Midazolam as a first‐line treatment for neonatal seizures: Retrospective study

Dao, Kim; Giannoni, Éric; Diezi, Manuel; Roulet-Perez, Eliane; Lebon, Sébastien

doi:10.1111/ped.13554

Cited by 11 publications

(12 citation statements)

References 14 publications

(32 reference statements)

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“…48 A recent clinical study on midazolam as a first-line treatment for neonatal seizures reported that the drug was well tolerated and suggested that, given its short half-life, it might be considered a useful, easy-to-use agent to stop ongoing seizures or break a cluster of seizures in neonates. 76 The present data indicate that disease-modifying efficacy is an added advantage of midazolam in neonates. That such efficacy may occur in human neonates was indicated by a study in which midazolam was administered after PB failed, which resulted in rapid control of seizures and significantly improved long-term neurodevelopment, which, however, was only assessed at 1 year of age.…”

supporting

confidence: 51%

“…Such comparison is needed in human neonates 48 . A recent clinical study on midazolam as a first‐line treatment for neonatal seizures reported that the drug was well tolerated and suggested that, given its short half‐life, it might be considered a useful, easy‐to‐use agent to stop ongoing seizures or break a cluster of seizures in neonates 76 . The present data indicate that disease‐modifying efficacy is an added advantage of midazolam in neonates.…”

Section: Discussionmentioning

confidence: 63%

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Midazolam Prevents the Adverse Outcome of Neonatal Asphyxia

Welzel

Schmidt

Johne

et al. 2022

Annals of Neurology

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Objective Birth asphyxia (BA) is the most frequent cause of neonatal death as well as central nervous system (CNS) injury. BA is often associated with neonatal seizures, which only poorly respond to anti‐seizure medications and may contribute to the adverse neurodevelopmental outcome. Using a non‐invasive rat model of BA, we have recently reported that the potent benzodiazepine, midazolam, prevents neonatal seizures in ~50% of rat pups. In addition to its anti‐seizure effect, midazolam exerts anti‐inflammatory actions, which is highly relevant for therapeutic intervention following BA. The 2 major aims of the present study were to examine (1) whether midazolam reduces the adverse outcome of BA, and (2) whether this effect is different in rats that did or did not exhibit neonatal seizures after drug treatment. Methods Behavioral and cognitive tests were performed over 14 months after asphyxia, followed by immunohistochemical analyses. Results All vehicle‐treated rats had seizures after asphyxia and developed behavioral and cognitive abnormalities, neuroinflammation in gray and white matter, neurodegeneration in the hippocampus and thalamus, and hippocampal mossy fiber sprouting in subsequent months. Administration of midazolam (1 mg/kg i.p.) directly after asphyxia prevented post‐asphyctic seizures in ~50% of the rats and resulted in the prevention or decrease of neuroinflammation and the behavioral, cognitive, and neurodegenerative consequences of asphyxia. Except for neurodegeneration in the thalamus, seizures did not seem to contribute to the adverse outcome of asphyxia. Interpretation The disease‐modifying effect of midazolam identified here strongly suggests that this drug provides a valuable option for improving the treatment and outcome of BA. ANN NEUROL 2023;93:226–243

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supporting

confidence: 51%

Section: Discussionmentioning

confidence: 63%

Midazolam Prevents the Adverse Outcome of Neonatal Asphyxia

Welzel

Schmidt

Johne

et al. 2022

Annals of Neurology

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“…Dao et al studied the use of midazolam (intravenous or intranasal) as first-line therapy for neonatal seizures in 72 neonates. 52 Though effectiveness could not be confirmed due to the absence of EEG monitoring, midazolam was well tolerated in both routes. GABAergic drugs are speculated to be less effective inhibitors during the neonatal age group due to a higher relative expression of chloride transporters NKCC1, which leads to higher intracellular chloride concentration.…”

Section: First-and Second-line Therapy and Relevant Studiesmentioning

confidence: 99%

Recent Advances in the Diagnosis and Treatment of Neonatal Seizures

Samanta

2020

Neuropediatrics

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Seizures are the most common neurological emergency in the neonates, and this age group has the highest incidence of seizures compared with any other period of life. The author provides a narrative review of recent advances in the genetics of neonatal epilepsies, new neonatal seizure classification system, diagnostics, and treatment of neonatal seizures based on a comprehensive literature review (MEDLINE using PubMED and OvidSP vendors with appropriate keywords to incorporate recent evidence), personal practice, and experience. Knowledge regarding various systemic and postzygotic genetic mutations responsible for neonatal epilepsy has been exploded in recent times, as well as better delineation of clinical phenotypes associated with rare neonatal epilepsies. An International League Against Epilepsy task force on neonatal seizure has proposed a new neonatal seizure classification system and also evaluated the specificity of semiological features related to particular etiology. Although continuous video electroencephalogram (EEG) is the gold standard for monitoring neonatal seizures, amplitude-integrated EEGs have gained significant popularity in resource-limited settings. There is tremendous progress in the automated seizure detection algorithm, including the availability of a fully convolutional neural network using artificial machine learning (deep learning). There is a substantial need for ongoing research and clinical trials to understand optimal medication selection (first line, second line, and third line) for neonatal seizures, treatment duration of antiepileptic drugs after cessation of seizures, and strategies to improve neuromorbidities such as cerebral palsy, epilepsy, and developmental impairments. Although in recent times, levetiracetam use has been significantly increased for neonatal seizures, a multicenter, randomized, blinded, controlled phase IIb trial confirmed the superiority of phenobarbital over levetiracetam in the acute suppression of neonatal seizures. While there is no single best choice available for the management of neonatal seizures, institutional guidelines should be formed based on a consensus of local experts to mitigate wide variability in the treatment and to facilitate early diagnosis and treatment.

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“…Available data regarding the use of benzodiazepines in neonates for seizures are primarily limited to retrospective studies. The response rate is varied with complete seizure response occurring in < 20% of neonates treated with 0.1 mg/ kg midazolam as first-line treatment [61] and between 0 and 100% when midazolam or clonazepam are used as secondline treatment for ongoing seizures [62][63][64]. Nearly half of the neonates treated with midazolam as first-line treatment had continued seizures [61]; given the limitations in study design this number may, in fact, be higher.…”

Section: Benzodiazepinesmentioning

confidence: 99%

Novel Therapeutics for Neonatal Seizures

2021

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Neonatal seizures are a common neurologic emergency for which therapies have not significantly changed in decades. Improvements in diagnosis and pathophysiologic understanding of the distinct features of acute symptomatic seizures and neonatal-onset epilepsies present exceptional opportunities for development of precision therapies with potential to improve outcomes. Herein, we discuss the pathophysiology of neonatal seizures and review the evidence for currently available treatment. We present emerging therapies in clinical and preclinical development for the treatment of acute symptomatic neonatal seizures. Lastly, we discuss the role of precision therapies for genetic neonatal-onset epilepsies and address barriers and goals for developing new therapies for clinical care.

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Midazolam as a first‐line treatment for neonatal seizures: Retrospective study

Cited by 11 publications

References 14 publications

Midazolam Prevents the Adverse Outcome of Neonatal Asphyxia

Midazolam Prevents the Adverse Outcome of Neonatal Asphyxia

Recent Advances in the Diagnosis and Treatment of Neonatal Seizures

Novel Therapeutics for Neonatal Seizures

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