Population Pharmacokinetics of Lidocaine Administered During and After Cardiac Surgery

Abstract

Objective The objective of this study was to determine the pharmacokinetics of lidocaine in a 48-hour infusion in patients undergoing cardiac surgery with cardiopulmonary bypass. Design A retrospective substudy of a clinical trial assessing the efficacy of intravenous lidocaine for postoperative cognitive decline. Setting University hospital. Participants 99 patients undergoing cardiac surgery with cardiopulmonary bypass. Interventions After induction of anesthesia, lidocaine was administered as bolus of 1 mg/kg and followed by a continuous infusion at 4 mg/min for the first hour, 2 mg/min for the second hour, and 1 mg/min for the next 46 hours. Measurements and Main Results Blood samples were taken at baseline, end of cardiopulmonary bypass, and 24 and 48 hours after cardiopulmonary bypass for measurement of plasma concentration of lidocaine. Lidocaine levels increased significantly over time despite a constant rate of infusion (p < 0.05). The pharmacokinetics of lidocaine was best described by a two-compartment model and body weight was found to be a significant factor for the volume of the central compartment and clearance. The final pharmacokinetic parameters were V1(L) = 0.0619*weight, V2(L) = 187, CL1(L/min) =0.00419*weight, CL2(L/min) = 8.92. Conclusions A two-compartment pharmacokinetic model best describes the plasma concentrations of 48-hour lidocaine infusion in patients undergoing heart surgery with cardiopulmonary bypass. The inclusion of body weight as a covariate on clearance and central compartment improves the model. Lidocaine infusions should be dosed by body weight and decreased after 24 hours to avoid potential toxicity in long-term infusions.

Effect of opioid-free anaesthesia on post-operative period in cardiac surgery: a retrospective matched case-control study

“…Accordingly, we did not demonstrate a higher incidence of postoperative vasoplegic syndrome. To date, we do not have observed clinical signs of local anaesthetic toxicity (arrhythmia, atrial-ventricular block, seizure) with our protocol, which confirms the existing data on lidocaine plasma levels [27][28][29].…”

Effect of opioid-free anaesthesia on post-operative period in cardiac surgery: a retrospective matched case-control study

“…Accordingly, we did not demonstrate a higher incidence of postoperative vasoplegic syndrome. To date, we do not have observed clinical signs of local anaesthetic toxicity (arrhythmia, atrialventricular block, seizure) with our protocol, which confirms the existing data on lidocaine plasma levels [27][28][29].…”

“…Our approach to OFA was based on published literature which demonstrates that each of the effects associated with opioids can be obtained with lidocaine (analgesic, hypnotic, and ANS control), dexamethasone (analgesic) and ketamine (analgesic and hypnotic) [11][12][13]. The lidocaine dosing regimen was based on the literature published since the 1990s that has demonstrated a safety profile with continuous infusion of lidocaine during cardiac and non-cardiac surgeries [27,28]. Lidocaine has effects that depend on the total dose, and detrimental effects can be seen with elevated doses of lidocaine [27].…”

“…The lidocaine dosing regimen was based on the literature published since the 1990s that has demonstrated a safety profile with continuous infusion of lidocaine during cardiac and non-cardiac surgeries [27,28]. Lidocaine has effects that depend on the total dose, and detrimental effects can be seen with elevated doses of lidocaine [27]. But lidocaine also has beneficial effects during surgery, providing (a) an anti-inflammatory effect; (b) an increase in the cardioprotective effect of cardioplegia; (c) a decrease in the risk of arrhythmias; and (d) a decrease in the risk of brain inflammation [15,16,28,29].…”

A randomised controlled trial of peri‐operative lidocaine infusions for open radical prostatectomy

“…Subcutaneous lidocaine can result in stable therapeutic plasma lidocaine concentrations . We modelled the subcutaneous lidocaine infusion regime on the doses described by studies of intravenous lidocaine . The lidocaine plasma levels that we measured were similar to those studies (2–5 mg.ml −1 ).…”