Lidocaine response rate in aEEG‐confirmed neonatal seizures: Retrospective study of 413 full‐term and preterm infants

Abstract

SUMMARYObjective: To investigate the seizure response rate to lidocaine in a large cohort of infants who received lidocaine as second-or third-line antiepileptic drug (AED) for neonatal seizures. Methods: Full-term (n = 319) and preterm (n = 94) infants, who received lidocaine for neonatal seizures confirmed on amplitude-integrated EEG (aEEG), were studied retrospectively (January 1992-December 2012). Based on aEEG findings, the response was defined as good (>4 h no seizures, no need for rescue medication); intermediate (0-2 h no seizures, but rescue medication needed after 2-4 h); or no clear response (rescue medication needed <2 h). Results: Lidocaine had a good or intermediate effect in 71.4%. The response rate was significantly lower in preterm (55.3%) than in full-term infants (76.1%, p < 0.001). In full-term infants the response to lidocaine was significantly better than midazolam as second-line AED (21.4% vs. 12.7%, p = 0.049), and there was a trend for a higher response rate as third-line AED (67.6% vs. 57%, p = 0.086). Both lidocaine and midazolam had a higher response rate as third-line AED than as second-line AED (p < 0.001). Factors associated with a good response to lidocaine were the following: higher gestational age, longer time between start of first seizure and administration of lidocaine, lidocaine as third-line AED, use of new lidocaine regimens, diagnosis of stroke, use of digital aEEG, and hypothermia. Multivariable analysis of seizure response to lidocaine included lidocaine as second-or third-line AED and seizure etiology. Significance: Seizure response to lidocaine was seen in~70%. The response rate was influenced by gestational age, underlying etiology, and timing of administration. Lidocaine had a significantly higher response rate than midazolam as second-line AED, and there was a trend for a higher response rate as third-line AED. Both lidocaine and midazolam had a higher response rate as third-line compared to second-line AED, which could be due to a pharmacologic synergistic mechanism between the two drugs.

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

“…A higher lidocaine success rate was noted in (near‐)term neonates. This is consistent with a retrospective study with 413 term and preterm neonates where a significantly lower success rate was observed in preterm vs term neonates (55.3 vs 76.1%); overall antiepileptic effectiveness of lidocaine was 71.4% . Seizure control in our study was lower but did not differ between the proposed and the old dosing regimen.…”

“…Lidocaine has proven to be effective in several observational studies in both term and preterm neonates and is favoured as a second‐ or third‐line anticonvulsant therapy in several European countries. The most important safety risk of the use of lidocaine is cardiac toxicity (bradycardia, arrhythmias or asystole), most likely to occur at plasma concentrations exceeding 9 mg/L …”

A Distinctive Ictal Amplitude-Integrated Electroencephalography Pattern in Newborns with Neonatal Epilepsy Associated with <b><i>KCNQ2</i></b> Mutations

“…AEDs acting on sodium channels, including CBZ and PHT, were found to be safe and effective in controlling seizures in KCNQ2-related epilepsy, and are now considered a first-line treatment [11,12,13] . While lidocaine is also a sodium-channel blocker, concerns about cardiac toxicity have limited its use in the NICU, even though a recent study showed the drug to be effective and safe in a large number of newborns [24]. CBZ is rarely used in the NICU [25,26].…”

Marked improvement in febrile infection-related epilepsy syndrome after lidocaine plus MgSO 4 treatment in a 12-year-old girl

“…Capizzi et al [4] assumed that lidocaine, being a local anesthetic drug as well as an antiarrhythmic drug (Class IB), has membrane-stabilizing effects and exhibits a central local anesthetic action on the inhibitory pathway fibers involved in direct cortical stimulation [4] . At present, lidocaine has been widely used in the control of neonatal seizures [7] . Magnesium sulfate (MgSO 4 ), a drug commonly used in eclampsia but rarely in FIRES, is a seizure prophylactic; its mechanism of action, however, remains unclear [8] .…”