Pharmacological Treatment of Neonatal Seizures

Slaughter, Laurel A.; Patel, Anup D.; Slaughter, Jonathan L.

doi:10.1177/0883073812470734

Cited by 98 publications

(69 citation statements)

References 50 publications

(146 reference statements)

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“…There are no evidence-based guidelines for the pharmacological management of neonatal seizures [48, 49]. Expert opinion supports use of pharmacological treatments with a goal of abolishing electrographic seizures, even those without clinical correlate [42].…”

Section: Pharmacologic Strategiesmentioning

confidence: 99%

Neonatal Seizures

Glass

2014

Clinics in Perinatology

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Synopsis Seizures occur in approximately 1–5 per 1,000 live births, and are among the most common neurologic conditions managed by a neonatal neurocritical care service. There are several, age-specific factors that are particular to the developing brain, which influence excitability and seizure generation, response to medications, and impact of seizures on brain structure and function. Neonatal seizures are often associated with serious underlying brain injury such as hypoxia-ischemia, stroke or hemorrhage. Conventional, prolonged, continuous video-electroencephalogram (cEEG) is the gold standard for detecting seizures, whereas amplitude-integrated EEG (aEEG) is a convenient and useful bedside tool. Evaluation of neonatal seizures involves a thorough search for the etiology of the seizures, and includes detailed clinical history, routine chemistries, neuroimaging (and preferably magnetic resonance imaging, MRI), and specialized testing such as screening for inborn errors of metabolism if no structural cause is identified and seizures persist after correction of transient metabolic deficits. Expert opinion supports rapid medical treatment to abolish electrographic seizures, however the relative risk versus benefit for aggressive medical treatment of neonatal seizures is not known. While there is increasing evidence to support a harmful effect of seizures on the developing brain, there is also evidence that commonly used medications are potentially neurotoxic in animal models. Newer agents appear less harmful, but data are lacking regarding optimal dosing and efficacy.

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Section: Pharmacologic Strategiesmentioning

confidence: 99%

Neonatal Seizures

Glass

2014

Clinics in Perinatology

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“…There are no evidenced-based guidelines for initiating or switching antiseizure drugs (ASDs) for HI-related seizures [10, 11]. In 1 large study involving 31 children's hospitals in the USA, 62% of infants were treated initially with a single nonbenzodiazepine ASD and 16% were treated with ≥ 2 nonbenzodiazepine ASDs (an interhospital range of 48–76 and 6–35%, respectively) [12].…”

Section: Introductionmentioning

confidence: 99%

EEG Monitoring Technique Influences the Management of Hypoxic-Ischemic Seizures in Neonates Undergoing Therapeutic Hypothermia

et al. 2017

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Electroencephalogram (EEG) monitoring techniques for neonatal hypoxia-ischemia (HI) are evolving over time, and the specific type of EEG utilized could influence seizure diagnosis and management. We examined whether the type of EEG performed affected seizure treatment decisions (e.g., the choice and number of antiseizure drugs [ASDs]) in therapeutic hypothermia-treated neonates with HI from 2007 to 2015 in the Johns Hopkins Hospital Neonatal Intensive Care Unit. During this period, 3 different EEG monitoring protocols were utilized: Period 1 (2007-2009), single, brief conventional EEG (1 h duration) at a variable time during therapeutic hypothermia treatment, i.e., ordered when a seizure was suspected; Period 2 (2009-2013), single, brief conventional EEG followed by amplitude-integrated EEG for the duration of therapeutic hypothermia treatment and another brief conventional EEG after rewarming; and Period 3 (2014-2015), continuous video-EEG (cEEG) for the duration of therapeutic hypothermia treatment (72 h) plus for an additional 12 h during and after rewarming. One hundred and sixty-two newborns were included in this retrospective cohort study. As a function of the type and duration of EEG monitoring, we assessed the risk (likelihood) of receiving no ASD, at least 1 ASD, or ≥2 ASDs. We found that the risk of a neonate being prescribed an ASD was 46% less during Period 3 (cEEG) than during Period 1 (brief conventional EEG only) (95% CI 6-69%, p = 0.03). After adjusting for initial EEG and MRI results, compared with Period 1, there was a 38% lower risk of receiving an ASD during Period 2 (95% CI: 9-58%, p = 0.02) and a 67% lower risk during Period 3 (95% CI: 23-86%, p = 0.01). The risk ratio of receiving ≥2 ASDs was not significantly different across the 3 periods. In conclusion, in addition to the higher sensitivity and specificity of continuous video-EEG monitoring, fewer infants are prescribed an ASD when undergoing continuous forms of EEG monitoring (aEEG or cEEG) than those receiving conventional EEG. We recommend that use of continuous video-EEG be considered whenever possible, both to treat seizures more specifically and to avoid overtreatment.

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“…electrolyte imbalance, metabolic abnormalities, infection, or other). 19,20 Phenobarbital and phenytoin were found to be equally effective in a randomized control trial of 59 neonates with seizures. 21 Both drugs were effective in less than half of these infants, and the neonates with normal or moderately abnormal EEG were most likely to respond.…”

Section: Diagnosis (Of Clinical and Electrographic Seizures)mentioning

confidence: 99%

“…Midazolam bolus and infusion is recommended as a third line of treatment for refractory seizures. 19,20,[23][24][25][26] The response to treatment is variable, and so is the treatment practice amongst neonatologists and neurologists. 20,[27][28][29] There is ongoing research into the use of topiramate and bumetanide for the treatment of neonatal seizures.…”

Section: Diagnosis (Of Clinical and Electrographic Seizures)mentioning

confidence: 99%

Neonatal seizures in hypoxic–ischaemic encephalopathy – risks and benefits of anticonvulsant therapy

Shetty

2015

Develop Med Child Neuro

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The risk of seizures is at its highest during the neonatal period, and the most common cause of neonatal seizures is hypoxic–ischaemic encephalopathy (HIE). This enhanced vulnerability is caused by an imbalance in the expression of receptors for excitatory and inhibitory neurotransmission, which is age dependent. There has been progress in detecting the electrophysiological abnormalities associated with seizures using amplitude‐integrated electroencephalography (aEEG). Data from animal studies indicate a variety of risk factors for seizures, but there are limited clinical data looking at the long‐term neurodevelopmental consequences of seizures alone. Neonatal seizures are also associated with increased risk of further epileptic seizures; however, it is less clear whether or not this results from an underlying pathology, and whether or not seizures confer additional risk. Phenobarbital and phenytoin are still the first‐line antiepileptic drugs (AEDs) used to treat neonatal seizures, although they are effective in only one‐third of affected infants. Furthermore, based on findings from animal studies, there are concerns regarding the risks associated with using these AEDs. Clinicians face a difficult challenge because, although seizures can be easily identified using aEEG, treatment options are limited, and there are uncertainties regarding treatment outcomes. There is a need to obtain long‐term follow‐up data, comparing groups of infants treated with or without current therapies. If these analyses indicate a definite benefit of treating neonatal seizures, then novel therapeutic approaches should be developed.

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Pharmacological Treatment of Neonatal Seizures

Cited by 98 publications

References 50 publications

Neonatal Seizures

Neonatal Seizures

EEG Monitoring Technique Influences the Management of Hypoxic-Ischemic Seizures in Neonates Undergoing Therapeutic Hypothermia

Neonatal seizures in hypoxic–ischaemic encephalopathy – risks and benefits of anticonvulsant therapy

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