Modeling Population Pharmacokinetics of Lidocaine

Kuipers, Jette A.; Boer, F.; Roode, Annemiek de; Olofsen, Erik; Bovill, J. G.; Burm, A. G. L.

doi:10.1097/00000542-200104000-00007

Cited by 15 publications

(3 citation statements)

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“…1-5 Much of the data also suggests that patients with congestive heart failure or hepatic disease have pronounced changes in the clearance of lidocaine. 4,6 This reduction in lidocaine metabolic clearance can lead to increased accumulation during long-term infusion and enhance the likelihood of toxicity, particularly in patients with cardiovascular disease. Using data from a previously published clinical trial assessing the effect of lidocaine upon postoperative cognition, 7 we therefore sought to develop a population pharmacokinetic model of lidocaine that may improve the accuracy and safety of longer-term lidocaine infusion during cardiac surgery with cardiopulmonary bypass (CPB).…”

Section: Introductionmentioning

confidence: 99%

Population Pharmacokinetics of Lidocaine Administered During and After Cardiac Surgery

Hsu

Somma²,

Newman

et al. 2011

Journal of Cardiothoracic and Vascular Anesthesia

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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.

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Section: Introductionmentioning

confidence: 99%

Population Pharmacokinetics of Lidocaine Administered During and After Cardiac Surgery

Hsu

Somma²,

Newman

et al. 2011

Journal of Cardiothoracic and Vascular Anesthesia

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“…A reduction in opioid consumption and improved bowel function are some of the stated advantages [22,[24][25][26][27]. The population pharmacokinetic model from Kuipers et al was used to perform simulated plasma concentrations for lidocaine [28].…”

Section: Discussionmentioning

confidence: 99%

“…The population pharmacokinetic model from Kuipers et al. was used to perform simulated plasma concentrations for lidocaine [28]. This study investigated the effect of cardiac output on lidocaine pharmacokinetics and concluded that adding cardiac output into the pharmacokinetic model only marginally improved its performance.…”

Section: Discussionmentioning

confidence: 99%

Compatibility and stability of an admixture of multiple anaesthetic drugs for opioid‐free anaesthesia

et al. 2022

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The ability to combine and use drugs in a single infusion device may be useful in resource-limited settings. This study examined the chemical stability of an opioid-sparing mixture of ketamine, lidocaine and magnesium sulphate when combined in a single syringe. High-performance liquid chromatography and atomic absorption spectrophotometry were performed on six syringes containing the three-drug mixture. Since most opioid-sparing techniques typically rely on a 24-hour infusion regime, we tested stability at the initial admixing and 24 hours later. Stability was defined as a measured drug concentration within 10% of expected, with the absence of precipitation or pH alterations. Pharmacokinetic simulations were conducted to further show that the achieved plasma drug concentrations were well within an effective analgesic range. All mixed drug concentration measurements were within the required 10% reference limit. No obvious precipitation or interaction occurred, and pH remained stable. Drug stability was maintained for 24 hours. Pharmacokinetic simulations showed that ketamine and lidocaine were within their minimum analgesic effect concentrations. Our results show that this three-drug mixture is chemically stable for up to 24 hours after mixing, with a pharmacokinetic simulation illustrating safe, clinically useful predicted plasma concentrations when using the described admixture.

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Basic Concepts of Recirculatory Pharmacokinetic Modelling

Reekers

Boer

Vuyk

2003

Advances in Modelling and Clinical Application of Intravenous Anaesthesia

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Modeling Population Pharmacokinetics of Lidocaine

Abstract: When population pharmacokinetic models are used for individualization of dosing schedules, physiologic covariates, e.g., cardiac output, can improve their ability to predict the individual kinetics.

Cited by 15 publications

References 0 publications

Population Pharmacokinetics of Lidocaine Administered During and After Cardiac Surgery

Population Pharmacokinetics of Lidocaine Administered During and After Cardiac Surgery

Compatibility and stability of an admixture of multiple anaesthetic drugs for opioid‐free anaesthesia

Basic Concepts of Recirculatory Pharmacokinetic Modelling

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