O15?Lidocaine plasma concentrations and anti-epileptic efficacy in term and preterm neonates: prospective validation of a new dosing regimen

摘要

Background Lidocaine is used as an add-on anti-epileptic drug (AED) in neonates when seizures persist despite treatment with first line anticonvulsants. Although lidocaine has shown to be an effective anticonvulsant, cardiac toxicity associated with plasma concentrations 9 mg/L have limited its wide scale use.sup1/sup Previous studies from our group have proposed a dosing regimen for effective and safe lidocaine use in term and preterm neonates with plasma concentrations not exceeding 9 mg/L.sup2,3/sup Aim The present study evaluated lidocaine use as anticonvulsant in neonates and prospectively validated the new dosing regimen. Methods Data were collected at the neonatal intensive care unit of the University Medical Centre Utrecht. Neonates refractory to at least one AED received lidocaine according to clinical protocol. Lidocaine was administered as a 2 mg/kg loading dose in 10 minutes followed by a three stage maintenance phase with tapering lidocaine doses. Lidocaine plasma concentrations were measured from blood samples taken at the end of the first stage (highest lidocaine dose) and during the second or third stage (tapered lidocaine dose). Efficacy was determined as abolishment of seizures during lidocaine therapy and no recurrence within 24 h after cessation. Results Lidocaine data were available from 75 neonates (gestational age 36.2 weeks [range 25.0–42.4, 36.0 38.7%], birth weight 2771 g [range 675–4875], male 64.0%, mortality 45.3%). 23 patients (30.7%) received the new dosing regimen, 52 patients (60.7%) the old regimen. Highest measured plasma concentration with the new regimen was 9.15 mg/L and 16.8 mg/L with the old regimen. Efficacy with the new regimen was 56.5% and 53.8% for the old regimen. No cardiac toxicity was observed in either group. Conclusions The new lidocaine dosing regimen leads to safe and effective lidocaine plasma concentrations and has similar efficacy compared to the previous dosing regimen. References Weeke LC, Toet MC, Van Rooij LGM, Groenendaal F, Boylan GB, Pressler RM, et al. Lidocaine response rate in aEEG-confirmed neonatal seizures: Retrospective study of 413 full-term and preterm infants 2015;233–42. Van den Broek MPH, Rademaker CMA, van Straaten HLM, Huitema ADR, Toet MC, de Vries LS, et al. Anticonvulsant treatment of asphyxiated newborns under hypothermia with lidocaine: efficacy, safety and dosing. Arch Dis Child Fetal Neonatal Ed 2013;98(4):F341–5. Van Den Broek MPH, Huitema a. DR, Van Hasselt JGC, Groenendaal F, Toet MC, Egberts TCG, et al. Lidocaine (lignocaine) dosing regimen based upon a population pharmacokinetic model for preterm and term neonates with seizures. Clin Pharmacokinet 2011;50(7):461–9.