Status Status Status Status EpilepticusEpilepticusEpilepticusEpilepticus in Childrenin Childrenin Childrenin Children

Azhar Daoud

Professor of Child Neurology

Jordan Univ of science and Tech

• 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

• The following presentation refers to

generalized, tonic-clonic 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

Types of Status

• Convulsive– Generalized convulsive status epilepticus (GCSE)

is the most common and the most dangerous form of SE

– If untreated, may progress to subtle status• Get an electromechanical dissociation (nonconvulsive)

• Nonconvulsive– Absence – considered benign

– Complex-partial – not benign; get cycling between levels of responsiveness and unresponsiveness

The longer SE persists,

– the lower is the likelihood of spontaneous

cessation

– the harder is it to control

– the 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

Climate and Geography• Jordan has a combination of Mediterranean and arid desert

climates, with Mediterranean prevailing in the North and West of

the country.

• while the majority of the country is desert. Generally, the country

has warm, dry summers and mild, wet winters

• The annual average temperatures ranges from 12 to 25 C

Petra

Causes

• Fever

• Medication change

• Unknown

• Metabolic

• Congenital

• Anoxic

• Other (trauma, vascular,

infection, tumor, drugs)

36%

20%

9%

8%

7%

5%

15%

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

Drugs which can cause

seizures• Antibiotics

– Penicillins

– Isoniazid

– Metronidazole

• Anesthetics,

narcotics

– Halothane, enflurane

– Cocaine, fentanyl

– Ketamine

• Psychopharmaceuticals

– Antihistamines

– Antidepressants

– Antipsychotics

– Phencyclidine

– Tricyclic antidepressants

Mortality

• Adults

• Children

15 to 22%

3 to 15%

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

Prolonged seizures

Temporary

systemic

changes

Life

threatening

systemic

changes

Death

Respiratory

• Hypoxia and hypercarbia

- ⇓⇓⇓⇓ ventilation (chest rigidity from muscle spasm)

- Hypermetabolism (⇑⇑⇑⇑ O2 consumption, ⇑⇑⇑⇑ CO2

production)

- Poor handling of secretions- Neurogenic pulmonary edema?

•• Hypoxia and Hypoxia and hypercarbiahypercarbia

-- ⇓⇓⇓⇓⇓⇓⇓⇓ ventilation (chest rigidity from muscle spasm)ventilation (chest rigidity from muscle spasm)

-- HypermetabolismHypermetabolism ((⇑⇑⇑⇑⇑⇑⇑⇑ OO22 consumption, consumption, ⇑⇑⇑⇑⇑⇑⇑⇑ COCO22

production)production)

-- Poor handling of secretionsPoor handling of secretions- Neurogenic pulmonary edema?

Hypoxia

• Hypoxia/anoxia markedly increase

(triple?) the risk of mortality in SE

• Seizures (without hypoxia) are much

less dangerous than seizures and

hypoxia

Towne ARTowne AR. . EpilepsiaEpilepsia 1994;351994;35((11):):2727--3434

Neurogenic pulmonary edema

• Rare complication of

SE in children

• Likely occurs as

consequence of

marked increase of

pulmonary vascular

pressure during SE

Johnston 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

0 min 60 min

Cerebral blood flow - Cerebral

O2 requirement

• Hyperdynami

c phase – CBF

• Exhaustion

phase– CBF drops as

hypotension

sets in

– Autoregulation

exhausted

O2 requirement

Blood flow

Blood pressure

–Neuronal

damage ensues

Seizure duration

Glucose

• Hyperdynamicphase – Hyperglycemia

• Exhaustion phase– Hypoglycemia

develops

– Hypoglycemia appears earlier in presence of hypoxia

Glucose

Seizure duration

30 min

SESE

SE + hypoxiaSE + hypoxia

Glucose

Seizure duration

30 min

SESE

SE + hypoxiaSE + 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

– Consider intubation, relaxation, ventilation

Other alterations

• Blood leukocytosis (50% of children)

• Spinal fluid leukocytosis (15% of children)

• ⇑ K+

• ⇑ creatine kinase

• Myoglobinuria

•• Blood Blood leukocytosisleukocytosis (50% of children)(50% of children)

•• Spinal fluid Spinal fluid leukocytosisleukocytosis (15% of children)(15% of children)

• ⇑ KK++

• ⇑ creatinecreatine kinasekinase

•• MyoglobinuriaMyoglobinuria

First line

Oxygen, oral airway. Avoid

hypoxia!

Consider bag-valve mask

ventilation.

Consider intubation

IV/IO access. Treat hypotension, but

NOT hypertension

A

B

C

Treatment

• 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

Initial investigations

• Labs

– Na, Ca, Mg, PO4 , glucose

– CBC

– Liver function tests, ammonia

– Anticonvulsant level

– Toxicology

Initial investigations

• Lumbar puncture

– Always defer LP in unstable patient, but

never delay antibiotic/antiviral rx if

indicated

• CT scan

– Indicated for focal seizures or deficit,

history of trauma or bleeding d/o

Treatment

• 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)

Treatment

• The longer you wait with anticonvulsant,

the more anticonvulsant you will need to

stop SE

• Most common mistake is ineffective dose

Anticonvulsants

• Rapid acting

Plus

• Long acting

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

Benzodiazepines

• Midazolam

– May be given i.m.

• Diazepam

– High lipid solubility

– Thus very rapid onset

– Redistributes rapidly

– Thus rapid loss of

anticonvulsant effect

– Adverse effects are

persistent:

• Hypotension

• Respir depression

•Lorazepam

–Low lipid solubility

–Action delayed 2 minutes

–Anticonvulsant effect 6-12 hrs

–Less respiratory depression than

diazepam

Lorazepam Superiority

IV Treatment in Out-of-hospital SE

SE at Time of Arrival at the ER

Lorazepam Diazepam Placebo

SE terminated 39 (59.1%) 29 (42.6%) 15 (21.1%)

Ongoing SE 27 (40.9%) 39 (57.4%) 56 (78.9%)

Alldredge BK, et al. N Eng J Med. 2001.

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 8.6

Extravasation well tolerated

– Onset 5-10 min

– May cause hypotension

– Expensive

Cutaneous Reactions in Patients

Receiving IV Phenytoin: Purple Glove

Syndrome (PGS)• PGS = delayed, soft-tissue injury of the hand

and forearm following IV administration of phenytoin

• PGS is frequently, but not exclusively, associated with phenytoin extravasation

• PGS is characterized by pain, edema, and purplish discoloration

• Skin may blister or slough prior to resolution

�Retrospective study of 152 patients who received IV phenytoin over 3

months at the Mayo Clinic

–9 patients (5.9%) developed PGS

O'Brien TJ et al. Neurology. 1998;51:1034-1039.

Purple Glove Syndrome

Hanna DR. J Neurosci Nur. 1992;24:340-345.

Anticonvulsants - Long acting

• Phenobarbital

– 20 mg/k g i.v. over 10 - 15 min

– Onset 15-30 min

–May cause hypotension, respiratory

depression

Third-Line Agents

Valoproat – load 20mg/kg at 3mg/kg/min

+no associations with hypotension or arrhythmias

+don’t need to place patient on monitor

+very few side effects even at high doses

-minimal data (80% effective in 2 trials)

Phenobarbital – load 15mg/kg at 100mg/min

+a lot of clinical experience with this

-prolonged sedation, hypotension, respiratory depression

Pentobarbital – like phenobarb. but faster acting, shorter t1/2

Propofol – don’t use in kids (metabolic acidosis and rhabdomyolysis)

-load 2mg/kg, then 5-10 mg/kg/hr

65 70 75 80 85 90 95 100

Lorazepam 0.1 mg/kg by IV push (<2 mg/min)

0 5 10 15 20 25 30 35 40

Time (Minutes)

Start EEG; do not delay treatment unless EEG

necessary to verify diagnosis

Fosphenytoin 20 mg PE/kg (up to 150 mg PE/min).

If only phenytoin is available: 20 mg/kg (<50 mg/min)

Additional fosphenytoin 5-10 mg PE/kg

Phenobarbital (PB) 20 mg/kg

(<100 mg/min)

Midazolam 0.2 mg/kg bolus, then

0.05-0.5 mg/kg/hr

Seizures continue

Seizures continue

Seizures continue

OR

Induce barbiturate coma:

Pentobarbital (5-15 mg/kg) slowly as

loading dose, then 0.5-5 mg/kg/hr

Continuous infusion propofol

1 mg/kg over 5 min, then

2-4 mg/kg/hrOR

45 50 55 60

Seizures continue

Valproate 20 mg/kg

(3 mg/kg/min) is an

alternative to PBCall for help

If SE persists

• Propofol infusion 5-10 mg/kg/hr after bolus 2 mg/kg

• Midazolam infusion 1 - 10 mcg/kg/min after bolus 0.15 mg/kg

• Pentobarbital infusion 1-3 mg/kg/hr after bolus 10 mg/kg

• Paraldehyde

• Isoflurane

• Leviteracetam? Lacosamide?

Non - convulsive status

epilepticus

• How do you tell that patient’s seizures

have stopped?

Non - convulsive SE ?

• Neurologic signs after termination of

SE are common:

– Pupillary changes

– Abnormal tone

– Babinski

– Posturing

– Clonus

–May be asymmetrical

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