STATUS EPILEPTIKUSSTATUS EPILEPTIKUS

EXCITATION INCREASEEXCITATION INCREASE

SEIZURESEIZURE

EPILEPSY- A CRITICAL BALANCEEPILEPSY- A CRITICAL BALANCE

INHIBITION DECREASEINHIBITION DECREASE

SEIZURESEIZURE

•NaNa+ + channel antagonistschannel antagonists

•CaCa2+2+ channel antagonists channel antagonists

•Glutamate receptor antagonistsGlutamate receptor antagonists

•GABAGABAAA agonists agonists

•Enhanced GABA levelsEnhanced GABA levels

•KK++ channels modulators channels modulators

Feb 4, 2005

STATUS EPILEPTIKUSSTATUS EPILEPTIKUS..Bangkitan yang berlangsung lebih dari 30 Bangkitan yang berlangsung lebih dari 30

mntmntatau adanya dua bangkitan/lebih dimana atau adanya dua bangkitan/lebih dimana

di –di –antara bangkitan tersebut tidak terdapat antara bangkitan tersebut tidak terdapat

pemu-pemu-lihan kesadaran.lihan kesadaran.Penyebab : . Penghentian obat tiba-tiba.Penyebab : . Penghentian obat tiba-tiba. . Kelelahan.. Kelelahan. . Adanya penyakit sistemik.. Adanya penyakit sistemik. . Adanya kelainan neurologi. Adanya kelainan neurologi yang progresif.yang progresif.

Definition - Status Definition - Status EpilepticusEpilepticus• continuous or rapidly repeating seizurescontinuous or rapidly repeating seizures

• no consensus on exact definition - “abn no consensus on exact definition - “abn prolonged”prolonged”– ““no recovery between attacks”no recovery between attacks”– ““20-30 min” --> injury to CNS neurons20-30 min” --> injury to CNS neurons– more practical definition: more practical definition: since isolated tonic - since isolated tonic -

clonic seizures rarely last > few minutes ... clonic seizures rarely last > few minutes ... consider Status if consider Status if sz > 30 min or 2 discrete sz sz > 30 min or 2 discrete sz with no regaining of consciousness betweenwith no regaining of consciousness between

• vs. vs. serialserial sz - close together - regained sz - close together - regained consciousness in betweenconsciousness in between

Epidemiology - SEEpidemiology - SE

• life threateninglife threatening

• USA: -102,000 -152,000 cases / yearUSA: -102,000 -152,000 cases / year - 52,000 deaths / year - 52,000 deaths / year

• of new cases of epilepsy, 12 -30%of new cases of epilepsy, 12 -30% present in Status present in Status

• generalized Status is most common generalized Status is most common form - and subject of this form - and subject of this reviewreview

Pathophysiology - SEPathophysiology - SE

• numerous mechanisms - poorly numerous mechanisms - poorly understoodunderstood

– excess excitation or ineffective inhibitionexcess excitation or ineffective inhibition– there are excitatory and inhibitory there are excitatory and inhibitory

receptors in the brain - activity is usually in receptors in the brain - activity is usually in balancebalance

Pathophysiology - SE Pathophysiology - SE cont’dcont’d

• GLUTAMATE = the major excitatory GLUTAMATE = the major excitatory AA neurotransmitter in brainAA neurotransmitter in brain– any factor which increases Glutamate any factor which increases Glutamate

activity can lead to seizuresactivity can lead to seizures– e.g. 1987- contaminated with Domoic e.g. 1987- contaminated with Domoic

acid, a glutamate analog --> profound acid, a glutamate analog --> profound SE / deathsSE / deaths

Pathophysiology - SE Pathophysiology - SE continuedcontinued• GABA = main inhibitory GABA = main inhibitory

neurotransmitterneurotransmitter– GABA antagonists can cause SE - GABA antagonists can cause SE -

eg Penicillins, other eg Penicillins, other antibioticsantibiotics

– prolonged sz can desensitize GABA prolonged sz can desensitize GABA receptorsreceptors

Pathophysiology - SE Pathophysiology - SE continuedcontinued

• CNS damage can occur - mechanism:CNS damage can occur - mechanism:– uncontrolled neuronal firing -> excess uncontrolled neuronal firing -> excess

glutamate -> this sustained high influx glutamate -> this sustained high influx of calcium ions into neurons leads to cell of calcium ions into neurons leads to cell death (“excitotoxicity”) death (“excitotoxicity”)

– GABA released to counteract this, but GABA released to counteract this, but GABA receptors eventually desensitizeGABA receptors eventually desensitize

– these effects worsened if hyperthermia, these effects worsened if hyperthermia, hypoxia, or hypotensionhypoxia, or hypotension

KLASIFIKASI:KLASIFIKASI: 1. STATUS EPILEPTIKUS KONVULSIF1. STATUS EPILEPTIKUS KONVULSIF ( BANGKITAN UMUM TONIK-KLONIK).( BANGKITAN UMUM TONIK-KLONIK).

2. STATUS EPILEPTIKUS NON KONVULSIF2. STATUS EPILEPTIKUS NON KONVULSIF ( BANGKITAN LENA,PARSIAL KOMPLEKS)( BANGKITAN LENA,PARSIAL KOMPLEKS)

Status epilepticusStatus epilepticus

• It is a medical emergency – requires It is a medical emergency – requires prompt and aggressive treatmentprompt and aggressive treatment

• Therapy should be aimed at:Therapy should be aimed at:

– Rapid termination of status epilepticusRapid termination of status epilepticus

– Prevention of seizure recurrencePrevention of seizure recurrence

– Treatment of underlying causeTreatment of underlying cause

Management of SEManagement of SE

• ABC’s (+ monitor / O2 / large IV’s)ABC’s (+ monitor / O2 / large IV’s)

• START PHARMACOTHERAPY START PHARMACOTHERAPY

• Metabolic acidosis common - if Metabolic acidosis common - if severesevere, give Bicarb , give Bicarb

• if intubating / ventilating - avoid if intubating / ventilating - avoid long-acting n-m blockers - sz long-acting n-m blockers - sz activityactivity

• beware hyperthermia 2º sz - in 30-beware hyperthermia 2º sz - in 30-80% 80% --> passive cooling --> passive cooling

Management of SE Management of SE continuedcontinued• consider....consider....

– ThiamineThiamine– GlucoseGlucose– Pyridoxine 5 gm IV (70 mg/kg kids)Pyridoxine 5 gm IV (70 mg/kg kids)

•reverses INH action inhibiting GABA reverses INH action inhibiting GABA synthesissynthesis

•now recommended routinely by NYC now recommended routinely by NYC Poison Control in Poison Control in REFRACTORYREFRACTORY SE d/t SE d/t frequency of INH ODfrequency of INH OD

Management of SE Management of SE continuedcontinued

• consider underlying causes:consider underlying causes:– infection (systemic / CNS)infection (systemic / CNS)– structural: trauma, CVA, IC bleedstructural: trauma, CVA, IC bleed– CNS malformationsCNS malformations– metabolic - hypoxia, abn electrolytes, metabolic - hypoxia, abn electrolytes,

hypoglycemiahypoglycemia– toxic - alcohol, other drugstoxic - alcohol, other drugs– drug withdrawal - AED’s, benzosdrug withdrawal - AED’s, benzos

Management of SE Management of SE continuedcontinued

•LAB: LAB: gluc, electrolytes, creat, BUN, gluc, electrolytes, creat, BUN, Mg, Phos, LFT’s, AED levels, Mg, Phos, LFT’s, AED levels, toxicology, PTT / INR , ( Blood Gase toxicology, PTT / INR , ( Blood Gase Analyse/ AGD )Analyse/ AGD )

Status Epilepticus - Status Epilepticus - TreatmentTreatment

Immediate treatmentImmediate treatment

1. Secure IV line draw blood for analysis 1. Secure IV line draw blood for analysis (including anticonvulsant levels).(including anticonvulsant levels).

2. Push 2. Push 50 cc of 50% Dextrose i.v., 50 cc of 50% Dextrose i.v.,

100mg thiamine i.v. 100mg thiamine i.v.

3. Monitor vital signs. 3. Monitor vital signs.

4. Examine patient. 4. Examine patient.

5. Protect airway, tongue, head, never 5. Protect airway, tongue, head, never leave patient alone leave patient alone

6. Intubate all patients if first line drugs fail.6. Intubate all patients if first line drugs fail.

Status Epilepticus-Definitive Treatment Status Epilepticus-Definitive Treatment Diazepam - Diazepam - 10mg IV push over 30-60 10mg IV push over 30-60

seconds repeat after 10-15mins upto 30mg seconds repeat after 10-15mins upto 30mg (5mg/min). Repeat after 2-4hrs. (5mg/min). Repeat after 2-4hrs. 100mg/day100mg/day

ii.Good results, easy to administer. (fast .Good results, easy to administer. (fast acting, short lasting) acting, short lasting)

ii.ii. If two doses fail to stop status, then If two doses fail to stop status, then further doses probably won't work either.further doses probably won't work either.

iiiiii. Side effects -- hypotension, . Side effects -- hypotension, bradycardia, respiratory depression, cardiac bradycardia, respiratory depression, cardiac arrest, depresses mental status.arrest, depresses mental status.

PENANGANAN STATUS EPILEPTIKUS.PENANGANAN STATUS EPILEPTIKUS.

0-10 mnt:0-10 mnt: ABC.dan Pasang Infus.ABC.dan Pasang Infus.0-60 mnt:0-60 mnt: Pemberian OAE Short action : DiazepamPemberian OAE Short action : Diazepam 10-20 IV ( maksimal 60 mg).10-20 IV ( maksimal 60 mg). Glukosa 40% 25 -50 cc dan thiamine 250 Glukosa 40% 25 -50 cc dan thiamine 250

mg.mg. Pemeriksaan status neurologi.Pemeriksaan status neurologi.0-60/90 mnt:0-60/90 mnt:

Bila terus kejang Phenitoin 15-18 mg/kg Bila terus kejang Phenitoin 15-18 mg/kg pelan pelan

(kecepatan 50 mg/mnt.)(kecepatan 50 mg/mnt.)90 mnt masih kejang rawat dengan pemberian 90 mnt masih kejang rawat dengan pemberian

anestesi.anestesi.

STATUS EPILEPTIKUS STATUS EPILEPTIKUS REFRAKTER.REFRAKTER.

80% SE KONVULSIKUS DAPAT DIHENTIKAN DENGAN DIAZEPAM DAN PHENYTOIN. BILA BANGKITAN MASIH BERLANGSUNG KITA SEBUT : SE REFRAKTER. HARUS RAWAT ICU DILAKUKAN TINDAKAN ANESTESI.

OBAT YANG DAPAT DIBERIKAN:OBAT YANG DAPAT DIBERIKAN:

MIDAZOLAM: 0,1 mg/kgBB KECEPATAN INFUS4 mg/mnt.DILANJUTKAN DOSIS0,05-0,4mg/kgBB/JAM INFUS.

THIOPENTHONE: 100-250 mg BOLUS PELAN.SELANJUTNYA 3-5 mg/kgBB/JAM.

PENTOBARBITAL: 10-20mg/kgBB KECEPATAN 25 mg/mnt.DILANJUTKAN 1-3mg/kgBB/JAM.

PROPOFOL: 2 mg/kgBB DITINGKATKAN 5-10mg/kgBB/JAM.

SE NON KOVULSIKUS:SE NON KOVULSIKUS: 1/3 DARI KASUS.PILIHAN OBAT : SE LENA : BENZODIAZEPINE IV VALPROAT IV. PARSIAL KOMP : CLOBAZAM LORAZEPAM/IV PHENYTOIN/IV. PADA PASIEN KOMA: PHENYTOIN/IV ANESTESI.

EPILEPSI REFRAKTER/INTRACTABLE EPILEPSY.

BANGKITAN YANG TIDAK BISA DATASIWALAU DENGAN OAE YANG MAKSIMAL.

ETILOGI : BIASANYA OLEH KARENA ADANYA SKLEROSIS PADA HIPOKAMPUS.

PENANGANAN EPILEPSI PENANGANAN EPILEPSI REFRAKTER.REFRAKTER.

1.TERAPI BEDAH.

2. STIMULASI NERVUS VAGUS.

3. MODIFIKASI TINGKAH LAKU.

4. RELAKSASI.

5. MENGURANGI DOSIS OAE.

ComaComaConsciousness requires arousal (coming Consciousness requires arousal (coming from the brainstem reticular formation) from the brainstem reticular formation) and content (the cerebral hemispheres)and content (the cerebral hemispheres)

Alterations in consciousness stem from:Alterations in consciousness stem from:– Disorders affecting the reticular Disorders affecting the reticular

formationformation– Disorders affecting both cerebral Disorders affecting both cerebral

hemisphereshemispheres– Disorders affecting the connections Disorders affecting the connections

between the brainstem and the between the brainstem and the hemisphereshemispheres

Anatomic correlation of Anatomic correlation of consciousnessconsciousness

Brainstem lesions that cause proximate damage to RAS

•Widespread damage in both hemispheres

•Global suppression of cerebral function

Conscious level—less severe

Conscious level--severe

Glasgow Coma ScaleGlasgow Coma Scale

• Three components. Score derived Three components. Score derived by adding the score for each by adding the score for each component.component.

•Eye opening (4 points)Eye opening (4 points)

•Verbal response (5points)Verbal response (5points)

•Best motor response (6 points)Best motor response (6 points)

Glasgow Coma ScaleGlasgow Coma Scale

• Eye openingEye opening•4 - spontaneous4 - spontaneous

•3 - to speech3 - to speech

•2 - to pain2 - to pain

•1 - none1 - none

• Verbal ResponseVerbal Response•5 - oriented5 - oriented

•4 - confused conversation4 - confused conversation

•3 - inappropriate words3 - inappropriate words

•2 - incomprehensible 2 - incomprehensible soundssounds

•1 - none1 - none

• Best Motor ResponseBest Motor Response•6 - obeys6 - obeys

•5 - localizes5 - localizes

•4 - withdraws4 - withdraws

•3 - abnormal 3 - abnormal flexionflexion

•2 - abnormal 2 - abnormal extensionextension

•1 - none1 - none

EXAMINE EXAMINE Coma Coma

• Four domains to examine:Four domains to examine:

– Pupillary responsesPupillary responses– Extraocular movementsExtraocular movements– Respiratory patternRespiratory pattern– Motor responsesMotor responses

Herniasi unkus, std. N III lanjutlanjut

Approach to the Comatose PatientApproach to the Comatose Patient

Initial TreatmentInitial Treatment

• AirwayAirway

• BreathingBreathing

• CirculationCirculation

• ABC - identify and address life ABC - identify and address life threatening inadequaciesthreatening inadequacies

• Treat rapidly progressive metabolic Treat rapidly progressive metabolic disorders -- hypoglycemiadisorders -- hypoglycemia

• Evaluate for intracranial hypertension Evaluate for intracranial hypertension and imminent herniation and treatand imminent herniation and treat

AirwayAirway• Intubate (protecting neck) “Intubate (protecting neck) “anyone anyone

who will let you”who will let you”– Any of the following are adequate Any of the following are adequate

criteriacriteria•GCS < 9GCS < 9

•Airway not secure or openAirway not secure or open

•Respiration not adequateRespiration not adequate

•Any significant respiratory failureAny significant respiratory failure

•Uncertainty regarding direction or rate of Uncertainty regarding direction or rate of mental status changes, particularly if mental status changes, particularly if constant observation not available (during constant observation not available (during CT scans, etc..)CT scans, etc..)

BreathingBreathing• Evaluate - is patient moving adequate Evaluate - is patient moving adequate

air, is respiratory rate appropriate, is air, is respiratory rate appropriate, is gas exchange adequate, are breath gas exchange adequate, are breath sounds adequate and symmetricalsounds adequate and symmetrical

• Must assure oxygenation and Must assure oxygenation and ventilationventilation

• If intubated don’t forget to ventilateIf intubated don’t forget to ventilate

• Identify and immediately treat Identify and immediately treat problems - pneumothorax, airway problems - pneumothorax, airway obstruction, etc..obstruction, etc..

CirculationCirculation

• Is patient in shock? Is patient in shock? •Check pulses, heart rate, blood pressure, Check pulses, heart rate, blood pressure,

perfusionperfusion

•Remember hypotension is Remember hypotension is latelate sign of sign of shockshock

• Start treatment for shockStart treatment for shock•Do not restrict fluids in comatose patient Do not restrict fluids in comatose patient

with inadequate intravascular volume. with inadequate intravascular volume.

•Cardiac output and cerebral perfusion are Cardiac output and cerebral perfusion are much more important than fluid restrictionmuch more important than fluid restriction

CirculationCirculation

• Use isotonic solutions and blood, Use isotonic solutions and blood, as indicated.as indicated.

• Do not use hypotonic solutions to Do not use hypotonic solutions to treat shock, particularly patients treat shock, particularly patients with coma or possible cerebral with coma or possible cerebral edemaedema

• Identify life threatening Identify life threatening hemorrhage and control it.hemorrhage and control it.