Another Win for Lidocaine, Another Loss for Magnesium?

摘要

Concern over the opioid epidemic and recognition that perioperative opioid use may increase the risk for long-term opioid dependence has stimulated a growing interest in nonopioid analgesics for perioperative analgesia. Medications such as lidocaine and magnesium are increasingly suggested for use in multimodal analgesia and enhanced recovery programs; reported benefits include reductions in postoperative pain, opioid consumption, and opioid-related side effects.1,2 However, these benefits have been shown to vary by medication and type of surgery. In this issue of Anesthesia & Analgesia, Kim et al3 report the effects of 2 interesting nonopioid analgesics: intravenous lidocaine and intravenous magnesium. They compared these drugs with placebo controls in female patients undergoing total thyroidectomy, using the quality of recovery (QoR) after surgery as the primary outcome. The results provide further evidence for the benefits of lidocaine while raising additional questions about the use of magnesium perioperatively. Intravenous lidocaine is frequently administered during induction of anesthesia to decrease pain from injection of propofol and to blunt hemodynamic responses to tracheal intubation. Lidocaine is also used as part of total intravenous anesthesia for procedures requiring neurophysiological monitoring because it does not adversely affect stimulation thresholds or signal amplitude. Continuous infusion of the compound also has analgesic effects, and several recent reviews and meta-analyses document the clinical benefits of intravenous lidocaine administered for postoperative analgesia.4–6 In open abdominal surgeries, intravenous lidocaine was shown to reduce visual analog scale pain scores at rest and with activity and to reduce opioid requirements in the first 24 hours after surgery.4,6 Lidocaine was also shown to decrease the incidence of postoperative nausea and vomiting and shorten the duration of postoperative ileus by an average of 8 hours, which may be due in part to an opioid-sparing effect.5 Intravenous lidocaine is typically administered as a bolus of 1–1.5 mg/kg followed by an infusion rate of 1.5–3 mg/kg/h, which achieves plasma concentrations similar to those obtained during epidural administration (~1 μmol/L or 0.23 μg/mL). The mechanism of action is not entirely understood. Preclinical studies suggest a likely mechanism through prevention of polymorphonuclear cell priming and interference with inflammatory signaling. Sodium channel blockade is less likely because polymorphonuclear do not express sodium channels and only a small proportion of neuronal sodium channels are inhibited at the plasma concentrations achieved with typical doses. In addition to open abdominal procedures, intravenous lidocaine has also been shown to be of benefit for other types of surgery including laparoscopic abdominal procedures, prostatectomy, thoracic surgery, and spine surgery.5 However, it may not provide the same clinical benefit for some other types of surgery, such as total abdominal hysterectomy and total hip arthroplasty.7 The reason for this specificity is poorly understood and adds to the challenge of clinical application. In this issue of Anesthesia & Analgesia, Kim et al3 demonstrate another type of surgery where intravenous lidocaine may be beneficial. In a randomized controlled trial of 135 female patients undergoing open thyroidectomy, the authors compared the effect of intraoperative intravenous lidocaine (2 mg/kg for 15 minutes followed by 2 mg/kg/h), magnesium (20 mg/kg over 15 minutes followed by 20 mg/kg/h), or saline infusion on postoperative recovery. These doses were chosen based on previous studies with the dose of intravenous lidocaine used here being fairly standard. However, typical doses of magnesium vary widely (bolus dose ranging from 30 to 50 mg/kg and infusion dose ranging from 6 to 25 mg/kg/h) with a low bolus dose but moderately high infusion dose used here. Unlike previous studies that report