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Phenytoin monitoring in status epilepticus in infants and children
M O Richard1, C Chiron, P d'Athis
1Département de Pharmacologie Périnatale et Pédiatrique, Hôpital Saint-Vincent de Paul, Paris, France.
Insights
Monitoring phenytoin (PHT) plasma levels is crucial for treating status epilepticus (SE) in children. Adjusting PHT doses based on concentration prevents overdosage and improves treatment efficacy, especially in younger patients.
Area of Science:
- Pediatric Neurology
- Clinical Pharmacology
- Epileptology
Background:
- Status epilepticus (SE) in children requires effective pharmacological management.
- Phenytoin (PHT) is a common antiepileptic drug used in SE treatment.
- Optimizing PHT dosing is essential to balance efficacy and toxicity.
Purpose of the Study:
- To evaluate two protocols for phenytoin (PHT) plasma concentration monitoring in pediatric status epilepticus (SE).
- To determine the impact of dose adjustments based on plasma PHT levels on treatment outcomes.
- To investigate the relationship between PHT concentrations, age, and treatment response in children with SE.
Main Methods:
- A study involving 60 children with SE, comparing two PHT dosing protocols.
- Protocol 1: Loading dose followed by three injections, with adjustments at 4 hours based on plasma PHT levels.
- Protocol 2: Similar to Protocol 1, but with additional dose monitoring at 16 and 24 hours to prevent PHT accumulation.
Main Results:
- Protocol 1 showed variable PHT concentrations, with higher levels in patients with partial effect.
- Protocol 2 demonstrated more consistent PHT levels within the therapeutic range, with lower concentrations in non-effect patients.
- Younger children in both protocols exhibited lower PHT concentrations and poorer treatment response.
Conclusions:
- Phenytoin (PHT) dosing in pediatric status epilepticus (SE) requires careful adjustment based on plasma concentration monitoring.
- Optimized PHT monitoring can prevent overdosage and paradoxical inefficacy.
- Age and potentially the etiology of SE are important factors influencing PHT response in children.
Abstract:
Two successive protocols of phenytoin (PHT) plasma concentration monitoring were tested in 60 children with status epilepticus (SE). In each protocol, a loading dose of 15 mg/kg was injected and followed by three injections during the first 24 h. Clinical evaluation was performed at the end of the study by grouping patients into three classes according to seizure frequency during treatment: complete effect, partial effect, and no effect. In protocol 1, a complementary dose at the fourth hour was adjusted from individual plasma concentrations. Plasma concentrations at the 40th hour were within the therapeutic range in the 19 patients with complete effect (CE, mean 19 mg/L) and in the 5 patients with no effect (NE, mean 23 mg/L) whereas in the 11 patients with partial effect (PE), plasma concentrations were higher (mean 31 mg/L). In protocol 2, we added monitoring of the doses injected at the 16th and 24th hours to prevent the increase in PHT concentration noted in protocol 1. All patients but 1 were classified as either CE (13 patients) or NE (4 patients). In NE patients, average plasma concentration at the 40th hour (mean 10.5 mg/L) was lower than in CE patients (mean 15.7 mg/L). In both protocols, the NE patients were the youngest. In SE, PHT doses should be adjusted according to plasma concentrations to avoid overdosage and paradoxical inefficacy. Younger children had lower concentrations and appeared to respond less well than older children, but the etiology of SE may also play an important role.
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