Pharmacological management of convulsive status epilepticus in children

Abstract

Convulsive status epilepticus (CSE) is the most common medical neurological emergency and continues to be associated with significant morbidity and mortality. The two primary determinants of outcome from CSE are underlying aetiology and seizure length. It is unclear whether a prolonged seizure worsens the prognosis of an underlying aetiology or whether a more severe underlying disorder is more likely to result in CSE 1 . Acceptance of the former hypothesis means that seizures need rapid treatment as their early termination could potentially reduce brain damage and morbidity. Pathophysiology, epidemiology, and outcomes from CSE have recently been reviewed elsewhere 2 .Treatment of acute seizures is most effectively carried out by parents/carers or paramedics in the prehospital setting. In the hospital setting, management of CSE may be considered to be analogous to management of cardiac arrest in that a structured series of interventions is likely to be more successful than a haphazard approach. Our enquiries suggest that hospitals lack structured guidelines. Thus guidelines on prehospital and hospital management are required and should contain general and child-specific points. Locally generated clinical guidelines on the hospital management of CSE are likely to improve treatment. (A proposed protocol is shown in Figure 1.) It is essential that appropriate doses of the chosen anticonvulsant are administered; inadequate dosage is the most common reason for seizures continuing after an initial dose of medication. It is important for all acute units to have access to ITU facilities as a small proportion of children will have CSE associated with a severe systemic or neurological disorder, CSE refractory to firstline anticonvulsant agents, or respiratory depression as a consequence of treatment.This article aims to provide adequate information for the development of clinical guidelines as well as providing an update on newer medications used in the treatment of CSE. Prehospital treatmentSeizures treated early in their course are more likely to stop than those treated later, but most seizures begin some way from a hospital 3,4 . As the systemic changes associated with CSE (hypertension, hypoxia, and tachycardia) are usually a direct result of the seizure, termination of the seizure will usually correct these abnormalities. Children usually have normal cardiorespiratory function and so pharmacological treatment of seizures without monitoring cardiorespiratory parameters is justified in the prehospital setting. As parenteral administration of anticonvulsants is not feasible, rectal diazepam has been introduced into clinical practice. Rapid absorption through the haemorrhoidal veins and then across the blood-brain barrier occurs, therapeutic levels are reached within 5 minutes and peak levels within 20 minutes after administration 4 . Approximately 80% of seizures will stop if the treatment is administered within 15 minutes of the start of the seizure compared with approximately 60% if the drug is administered after this ...

Comparison of Buccal Midazolam With Rectal Diazepam in the Treatment of Prolonged Seizures in Ugandan Children: A Randomized Clinical Trial

“…A recent study showed that intranasal lorazepam was as effective as intramuscular paraldehyde in stopping seizures in Malawi 28 ; however, both of these agents have important drawbacks, including high cost and need for refrigeration of parenteral lorazepam and risk for sterile abscesses with intramuscular paraldehyde. 16,29 Considering available options, buccal midazolam seems to be the superior simple therapy for prolonged seizures in African children.…”

“…The difference between diazepam and midazolam was likely attributable to the shorter duration of action of diazepam in the brain (active half-life of diazepam: ϳ1 hour), 30 which is explained by the rapid decline in diazepam brain concentration levels during the redistribution of diazepam from cerebral gray matter into white matter, brainstem, and body fat. 14,16 The active half-life of midazolam is 2 to 3 hours in healthy children and Ͼ 5 hours in very ill children. [31][32][33] The benefits of buccal midazolam were pronounced in children who did not have malaria diagnosed at the time of presentation with seizures, but there was no difference in efficacy in children who had convulsions associated with malaria.…”

“…16,17 This is of particular concern in units without infrastructure to provide ventilatory support. An additional concern is that a combination of diazepam, in multiple doses, and phenobarbital has been associated with an increased risk for mortality from respiratory depression in children with cerebral malaria.…”

Autonomic Status Epilepticus in Panayiotopoulos Syndrome and Other Childhood and Adult Epilepsies: A Consensus View

“…This has a particular justification when applied to tonic–clonic SE as experimental evidence shows that “decompensation” is unlikely before 30 min but becomes increasingly likely thereafter. However, because of clinical and pathophysiological evidence that tonic–clonic seizures lasting more than 5–10 min were different from shorter seizures and because it would not be appropriate to delay treatment of such seizures until 30 min, it has been argued that the “cutoff” time should be 10 or even 5 min (Scott and Neville, 1999; Chen and Wasterlain, 2006).…”

The Acute Anticonvulsant Effects of Deoxycorticosterone in Developing Rats: Role of Metabolites and Mineralocorticoid‐receptor Responses

“…Corticosteroids appear to be proconvulsant in adults with epilepsy (2,3). They are anticonvulsant, however, in children with seizure disorders such as infantile spasms and the Lennox–Gastaut syndrome (4–6). The reasons for these age‐related differences may relate to age‐dependent changes in the brain receptors that bind adrenal corticosteroids—the mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) (7).…”