Cardiac electrophysiology and arrhythmias (10)
Chronic Kidney Disease and Diabetes (10)
Glycosylation and Glycoproteins Research (9)
Mass Spectrometry Techniques and Applications (9)
Plant-based Medicinal Research (8)
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.
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.