Pain following hepatectomy may delay recovery and increase opioid use. We tested the primary hypothesis that combining lidocaine and low-dose esketamine would reduce movement-evoked pain 24 h after hepatic resection. We also evaluated whether this approach reduced opioid consumption and improved quality of recovery. Patients having elective hepatic resections were allocated randomly to receive lidocaine-esketamine or placebo from induction of anaesthesia until the end of surgery. After surgery, patients allocated to lidocaine-esketamine were given a continuous infusion of lidocaine with esketamine for 72 h. All patients received transversus abdominis plane blocks with ropivacaine 2 mg.kg after induction of anaesthesia. Postoperative analgesia was provided by patient-controlled intravenous analgesia with sufentanil. In total, 304 patients were included, of whom 145 (48%) had open surgery. Lidocaine-esketamine infusion reduced median (IQR [range]) pain scores with movement at 24 h (3 (2-4 [1-6]) vs. 4 (3-5 [1-9]), p < 0.001); 48 h (3 (2-4 [0-7]) vs. 4 (3-5 [0-8]), p < 0.001); and 72 h (2 (1-3 [0-6]) vs. 3 (2-4 [0-7]), p < 0.001), respectively. Moderate-to-severe movement-evoked pain at 24 h was evident in 52/152 (34%) patients who received lidocaine-esketamine vs. 85/152 (56%) who received placebo (p < 0.001). Cumulative sufentanil equivalents were significantly reduced at each measurement time and quality of recovery scores were significantly higher through the first 72 h for lidocaine-esketamine compared with placebo, but these changes were clinically modest. The combination of lidocaine with esketamine reduced movement-evoked pain and opioid consumption whilst improving quality of recovery during the initial 72 h after hepatic resection. However, treatment effects were modest and of limited clinical importance.
Fospropofol disodium (fospropofol), a water-soluble prodrug of propofol, reduces injection pain and anesthetic requirements but frequently causes paresthesia. Intravenous lidocaine has been shown to alleviate dexamethasone-induced paresthesia, yet its effect on fospropofol-related symptoms remains uncertain. We combined preclinical and clinical studies, first evaluating the safety and pharmacological changes of fospropofol premixed with lidocaine through in vitro and in vivo experiments and then conducting a randomized controlled trial in adult surgical patients to evaluate whether the lidocaine premixing strategy affects the occurrence of fospropofol-induced paresthesia. In the preclinical study, the findings indicated that mixture of fospropofol and lidocaine remained physicochemically stable, with faster onset and longer sedation duration compared with fospropofol alone, without additional adverse effects. In the clinical trial, 74 patients received fospropofol dissolved in either 20 mL of normal saline or 0.75% lidocaine and 72 were included in the primary outcome analysis of paresthesia. This adverse reaction occurred in 83.3% of patients in both groups, mainly within 40-60 s after administration. No group differences were observed in plasma inflammatory markers and phosphate; however, phosphate levels increased postadministration in both groups. This study provides important guidance for clinical practice, showing that premixing lidocaine does not effectively alleviate paresthesia induced by fospropofol.
Esophageal cancer is the eighth most prevalent malignant tumor in the world and has the sixth highest mortality rate. Postoperative pulmonary complications (PPCs) are one of the most common complications of minimally invasive esophagectomy (MIE). The non-local anesthetic effects of lidocaine have been widely reported, but only a few studies have focused on its effects on lung protection in MIE. This study is designed to test the hypothesis that intraoperative intravenous lidocaine infusion can reduce the incidence of PPCs in patients undergoing MIE. In this double-center, randomized, double-blind, placebo-controlled superiority trial, 770 participants from three centers will be randomly assigned to two groups, namely the lidocaine group and the placebo group in a 1:1 ratio. The primary outcome is the incidence of PPCs within 7 days following surgery. The secondary outcomes include the incidence of (1) respiratory infection; (2) respiratory failure; (3) pneumothorax; (4) atelectasis; (5) pleural effusion; (6) bronchospasm; (7) aspiration pneumonitis; (8) anastomotic fistula; (9) moderate to severe pain within 24 and 48 h at rest and when coughing; (10) additional rescue analgesics use. This study aims to address a significant gap in the prevention of PPCs in patients undergoing MIE for esophageal cancer. PPCs are common and can negatively impact recovery and survival outcomes, making effective prevention strategies crucial. While lidocaine's non-local anesthetic properties, including anti-inflammatory and analgesic effects, have been well-documented, few studies have focused on its role in lung protection during MIE. By assessing the incidence of PPCs and other secondary outcomes, this trial seeks to determine whether intraoperative lidocaine infusion can offer a novel, non-invasive approach to reducing PPC risk and improving overall postoperative recovery. If lidocaine proves effective, this study will provide a new way to improve patient outcomes, particularly for those with high PPCs risk. Furthermore, the results could expand the scope of lidocaine use in surgical settings, suggesting a potentially low-cost and accessible intervention for broader perioperative lung protection. NCT06138041 (ClinicalTrials.gov, registration date: 2024-10-22). This study will provide a reliable conclusion investigating the effect of intraoperative intravenous lidocaine infusion on postoperative pulmonary complications in patients undergoing minimally invasive esophagectomy. The study includes an appropriate sample size and a double-center, randomized, and double-blind placebo-controlled design, which reduces potential bias. The full analysis set consists of all participants according to the intention-to-treat principle and the per-protocol set will be both performed. Per-protocol analysis will be used for sensitivity analyses. Intravenous lidocaine infusion is only continued until patients are transferred out of the post-anesthesia care unit, while the benefit of prolonged infusion in the ward will not be investigated.
The concurrent use of a ropivacaine transversus abdominis plane (TAP) block with intravenous lidocaine infusion, though effective for pain relief, raises safety concerns regarding local anesthetic systemic toxicity (LAST). This study aimed to assess the dose-risk relationship of LAST in this combination by escalating the ropivacaine dose while fixing the lidocaine dose. In this dose-escalation study, adult patients undergoing colorectal cancer surgery received a 0.2% ropivacaine TAP block (1.5, 2.0 or 2.5 mg kg) and intravenous lidocaine infusion (2 mg kg bolus, followed by 2 mg kg h), both dosed according to ideal body weight (IBW). The primary outcome was the occurrence of LAST, identified by clinical symptoms, new-onset ECG irregularities, etc. Secondary outcomes included plasma concentrations of ropivacaine and lidocaine. Nine patients were included in the per-protocol analysis, and 26 were included in the intention-to-treat analysis. No signs of LAST were observed. Plasma ropivacaine concentrations remained consistently below 2.2 µg mL, however, eight patients in the intention-to-treat population and three patients in the per-protocol population had plasma lidocaine concentrations exceeding 5.0 µg mL at 10 min post-bolus. In the per-protocol population, peak plasma ropivacaine concentrations occurred at 30 min (range, 20-60) post-TAP block, with median values of 1.14 (range, 0.85-1.18), 1.42 (range, 1.29-1.80), and 1.96 (range, 1.47-2.06) µg mL across dose groups. The peak plasma lidocaine concentrations in patients occurred at 10 min post-bolus infusion, with median values of 4.59 µg mL (range, 3.24-6.67) and gradually decreased after 2 h. The intention-to-treat analysis found similar results. Although no signs of LAST were observed with the combination of a 1.5 to 2.5 mg kg ropivacaine TAP block and intravenous lidocaine infusion under general anaesthesia, extreme caution is still warranted regarding the potential risk of LAST. This trial was registered at ClinicalTrials.gov (NCT06006026) on 23 August 2023.
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).
Lidocaine is increasingly used for surgical patients requiring general anesthesia. However, its clinical benefits on postoperative recovery quality are not well established. Our main objective aims to summarize the evidence regarding the effectiveness of perioperative lidocaine infusion on postoperative subjective quality of recovery (QoR). This protocol will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guideline. This systematic review will include randomized controlled trials (RCTs) from their inception until December 31st, 2024 with no language restrictions. The major databases including PubMed, Embase, and the Cochrane library will be comprehensively searched and supplemented by a hand searching reference lists of all included articles. Searches will involve studies assessing the efficacy of the perioperative lidocaine infusion for improving postoperative QoR, in comparison to placebo, or on treatment. The two authors will independently screen studies, extract study data and assess bias risk of the studies. The subjective QoR (QoR-15, QoR-40) on postoperative day 1-3 will be defined as primary outcome, whereas secondary outcomes will include morphine consumption, incidence of postoperative nausea and vomiting, time to first bowel movement, time to first flatus, and length of hospital stay. A meta-analysis will be performed using Review Manager 5.3 software. Sensitivity analyses, subgroup analysis and publication bias will also be conducted. The evidence quality of pooled results will be assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. This review and meta-analysis is anticipated to provide the evidence for the role of intravenous lidocaine on the subjective quality of recovery after surgery. In addition, the findings from this review will help clinicians with developing effective and safe perioperative anesthetic management regimens for surgery patients. PROSPERO registration number: CRD42024585866.
Reducing postoperative pain is still a tremendous challenge for perioperative clinicians. Lidocaine is a local anesthetic that belongs to the amide class and has anti-inflammatory, anti-hyperalgesic, and analgesic effects. Extensive research has been conducted to determine the optimal route for its administration. To compare the efficacy of perioperative intravenous lidocaine with that of intraperitoneal lidocaine on postoperative analgesia in patients undergoing abdominal surgery. EMBASE, PubMed, and The Cochrane Library were searched for randomized controlled trials published through December 2022 that compared patients receiving perioperative intravenous lidocaine with those receiving intraperitoneal lidocaine. The primary outcome measures included the pain score, as evaluated by the Visual Analog Scale, and opioid analgesia requirements. The secondary outcome measures were hospitalization length, gastrointestinal function recovery, etc. The data were acquired and recorded in electronic spreadsheets that had been designed for this purpose. This systematic review's design was based on the Cochrane Handbook for Systematic Reviews of Interventions and was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method was used to examine the certainty of the evidence. Furthermore, we examined the dependability of the calculated (favorable) treatment effects through considerations of information size and modified significance thresholds (trial sequential analysis). Seven trials including 478 patients were included. Our meta-analysis demonstrates that compared with intravenous lidocaine, patients who received intraperitoneal lidocaine had lower pain scores at 4 hours (mean difference [MD] 1.40; 95% CI, 0.22 to 2.59); 12 hours (MD 0.18; 95% CI, 0.06 to 0.30); and 24 hours (MD -0.12; 95% CI -0.40 to 0.17) postsurgery. However, no obvious difference in opioid consumption (P > 0.05) was found. In addition, the intraperitoneal lidocaine group had a longer postsurgery hospital stay than the intravenous lidocaine group (95%CI, -0.17 to -0.00; I2 = 0%). Intravenous lidocaine was more beneficial for achieving gastrointestinal return than intraperitoneal lidocaine (95% CI, -0.26 to -0.10; I2 = 2%). The sample size of enrolled RCTs was small, which could potentially result in an overestimation or underestimation of the treatment effect in the collected data. There was high heterogeneity among the studies. This meta-analysis suggests that post-abdominal surgery intraperitoneal lidocaine administration has a better analgesic effect than intravenous lidocaine, with a lower pain score. However, intravenous lidocaine is more beneficial for gastrointestinal recovery after abdominal surgery.
Solid organ transplant recipients are at high risk for developing severe zoster-associated neuralgia, and the pharmaceutic therapies of pain management for these patients with limited organ function are challenging. Intravenous lidocaine infusion showed positive analgesic effects and is used for the management of neuropathic pain. This case series reports the safety and effectiveness of intravenous lidocaine infusion in the treatment of intractable zoster-associated neuralgia in solid organ transplant recipients. Five solid organ transplant recipients suffering from refractory zoster-associated neuralgia (numeric rating scale 8-10, despite using high doses of antiepileptic drugs or combined with opioids) were enrolled. Intravenous lidocaine (5 mg/kg ideal bodyweight) was administered over 1.5 h with the monitoring of vital signs. Pain intensity, patient satisfaction, adverse events, typical liver, and kidney function were evaluated. All subjects reported high satisfaction with their treatment and effective pain relief at the 6-month follow-up. One patient experienced short and mild numbness in the mouth and dizziness after the therapy, but no major adverse reactions were reported. This case series provides evidence that intravenous lidocaine infusion provided effective pain relief as an analgesic treatment option for transplant patients with intractable zoster-associated neuralgia.
