Status Epilepticusin Children

Status Epilepticus in Children儿童癫痫的连续状态

-2010 update

林口长庚儿童加护科

林建志医师

2010-7-21

P D F c r e a t e d w i t h p d f F a c t o r y t r i a l v e r s i o n www.pdffactory.com

http://www.pdffactory.com


Outline - Status Epilepticus• Case Presentation• Definitions• Epidemiology• Clinical Features• Causes / Outcomes• Pathophysiology• Management *

– General– Drugs




Seizure movies




Clinical senario




现病史

• 3 years and 8 months Female• ED visit time: 2010/3/20 23:37

• CC: Seizure for 20 minutes




现病史

• 22:00 cough, vomit once• 22:10 seizure attack with staring gaze,

generalized tonic-clonic seizure, drooling, lip cyanosisè sent to LMD, seizure stopped 20

minutes later• 23:37 sent to our ED due to still

unconsciousness




Triage & Vital sign at our ER

• T 38.0 P 120 R 26, BP?, SpO2 98%• GCS: E2V2M4• BW 15kg

• 体格检查• Consciousness: drowsy,E2V2M4• Pupil: 3mm/3mm; Light reflex: +/+• Neck: supple, no lymphadenopathy; • Brudzinski sign : negative,Kernig sign:

negative




现病史– continued (2)

• However, seizure attack again without conscious recovery between the seizure episode.




儿童癫痫的连续状态

诊断




Q1: The definition of following disease

Impending Status Epilepticus

Convulsive SEConvulsive SE

Subtle SESubtle SE

NonconvulsiveNonconvulsiveSESE




Definition of Status Epilepticus

• 癫痫持续状态是指持续、频繁的癫痫发作，发作时间持续30分钟以上或连续多次发作，发作间期意识不恢复。 ”

• Clinical or electrographic seizures lastingmorethan 30 minor withoutfull recovery of consciousness between seizures– “no recovery between attacks”– “20-30 min” --> risk of injury to CNS neurons





• Continuous or intermittent seizures lasting more than 5 min without full recovery of consciousness between seizures– more practical definition: since isolated tonic - clonic

seizures rarely last > few minutes ... consider Status if sz > 5 min or 2 discrete sz with no regaining of consciousness between

• Treat as aggressively as confirmed status epilepticus




Subtle Status Epilepticus• The first description by Dr. David Treiman (1984). • It is defined subtle status epilepticus as

consisting of “nystagmus, eye blinking, and/or mild motor movements…with marked impairment of consciousness and continuous or nearly continuous, usually bilateral, ictalpatterns on the EEG.”

• Both the motor and EEG expression of seizures become less florid, however prognosis and therapeutic implications remain the same




Nonconvulsion status epilepticus

• Nonconvulsive status epilepticus (NCSE) is an important status epilepticus (SE) type and is defined as a mental status changes from baseline of at least 30 to 60 minutes duration associated with continuous or near continuous ictaldischarges on EEG.

Kaplan PW. Nonconvulsive status epilepticus. Seminars in Neurology 1996;16:33-40.




Spectrum of Disease


Convulsive SEConvulsive SE

Subtle SESubtle SE

NonconvulsiveNonconvulsiveSESE




Epidemiology - SE

• Life threatening• USA: -102,000 -152,000 cases / year

(Adult) - 52,000 deaths / year• Of new cases of epilepsy, 12 -30%

present in Status• Generalized Status is most common

form




Clinical - Generalized SE• At onset - usually obvious tonic / clonic• As continues often subtle - slight twitch of

face / extremities, nystagmoid eye movements

• May be NO observable motor sz ***still risk for CNS injury - assume still seizing if SE pt not waking

• need EEG to definitely dx - not uncommon in comatose hospital inpatients




Cause of SESE in children can be classified broadly into one of

three categories based on etiology:1. Reactive

-Status is caused most commonly by fever ("Febrile seizures".)

2. Symptomatic, acute or remote- Acute symptomatic causes include infection, hypoxia, glucose and electrolyte imbalance, trauma, and hemorrhage or stroke. - Remote symptomatic refers to seizures caused by an insult earlier in life, such as perinatal hypoxic-ischemic injury, trauma, infection, or a congenital brain malformation.

3. Idiopathic or cryptogenic— No known or identifiable cause.




Cause of SE

• Chronic (Remote symptomatic) causes - usually better response to Rx– known epilepsy - breakthrough sz +/- low

anticonvulsant levels– remote CNS process (eg brain surgery / CVA

/ trauma) --> SE after long latent period




Outcome of SE

• Overall adult mortality 20% (>80 yr : 50%)• Children - better outcomes - mortality 2.5 %

• Worse outcome if prolonged / severephysiologic disturbance

• Outcome depends on cause




Pediatr Neurol 2009;41:413-418.




Lin K-L, Lin J-J. Analysis of convulsive status epilepticus in children of Taiwan. Pediatr Neurol 2009;41:413-418




Outcome of SE

• Overall adult mortality 20% (>80 yr : 50%)• Children - better outcomes - mortality 2.5 %

• Worse outcome if prolonged / severephysiologic disturbance

• Outcome depends on cause




Basic Mechanism of SE

• Appears that SE can become self‐sustaining(自我持续的)

• Animal models (chemical or electrical) of SE• Human observations (no real “proof”)




Self‐Sustaining(自我持续的)SESeconds to minutes-Receptor trafficking• Existing receptors move from synaptic

membrane to endosomes• Can move from storage to synaptic membranesMinutes to hours• Increase inproconvulsive neuropeptides• Depletion ofinhibitory neuropeptidesHours to days• Change in gene expression• Neuronal death




Chen JWY, Wasterlain CG, Lancet Neurol. 2006; 5:246-256

Receptor trafficking(受体运输)

↓GABA R

↑Glutamate R




Self‐sustaining SE (自我持续的SE)

• Easily stopped only by drugs that directly or indirectlyinhibit glutamatergicneurotransmission

• GABAergic and barbituates loose potency




Pharmaco-resistance(药物抗药性)

• Time‐dependant resistanceto benzodiazepines (GABA-R) and others well documented in animal models

• In humans –early treatment more effectiveimplying resistance is one possible explanation




OUTLINE - Management of SE

• General approach• Anti - Epileptic Drugs




Management of SE-Clinical senario




Management of SE

• ABC’s (+ monitor / O2 / large IV’s)• Search and treat underlying causes

• START PHARMACOTHERAPY ASAP




Management of SE continued

• History & Physical - do once Rx initiated

• Hx: events, trauma, meds, sz hx, infx• P/E: Neuro - look for focal signs vs.

generalized tonic-clonic– look for signs of underlying causes -

trauma, infection, etc




Is neuroimage needed to arrange ???

• Neuroimaging is generally deferred until the patient is stabilized.

• However, if LP is considered, computed tomography (CT) may be recommended beforehand to exclude a mass lesion, especially in a patient with focal neurologic signs.

• Later, a magnetic resonance imaging study (MRI) is recommended if the etiology of SE is unknown.




Brain CT





• General approach• Anti - Epileptic Drugs

Whic drug do you want to choice?




Drug Rx of SE

• Starting Rx ASAP has been correlated with a better response rate to drug Rx, and lower morbidity– Lowenstein DH, Alldredge BK

Neurology 1993 (43): 483-8• < 30 min - 80% stopped• > 120 min - < 40% stopped





• General approach• Anti - Epileptic Drugs:

– Benzodiazepines– Phenytoin / Fosphenytoin– Barbiturates– Propofol– others / new possibilities




Lancet Neurol 2006; 5: 252




Which drug do you want to choice first ?




Benzodiazepines

• Diazepam:地西泮 (安定) enters CNS in 10 sec, lasts 20-30 min; rectal gel (10mg) effective in 75-90% of cases

• Lorazepam:劳拉西泮（氯羟安定)： enters CNS in 2-3 mins; lasts 2-3 hours

• Midazolam:咪唑安定 0.15 mg/kg load then drip @1-18 mic/kg/min iv, im, sl




Lorazepam vs. Diazepam

Lorazepam Diazepam

Duration of action

*12-24 hr *< 1 hr

Onset of action

2-3 min 1-3 min

Sedation + ++




Which Benzo Do I Use?

• Lorazepam is preferred due to long activity• In the absence of intravenous access,

Diazepam can be given via rectal route until access is established

• Midazolam is generally reserved for refractory status epelipticus




Which drug do you want to use as 2nd line choice ?




Drug, Routine, Dosage and Maximum dose

• Dilantin苯妥英钠 (250mg/5ml/amp) IV• Loading dose:20 mg/kg/dose, Max: 700-

750mg/dose• Maintain: 2mg/kg/dose Q8H (6mg/kg/day)

• Luminal 苯巴比妥 (100mg/ml/amp) IV • Loading dose:20 mg/kg/dose, max: 700mg/dose• Maintain : 2mg/kg/dose Q8H (6mg/kg/day)




Drug Rx of SE

• Existing agents - adverse effects: – Benzos / Bbts - decrease LOC / respiration– Dilantin / (Fosphenytoin) - infusion rate-

related hypotension / dysrhythmias– Dilantin / Bbts / (Fosphen) - slow onset d/t

limited rate of administration




Drug Rx - Refractory SE• Anesthetic doses of:

- Valproic acid(1-2.5mg/kg/hr drip)– Midazolam (IV infusion 2 - 20 mcg/kg/min )– Propofol (1-2 mg/kg)– Barbiturates (Thiopental, high dose

Phenobarbital, Pentobarbital)– Inhalational anesthetics (Isoflurane)

1. ACEP Clinical Policies Committee and the Clinical Policies Subcommittee on Seizures. Critical Issues in the Evaluation and Management of Adult Patients Presenting to the Emergency Department With Seizures. Ann Emerg Med. 2004;43:605-625.

2. Chen, Wasterlain. Status epilepticus: pathophysiology and management in adults. Lancet Neurol 2006; 5: 246–56.




Possible new drugs for Status

• Lidocaine 利多卡因- some positive trials• Topomax• Gabapentin / Vigabatrin / Lamotrigine• Felbamate - blocks NMDA receptors• Ketamine - blocks NMDA receptors

– Ketamine (only if CT head is negative for mass or hydocephalous)




Drug Rx of SE

• 1st - Benzodiazepines– *Lorazepam, Diazepam

• 2nd - > 1 y/o Phenytoin, Fosphenytoin• < 1 y/o Phenobarbital• 3nd – Valproic acid 丙戊酸钠 (德巴金)• Loading:15mg/kg/doseà 100mg/kg/dose• Max: 800mg/dose• Maintain: 10-20mg/kg/dose Q8H• (30-60mg/kg/day)




Drugs-reference • Standard Protocol• Lorazepam 0.1 mg/kg (max 4

mg)• Diazepam 0.3 mg/kg (max 10

mg)• Midazolam 0.2 mg/kg (max 10

mg)• Phenytoin or Fosphenytoin

15‐20mg/kg (up to 30 mg/kg) (I start ½ dose immediately)

• Propofol 1‐2 mg/kg load then 2‐10mg/kg/hr (ranges as high as 2‐5mg/kg load have been used) (not forkids)

• Pentobarbital 10‐15 mg/kg bolus then 0.5‐1 mg/kg/hr

• Midazolam drip 0.05‐2.0 mg/kg/hr

• Others• Valproic Acid 20‐30 mg/kg (in

Europe up to (40‐60 mg/kg) at 3mg/kg/min (faster rates fro SE). It is approved for SE in (Norway and Germany ??? Others now) . Avoid if severe liver disease or mitochondria disease.

• Levetiracetam (Keppra) dose not standard but up 2‐4 grams over 15 minutes administered to volunteers.

• Not approved for SE but may have advantages for critically ill liver disease patient (renal metabolism)

• Lidocaine really old school but Japan




CGMH Website: http://www.cgmh.org.tw/chldhos/intr/c4a00/bigwig/bulletin/neuro/03.htm


http://www.cgmh.org.tw/chldhos/intr/c4a00/bigwig/bulletin/neuro/03.htm



CGMH Website: http://www.cgmh.org.tw/chldhos/intr/c4a00/newworkbook/15.pdf

Page 41


http://www.cgmh.org.tw/chldhos/intr/c4a00/newworkbook/15.pdf



Take-Home points - Status• Better outcome if seizure stopped earlier• Consider/ correct underlying disease• AED Drug treatment

1st - Benzodiazepines– * Lorazepam, Diazepam

2nd - >1y/o Phenytoin, Fosphenytoin-Fosphenytoin - surpasses Phenytoin for SE,

and for any patient with altered mental status who would otherwise need IV Phenytoin - hopefully more available soon< 1y/o Phenobarbital

• Transfer Patients to ICU if refractory SE




Thank you for your attention

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Status Epilepticusin Children

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