title: Lidocaine response rate in aEEG-confirmed neonatal seizures: Retrospective study of 413 full-term and preterm infants.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Weeke
authors.affiliation: Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Mona C
authors.initials: MC
authors.lastname: Toet
authors.affiliation: Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Linda G M
authors.initials: LG
authors.lastname: van Rooij
authors.affiliation: Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Floris
authors.initials: F
authors.lastname: Groenendaal
authors.affiliation: Irish Centre for Fetal and Neonatal Translational Research, University College Cork, Cork, Ireland.
authors.forename: Geraldine B
authors.initials: GB
authors.lastname: Boylan
authors.affiliation: Section of Clinical Neurosciences, UCL - Institute of Child Health, London, United Kingdom.
authors.forename: Ronit M
authors.initials: RM
authors.lastname: Pressler
authors.affiliation: Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Hellström-Westas
authors.affiliation: Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Marcel P H
authors.initials: MP
authors.lastname: van den Broek
authors.affiliation: Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Linda S
authors.initials: LS
authors.lastname: de Vries
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use*; D002494:Central Nervous System Infections / Q000453:epidemiology; D015331:Cohort Studies; D004569:Electroencephalography; D005260:Female; D005865:Gestational Age; D006801:Humans; D007036:Hypothermia, Induced / Q000706:statistics & numerical data; D020925:Hypoxia-Ischemia, Brain / Q000453:epidemiology; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D020300:Intracranial Hemorrhages / Q000453:epidemiology; D008012:Lidocaine / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008874:Midazolam / Q000627:therapeutic use; D015999:Multivariate Analysis; D009426:Netherlands / Q000453:epidemiology; D012189:Retrospective Studies; D012640:Seizures / Q000188:drug therapy* / Q000453:epidemiology; D020521:Stroke / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome; D061567:Voltage-Gated Sodium Channel Blockers / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D061567:Voltage-Gated Sodium Channel Blockers; D008012:Lidocaine; D008874:Midazolam
keywords: Antiepileptic drugs; Lidocaine; Midazolam; Neonatal seizures; Response rate