High Effectiveness of Midazolam and Lidocaine in the Treatment of Acute Neonatal Seizures

José Ramón Castro Conde; Candelaria González Campo; Desiré González Barrios; Beatriz Reyes Millán; Candelaria Leticia Díaz González; Alejandro Jiménez Sosa

doi:10.1097/WNP.0000000000001013

High Effectiveness of Midazolam and Lidocaine in the Treatment of Acute Neonatal Seizures

J Clin Neurophysiol. 2023 Apr 25. doi: 10.1097/WNP.0000000000001013. Online ahead of print.

Authors

José Ramón Castro Conde^{1

2}, Candelaria González Campo^{1

2}, Desiré González Barrios³, Beatriz Reyes Millán⁴, Candelaria Leticia Díaz González², Alejandro Jiménez Sosa⁵

Affiliations

¹ Pediatric Department, Faculty of Medicine, Universidad de La Laguna, S/C Tenerife, Spain.
² Department of Neonatology, Hospital Universitario de Canarias, S/C Tenerife, Spain.
³ Department of Neonatology, Hospital Universitario Nuestra Señora de la Candelaria, S/C Tenerife, Spain.
⁴ Neuropediatrics Unit, Department of Pediatrics, Hospital Universitario Nuestra Señora de la Candelaria, S/C Tenerife, Spain; and.
⁵ Research Unit Hospital Universitario de Canarias, S/C Tenerife, Spain.

PMID: 37099703
DOI: 10.1097/WNP.0000000000001013

Abstract

Purpose: To assess the clinical effectiveness of treating acute seizures with midazolam and lidocaine infusion.

Methods: This single-center historical cohort study included 39 term neonates with electrographic seizures who underwent treatment with midazolam (1st line) and lidocaine (2nd line). Therapeutic response was measured using continuous video-EEG monitoring. The EEG measurements included total seizure burden (minutes), maximum ictal fraction (minutes/hour), and EEG-background (normal/slightly abnormal vs. abnormal). Treatment response was considered good (seizure control with midazolam infusion), intermediate (need to add lidocaine to the control), or no response. Using clinical assessments supplemented by BSID-III and/or ASQ-3 at 2 to 9 years old age, neurodevelopment was classified as normal, borderline, or abnormal.

Results: A good therapeutic response was obtained in 24 neonates, an intermediate response in 15, and no response in any of the neonates. Babies with good response showed lower values in maximum ictal fraction compared with those with intermediate response (95% CI: 5.85-8.64 vs. 9.14-19.14, P = 0.002). Neurodevelopment was considered normal in 24 children, borderline in five, and abnormal in other 10 children. Abnormal neurodevelopment was significantly associated with an abnormal EEG background, maximum ictal fraction >11 minutes, and total seizure burden >25 minutes (odds ratio 95% CI: 4.74-1708.52, P = 0.003; 1.72-200, P = 0.016; 1.72-142.86, P = 0.026, respectively) but not with the therapeutic response. Serious adverse effects were not recorded.

Conclusions: This retrospective study suggests that the midazolam/lidocaine association could potentially be efficacious in decreasing seizure burden in term neonates with acute seizures. These results would justify testing the midazolam/lidocaine combination as a first-line treatment for neonatal seizures in future clinical trials.