probably many more
3、.,Do they work?,Epinephrine,Mechanism: vasoconstriction via 1-activation reduces blood flow to the nerve, decreasing clearance of the LA and prolonging exposure of the nerve to the LA. Epi has been shown to prolong the duration of PNB anesthesia in many studies, however, much more pronounced with sh
4、orter-acting agents: 70% longer duration with Lidocaine 20% longer duration with Bupivacaine or RopivacaineOther benefits: Decrease systemic absorption: LA plasma levels 30-50% lower with Epi. Most texts list higher acceptable LA doses with addition of epinephrine Can be used as an “intravascular ma
5、rker” during PNB,Epinephrine,Dose: 1:200,000 (5 mcg/ml) commonly used for neuraxial, but lower doses recommended for PNB (1:400,000 or 2.5 mcg/ml) Concerns: Systemic “reaction” (ie, tachycardia, anxiety, etc) Decreased PNF may be detrimental. ? increased risk for LA-induced nerve injury? Evidence fo
6、r this is limited, but reduction in PN blood supply can be significant, and some patients (DM, HTN, smoking) may be more susceptible to injury.,Sodium Bicarbonate,Increases the nonionized form of LA, speeding onset; but has no effect on block duration. Useful for Lidocaine and mepivacaine, but can c
7、ause precipitation when mixed with bupivacaine or ropivacaine Data exists supporting its use for neuraxial blockade, but studies of its use with PNB shows little efficacy.,Clonidine,2-agonist (with some limited 1-stimulatory effects) Has some LA properties, and produces inhibition of hyperpolarizati
8、on-activated cation current (Ih current). Affects C fibers (pain) A-fibers (motor) Dose: 100-150 mcg Side effects (more common with dose 100 mcg): Bradycardia, hypotension, sedation.,Clonidine,Efficacy: An analgesic benefit has been demonstrated by multiple meta-analyses and systematic reviews Altho
9、ugh many studies have examined the effect of clonidine added to PNB, only a few studies had a control for systemic effects. Most dramatic findings by Singelyn, et al: 3 groups (Mepiv alone; Mepiv + clonidine SQ; Mepiv/clonidine mix). Group 3 showed 2-fold increase in analgesic duration. Most studies
10、 using longer acting LA (bupiv or ropiv) show little or no benefit Meta-analysis by Popping, et al., estimates that adding clonidine to long-acting LA nerve blocks extends analgesic effect by approx 100 minutes, on average.,Dexmedetomidine,Pure 2-agonist. Likely similar in efficacy to clonidine, but
11、 evidence is limited. Increased duration of sensory and motor blockade with Bupi/Ropi demonstrated in rat sciatic nerves Only 2 human studies: Time to rescue analgesia extended with Dex + Bupi (vs Bupi alone) for greater palatine blocks in children getting cleft palate repair (22hr vs 14hr) Improved
12、 onset time (by 1 minute) and duration (14hr vs 11hr) with 100 mcg Dex + 40 mL Levobupiv for axillary blocks; but Dex group had episodes of bradycardia requiring Tx with atropine *Neither study had systemic Dex control group*,Opioids,Use of traditional opioids (ie, fentanyl, morphine, sufentanil, al
13、fentanil) as adjuncts to LA for PNB is poorly supported by the literature.,Outcomes of studies examining the effect of perineural opioids (excluding tramadol and buprenorphine)*,*Table 9-1. Hadzic A. Textbook of Regional Anesthesia and Acute Pain Management. 2007. Ch 9, p. 149.,Buprenorphine,Partial
14、 opioid -receptor agonist and - and -receptor antagonist; has both analgesic and antihyperalgesic properties Candido KD, et al, have published several studies using buprenorphine as an additive for PNB, with varying results. 2 studies showed significant prolongation of block using buprenorphine as a
15、n adjunct for brachial plexus and axillary blocks, although only 1 of these used a systemic control (IM inj). A 3rd, more recent and much larger study, found no difference between buprenorphine given systemically vs. peripherally with LA *Important to avoid use in opioid-tolerant patients, as it ren
16、ders other full opioid agonists much less effective. May be difficult to treat patients requiring rescue analgesia.*,Nalbuphine,Mixed opioid agonist/antagonist. (-antagonist; -agonist). Some positive/mixed results as neuraxial adjunct, but no PNB data available. Anecdotally, it may lengthen duration
17、 and improve analgesia in most patients, but has some significant drawbacks: Since it blocks -receptors, patients who need additional/rescue analgesia require much higher doses of traditional opioids to achieve desired effect. In opioid-tolerant patients, administration of nalbuphine can precipitate acute withdrawal symptoms.,
