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Prof. Dr. Nussbaum Laura – Președinte SNPCAR

Informații şi înregistrări: vezi primul anunț


Autor: Marija Knežević-Pogančev A. Doronjski M. Pavlović T. Redżek-Mudrinić
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Convulsive status epilepticus is the most common neurological medical emergency in children, associated with signifi cant neurological morbidity and mortality, with diff erent hazards and outcome. Convulsive status epilepticus is not a syndrome with a tight age frame, seizure semiology, and a reasonably predictable outcome. Episodes of convulsive status epilepticus can occur in symptomatic and febrile convulsions as well as in nearly all epileptic syndromes of childhood. Although the outcome is dependent on etiology, it is known that appropriate early management may reduce some of the morbidity associated with convulsive status epilepticus. In practical management we need to stop prolonged seizures as soon as possible.





Generalized convulsive status epilepticus (CSE) is the most common and life-threatening type of SE (1). Status epilepticus (SE) is a disorder in which the mechanisms required for seizure termination fail. International League against Epilepsy defi ned SE as a seizure that “persists for a suffi cient length of time, or is repeated frequently enough that recovery between attacks does not occur.” Th e lack of a specifi c duration of the seizures has made this defi nition diffi cult to use (2,3). Gastaut wrote that SE is “a condition characterized by an epileptic seizure that is so frequently repeated or so prolonged as to create a fi xed and lasting epileptic condition” (4). Pathophysiological, epidemiological, and outcome purposes a defi nition of convulsions persisting for at least 15 minutes seems appropriate to identify those at risk of developing structural brain damage. Convulsive status epilepticus in children shall be defi ned as generalized tonic-clonic seizures that persist for 15 minutes or more.


Convulsive status epilepticus occurs most frequently in the young extremes of the population, with no history of seizures or epilepsy. Because the defi nition of CES is somewhat arbitrary, determining the actual incidence is diffi cult (5). Th e incidence in developed countries is between 17 and 23/100,000 (41/100000 world while) but this fi gure was 147/100 000 in infants aged 1 month to 1 year (6).


It is useful to categorize the causes according to acute and chronic processes, because there are diff erences between the two in management, response to treatment, and outcome. Acute processes that cause CSE include metabolic disturbances (e.g., electrolyte abnormalities, renal failure, and sepsis), central nervous system infection, stroke, head trauma, tumors or stroke, drug toxicity, and hypoxia (7). Seizures in this category are often diffi cult to control and are associated with a higher mortality (8). Chronic processes that cause CSE include preexisting epilepsy in which CSE is due to break through seizures or the discontinuation of antiepileptic drugs (AED).


The increased incidence of CSE in childhood is probably caused by a combination of increased seizure susceptibility and decreased ability to mount an adequate inhibitory response. Excitatory synapses mature earlier than inhibitory synapses and this, coupled with an increase in the susceptibility of excitatory neurotransmitter receptors, increases the likelihood that an excitation-inhibition imbalance may occur. Stimulation of GABAA receptors in the immature brain results in depolarization rather than hyperpolarization, as occurs in the adult brain (9). Th e immature cerebral cortex has a high synaptic density at around 2 months of age and this may contribute to the development of hypersynchrony of neural groups. Th e excitatory amino acid neurotransmitter glutamate increases at the site of the seizure focus of generalized convulsive seizures. Inhibitor neurotransmitters such as GABA later increase at the seizure focus and redress the balance between excitation and inhibition. GABA also increases in the substantia nigra pars reticulata, an area that can modulate a cortical inhibitory response. Other mechanisms of inhibitory receptor modulation, such as adenosine receptor agonism, may also contribute to seizure termination (10). “Vulnerable areas” may demonstrate neuronal injury—that is, brain damage—within 30 to 60 minutes after the onset of CSE. Increased glutamate-mediated excitatory neurotransmission and decreased γ-aminobutyric acidmediated inhibitory neurotransmission during CSE may increase epileptogenesis and contribute to neuronal cell death (11).


Convulsive status epilepticus in childhood is a medical emergency and its etiology and outcome mean that it should be studied separately from adult CSE (12). It is overt in its presentation, but as the duration of CSE increases, its presentation may become more subtle. Partial and secondary generalized seizures accounted for most of the episodes of CSE in the pediatric age group, although primary generalized CSE occurred in 45% of cases. Even hyperthermia occurs relatively frequently during SE (28-79%), and in many cases it is primarily a manifestation of the seizures rather than evidence of an infection (13,14). CSE may lead to systemic complications and neuronal damage and untreated or inadequately treated is often fatal (15,16).


Observation of the patient is usually all that is necessary to confi rm the diagnosis before treatment. Certain clinical states, however, may mimic CSE and need to be considered (postanoxic myoclonus patients who emerge from pentobarbital-induced coma or general anesthesia). Blood tests should include standard laboratory studies (chemistry and hematology) as well as a toxic drug screen and antiepileptic drug (AED) levels. Medical and neurologic examinations should be performed concomitant with initial managemen. Electroencephalography is not a diagnostic goal for CSE (17).


The goal of treatment is to stop status epilepticus immediately. In eff orts to avoid potential neurologic morbidity, treatment must begin even before the diagnostic evaluation (18).

Generally for emergency pediatric treatment purposes the defi nition should state at least a time of five minutes, and means that the child is at risk of having a seizure lasting 15 minutes or more. The initial management of patients with CSE is provision of appropriate life support. The airway must be secured, and cardiorespiratory resuscitation should be initiated if indicated. Hypotension, hypoglycemia, and hypoxia are important detrimental metabolic alterations that may occur in patients with CSE and substantially increase the likelihood of neurologic morbidity. The blood pressure, respiratory rate, pulse, and electrocardiogram should be continuously monitored and arterial blood gas studies or oximetry should be performed to assess oxygenation. Most patients cannot be safely intubated during tonic-clonic movements.

Drug treatment for CSE should be started without delay after the diagnosis has been established. Th is approach is supported by the correlation between the duration of CSE and the extent of neurologic morbidity. Ideally, a drug used in this setting would be easy to administer, have an immediate and long-lasting antiseizure eff ect, and be free of serious eff ects on cardiorespiratory function and the level of consciousness. Unfortunately, all current therapies fall short of this ideal.

Convulsive status epilepticus that does not respond to a benzodiazepine, phenytoin, or phenobarbital is considered refractory and requires more aggressive treatment. Continuous intravenous infusions with anesthetic doses of midazolam, propofol, or barbiturates are the most useful treatments. Midazolam and propofol have the substantial advantage over barbiturates of rapid clearance, and midazolam has less pronounced hypotensive eff ects. Short-acting anesthetic drugs are the most commonly used agents for treating resistant CSE (19). Th e infusion is typically maintained for 12 to 24 hours and is then withdrawn gradually while the patient is observed for clinical or electrographic evidence of seizure recurrence. A team approach to patient care, including the participation of an experienced neurologist-neuropediatritian and an intensivist, is often useful because of the need for higher-level neurologic and cardiovascular monitoring and ventilator support. Phenobarbital is the second most commonly used long-acting AED for the management of CSE, but fi rst in Serbia. Th e peak concentration of Phenobarbital may be achieved approximately 60 minutes or longer after the intravenous infusion. Potential toxic eff ects of intravenously administered Phenobarbital include hypotension and respiratory depression.


CES frequently occurs outside the hospital in situations in which treatment with intravenous medications is not feasible or in which there are inadequate resources to manage the potential complications of intravenous therapy. Rectal, bucal and intramuscular routes of drug administration may be useful in these settings. Bucal midazolam (0,3 mg/kg) is rapidly absorbed. Rectal administration of diazepam solution (0.5 mg/kg, maximal dose, 20 mg) is approximately 80% eff ective in controlling prolonged seizures in children, usually within 15 minutes.


Approximately 65% of patients with will have responded to diazepam and phenytoin. Potential reasons for resistant seizure activity include inadequate doses of phenytoin or phenobarbital, intramuscular or rectal administration of AEDs, an uncorrected metabolic abnormality (for example, hyponatremia or hypocalcaemia), or a cerebral mass (such as a tumor).

Convulsive status epilepticus is the most common and life-threatening type of SE, with mortality between 3% and 6%, and observed neurological sequel ranging from minor motor problems to persistent vegetative states in 33-53% (20,21,22,23).


Continued convulsive activity in CSE is leading in all organs and systems decompensation with direct endangering child’s life. Seizure activity in CES is associated with neuronal damage. The aim should be to halt this activity urgently using ideal 100% effective drug, administered quickly without compromising conscious level or other negative effects on cardiovascular, respiratory function or other unexpected effects.


Table 1. Convulsive status epilepticus pharmacotherapy

 Dose  Application speed  Maximal used dose
Diazepam 0.1-1mg/kg

0,5-0,7mg/kg per rectum

5 mg/min  2 mg/kg/30 min
(serum conc.150-300μg/ml)
 Midazolam 0,2 mg/kg iv

0,15-0,30 mg/kg im

0,15-0,30 mg/kg bucal

 0.75-10 μg/kg/min  5 mg at once
 Lorazepam 0,05-0,5 mg/kg  2 mg/min
 Pentobarbital 10 -15 mg/kg  0,5-3 mg/kg/h
 Phenobarbital 20 mg/kg  50-75 mg/min
 Phenytoin 20 mg/kg  50 mg/min
 Fosfenitoin 20 mg/kg  150 mg/min
Propofol 1-2 mg/kg

2-10 mg/kg/h

Valproic acid 30 mg/kg 100 mg/kg/24h



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