Pablo A. Alvarez-Aguilar, n/a
Intensive Care Specialist
Critical Care Department, Hospital Mexico, Caja Costarricense del Seguro Social, San José, Costa Rica and Physiology Department, School of Medicine, University of Costa Rica
San José, San Jose
NaV1.8 sodium-channel blockers have been proposed as effective adjuncts in multimodal postoperative analgesia, acting peripherally without central nervous system depression. While multiple randomized controlled trials (RCTs) have evaluated their short-term efficacy and tolerability, the overall risk–benefit profile remains uncertain.
Purpose/Objectives:
To synthesize these data and clarify their risk–benefit balance, we conducted a systematic review and meta-analysis assessing the analgesic effectiveness and adverse events associated with NaV1.8 blockade after surgery.
Methods:
We systematically searched PubMed, Embase, LILACS, and the Cochrane Central Register of Controlled Trials for RCTs comparing full-dose adjunctive NaV1.8 blockers versus placebo in multimodal postoperative regimens. The primary outcome was absolute pain intensity at 24 and 48 hours, measured using the Numerical Pain Rating Scale (NPRS). Secondary outcomes included change from baseline and adverse events. A random-effects meta-analysis was conducted using inverse-variance weighting. Mean differences (MDs) and 95% confidence intervals (CIs) were calculated using the Wald-type method. Between-study heterogeneity was quantified using I² and tau² (REML), and a 95% prediction interval was reported.
Results:
Four RCTs (n = 1584) were included. Mean age was 44.9 years; 92.3% were women. Surgeries included abdominoplasty (52%) and bunionectomy (48%). NaV1.8 blockade reduced NPRS scores at 24 hours (MD –0.93; 95% CI –1.20 to –0.65) and 48 hours (MD –1.02; 95% CI –1.20 to –0.84), both p < 0.001. Pooled analysis showed consistent benefit at both time points. NaV1.8 blockers also reduced dizziness (RR, 0.57; p = 0.01) and nausea (RR, 0.68; p = 0.001). No significant differences were observed in headache, vomiting, or constipation.
Conclusions/Implications for future research and/or clinical care:
NaV1.8 blockade significantly reduces postoperative pain and select AEs, supporting its role as a valuable component of multimodal analgesia. These findings support the integration of NaV1.8 inhibitors into multimodal analgesic strategies, particularly in patients at risk for opioid-related side effects.
Future research should aim to identify the specific surgical populations that derive the greatest benefit from NaV1.8 blockade and explore optimal dosing strategies to enhance analgesic efficacy while minimizing adverse effects. Additionally, head-to-head comparisons with other non-opioid analgesics are warranted.