Dr. Ravindra K. SharmaPediatric Specialist

Fujairah Hospital,UAE

Status Epilepticus

TAJ MAHAL, AGRA, INDIATAJ MAHAL, AGRA, INDIA

“Status epilepticus is a medical emergency that requires an

organized and skillful approach to minimize the associated mortality

and morbidity”

Status epilepticus (SE) presents in a multitude of forms, dependent on etiology and patient age (myoclonic, tonic, subtle, tonic-clonic, absence, complex partial etc.)

Generalized, tonic-clonic SE is the most common form of SE.

Definition:Conventional definition:

Single seizure > 30 minutes

Series of seizures > 30 minutes without full recovery

Definition:…. “If appropriate therapy is delayed, SE can

cause permanent neurologic sequelae or death …”

thus

“ … any child who presents actively convulsing should be assumed to have SE.”

Haafiz A. Pediatr Emerg Care 1999;15(2):119-29

The longer SE persists,the lower is the likelihood of spontaneous cessationthe harder is it to controlthe higher is the risk of morbidity and mortality

Treatment for most seizures needs to be instituted after > 5 minutes of seizure activity

Bleck TP. Epilepsia 1999;40(1):S64-6

But This is not practical operational definition. Longer periods with uncontrolled seizure

activity, more likely to develop a RSE syndrome.

More practical guidelines needed to draw that arbitrary ‘line in sand’, beyond which substantial risk of developing clinical SE exists.

“Continuous seizures lasting at least 5 minutes or two or more discrete seizures between which

there is an incomplete recovery of consciousness”

Operational Definition:

Causes. Fever Medication change Unknown Metabolic Congenital Anoxic Other (trauma, vascular,

infection, tumor, drugs,endocrine)

36 %20 % 9 % 8 % 7 % 5 %15 %

DeLorenzo RJ. Epilepsia 1992;33 Suppl 4:S15-25

Pathophysiology GLUTAMATE = the major excitatory AA

neurotransmitter in brain Any factor increases Glutamate activity can lead to

seizures NMDA(N-methyl-D-aspartic acid) is an AA derivative

which acts as a specific agonist at the NMDA receptor mimicking the action of glutamate

GABA = main inhibitory neurotransmitter, ; GABA antagonists can cause SE

Drugs which can cause seizures Antibiotics

Penicillins Isoniazid Metronidazole

Anesthetics, narcotics Halothane, enflurane Cocaine, fentanyl Ketamine

Psychopharmaceuticals Antihistamines Antidepressants Antipsychotics Phencyclidine Tricyclic antidepressants List of drugs

Mortality

Adults Children

15 to 22% 3 to 15%

Reviewed in: Fountain NB. Epilepsia 2000;41 Suppl 2:S23-30Reviewed in: Fountain NB. Epilepsia 2000;41 Suppl 2:S23-30

Prolonged seizures

Duration of seizureDuration of seizure

Life Life threateningthreatening

systemicsystemicchangeschanges

DeathDeathTemporaryTemporary

systemicsystemicchangeschanges

Respiratory Hypoxia and hypercarbia

- ventilation (chest rigidity from muscle spasm)- Hypermetabolism ( O2 consumption, CO2 production)- Poor handling of secretions- Neurogenic pulmonary edema?

Hypoxia Hypoxia/anoxia markedly increase the risk of

mortality in SE Seizures (without hypoxia) are much less dangerous

than seizures and hypoxia

Towne AR. Epilepsia 1994;35(1):27-34

Neurogenic pulmonary edema

Rare complication Likely occurs as consequence of marked increase of pulmonary vascular pressure

Johnston SC. Postictal pulmonary edema requires pulmonary vascular pressure increases. Epilepsia 1996;37(5):428-32Johnston SC. Postictal pulmonary edema requires pulmonary vascular pressure increases. Epilepsia 1996;37(5):428-32

Acidosis Respiratory Lactic

Impaired tissue oxygenation Increased energy expenditure

Hemodynamics Sympathetic overdrive

Massive catecholamine / autonomic discharge

Hypertension Tachycardia High CVP

Exhaustion Hypotension Hypoperfusion

Exhaustion Hypotension Hypoperfusion

0 min0 min 60 min60 min

COMMON WEALTH GAMES, DELHI 2010.

Cerebral blood flow - Cerebral O2 requirement

Blood pressure

Blood flow

O2 requirement

Seizure duration

HyperdynamicHyperdynamic phasephase CBF meets CMROCBF meets CMRO22

Exhaustion phaseExhaustion phase CBF drops as CBF drops as

hypotension sets inhypotension sets in Autoregulation Autoregulation

exhaustedexhausted Neuronal damage ensues

HyperdynamicHyperdynamic phasephase CBF meets CMROCBF meets CMRO22

Exhaustion phaseExhaustion phase CBF drops as CBF drops as

hypotension sets inhypotension sets in Autoregulation Autoregulation

exhaustedexhausted Neuronal damage ensues

GlucoseG

luco

se

Seizure duration

30 min

SE

SE + hypoxia

Hyperdynamic phase Hyperglycemia

Exhaustion phase Hypoglycemia

develops Hypoglycemia appears

earlier in presence of hypoxia

Neuronal damage ensues

Hyperdynamic phase Hyperglycemia

Exhaustion phase Hypoglycemia

develops Hypoglycemia appears

earlier in presence of hypoxia

Neuronal damage ensues

Hyperpyrexia Hyperpyrexia may develop during protracted

SE, and aggravate possible mismatch of cerebral metabolic requirement and substrate delivery

Treat hyperpyrexia aggressively Antipyretics, external cooling

Other alterations Blood leukocytosis (50% of children) Spinal fluid leukocytosis (15% of children) K+

creatine kinase Myoglobinuria

Boring!

Acute Management of Seizures

Oxygen, oral airway. Avoid hypoxia!

Consider bag-valve mask ventilation. Consider intubation

IV/IO access. Treat hypotension, but NOT hypertension

AA

BB

CC

Common Sense:0-5 minutesStabilize the patient-

(0-5 minutes)… Arterial blood gas?

All children in SE have acidosis. It often resolves rapidly with termination of SE

Intubate? It may be difficult to intubate the actively seizing child Stop or slow seizures first, give O2, consider BVM ventilation If using paralytic agent to intubate, assume that SE continues

0-5 minutes…. Give glucose (2-4 ml/kg D25%, infants 5 ml/kg D10%), unless

normo- or hyperglycemic Hyperglycemia has no negative effect in SE

(as long as significant hyperosmolality is being avoided)

Adoloscent-Thiamin 100 mg IV first

Initial investigations(0-5 minutes)…. Labs

Na,K, Ca, Mg, PO4 , BUN, Cret, glucose CBC Liver function tests, ammonia Anticonvulsant level Toxicology Blood C/S

Initial screening history and Physical examination

Work-Up (when stable) Lumbar puncture

Always defer LP in unstable patient, but never delay antibiotic/antiviral rx if indicated

CT scan/MRI scan Indicated for focal seizures or deficit, history of trauma or

bleeding d/o EEG

Treatment (Pharmacotheraqpy)5-15 minutes.. The longer we wait with anticonvulsant, the

more anticonvulsant we will need to stop SE

Most common mistake is ineffective dose

Anticonvulsants Rapid acting

plus

Long acting

Anticonvulsants - Rapid acting Benzodiazepines

Lorazepam 0.05- 0.1 mg/kg i.v.(rectal dose same) upto 4-6 mg over 1-2 minutesor

Diazepam 0.2- 0.5 mg/kg i.v. upto 6-10mg over 1-2 minutes Diazepam 0.5 mg/kg rectally Midazolam 0.15-0.3 mg/kg IV ; nasal or Buccal (0.5 mg/kg) is

used if no IV line If SE persists, repeat every 5-10 minutes

Benzodiazepines Diazepam

High lipid solubility Thus very rapid onset Redistributes rapidly Thus rapid loss of

anticonvulsant effect Adverse effects are

persistent: Hypotension Resp. depression

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

diazepam

Midazolamfor brief seizures May be given i.m. to treat refractory SE

Anticonvulsants :15-35 minutes(If seizures persists) Phenytoin

15-20 mg/kg i.v. over 15-20 min pH 12

Extravasation causes severe tissue injury

Onset 10-30 min May cause hypotension,

dysrhythmia Dilute with Dext. free solution Cheap

Fosphenytoin 15-20 mg PE/kg i.v./i.m. over 5-

7 min PE = phenytoin equivalent Fosphenytoin 150 mg is equal to 100

mg phenytoin pH 8.6

Extravasation well tolerated Onset 5-10 min May cause hypotension Expensive

Anticonvulsants :(15-35 minutes) Phenobarbital

15-20 mg/kg (neonate 20-30 mg/kg)i.v. over 15-20 min

Onset 15-30 min May cause hypotension, respiratory

depression

Initial choice of long acting anticonvulsants in SE

Is patient an infant?Is patient already receiving phenytoin?

YesNo

At high risk for extravasation ?(small vein, difficult access etc.)?

Phenobarbital

YesYesNoNo

Phenytoin Fosphenytoin

Preffered in Cardiac patient, Head trauma,

If SE persists (45 minutes) Phenobarbital if Phenytoin used Additional phenytoin or FP 5 mg/kg (Nelson 10 mg/kg

increment) max upto 30 mg , Additional phenobarbital 5 mg/kg/dose every 15–30

min (max total dose of 30 mg/kg) be prepared to support respirations Consider IV valproate, especially for partial status

epilepticus

Seizures Persists (60 minutes) Consider Diazepam infusion, pentobarbital

(Barbiturate coma), midazolam, paraldehyde or general anesthesia infusion in PICU

Midazolam 0.2 mg/kg bolus & 20-400 mcg/kg/hr infusion

Propofol 1-2 mg/kg then 2-10 mg/kg/hr infusion Avoid paralytics

Still Seizures Persists…. Induction of Barbiturate coma for 48 hrs IV loading thiopental 2–4 mg/kg till a burst

suppression EEG pattern till 48 hrs check phenobarbital level to be normal.

Paraldehyde :loading 150–200 mg/kg IV for 15–20 min, then 20 mg/kg/hr in a 5% concentration in a glass bottle freshly prepared

Still Seizures Persists…. General anesthesia: if barbiturate coma is not

option. halothane and Isoflurane. Acts by reversing cerebral anoxia and metabolic

abnormalities, allowing the previously administered anticonvulsants to exert their effect.

Possible new drugs for Status Lidocaine - some positive trials Valproate - IV form available

10-15 mg/kg IV. Gabapentin / Vigabatrin / Lamotrigine Felbamate - blocks NMDA receptors Ketamine - blocks NMDA receptorsUse of AED after status episode is controversial especially idiopathic or febrile seizure.

Non - convulsive status epilepticus?NCSE is a term used to denote a range of conditions

in which electrographic seizure activity is prolonged and results in non convulsive clinical symptoms.

Non - convulsive SE ?

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

Non - convulsive SE ?

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

Summary Status Epilepticus is >5 min of seizures or two seizures

without return to consciousness Status Epilepticus is common Delay in therapy makes SE harder to rest Mortality and morbidity is increased in prolonged SE BZD, Pheny/Pheno, Call for PICU Status Epilepticus needs a DIAGNOSIS

Take-Home points - Better outcome if seizure stopped earlier, so no need to

wait Always ABC D FIRST Lorazepam - best 1st line Rx Fosphenytoin - surpasses Phenytoin for SE, and can be

given IM in difficult situation Propofol - advantages over barbiturates for resistant SE,

low toxicity , quick action, and fast recovery upon discontinuation