The Facilitatory Effects of Adjuvant Pharmaceutics to Prolong the Duration of Local Anesthetic for Peripheral Nerve Block: A Systematic Review and Network Meta-analysis

Abstract

BACKGROUND: Peripheral nerve block (PNB) with perineural local anesthetic is used for anesthesia or analgesia with many benefits. To extend these benefits, various adjuvant drugs have been used to prolong the duration of analgesia. We aimed to evaluate the effectiveness of various adjuvants at prolonging the duration of sensory and motor blockade for PNB. METHODS: A network meta-analysis of placebo-controlled and active randomized controlled trials was performed comparing 10 adjuvants. Embase, PubMed, Web of Science, and Cochrane library were searched, with articles before May 21, 2020 included. Two authors independently selected studies and extracted data. The primary outcomes were sensory block (SB) and motor block (MB) time, and the secondary outcome was time of first analgesia rescue (FAR). Effect size measures were described as mean differences (MD) with 95% confidence intervals (CIs). Confidence in evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). The study protocol was preregistered with the prospectively registered systematic reviews in health and social care international database (PROSPERO), as number CRD42020187866. RESULTS: Overall 16,364 citations were identified, of which 53 studies were included with data for 3649 patients. In network meta-analyses, 4 of 7 included treatment strategies were associated with more efficacious analgesia compared with placebo therapy, including dexamethasone (SB time: 5.73 hours, 95% CI, 4.16–7.30; MB time: 4.20 hours, 95% CI, 2.51–5.89; time of FAR: 8.71 hours, 95% CI, 6.63–10.79), dexmedetomidine (SB time: 4.51 hours, 95% CI, 3.52–5.50; MB time: 4.04 hours, 95% CI, 2.98–5.11; time of FAR: 5.25 hours, 95% CI, 4.08–6.43), fentanyl (SB time: 3.59 hours, 95% CI, 0.11–7.06; MB time: 4.42 hours, 95% CI, 0.78–8.06), and clonidine (SB time: 2.75 hours, 95% CI, 1.46–4.04; MB time: 2.93 hours, 95% CI, 1.69–4.16; time of FAR: 3.35 hours, 95% CI, 1.82–4.87). In a subgroup analysis, addition of dexamethasone to ropivacaine significantly increased the time of FAR when compared to dexmedetomidine (time of FAR: 5.23 hours, 95% CI, 2.92–7.54) or clonidine (time of FAR: 6.61 hours, 95% CI, 4.29–8.92) with ropivacaine. CONCLUSIONS: These findings provide evidence for the consideration of dexmedetomidine, dexamethasone, and clonidine as adjuvants to prolong the duration of PNB. The addition of dexamethasone to ropivacaine has a longer time of FAR compared with clonidine or dexmedetomidine.

Patient-Controlled Intravenous Analgesia with or without Ultrasound-Guided Bilateral Intercostal Nerve Blocks in Children Undergoing the Nuss Procedure: A Randomized, Double-Blinded, Controlled Trial

“…is might be partly due to the effects of the dexamethasone added to ropivacaine. Previous studies have indeed shown that adding dexamethasone enhances the effects of peripheral nerve block and prolongs the duration of the sensory block of local anesthetics used for peripheral nerve blocks [16,17]. Possible beneficial mechanisms of dexamethasone include peripheral/central anti-inflammatory effects, inhibition of ectopic neural discharge, suppression of nociceptive C fibers, and suppression of the neuropeptide immune response to injury [18].…”

SP49 Adjuvants or dexamethasone as multimodal analgesics at high doses?

“…Adjuvants Dexamethasone, dexmedetomidine, clonidine and fentanyl have all been shown to prolong sensory and motor block duration, as well as increasing the time to first analgesia. 12 Among these adjuvants, dexamethasone seems to be the most effective. 12-13 a 2 -adrenergic agonists Clonidine prolongs sensory and motor block, and increases the time to first analgesia compared with placebo, but to a lesser degree than dexmedetomidine.…”

“…12-13 a 2 -adrenergic agonists Clonidine prolongs sensory and motor block, and increases the time to first analgesia compared with placebo, but to a lesser degree than dexmedetomidine. 12,[14][15] Recent meta-analyses have shown that compared with placebo, dexmedetomidine prolonged a brachial plexus block by 292 minutes (95% CI: 245 to 329) and clonidine by 176 minutes (95% CI: 118 to 205). In the studies directly comparing the two a 2 -agonists, dexmedetomidine prolonged analgesia by approximately three hours.…”

“…14 Dexamethasone Dexamethasone increases time to first request of analgesics by 8.7 hours (95% CI: 6.6 to 10.8) compared with placebo. 12 In comparison, the meta-analyses comparing the two a 2 -agonists to placebo have shown that dexmedetomidine prolongs analgesia by about five hours and clonidine by about three hours. 12,14 A recent systematic review by Albrecht et al 13 only retrieved one study directly comparing dexamethasone to dexmedetomidine, reporting that dexamethasone prolongs analgesic duration by about 2 hours.…”

“…12 In comparison, the meta-analyses comparing the two a 2 -agonists to placebo have shown that dexmedetomidine prolongs analgesia by about five hours and clonidine by about three hours. 12,14 A recent systematic review by Albrecht et al 13 only retrieved one study directly comparing dexamethasone to dexmedetomidine, reporting that dexamethasone prolongs analgesic duration by about 2 hours. 16 Because of the scarcity of direct comparisons, Albrecht et al performed an indirect comparison between perineural dexamethasone and perineural dexmedetomidine, finding that dexamethasone significantly prolongs the duration of analgesia by a mean difference of 148 minutes (95% CI: 37 to 259 minutes).…”