Anticonvulsant treatment of asphyxiated newborns under hypothermia with lidocaine: efficacy, safety and dosing
- Marcel P H van den Broek1,
- Carin M A Rademaker1,
- Henrica L M van Straaten2,
- Alwin D R Huitema3,
- Mona C Toet4,
- Linda S de Vries4,
- Antoine C G Egberts1,5,
- Floris Groenendaal4
- 1Department of Clinical Pharmacy, University Medical Centre Utrecht, Utrecht, The Netherlands
- 2Department of Neonatology, Isala Clinics, Zwolle, The Netherlands
- 3Department of Pharmacy and Pharmacology, Slotervaart Hospital/the Netherlands Cancer Institute, Amsterdam, The Netherlands
- 4Department of Neonatology, Wilhelmina Childrens’ Hospital/UMCU, Utrecht, The Netherlands
- 5Department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
- Correspondence to Marcel P H van den Broek, Department of Clinical Pharmacy, University Medical Centre Utrecht, P.O. Box 85500, Utrecht 3508 GA, The Netherlands;
- Received 17 July 2012
- Revised 28 November 2012
- Accepted 29 November 2012
- Published Online First 8 January 2013
Background Lidocaine is an antiarrythmicum used as an anticonvulsant for neonatal seizures, also during therpeutic hypothermia following (perinatal) asphyxia. Hypothermia may affect the efficacy, safety and dosing of lidocaine in these patients.
Objective To study the efficacy and safety of lidocaine in newborns with perinatal asphyxia during moderate hypothermia, and to develop an effective and safe dosing regimen.
Methods Hypothermic newborns with perinatal asphyxia and lidocaine for seizure control were included. Efficacy was studied using continuous amplitude-integrated electroencephalography. Safety was assessed using continuous cardiac monitoring. An optimal dosing regimen was developed with simulations using data from a pharmacokinetic model. Plasma samples were collected during hypothermia on consecutive mornings.
Results A total of 22 hypothermic and 26 historical normothermic asphyxiated newborns with lidocaine were included. A response of 91% on epileptiform activity on the amplitude-integrated EEG was observed for lidocaine add-on therapy. No relationship between lidocaine or MEGX plasma concentrations and heart frequency could be identified. None of the newborns experienced cardiac arrythmias. Hypothermia reduced lidocaine clearance by 24% compared with normothermia. A novel dosing regimen was developed an initial bolus loading dose of 2 mg/kg, for patients with body weight 2.0–2.5 kg followed by consecutive continuous infusions of 6 mg/kg/h (for 3.5 h), 3 mg/kg/h (for 12 h), 1.5 mg/kg/h (for 12 h), or for patients with bodyweights 2.5–4.5 kg 7 mg/kg/h (for 3.5 h), 3.5 mg/kg/h (for 12 h), 1.75 mg/kg/h (for 12 h), before stopping.
Conclusions Lidocaine can be assumed to be an effective antiepileptic drug during hypothermia in asphyxiated neonates.