Lidocaine and its active metabolites are metabolized mainly by the liver, and liver-compromised may slow the metabolism of lidocaine and its active metabolites. In addition to excessive lidocaine, accumulated active metabolites may also lead to lidocaine-related toxicity in liver-compromised patients. This study aimed to describe the population pharmacokinetics of lidocaine and its active metabolites in partial hepatectomy patients and propose a novel drug regimen involving lidocaine-weighted active metabolites. The concentrations of lidocaine and its active metabolites from thirty-five patients underwent partial hepatectomy were analysed by non-linear mixed-effects models. The mean loading dose was 86.07 mg, and the median continuous infusion dose was 57.97 mg/h. A population pharmacokinetic model fitting the plasma concentrations of lidocaine and its active metabolites was built to explore the factors affecting the concentrations of lidocaine and its active metabolites. A two-compartment model with first-order elimination was used to determine the concentrations of lidocaine and its active metabolites. The different dosing simulations revealed that the selected appropriate loading dose did not exceed 1.5 mg/kg, and the continuous infusion dose of lidocaine should preferably not surpass 1.5 mg/kg/h in Chinese hepatectomy patients. The simulation results of long-term infusion of lidocaine during the postoperative stage after liver resection that showed there was a significant accumulation of MEGX after more than 24 hours of lidocaine infusion, and when the infusion rate reached 1 mg/kg/h, the MEGX concentration exceeded 5 µg/mL. This study proposes for the first time the integration of lidocaine concentration with active metabolites and simulation-based dosing recommendations. During the 24-hour medication period for Chinese hepatectomy patients, the recommended safe dosage includes a loading dose not exceeding 1.5 mg/kg and an infusion dose not exceeding 1.5 mg/kg/h. Monitoring of active metabolites, in addition to lidocaine is also necessary for continuous infusion of lidocaine. The trial is registered at chictr.org.cn (ChiCTR2100042730).
Hysterectomy or myomectomy is a common gynaecological procedure that results in moderate to severe acute postoperative pain, which can cause many adverse effects. This study aimed to compare the postoperative analgesic efficacy, opioid consumption, quality of postoperative recovery (QOR) and adverse reactions of intravenous coinjection of lidocaine and dexmedetomidine versus lidocaine or dexmedetomidine alone in gynaecological surgery. Systematic review and meta-analysis was performed. The PubMed, Embase, Cochrane Library and Web of Science databases were used to access the articles. Electronic databases were searched for eligible studies published before 1 May 2024. All randomised controlled trials (RCTs) were included in the final analysis in which the intraoperative intervention group received intravenous coinjection of lidocaine and dexmedetomidine, and the control group received intravenous injection of lidocaine or dexmedetomidine alone in gynaecologic procedures. Study retrieval, literature screening, data extraction and risk of bias assessment were performed independently by two reviewers. The quality of included studies was assessed by the Cochrane Collaboration Risk of Bias (ROB V.2.0). Data were expressed as standardised mean difference, weighted mean difference or relative risk with 95% CI. Review Manager V.5.4 was used for data analysis. A total of five RCTs were included, involving 672 patients, of which 224 patients received coinjection of lidocaine and dexmedetomidine. The results revealed that coinjection of lidocaine and dexmedetomidine was superior to individual lidocaine in the visual analogue scale (VAS) scores at 1 hour (MD=-0.90, 95% CI (-1.11 to -0.69), p<0.001), 2 hours (MD=-0.99, 95% CI (-1.19 to -0.80), p<0.001), 4 hours (MD=-1.20, 95% CI (-1.75 to -0.66), p<0.001), 6 hours (MD=-1.09, 95% CI (-1.48 to -0.70), p<0.001), 8 hours (MD=-1.22, 95% CI (-1.61 to -0.83), p<0.001) and 12 hours (MD=-0.76, 95% CI (-1.35 to -0.17), p=0.o1) after surgery. Compared with the dexmedetomidine group, the lidocaine+dexmedetomidine group had low VAS scores at 1 hour (MD=-0.60, 95% CI (-0.83 to -0.37), p<0.001), 2 hours (MD=-0.70, 95% CI (-0.87 to -0.53), p<0.001), 6 hours (MD=-0.79, 95% CI (-0.98 to -0.59), p<0.001), 8 hours (MD=-0.77, 95% CI (-1.25 to -0.28), p=0.002) and 12 hours (MD=-0.56, 95% CI (-1.00 to -0.11), p=0.01) after surgery. Coinjection of lidocaine and dexmedetomidine resulted in significantly lower postoperative opioid consumption, postoperative nausea and vomiting and bradycardia than lidocaine alone (all p<0.05). Compared with the dexmedetomidine group, the lidocaine+dexmedetomidine group shortened the time to intestinal transit resumption (p=0.003). Coinjection of lidocaine and dexmedetomidine reduced intraoperative opioid consumption and increased QOR scores compared with lidocaine and dexmedetomidine alone (all p<0.05). Lidocaine combined with dexmedetomidine had superior analgesic efficacy and safety. However, due to the limitation in the number of available studies, more large-scale, prospective RCTs are needed for further investigation.PROSPERO registration numberCRD42023384018.