Treatment Of Convulsive Status Epilepticus Research Articles

Treatment of convulsive status epilepticus in childhood: Recommendations of the Italian League Against Epilepsy

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.

P48 – 1793 Treatment of convulsive status epilepticus in the UMCG: a retrospective, observational study

Objectives: Little is known about clinical practice with respect to the application of guidelines in the treatment of Convulsive Status Epilepticus (CSE). This retrospective, observational study evaluated treatment of episodes of CSE in children at the University Medical Centre Groningen (UMCG). Material and methods: Episodes of CSE were derived from the UMCG database of children with epilepsy aged 1 month. Treatments used in the UMCG were compared with recommendations from two most recent Dutch treatment guidelines for CSE in children aged >1 month. Results: 269 episodes of CSE occurring in 69 children (53.6% male, median age 4.3 years; range 0.1-16.3 years) were included; 219 (81.4%) of the episodes started outside the hospital, 118 (43.9%) had remote symptomatic aetiology, 96 (35.7%) were accompanied by fever. Half of the CSE episodes lasted

The historical evolution of, and the paradigms shifts in, the therapy of convulsive status epilepticus over the past 150 years

The evolution of the treatment of convulsive status epilepticus since the mid- nineteenth century is outlined. Therapy has been advanced not only by the use of new drugs, but also by advances in the approach to therapy. The major pharmacologic developments were the introductions of bromide, anesthetics, barbiturate, phenytoin, paraldehyde, chlormethiazole, and the benzodiazepines. Throughout this period, the emphasis of therapy was on "sedation" and anesthesia, and the development of technologies for safe anesthesia in the postwar years were an important step. Since 1970, changes to the approach to therapy have been more important than any pharmacologic advance, and it is only recently that new drugs have been introduced into the therapy of status epilepticus. We may now be on the threshold of significant new paradigm shifts.

Treatment of convulsive status epilepticus in children

Treatment of convulsive status epilepticus in children

Estado de mal convulsivo. Protocolo terapêutico.

Convulsive status epilepticus (CSE) in a medical emergency with a prognosis associated to its duration, claiming an early and effective treatment. The authors present the treatment protocol proposed at the Hospital de Santa Maria. The chosen definition of CSE allows its rapid treatment, and the electroencephalographic record the monitoring of its real efficacy. The treatment protocol is initiated whenever there are: continuous seizures persisting for more than 5 min, or two or more seizures surveying without regain of consciousness between them. The goal is stopping convulsive activity in less than 30 min and interrupting any epileptiform electroencephalographic activity. The initial pharmacological treatment of CSE includes lorazepam and fosphenitoin, a phenitoin prodrug. The first is chosen by the longer duration of its antiseizure effect as compared with diazepam; the second allows the administration of an identical dose but in a shorter period of time as compared to the mother drug; besides, it has few local and systemic effects and can be given intramuscularly after stopping the CSE. Drugs with a rapid clinical effect and rapid clearance, as midazolam and propofol should be used for treating refractory SE. Pentobarbital is the last anesthetic drug to be used because of its adverse cardiovascular effects and long-lasting action which can delay weaning from ventilatory support.

Established Status Epilepticus Treatment Trial (ESETT)

Phenytoin (PHT) has been the standard treatment for convulsive status epilepticus (SE) where initial benzodiazepines have failed for many years, despite that it has many limitations in the emergency situation. Valproate (VPA) and levetiracetam (LEV) are emerging as potentially superior alternatives, and there is an urgent need for an adequately powered comparative randomized controlled trial (RCT). An international group, having not succeeded in obtaining funding from the United Kingdom in 2010, is now preparing a revised proposal for submission to the National Institute of Neurological Disorders and Stroke (NINDS) to undertake a blinded comparative RCT using an adaptive design. This will be necessarily international and multicenter, requiring up to 1,500 patients from over 50 centers, and if successful will commence recruiting in 2012. The primary outcome, agreed from the 2009 SE workshop as pragmatic, generalizable, and clinically meaningful, will be cessation of seizures without need for other drug or sedation, and without serious adverse events, maintained for at least 2 h.

La prise en charge d’urgence due patient pédiatrique en état de mal épileptique convulsif généralisé

The present guideline paper addresses the emergency management of generalized convulsive status epilepticus (CSE) in children and infants older than one month of age. It replaces the previous statement from 1996, and includes a new treatment algorithm and table of recommended medications, reflecting new evidence and the evolution of clinical practice over the past 15 years. The document focuses on the acute pharmacological management of CSE, but some issues regarding supportive care, diagnostic approach and treatment of refractory CSE are discussed.

Emergency management of the paediatric patient with generalized convulsive status epilepticus

The present guideline paper addresses the emergency management of generalized convulsive status epilepticus (CSE) in children and infants older than one month of age. It replaces the previous statement from 1996, and includes a new treatment algorithm and table of recommended medications, reflecting new evidence and the evolution of clinical practice over the past 15 years. The document focuses on the acute pharmacological management of CSE, but some issues regarding supportive care, diagnostic approach and treatment of refractory CSE are discussed.

Convulsive status epilepticus in children: Etiology, treatment protocol and outcome

This study aimed to determine the etiology, treatment protocol and outcome of convulsive status epilepticus (SE) in children. An institutional treatment protocol using benzodiazepines (diazepam and midazolam) was assessed in a retrospective case study. The treatment protocol (Ege Pediatric Status Epilepticus Protocol or EPSEP) was developed based on an operational definition of pediatric SE according to the duration of seizure activity. Pediatric SE is divided into three categories: initial SE (20–30 min), established SE (30–60 min) and refractory SE (>60 min). Eight (30%) of the studied episodes were initial SE, 10 (37%) were established SE, and 9 (33%) were refractory SE. With respect to the etiological spectrum of SE, 11 (40%) children had meningitis or encephalitis. Febrile SE was identified in 7 (26%) patients. Only 2 episodes of initial SE (7.5%) were controlled with first step of the protocol (two concomitant-doses of rectal diazepam). Midazolam bolus and infusions (up to 1.2 μg/kg/min) were used to treat 22 episodes of SE (9 refractory SE, 10 established SE and 3 initial SE). Complete arrest of convulsive SE was achieved in 21 of 22 (95%) episodes with midazolam infusion. We concluded that the combined use of benzodiazepines (diazepam + midazolam) was safe and effective in the treatment of convulsive SE in children.

Adult convulsive status epilepticus in the developing country of Honduras

Epidemiologic data on convulsive status epilepticus (CSE) is needed to develop preventative strategies. Epilepsy is one of the known risk factors for CSE. A systematic review of epidemiologic studies on status epilepticus (SE) completed in the United States and Europe reports that people with epilepsy account for less than 50% of cases of SE in all age groups. Less is known about the epidemiology of SE in developing countries including those in Central America. A high incidence of epilepsy, widespread non-adherence to anti-epileptic drugs (AED), and common use of complementary and alternative medicines have been shown in all ages in the developing country of Honduras, Central America. In 2003, an epidemiologic study of CSE in Honduran children demonstrated it is common and exhibits a long duration until onset of treatment. The etiologies, treatment, and outcomes of CSE in Honduran adults have not been thoroughly studied. This study is a consecutive case series of 31 adult patients presenting with CSE to the adult medicine emergency department of the tertiary care “Hospital Escuela” in the capital city Tegucigalpa, Honduras. The majority (77.4%) of patients had a prior history of epilepsy. Non-adherence to AED was the most common etiology of CSE (75.0%). The mortality rate in this pilot CSE study was 14.8%, which is similar to studies from industrialized countries where mortality from status epilepticus ranged from 7.6 to 22% for all age groups. However, this rate is concerning given that CSE from epilepsy and AED non-adherence generally carries a good prognosis. Improving AED adherence in this population appears to be the most effective approach in decreasing the rate, and possibly the mortality of Honduran adult CSE.

Successful treatment for refractory convulsive status epilepticus by non‐parenteral lacosamide

Lacosamide (Vimpat) is a newly licensed novel antiepileptic drug. We report a case of refractory convulsive status epilepticus (CSE) that was successfully controlled with lacosamide. The 38-year-old male patient was admitted for a series of complex partial seizures with secondary generalization leading to refractory CSE. During the transport to the hospital the patient was given 22.5 mg diazepam, 12.5 mg etomidate, and 5 mg midazolam without success. An additional dose of 4 mg lorazepam and a dose of 1,500 mg levetiracetam after admission were yet without clinical effect. A further treatment with lacosamide (300 mg via percutaneous gastric fistula) resulted in complete clinical remission of the epileptic activity within 30 min. The application of lacosamide resulted in cessation of CSE and was well tolerated. To our knowledge, this is the first case of successful treatment of refractory CSE with lacosamide. Further studies are needed to evaluate the safety and efficacy of lacosamide in treatment of SE.

Lorazepam versus diazepam–phenytoin combination in the treatment of convulsive status epilepticus in children: A randomized controlled trial

Lorazepam versus diazepam–phenytoin combination in the treatment of convulsive status epilepticus in children: A randomized controlled trial

Status epilepticus in resource‐poor countries

Status epilepticus is common in patients admitted to hospitals in resource poor countries (RPC). However, there appear to be differences in the epidemiology, aetiology and outcome of status epilepticus in these regions compared to the West, although there is little data from the former regions. RPC countries are those classified by the World Bank as low income or middle-low income countries encompass those situated in the tropical and subtropical regions. The International League Against Epilepsy (ILAE) definition of status epilepticus (ILAE, 1993) is problematic in these areas, since patients often present to health facilities, without adequate documentation of the duration of convulsion. Thus more pragmatic definitions have been developed (Sadarangani et al., 2008). Most studies on status epilepticus in RPC describe convulsive status epilepticus (CSE) (Misra et al., 2008;Sadarangani et al., 2008), since non-convulsive epilepticus is rarely detected in these regions. Although one study non-convulsive status epilepticus was detected in 11% of adults with altered mental status (Narayanan and Murthy, 2007). The incidence of convulsive status epilepticus appears to be higher in RPC than the West, but there has been only one epidemiological study conducted. In this study, the incidence of children fulfilling the ILAE definition of CSE who presented to a Kenyan District General Hospital was 35/100,000/year, with 268/100,000/year in children aged 1-11 months old. The incidence is higher if those with probable epilepsy are also included (35/100,000/year, with 268/100,000/year). These figures are likely to be an underestimate; since many children with CSE are not admitted hospital, either because convulsions are thought to be caused by traditional causes or the children die before they reach hospital. Thus the rate in this area of Kenya is 2-5 times that of similar study in London, United Kingdom (Chin et al., 2006). CSE appears to be more common in children than adults; mainly because acute symptomatic seizures or febrile status epilepticus are more common, particularly in RPC(Sadarangani et al., 2008;Tabarki et al., 2001). A significant proportion of people with epilepsy in RPC have an episode of CSE, usually in childhood and often as the first reported seizure. Thus in a cross-sectional study of active convulsive epilepsy in Kenya, 35% of those identified with active convulsive epilepsy had a history of prolonged seizures (probable CSE), of which 75% were associated with a febrile illness(Edwards et al., 2008). Thus, the high incidence of acute symptomatic epilepsy in many RPC may account for the increased incidence and prevalence of epilepsy in these regions. Most CSE is symptomatic, with the increased incidence attributed to the increased incidence of infections (Misra et al., 2008;Sadarangani et al., 2008). In malaria endemic areas, malaria is an important cause of CSE in children (Sadarangani et al., 2008), whist bacterial meningitis and viral encephalitis are important causes in other areas (Murthy et al., 2007). Patients appear to be in status for longer periods, although there is little reliable data on the duration of CSE in patients presenting to hospital. The increase duration may be due to the lack of treatment prior to admission to hospital, inadequate treatment on admission to hospital and/or a reduction in the responsiveness to the benzodiazepines. The mortality associated with CSE in RPC is greater (11-15%), both in adults (Murthy et al., 2007) and children (Sadarangani et al., 2008); but the long-term outcome in terms of premature mortality and neurocognitive sequelae is undetermined. Risk factors for mortality i.e. young age (< 1 years), aetiology (particularly bacterial meningitis), focal seizures and duration of seizure, are similar to the West. The neuro-cognitive outcome of CSE appears worse with 36% of Tunisian children having intellectual disability or epilepsy (Tabarki et al., 2001). The risk factors for neuro-cognitive impairment include young age (<1 year), focal seizures. Many hospitals in RPC, particularly those in rural areas have few drugs to treat CSE, and many hospitals do not have intensive care facilities such as ventilators or sufficient staff to provide optimal management. The antiepileptic drugs are limited to benzodiazepines, particularly Diazepam and Phenobarbital. However, the response to diazepam appears poorer in many areas, either because the patients present with seizures lasting many hours or possibly the aetiology such as malaria makes them more resistant to these compounds. The treatment of CSE in RPC is further complicated by the lack of rectal preparations of diazepam (parenteral preparation is often used, but has erratic absorption (Ogutu et al., 2002)) and lack of supply of parenteral Phenobarbital (Wilmshurst and Newton, 2005). These issues may affect the outcome. Thus, CSE appears to be more common, with a worse outcome in RPC than in the West; but at present, there is little data on which to base the burden and recommendations of treatment in these countries.

Pearls &amp; Oy-sters: Soft-tissue necrosis as a result of intravenous leakage of phenytoin

1. Phenytoin leakage can cause potentially serious side effects ranging from mild edema to soft-tissue necrosis. 2. To avoid such events, one should consider using: 1. a dedicated IV catheter inserted in a large peripheral vein to infuse phenytoin; 2. administration rate ≤50 mg/min; 3. periodic flushing with saline after each bolus; 4. continuous monitoring for signs of extravasation, hypotension, and bradycardia. 3. The ease of administration, rapid onset of action, minimal morbidity, and IV solution compatibility are potential advantages of some of the second-line anticonvulsant agents, like valproate. In the past 70 years, phenytoin (PHT) has been used in the management of seizures and remains, despite the advent of newer antiepileptic drugs,1 one of the preferred long-acting antiepileptic drugs in the treatment of convulsive status epilepticus.2 Injury due to PHT leakage may result in damage ranging from simple, mild phlebitis to severe lesions such as soft tissue necrosis.3,4 Up to 20% of IV administration of all drugs results in recognized episodes of extravasation.5 Nevertheless, few studies address the adverse events associated with the IV use of PHT.2,6 Factors believed to affect the extent of injury include the …

The clinical feature and prognosis predictors associated with outcome for convulsive status epilepticus children

Objective To investigate the clinical manifestation of convulsive status epilepticus (CSE) associated with the outcome of children contracted this illness in order to make an effort to prevent and treat those children. Method The patients with CSE admitted from October 1998 to October 2008 were prospectively and consecutively enrolled. All the patients met the diagnostic criteria set by International Anti-epilepsy Union (ILAE) in 1993. The prognosis predictors of outcome were analyzed with the Rank sum test, Chi-square analysis and Logistic regression analysis. Results A total of 169 patients with CSE were enrolled. Of them, 92 patients were from rural areas (54.4% ). The primary cause was central nervous system infection, and the minor ones were a reduction of dose or withdrawal of the antiepileptics, and cerebral hemorrhage. The duration of CSE before treatment was longer in rural patients than in urban residents ( P < 0.01) . The duration of CSE before treatment and the total persistence time of CSE was significantly associated with the mortality 14.2% . The source of patients, the duration before treatment, and respiratory depression were independent prognostic predictor variables of CSE (P < 0.05) .Conclusions The rural patients account for the major ratio of convulsive status epilepticus. Central nervous system infection is the primary cause. The duration before treatment and total persistence time of CSE are highly related to the mortality and morbidity. Key words: Children; Eclampsia; Status epilepticus; Prognosis

Lorazepam versus diazepam–phenytoin combination in the treatment of convulsive status epilepticus in children: A randomized controlled trial

Background Convulsive status epilepticus demands urgent and appropriate management with anticonvulsants. Intravenous diazepam is an established drug in the management of convulsive status epilepticus in adults as well as in children. The efficacy of intravenous lorazepam has not been well established in children. Objective To determine whether intravenous lorazepam is as efficacious as diazepam–phenytoin combination in the treatment of convulsive status epilepticus in children. Study design Randomized controlled trial. Methods A total of 178 children were enrolled in the study; 90 in the lorazepam group and 88 in the diazepam–phenytoin combination group. Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus, presenting in pediatric emergency of a tertiary care hospital. They were randomized to receive either intravenous lorazepam (0.1 mg/kg) or intravenous diazepam (0.2 mg/kg)–phenytoin (18 mg/kg) combination at admission and were followed up for subsequent 18 h. Results The overall success rate of therapy was 100% in both the groups. There was no statistically significant difference in the two groups (lorazepam versus diazepam–phenytoin combination) in the median time taken to stop the seizure [20 s in both groups], the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(6.7%) versus diazepam–phenytoin combination: 14 (15.9%); adjusted RR (95% CI) = 0.377 (0.377, 1.046); P = 0.061] and the number (%) of patients having respiratory depression [lorazepam 4(4.4%) versus diazepam–phenytoin combination 5 (5.6%)]. None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure. No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimen. Conclusion Lorazepam is as efficacious and safe as diazepam–phenytoin combination. We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam–phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus.

An audit of treatment of convulsive status epilepticus

An audit of treatment of convulsive status epilepticus

Introduction–Decision points in epilepsy: Bedside to bench

Introduction–Decision points in epilepsy: Bedside to bench

Treatment of convulsive status epilepticus in infants and young children in Japan

We review the types and causes of convulsive status epilepticus (CSE) in infants and young children in Japan, and discuss the current recommendations for the use of intravenous (IV) drugs in managing this condition, and report on our clinical experiences. There are prolonged or continuous CSE and clustered or intermittent CSE, and treatments are different between them. In Japan, fosphenytoin and IV preparation of lorazepam and phenobarbital are not available. Recently, midazolam and lidocaine (LDC) have been widely used, although neither of these drugs have official approval for the management of CSE. Febrile seizures and epilepsies are common causes of CSE in infants and young children in Japan, followed by benign infantile convulsions (BIC), convulsions with gastroenteritis (CwG), and acute encephalitis with refractory CSE and intractable epilepsy (AECSEE), which are familiar disorders in Japan. BIC and CwG frequently present with clustered CSE and do not respond to IV diazepam, but have an excellent response with oral carbamazepine or IV LDC. CSE in AECSEE requires control with barbiturate coma. The Research Committee on Clinical Evidence of Medical Treatment for Status Epilepticus in Childhood has developed a proposed guideline for the treatment of CSE in childhood in Japan by an evidence-based approach and consensus conference. Initial management of seizures should be attempted mainly with IV diazepam, the second-line treatment involves IV midazolam followed by IV phenytoin if seizures persist, and the third-line treatment requires barbiturate coma. However, our experience of 247 episodes of CSE in 77 patients, predominantly with chronic epilepsy, required different second-line treatments for prolonged CSE compared with clustered CSE: the former were treated with IV midazolam or pentobarbital, and the latter were given IV phenytoin or LDC. We propose modifications to the guideline for CSE that the second-line treatment is divided by prolonged CSE and clustered CSE, and that the procedures for brain protection and systemic management are added.

Stimulus‐sensitive burst‐spiking in burst‐suppression in children: implications for management of refractory status epilepticus

ABSTRACT Status epilepticus refractory to sequential trials of multiple medication is a rare but significant problem in children. We describe stimulus sensitivity arising during the treatment of convulsive status epilepticus in children (stimulus‐sensitive burst‐spiking in burst‐suppression). We reviewed retrospectively clinical and EEG features in six children (three months to ten years), with status epilepticus requiring intensive care, in whom tactile, auditory and visual stimulation induced myoclonic jerks and bursts of EEG spikes. Sensitivity was not present at onset, but appeared after 24 hours as myoclonic jerks of the eyes, face and limbs, irrespective of the modality and site of stimulation. These were associated with burst‐suppression in the EEG, the induced spiking forming the burst component. Various antiepileptic drugs, including GABAergic and NMDA blockers had no effect, but halogenated agents (used in two patients) abolished the sensitivity. Two children died, but the remainder returned to their previous clinical state. We conclude that stimulus sensitivity may appear in the context of refractory status epilepticus treated with high‐dose barbiturates. Outcome may be more favorable than previously reported in adults, mostly in the context of post‐anoxic or toxic coma. Evaluation of ventilated children in status epilepticus should include electroclinical assessment using sensory stimulation. If present, the drug regime should be reviewed and halogenated agents considered.