Management of the Paediatric Patient with Generalized Convulsive Status Epilepticus in the Emergency Department

Management of the paediatric patient with generalized convulsive status epilepticus in the emergency department

Status epilepticus is a condition characterized by continuous seizure activity or intermittent convulsive activity with failure to regain consciousness between convulsions for a duration of longer than 30 minutes. When the exact time of onset of the convulsion is unknown, any convulsing patient arriving in the emergency department should be managed as though he/she fits the definition for status epilepticus. For purposes of this discussion, convulsions are generalized, tonic-clonic and associated with loss of consciousness. The management of nonconvulsive status will not be discussed.

The mortality from status epilepticus has been reported to be between 3% and 11% in children. It has been hypothesized that the lower mortality of 3% may be the result of such factors as early detection of the convulsion, immediate care of the patient, aggressive anticonvulsant treatment and fewer children in the population with severe underlying neurologic impairment.^1-3 It is felt that previously reported high morbidity rates may also be reduced by appropriate rapid management. Maytal found "new" morbidity (presumed to be a result of the episode of status) in 9.1% of the patients with status epilepticus. He states that "in the modern emergency department the outcome is primarily a function of the underlying etiology."⁴ When there has been no acute or progressive CNS insult, morbidity and mortality are low.⁵

The objectives for the emergency department management of status epilepticus, in order of priority, are as follows:

Management of adequate airway, breathing and circulation (A,B,C's)

Inability to maintain the airway is the most important immediate risk to the patient with status epilepticus. Factors responsible for the airway and ventilation being at risk include a clenched jaw, poorly coordinated respirations, production of secretions and vomitus, leading to varying degrees of blockage of the airway and ineffective ventilation. Hypoxia is frequently present.

Management of the airway includes positioning the patient on his/her side and suctioning the secretions which are easily accessible with tonsillar suction. If there are copious nasal secretions, a flexible catheter may be used to remove them. The teeth should not be pried apart nor should a flexible suction catheter be placed between clenched teeth. It is necessary to administer 100% oxygen using a clear plastic face mask with a reservoir bag attached. Airway problems usually improve rapidly with cessation of the convulsion.

Increased heart rate and blood pressure are usually seen in the convulsing patient. They will return to normal when the convulsion is stopped. An arrhythmia, however, may suggest an etiology for the convulsion (eg, intoxication with tricyclic antidepressant). Bradycardia, hypotension and poor perfusion are ominous signs. They imply severe hypoxia and an immediate need to establish the airway and ventilate the patient, either by bag-valve mask ventilation or intubation.

Termination of convulsive activity and prevention of recurrence

Before any medications are given, it is essential to obtain a brief history to determine if this patient has had the following: convulsive disorder, medication usage, chronic disease or allergies to medications. This can be done by a designated person not immediately involved in the acute resuscitation.

This history will allow the process of a simultaneous search for cause while termination of the seizure is undertaken.

A bedside glucose determination will establish the need for a bolus of dextrose. The recommended dose is 2-4 ml/kg of a 25% solution (0.5-1.0 g/kg) intravenously. Drug therapy for status epilepticus is listed in Table 1 and Figure 1. The first-line anticonvulsant medications are indicated in bold print.

Difficulty with intravenous access is one of the main factors leading to delay in treatment. However, anticonvulsant medications can be administered by several routes: intravenous (diazepam, Iorazepam, phenobarbital, phenytoin), rectal (diazepam, paraldehyde) and sublingual (lorazepam).^6-10 Intravenous and rectal administration are the routes of choice. Data relating to the intra-osseous route for all anticonvulsants are limited to animal studies and a few clinical case reports.^11-17 Administration of the anticonvulsant by the intra-osseous route (while not preferred) is better than not giving any anticonvulsant or relying on muscular paralysis alone. The intraosseous route should be used only when diazepam or paraldehyde rectally have failed to stop the convulsion and IV access cannot be obtained. IV and intra-osseous drug administration should be followed by a flush of normal saline to improve distribution to the main circulation. Any of the above anticonvulsants (with the exception of paraldehyde) could be given orally through a nasogastric tube. This is rarely done in the acute situation owing to uncertainty of absorption, possible slow onset of action and risk of aspiration. The intravenous solution of first choice, to ensure compatibility with all intravenous anticonvulsants, is normal saline.

There are many different regimes for the use of anticonvulsants in the patient with status epilepticus.^18-21 It is important for the treating physician to develop his/her own protocol and become familiar with the drugs to be used in that protocol.

Lorazepam or diazepam may be used as first-line anticonvulsants given that the effectiveness of the two medications is similar (80-90%). Lorazepam is favoured by some because of its longer duration of action, although this advantage may not be significant as many children will subsequently be given a long-acting anticonvulsant. The need to keep lorazepam refrigerated, and to dilute it prior to administration, may make diazepam easier to administer in the acute situation.²² Both medications may cause respiratory depression (especially if administered rapidly), and the physician must be prepared to assist ventilation in all cases.²³ Bag-valve mask ventilation should be the initial management technique of the hypopneic or apneic patient after ensuring that the airway is patent and well positioned. In the majority of patients bag-valve mask ventilation for 2-30 minutes may be all that is necessary to avoid the complications of intubation.


SHORTER TERM/ACUTE CESSATION OF SEIZURE
Drug and Route	Dose	Maximum	Rate	Repeat	Risks	Comments
Lorazepam (IV,SL,I0)	0. 1 mg/kg	4 mg	<2 mg/min	q10 min x 2	Hypotension, respiratory depression	Must be refrigerated and diluted before administration
Diazepam (IV,IO)	0.3 mg/kg	10 mg	< 2 mg/min	q5 min x 2-3		Administer as close to vein as possible without dilution
Diazepam (PR)	0.5 mg/kg	10 mg		q5-10 min		Use undiluted IV preparation
Paraldehyde (PR)	0.3 mL/kg	10 mL			Mucosal irritation	Dilute 1/1 in oil in glass syringe
LONGER-ACTING ANTICONVULSANTS/ACUTE CESSATION AND PREVENTION (not previously on medications)
Phenytoin* (IV,IO)	20 mg/kg	1000 mg (30 mg/kg)	1 mg/kg/min	May give additional 5 mg/kg IV if unable to stop seizure	Hypotension, arrythmia, need to be on cardiac monitor	Must be given in non glucose containing solution
Phenobarbital* (IV,I0)	20 mg/kg	600 mg (30 mg/kg)	1 mg/kg/min	May give additional 5 mg/kg IV if unable to stop seizure	Respiratory depression, especially if Valium has been used	First choice in neonates
* If a patient is already on phenytoin or phenobarbital, a booster dose of 5 mg/kg may be given. Subsequent doses may be given based on anticonvulsant levels.

Drugs in boldface type is the first-choice drug; others are good alternatives or additions.
IV = intravenous; SL = sublingual; PR = per rectum; 10 = intra-osseous.

In the absence of intravenous access, diazepam can be given effectively by the rectal route. Diazepam is given without dilution by inserting the smallest possible syringe or a small catheter on the end of the syringe. If the dose is less than 5 mg, a tuberculin syringe is ideal. The medication should be placed a distance of 4 cm into the rectum adjacent to the rectal mucosa. The buttocks should be elevated and squeezed together for 5 minutes to avoid evacuation of the rectal contents following administration of the drug. Diazepam may be repeated twice, 5-10 minutes apart.

In adult volunteers given lorazepam rectally, the peak drug levels are lower and delayed, compared with the intravenous route. Rectal lorazepam in children is not an established treatment.

The patient with status epilepticus (convulsion lasting longer than 30 minutes) should receive a loading dose of a long-acting anticonvulsant after the first dose of benzodiazepine. An exception to this statement may be a child who is known to have a seizure associated with fever which has stopped with the first dose of benzodiazepine. In this scenario and some others, the clinical history and physical examination may suggest a low probability of a recurrent seizure.

For those children requiring long-term anticonvulsant therapy, but not already on it, phenytoin is preferable to phenobarbital because of the increased incidence of respiratory depression associated with concurrent use of phenobarbital and benzodiazepines. Phenytoin is less sedating than phenobarbital and may make it easier to follow neurological vital signs in these patients.

The initial dose of phenytoin is 20 mg/kg. This must be administered intravenously in normal saline, since it precipitates in glucose-containing solutions. It must not be given by the intramuscular route. If the convulsion continues, additional 5 mg/kg increments of phenytoin may be given. A maximum total dose of phenytoin of 30 mg/kg (up to 1000 mg) can be given. The phenytoin should be given at the rate of 1 mg/kg/min. Phenobarbital 20 mg/kg may be given after the loading dose of phenytoin if the seizure continues. As with phenytoin, additional 5 mg/kg increments of phenobarbital may be given if continuous seizure activity is present. A maximum total dose of phenobarbital of 30 mg/kg (up to 600 mg) may be given.

In neonates with status epilepticus, phenobarbital is the drug of choice. Phenobarbital is often used as the first-line anticonvulsant in children with status epilepticus associated with fever, although there is no evidence that it is more efficacious than phenytoin in this situation.

The administration of the above medications includes benzodiazepine administration within the first 5 minutes, phenytoin administration over 20 minutes and subsequent phenobarbital administration over the ensuing 20 minutes, giving a total time period of 45 minutes.

Although lorazepam, diazepam and phenytoin are the first-line medications, other long- and short-acting anticonvulsants listed in Table 1 are acceptable alternatives. The utility of intravenous paraldehyde has been demonstrated, but its use has been limited by the availability of other medications and routes, as well as the potential for significant side effects which include cyanosis, cough, hypotension and pulmonary edema.²⁴ Rectal paraldehyde may be effective and may be given in a dosage of 0.3 mL/kg (maximum 10 mL) diluted 1/1 with oil in a glass syringe. Valproic acid is another medication that may be given by the rectal route, in a dosage of 20 mg/kg using the oral syrup diluted 1/1 with water and given as a retention enema.

During the administration of medications, pulse rate, respiratory rate, blood pressure, cardiac monitoring, colour, and oxygen saturation via pulse oximeter should be followed. Anticonvulsant levels may be helpful if taken 30 minutes after administration of loading doses of medications in order to help determine further therapy, especially for patients in whom seizure control is difficult or for those already on long-term anticonvulsant therapy. Most patients will respond to this recommended regime. Failure to respond indicates the need for an early admission to a paediatric critical care unit and a neurological consultation.

With multiple medications and repeated doses, respiratory depression becomes more likely and ventilatory support may be required. Physical examination and capillary or arterial gas determination will help assess if ventilation is adequate. Inappropriate interpretation of the blood gases, such as overconcern with a transient elevation of the pCO₂, may lead to unnecessary intubation. In contrast, a profound metabolic acidosis with an increased anion gap may suggest intoxication as the etiologic agent for the seizures.

If the patient remains in status epilepticus, he/she may need to be paralyzed and intubated by an individual skilled in airway management.

It is recognized that paralysis may aid ventilation and prevent the motor manifestations of seizures, but it does not terminate the seizure activity in the brain. At this point, the patient's care is beyond the scope of the usual emergency department setting, and transfer to a paediatric intensive care unit with neurological consultation for further management will be necessary. The nature of this further management will depend on the previous experiences in the individual tertiary care centres involved and may include intravenous pentobarbital therapy with intermittent EEG monitoring.²⁵

Diagnosis and initial therapy of the life-threatening causes of status epilepticus

Investigations should be individualized according to the clinical scenario. The most common cause of status epilepticus is a prolonged febrile seizure. These children may not require an extensive work-up. The same may also apply to the patient with a known seizure disorder already on anticonvulsant therapy. However, a full clinical assessment should involve a search for precipitating causes, focusing on signs of trauma, infection, meningeal irritation, petechial or purpuric lesions, focal neurologic deficits and intoxication. Although uncommon, the possibility of psychogenic seizures must be considered if the seizures appear atypical.²⁶ It is important not to mistake the unusual posturing of decortication or decerebration for seizures. Where the etiology of the seizure is unclear, the following should obtained: blood for complete blood count, glucose (to verify earlier bedside determination), cultures (if suspected sepsis), capillary or arterial gas (perfusion must be adequate for capillary gas) and electrolytes. Anticonvulsant levels should be obtained on all patients on long-term anticonvulsant therapy. Urine, blood, and gastric aspirate should be put on hold for potential toxic screen. Serum calcium, urea nitrogen, magnesium, liver enzymes and ammonia may be required in selected cases, but are not considered part of the routine work-up.

Lumbar puncture should be deferred until the patient's vital signs are stable and the convulsion has stopped. If sepsis is felt to be likely, intravenous antibiotics may be given immediately without waiting to do the lumbar puncture. Prolonged attempts at obtaining cultures should not delay treatment.

A history of trauma, evidence of raised intracranial pressure, focal neurologic signs, unexplained loss of consciousness or suspicion of cerebral herniation are indications for computerized tomography. Computerized tomography of the brain may be undertaken after the convulsion has terminated and airway, breathing and circulation are stabilized.

If there are clinical indications of raised intracranial pressure or herniation, this must be treated prior to investigation. A normal CAT scan does not rule out significantly raised intracranial pressure. Lumbar puncture must be avoided if clinical or radiological signs of raised intracranial pressure are present.

Consideration should always be given to the possibility of intoxication. If intoxication is proven or strongly suspected, and the convulsive activity has stopped, activated charcoal can be given, once the airway has been fully secured to prevent aspiration.

Arranging for transport to an appropriate location or facility for further care

Children without a previous history of epilepsy or febrile seizures who present with status epilepticus should be referred to either a secondary or tertiary care hospital for further treatment and investigation. Unstable vital signs or continuing status epilepticus require transport to a paediatric intensive care unit. Stabilization of the child prior to transport must be discussed with an individual skilled in paediatric critical care.

References

Members: Drs. Dorothy Anna Jarvis, The Hospital for Sick Children, Toronto ON; Jim Kellner, The Hospital for Sick Children, Toronto ON; Marilyn Li, Children's Hospital of Eastern Ontario, Ottawa ON; David McGillivray (principal author) Montreal Children's Hospital, Montreal QC; Robert Thivierge, Hôpital Ste-Justine, Montréal QC; David Warren, Children's Hospital of Western Ontario, London ON.
Principal author: Dr. David McGillivray, Montreal Children's Hospital, Montreal QC.