Pediatric Status Epilepticus

Dr Abunada Mohamed

Status Epilepticus Status Epilepticus is a neurologic emergency

associated with high mortality and long-term disability

– Adverse consequences can include hypoxia, hypotension, acidosis and hyperthermia

– Know the recommended sequential protocol for treatment with benzodiazepines, phenytoin, and barbiturates.

– Goal: stop seizures as soon as possible

Epidemiology

• The annual incidence of SE in children is reported as 10 to 73 episodes/100,000 children and is highest (135/100,000 to 156/100,000 children) in children younger than two years of age.

• Mortality has been reported to be between 2.7% and 8%, with an overall morbidity of between 10% and 20%

Definition

• SE was defined as a seizure lasting longer than 30 minutes or a series of seizures without a return to baseline level of alertness between the seizures.

• There is increasing recognition that most seizures are brief (3-4 minutes) and medication administration delay is associated with more refractory seizures.

• This has led to a change in clinical practice that has shortened the seizure duration of SE over the last decade to a seizure lasting longer than 5 minutes.

• Recent commentaries have proposed that aggressive management be initiated even earlier than 5 minutes.

The longer SE persists,

the lower is the likelihood of spontaneous cessation

the harder it is to control the higher is the risk of morbidity and mortality

Bleck TP. Epilepsia 1999;40(1):S64-6The Status Epilepticus Working Party. Arch Dis Child 2000;83(5):415-9.

Based on timing

SE may be categorized based on etiology, seizure type, ortiming. Attention to the timing stage of SE ensures managementproceeds without delay. In the initial 5 minutes of seizure, a period referred to as the prodromal

stage, it is unknown whether the seizure will self-terminate or evolve into SE.

Persisting SE may be divided into early SE ‘impending’ (5-30 minutes), established SE (30 minutes), or Refractory SE (RSE) (seizures that persist despite treatment

with adequate doses of an initial 2 or 3 anticonvulsant medications).

Based on seizure type

SE can be classified based seizure type into

Generalized Convulsive Status Epilepticus (GCSE) ,the most easily recognizable form

Non - convulsive status epilepticus (NCSE) on

the basis of both clinical and electrographic criteria.

Common etiologies of pediatric CSE Prolonged febrile convulsion (23% to 30%) Acute symptomatic (17% to 52%) – Acute CNS infection (bacterial meningitis, viral meningitis or encephalitis)– Metabolic derangement (hypoglycemia, hyperglycemia, hyponatremia, hypocalcemia or anoxic injury)– Antiepileptic drug noncompliance or withdrawal– Non-antiepileptic drug overdose Remote (16% to 39%)

- Cerebral migrational disorders (lissencephaly or schizencephaly)

- Cerebral dysgenesis

- Perinatal hypoxic-ischemic encephalopathy

- Progressive neurodegenerative disorders Idiopathic/cryptogenic (5% to 19%)

Status epilepticus

Drugs which can cause seizures

AntibioticsPenicillin'sIsoniazidMetronidazoleAnesthetics, narcoticsHalothane, enfluraneCocaine, fentanylKetamine

PsychopharmaceuticalsAntihistaminesAntidepressantsAntipsychoticsTricyclic antidepressants

Status epilepticus

Prolonged seizures

Duration of seizure

Life threatening

systemicchanges

DeathTemporary

systemicchanges

Pathophysiology• Status Epilepticus results from a combination of persistent cellular

excitation and a failure of centrally mediated mechanisms to suppress sustained seizure activity

• Generalized SE is also associated with several systemic physiologic changes as a result of a massive release of catecholamines.

• Early manifestations (during the first 30 minutes of SE) include Cardiac arrhythmia Hyperglycemia Hypertension Lactic acidosis Tachycardia. • Just beyond 30 minutes, blood pressure and glucose concentration

may begin to normalize, or even reverse in abnormality.

Prolonged SE (beyond 60 minutes) may be associated with

Hyperthermia, Hypoglycemia, Hypotension, Pulmonary edema,Renal failureRhabdomyolysis.Cerebral ischemia from hypoperfusion

Imaging Evidence of SE Damage

The objectives for the acute management of CSE are as follows:

1. Maintenance of adequate airway, breathing and circulation (ABCs).2. Termination of the seizure and prevention of recurrence.3. Diagnosis and initial therapy of life-threatening causes of SE (eg, hypoglycemia, meningitis and cerebral space-occupying lesions).4. Management of refractory status Epilepticus (RSE).

1 .Maintenance of adequate ABCS

• Inability to maintain the airway is the most important immediate risk to the patient with CSE.

• Factors responsible for the airway and ventilation being at risk include

a clenched jaw,poorly coordinated respirations, and production of secretions and vomitus. • Management of the airway includes positioning the child on the side suctioning the easily accessible secretions.

• After suctioning, the patient should be repositioned on the back and a chin lift or jaw thrust should be applied, if necessary, to help open the airway.

Hypoxia is frequently present. • Oxygen (100%) should be given by face mask, and

cardiorespiratory and oxygen saturation monitors should be used.

• Breathing should be carefully monitored. • Assisted ventilation should be considered if signs of

respiratory depression or if oxygen saturations remain low despite receiving 100% oxygen by face mask.

• Increased heart rate and blood pressure (BP) are usually observed in the convulsing patient.

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.• Intravenous (IV) access should be obtained

immediately (two large-bore IV lines if possible) and the bedside blood glucose level should be checked.

Further testing should be considered once the ABCs have been stabilized.

2 .Termination of the seizure andprevention of recurrence The major goal of treatment is to stop the seizure and

prevent brain injury. In animal models, ischemic and excitotoxic neuronal cell

loss starts to occur after 30 min of seizure activity. Seizures that last longer than 5 min to 10 min are at high

risk of continuing for at least 30 min, so early treatment is associated with the best outcome.

This is the rationale behind assuming that any child who arrives in the ED with acute GTC convulsions is in early SE, which should immediately trigger the first-line treatment with benzodiazepines.

IV access • If IV access is unavailable, then other routes

(eg, buccal, intranasal and rectal) should be used while efforts to establish access continue.

• Consideration should be given to starting an

intraosseous (IO) line if IV access is not possible and the seizure is prolonged or the patient is decompensating.

Important to obtain a brief history • It is important to obtain a brief history including any

history of seizure disorder, other symptoms (eg, fever), medication usage and allergies to medications.

• This can be completed by a designated person not immediately involved in the acute resuscitation.

• This history will allow a simultaneous search for cause and focused physical examination to be completed while termination of the seizure is undertaken.

Bedside glucose determination • A bedside glucose determination will establish the

need for a bolus of dextrose. • If the blood glucose level is 2.6 mmol/L or lower,

then the recommended management is 5 mL/kg of 10% dextrose water (0.5 g/kg) by IV.

• If the patient is hypoglycemic, the bedside glucose level should be rechecked 3 min to 5 min post bolus, and a repeat bolus should be given as necessary.

• Increased intracranial pressure (ICP) or sepsis should be suspected and treated as needed.

• During the administration of medications, pulse rate, respiratory rate, BP, cardiac monitoring and oxygen saturation via pulse oximeter should be followed on a regular basis.

• Anticonvulsant medications may cause loss of airway reflexes, respiratory depression, hypotension and cardiac arrhythmias.

• Monitor the child’s temperature and aim for normothermia using acetaminophen and ibuprofen as appropriate.

First-line treatmentFirst-line treatment usually begins outside the hospital. It has been shown that prehospital treatment of children

reduces seizure length but often is not utilized.Benzodiazepines are the first-line drugs of choice in the

treatment of SE. If used within the first 20 min of seizure onset, termination

rates of seizures can be as high as 70% to 85%. Because IV administration results in more rapid onset of

action and improved bioavailability and efficacy, IV access should be obtained as soon as possible.

Status epilepticus

The longer you wait to administer anticonvulsants, the more anticonvulsants you will need to stop SE

Most common mistake is ineffective dose.Alternative routes of administration . If IV access is delayed or impossible, many AEDs can be given by alternative routes, such as rectal , buccal or interosseous administration. Intranasal midazolam is effective, and i.m. fosphenytoin are safe, well tolerated, and absorbed quickly.

Status epilepticus29

Anticonvulsants - Rapid acting

• Benzodiazepines– Lorazepam 0.1 mg/kg i.v. over 1-2 minutes– Diazepam 0.2 mg/kg i.v. over 1-2 minutes

– If SE persists, repeat every 5-10 minutes

Status epilepticus

Benzodiazepines

• Diazepam– High lipid solubility– Thus very rapid onset – Thus rapid loss of

anticonvulsant effect– Adverse effects are

persistent:• Hypotension• Respiratory

depression

• Lorazepam– Low lipid solubility– Action delayed 2 minutes– Anticonvulsant effect 6-12 hrs– Less respiratory depression

than diazepam

• Midazolam– May be given i.m.

Status epilepticus

Benzodiazepine - Rectal

• Rectal diazepam– 0.3 to 0.5 mg/kg rectal gel, typically reaches

anticonvulsant levels within 5-10 minutes– Intravenous solution given rectally is equally effective

( and much cheaper) Seigler RS. J Emerg Med1990;8(2):155-9.

– Cost : • 5 mg Diastat rectal gel Shekel 38.00• 5 mg diazepam intravenous solution Shekel 4.00

Status epilepticus

Benzodiazepine - Intramuscular

• Intramuscular midazolam– 0.2 mg/kg i.m. – Aqueous solution is rapidly absorbed,

anticonvulsant effect begins after 2 minutes• Intramuscular lorazepam

– Can be given, but lacks water solubility, thus later onset than midazolam

Chamberlain JM. Pediatr Emerg Care 1997;13(2):92-4.Towne AR. J Emerg Med 1999;17(2):323-8.

Prehospital

• Treatment varies depending on local practices and availability, but options include the following:

Buccal or rectal lorazepam; Buccal or intranasal midazolamRectal diazepam. • If available, some would consider buccal or

intranasal midazolam to be the first-line management in children without IV access.

In hospital:• IV lorazepam is usually the first-line

treatment.It has a longer-lasting anticonvulsant activity causes less respiratory depression than diazepam ,more effective than diazepam or phenytoin in stopping

seizures .• Note that repeat doses are much less likely to be

effective (17% versus 85% for the first dose). • If children have received benzodiazepines in the

prehospital setting, one repeat IV dose may be adequate before moving to second line treatments if necessary.

NO IV LINE

Because timing is critically important, if no IV access is available, a second dose of benzodiazepine (lorazepam, midazolam or diazepam) should be given through the buccal, intranasal, rectal or intramuscular (IM) route while IV access is being obtained. • Treatment with more than two doses of

benzodiazepines is associated with respiratory depression.

Second-line treatment

• Fosphenytoin/phenytoin is generally preferred over phenobarbital because it is less likely

to cause respiratory depressionto alter the level of consciousness of the child,

which can complicate the assessment. • If no IV access is available, then IM fosphenytoin,

IO phenytoin are alternative options. • Note that evidence for the safety and efficacy of

IO phenytoin or phenobarbital is scant.

Phenytoin and fosphenytoin :• Phenytoin has been shown to control 60% to 80% of seizures with a 20 mg/kg dose . • It must be administered in normal saline (NS) because it precipitates in glucose-

containing solutions. • It is infused over approximately 20 min. • Because of its high pH, extravasation of phenytoin can result in severe subcutaneous

irritation (‘purple glove syndrome’) characterized by edema, discolouration and pain distal to the site of administration.

• This side effect does not occur with fosphenytoin (20 mg/kg/dose), which is a water-soluble prodrug of phenytoin. more rapid IV infusion may be given by IM injection, but more expensive not universally available• Side effects of both phenytoin and fosphenytoin include cardiac arrhythmias,

bradycardia and hypotension, so continuous BP and ECG monitoring is recommended during infusion.

Status epilepticus

Anticonvulsants - Long acting

• Phenytoin– 20 mg/kg i.v. over 20

min– pH 12

Extravasation causes severe tissue injury

– Onset 10-30 min– May cause hypotension,

dysrhythmia– Cheap

• Fosphenytoin– 20 mg PE/kg i.v. over 5-7

min PE = phenytoin equivalent

– pH 8.6Extravasation well

tolerated– Onset 5-10 min– May cause hypotension– Expensive

Phenobarbital:• Phenobarbital has similar anticonvulsant activity as phenytoin,

but a greater incidence of respiratory depression, especially when used in conjunction with benzodiazepines.

• The mechanism of action is similar to benzodiazepines, so it may be less effective in treating seizures refractory to these drugs.

• It is still routinely used for the treatment of neonatal seizures, as well as for children who are already on phenytoin maintenance.

• The loading dose is 20 mg/kg in NS or 5% dextrose water over 20 min.

• Side effects include sedation, respiratory depression and hypotension, especially if a benzodiazepine has already been given.

3. Diagnosis and initial therapy of life threatening causes of SE

• Investigations should be individualized according to the clinical scenario

• The most common cause of SE is a prolonged febrile seizure.

• The same may apply to children with a known seizure disorder who are already on anticonvulsant therapy.

However, a full clinical assessment should involve a search for precipitating causes, focusing on signs of infection, meningeal irritation, trauma, focal neurological deficits and intoxication.

Investigations• When the etiology of the seizure is unclear, the following

investigations should be considered : glucose (to verify earlier bedside determination) Electrolytes, Serum calcium CBC and differential cultures (if sepsis is suspected) arterial blood gas (ABG) Anticonvulsant levels (for patients on long-term

anticonvulsant therapy) Urine and blood for toxicology screening, blood urea nitrogen,

magnesium, liver enzymes, lactate and ammonia may be required in selected cases.

lumbar puncture (LP)• A decision regarding the need for (LP) should be

deferred until the patient’s vital signs are stablethere is no suspicion of increased ICP and the convulsion has stopped. • If sepsis is believed to be likely, IV antibiotics

may be given immediately after blood cultures without waiting to perform the LP.

• Prolonged attempts at obtaining cultures should not delay treatment.

Computed tomography (CT) of the head• Head CT may be performed after the ABCs have been stabilized and the

convulsion has terminated(CT) head Indications A history of trauma, Evidence of increased ICP Focal neurological signs Unexplained loss of consciousness or Suspicion of cerebral herniation • If there are clinical indications of raised intracranial pressure or herniation,

these must be treated immediately before further investigation. • A normal CT scan does not exclude significantly increased ICP. • LP must be deferred if clinical or radiological signs of increased ICP are

present.

4 .Management of RSE• SE that is unresponsive to two different

antiepileptic medications (eg, a benzodiazepine and phenytoin) is considered to be refractory, although some authorities have added a duration criterion such as longer than 30 min or longer than 60 min .

• Escalation to anesthetic support with subspecialist and intensive care consultation and initiation of a midazolam infusion

• 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.

Pharmacotherapy in RSE• There are currently no published controlled trials

examining different treatment options for RSE in children.

• A number of Canadian hospital guidelines have incorporated a continuous infusion of midazolam as the first step.

• If this fails, then anesthetizing doses of barbiturates should be considered.

• Most recently, the use of topiramate and levetiracetam has been suggested, but the role of these drugs remains unclear at the present time.

Status epilepticus47

Non - convulsive status epilepticus

• How do you tell that patient’s seizures have stopped?

Status epilepticus

Non - convulsive SE?

• Up to 20% of children with SE have non - convulsive SE after tonic - clonic SE

• Particularly common in infants < 2 months

Mitchell WG. J Child Neurol 2002;17 Suppl 1:S36-43.

Status epilepticus49

Non - convulsive SE?

• If child does not begin to respond to painful stimuli within 20 - 30 minutes after tonic - clonic SE stops, suspect non - convulsive SE– Urgent EEG

Conclusion

• There have been a number of changes in the emergency management of SE over the past 15 years based on the emergence of new evidence and medications.

• It is important for all those involved in the acute medical management of children to have an up-to-date, evidence-based approach to the emergency management of children with CSE.

GUIDELINE FOR THE MANAGEMENT OF CONVULSIVE STATUS EPILEPTICUS IN PEDIATRICS

yes no

no yes

yes no

Rapid sequence intubation

Consider: High-dose phenobarbital thiopental infusion propofol

Admit to ICU/call anesthetist

-IV/IO midazolam 0.1 mg/kg loading dose (max of 8 mg) over 2–3 min Then 120 μg/kg/hour infusion. Increase by 120 μg/kg/hour every 5 min if the seizure continues (Maximum 1440 μg/kg/hour).

Admit to hospital, investigate and treat potential causes of status epilepticus

- IV/I0 phenytoin 20 mg/kg in N saline over 20 min (max 1000 mg) If no response ,then -IV phenobarbital 20 mg/kg over 20 mins

IV phenobarbital 20 mg/kg over 20min Or -IV/I0 phenytoin 10 mg/kg in N Saline over 20 min (max 500 mg) Give phenytoin or phenobarbital after the first dose of benzo. unless febrile and the seizure has stopped.

Is child on phenytoin?

Insert intraosseous (IO) needle if seizure is not stopped with rectal benzodiazepines.

Buccal midazolam 0.5 mg/kg (max 10mg) Or Intranasal midazolam 0.2 mg/kg (max 10 mg) Or Rectal diazepam 0.5 mg/kg/ (max 10 mg) Benzodiazepine can be repeated once after 5 min

- IV diazepam 0.3 mg/kg over 2 min (max 5 mg in infants and 10 mg in child) Benzodiazepine can be repeated once after 5 min

IV attempts should be limited to 3 tries or 90 seconds

CONVULSION > 5 MIN

Manage ABCs 1.Cardiac monitor; oximeter 2.Establish IV access 3.Place in the recovery position

Blood tests 4.CBC, electrolytes and glucose; glucometer 5.Measure blood level if on Phenobarbital, Phenytoin, Carbamazepine or Valproate.

Rapid IV access

obtained?

Seizure stopped?