Development of an optimal lidocaine infusion strategy for neonatal seizures.
BACKGROUND
Lidocaine is an effective drug for the treatment of neonatal convulsions not responding to traditional anticonvulsant therapy. However, one of the side-effects is a risk of cardiac arrhythmias. The aim of this study was to develop an optimal dosing strategy with minimal risk of cardiac arrhythmias.


METHODS
As a first step, we studied 20 neonates during routine treatment of neonatal seizures with lidocaine. All were given a loading dose of 2 mg/kg in 10 min, followed by the continuous infusion of 6 mg/kg per hour for 12 h, 4 mg/kg per hour for 12 h and finally 2 mg/kg per hour for 12 h. Effectiveness, cardiac toxicity and lidocaine plasma concentrations were then determined.


RESULTS
No cardiac arrhythmias were observed, and lidocaine was effective in 76% of the treatments. In most of the treatments (13 out of 20) maximal lidocaine plasma concentrations were >9 mg/L. Plasma levels >9 mg/L have been related to cardiac toxicity when used as an anti-arrhythmic drug in adults. It was of interest that all preterm infants showed high lidocaine plasma levels. Secondly, we developed the optimal dosing regimen, which was defined as an infusion regimen at which maximal lidocaine plasma concentrations are <9 mg/L. Simulations with the developed pharmacokinetic model indicated a reduction in the infusion duration of lidocaine at 6 mg/kg per hour from 12 to 6 h. Thirdly, the new lidocaine dosing regimen was evaluated. Fifteen neonates (16 treatments) were studied. No cardiac arrhythmias were observed, and lidocaine was effective in 78% of the treatments. In most of the treatments (11 out of 16) maximal lidocaine plasma concentrations were <9 mg/L. Again preterm infants showed relatively high lidocaine plasma levels.


CONCLUSIONS
A new lidocaine dosing schedule was developed. This new regimen should have a lower risk of cardiac arrhythmias and appears to be as effective in term infants. For preterm infants the optimal regimen needs to be determined.
Malingré
Mirte M
MM
Department of Pharmacy, University Medical Centre Utrecht/Wilhelmina Children's Hospital, Utrecht, The Netherlands.
Van Rooij
Linda G M
LG
Rademaker
Carin M A
CM
Toet
Mona C
MC
Ververs
Tessa F F T
TF
van Kesteren
Charlotte
C
de Vries
Linda S
LS
D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D007363:Intensive Care Units, Neonatal; D008012:Lidocaine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D009426:Netherlands; D012008:Recurrence; D012307:Risk Factors; D012640:Seizures / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome
D000889:Anti-Arrhythmia Agents; D000927:Anticonvulsants; D008012:Lidocaine