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

Epilepsia. 2016 Feb;57(2):233-42. doi: 10.1111/epi.13286. Epub 2015 Dec 31.


Objective: 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.

Keywords: Antiepileptic drugs; Lidocaine; Midazolam; Neonatal seizures; Response rate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticonvulsants / therapeutic use*
  • Central Nervous System Infections / epidemiology
  • Cohort Studies
  • Electroencephalography
  • Female
  • Gestational Age
  • Humans
  • Hypothermia, Induced / statistics & numerical data
  • Hypoxia-Ischemia, Brain / epidemiology
  • Infant
  • Infant, Newborn
  • Infant, Premature
  • Intracranial Hemorrhages / epidemiology
  • Lidocaine / therapeutic use*
  • Logistic Models
  • Male
  • Midazolam / therapeutic use
  • Multivariate Analysis
  • Netherlands / epidemiology
  • Retrospective Studies
  • Seizures / drug therapy*
  • Seizures / epidemiology
  • Stroke / epidemiology
  • Time Factors
  • Treatment Outcome
  • Voltage-Gated Sodium Channel Blockers / therapeutic use*


  • Anticonvulsants
  • Voltage-Gated Sodium Channel Blockers
  • Lidocaine
  • Midazolam