Treatment of pediatric refractory status epilepticus with topiramate.
ABSTRACT We evaluated a topiramate (TPM) regimen for treating refractory status epilepticus in the largest pediatric series, reported to date.
Fourteen patients received TPM via the nasogastric route. Initially, all patients received TPM as a 5 mg/kg loading dose followed by 5 mg/kg/day in two doses as maintenance. Thereafter, patients were divided into three groups based on the response to TPM therapy and seizure cessation time (full responder, partial responder, and nonresponder). Four patients received only thiopental, two received thiopental, and high-dose midazolam, one received thiopental, high-dose midazolam, and propofol, two received only propofol, one received propofol, and high-dose midazolam and four patients were on a high-dose midazolam infusion.
The median time to seizure cessation was 5.5 h (range 2-48 h). Nine patients were full responders, three were partial responders, and two were nonresponders At follow-up, six patients were weaned successfully from thiopental, two patients from high-dose midazolam and three patients from propofol. Three patients developed mild metabolic acidosis during TPM theraphy.
Most of the patients responded to this treatment which was well tolerated. So we recommended its use for terminating refractory status epilepticus in children.
- SourceAvailable from: Raoul Christian Sutter[Show abstract] [Hide abstract]
ABSTRACT: Refractory status epilepticus (RSE) is the most severe manifestation of status epilepticus (SE), often requiring intensive care and therapeutic coma. It is associated with prolonged intensive care unit (ICU) and hospital stays, as well as increased morbidity and mortality. Treatment involves both intravenous anaesthetics and antiepileptic drugs (AEDs) that can be administrated intravenously, by nasogastric tube or by percutaneous endoscopic gastrostomy. Experience with some of the newer AEDs for the treatment of RSE is restricted and higher-class evidence regarding tolerability and efficacy is lacking. Topiramate is a potent broad-spectrum AED with several modes of action, including blockade of the ionotropic glutamatergic AMPA receptor, which is likely to be an important mechanism for the treatment of SE. While there is no commercially available intravenous formulation, topiramate can be administered enterally, which may make it suitable for the treatment of RSE. The objective of this study was to evaluate the tolerability, safety profile and efficacy of adjunctive and enterally administered topiramate in patients with RSE. A medical chart review was performed of all consecutive patients treated for RSE between August 2004 and December 2011 at the ICU of the University Hospital Basel (Basel, Switzerland). Results: 113 (43%) of all consecutive 268 patients with SE developed RSE. Of those, 35 (31%) were treated with topiramate. Median age was 60.5 years. Topiramate was used as an add-on treatment after 1-6 (median 4) prior administered AEDs had failed. It was introduced after a median of 2 (range 2-23) days for a duration of 1-24 (median 3) days. The response rate after topiramate administration as the third AED was 86% (6/7 patients), and remained stable at 67% after administration as the fourth, fifth, sixth or seventh AED when the groups of successfully and probably successfully treated patients were pooled. Overall, RSE was terminated in 71% of patients within 72 hours after first administration of topiramate, in 9% of patients, within 24 hours (none in the 800 mg/day group; 9% in the 400-799 mg/day group; and 11% in the <400 mg/day group). Mortality was 31% and was not strictly dependent on failure to terminate RSE, but also on the underlying aetiology of RSE. There were no serious or fatal adverse events directly attributable to topiramate. Adverse effects included slight hyperchloremic acidosis and hyperammonemia (all associated with co-medication with valproic acid). Treatment with enterally administered topiramate was feasible, well tolerated and had a good safety profile in patients with RSE in this observational, single-centre, cohort study. Refractory SE was terminated in the majority of patients within 3 days after initiation of topiramate. Prospective studies are warranted to further evaluate topiramate for the treatment of RSE.CNS Drugs 07/2012; 26(9):761-772. · 4.38 Impact Factor
Article: Pediatric seizures.[Show abstract] [Hide abstract]
ABSTRACT: Seizures are a commonly encountered condition within the emergency department and, because of this, can engender complacency on the part of the physicians and staff. Unfortunately, there is significant associated morbidity and mortality with seizures, and they should never be regarded as routine. This point is particularly important with respect to seizures in pediatric patients. The aim of this review is to provide a current view of the various issues that make pediatric seizures unique and to help elucidate emergent evaluation and management strategies.Emergency medicine clinics of North America 08/2013; 31(3):733-54. · 0.96 Impact Factor
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ABSTRACT: The Italian League Against Epilepsy Commission Guidelines Subcommittee on Status Epilepticus (SE) has published an article on the management of SE in adults, and now presents a report on the management of convulsive status epilepticus (CSE) in children, excluding the neonatal period. Children's greater susceptibility than adults to epileptic seizures results from many factors. Earlier maturation of excitatory than inhibitory synapses, increased susceptibility and concentration of receptors for excitatory neurotransmitters, peculiar composition of the receptor subunits resulting in slower and less effective inhibitory responses, all cause the high incidence of SE in the pediatric population. The related morbidity and mortality rates, although lower than in adults, require immediate diagnosis and therapy. The division into focal and generalized, nonconvulsive and convulsive SE is applied in children and adolescents, as is the distinction in the three different stages according to the time elapsed since the start of the event and the response to drugs (initial, defined, and refractory SE). In children and adolescents, an "operational definition" is also accepted to allow earlier treatment (starting at 5-10 min). Maintenance and stabilization of vital functions, cessation of convulsions, diagnosis, and initial treatment of potentially "life-threatening" causes are the objectives to be pursued in the management of children with CSE. The need for early pharmacologic intervention stresses the need for action in the prehospital setting, generally using rectal diazepam. In hospital, parenteral benzodiazepines are used (lorazepam, diazepam, or midazolam). When first-line drugs fail, sodium phenytoin and phenobarbital should be used. As alternatives to phenobarbital, the following can be considered for treatment of refractory CSE: valproate, levetiracetam, and lacosamide. In cases with refractory CSE, pharmacologic options can be thiopental, midazolam, or propofol in continuous intravenous infusions to suppress electroencephalographic bursts and convulsive activity. These drugs need to be administered in intensive care units to ensure the monitoring and support of vital signs and brain electrical activity.Epilepsia 10/2013; 54(suppl 7):23-34. · 3.91 Impact Factor