Oct 31, 2019

Lidocaine as treatment for neonatal seizures: evaluation of previously developed population pharmacokinetic models and dosing regimen

British Journal of Clinical Pharmacology
Laurent M A FaviéPharmaCool Study Group

Abstract

Lidocaine is used to treat neonatal seizures refractory to other anticonvulsants. It is effective, but also associated with cardiac toxicity. Previous studies have reported on the pharmacokinetics of lidocaine in preterm and term neonates and proposed a dosing regimen for effective and safe lidocaine use. The objective of this study was to evaluate the previously developed pharmacokinetic models and dosing regimen. As a secondary objective, lidocaine effectiveness and safety were assessed. Data from preterm neonates and (near-)term neonates with and without therapeutic hypothermia receiving lidocaine were included. Pharmacokinetic analyses were performed using non-linear mixed effects modelling. Simulations were performed to evaluate the proposed dosing regimen. Lidocaine was considered effective if no additional anticonvulsant was required and safe if no cardiac adverse events occurred. Data were available for 159 neonates; 50 (31.4%) preterm and 109 term neonates of whom 49 (30.8%) were treated with therapeutic hypothermia. Lidocaine clearance increased with postmenstrual age by 0.69%/day (95% CI 0.54% - 0.84%). During therapeutic hypothermia (33.5 °C), lidocaine clearance was reduced by 21.8% (7.26%/°C, 95% CI 1.63% - 11.2%)...Continue Reading

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Mentioned in this Paper

Study
Treatment Protocols
Anticonvulsants
Evaluation
Plasma
Lidocaine
Adverse Event Associated With Cardiac Arrhythmia
Simulation
Hypothermia, Induced
Population Group

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