Abstract
Objective
To compare the efficacy and safety of intravenous Levetiracetam and Phenobarbitone in the treatment of neonatal seizures.
Design
Open labelled, Randomized controlled trial.
Setting
Level III Neonatal Intensive Care Unit (NICU).
Participants
100 neonates (0–28 days) with clinical seizures.
Intervention
If seizures persisted even after correction of hypoglycemia and hypocalcemia, participants were randomized to receive either Levetiracetam (20 mg/kg) or Phenobarbitone (20 mg/kg) intravenously. The dose of same drug was repeated if seizures persisted (20 mg/kg of Levetiracetam or 10 mg/kg of Phenobarbitone) and changeover to other drug occurred if the seizures persisted even after second dose of same drug.
Main outcome measures
Cessation of seizures with one or two doses of the first drug, and remaining seizure-free for the next 24 hours.
Results
Seizures stoped in 43 (86%) and 31 (62%) neonates in Levetiracetam and Phenobarbitone group, respectively (RR 0.37; 95%CI 0.17, 0.80, P<0.01). 10 neonates had adverse reactions in the phenobarbitone group (hypotension in 5, bradycardia in 3 and requirement of mechanical ventilation in 2 neonates) while none had any adverse reaction in Levetiracatam group.
Conclusion
Levetiracetam achieves better control than Phenobarbitone for neonatal seizures when used as first-line antiepileptic drug, and is not associated with adverse drug reactions.
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References
Thibeault-Eybalin MP, Lortie A, Carmant L. Neonatal seizures: Do they damage the brain? Pediatr Neurol. 2009;40:175–80.
Ronen GM, Penney S, Andrews W. The epidemiology of clinical neonatal seizures in Newfoundland: a population-based study. J Pediatr. 1999;134:71.
Saliba RM, Annegers JF, Walker DK, Tyson JE, Mizrahi EM. Incidence of neonatal seizures in Harris County, Texas, 1992–1994. Am J Epidemiol. 1999;150:763.
Van Rooij LG, Hellström-Westas L, deVries LS. Treatment of neonatal seizures. Semin Fetal Neonatal Med. 2013;18:209–15.
Bartha AI, Shen J, Katz KH, Mischel RE, Yap KR, Ivacko JA, et al. Neonatal seizures: multicenter variability in current treatment practices. Pediatr Neurol. 2007;37:85–90.
Wheless JW, Clarke DF, Arzimanoglou A, Carpenter D. Treatment of pediatric epilepsy: European expert opinion, 2007. Epileptic Disord. 2007;9:353–412.
Painter MJ, Scher MS, Stein AD, Armatti S, Wang Z, Gardiner JC, et al. Phenobarbital compared with phenytoin for the treatment of neonatal seizures. N Engl J Med. 1999;341:485–9.
Manthey D, Asimiadou S, Stefovska V, Kaindl AM, Fassbender J, Ikonomidou C, et al. Sulthiame but not levetiracetam exerts neurotoxic effect in the developing rat brain. Exp Neurol. 2005;193:497e503.
Mruk AL, Garlitz KL, Leung NR. Levetiracetam in neonatal seizures: A review. J Pediatr Pharmacol Ther. 2015;20:76–89.
McHugh DC, Lancaster S, Manganas LN. A systematic review of the efficacy of levetiracetam in neonatal seizures. Neuropediatrics. 2018;49:12–17.
Han JY, Moon CJ, Youn YA, Sung IK, Lee IG. Efficacy of Levetiracetam for neonatal seizures in preterm infants. BMC Pediatr. 2018;18:131.
Boylan GB, Rennie JM, Pressler RM, Wilson G, Morton M, Binnie CD. Phenobarbitone, neonatal seizures, and video EEG. Arch Dis Child Fetal Neonatal Ed. 2002;86:165–70.
Ramantani G, Ikonomidou C, Walter B, Rating D, Dinger J. Levetiracetam: Safety and efficacy in neonatal seizures. Eur J Paediatr Neurol. 2011;15:1–7.
Khan O, Chang E, Cipriani C, Wright C, Crisp E, Kirmani B. Use of intravenous levetiracetam for management of acute seizures in neonates. Pediatr Neurol. 2011;44:265–9.
Abend NS, Gutierrez-Colina AM, Monk HM, Dlugos DJ, Clancy RR. Levetiracetam for treatment of neonatal seizures. J Child Neurol. 2011;26:465–70.
Rakshasbhuvankar A, Rao S, Kohan R, Simmer K, Nagarajan L, J Clin Neurosci. 2013;20:1165–7.
Koppelstäetter A, Buhrer C, Kaindl AM. Treating neonates with levetiracetam: A survey among German university hospitals. Klin Pediatr. 2011;223:450–2.
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VR: conceptualization of study, and critical inputs to manuscript for important intellectual content; AR: data collection and writing the manuscript; NS and NB: data collection and analysis, and critical inputs to manuscript writing; AB: supervision of the work and revision of manuscript.
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Gowda, V.K., Romana, A., Shivanna, N.H. et al. Levetiracetam versus Phenobarbitone in Neonatal Seizures — A Randomized Controlled Trial. Indian Pediatr 56, 643–646 (2019). https://doi.org/10.1007/s13312-019-1586-3
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DOI: https://doi.org/10.1007/s13312-019-1586-3