1 - Status Epilepticus

8/13/2019 1 - Status Epilepticus

1/83

CURRICULUM VITAE

dr. Imam Rusdi,Sp S (K)

Lahir : Yogyakarta, 16 September 1952 Pekerjaan : Dosen /dokter Alamat : Jl Sisingamangaraja 76 Jogja

Riwayat PendidikanSpesialis Saraf UGM (1997)

Riwayat Jabatan / pekerjaan- KepalaSMF Saraf/BagianSarafRS Sardjito/FK UGM- Anggota PERDOSSI- AnggotaPokdiNyeri&NyeriKepala- AnggotaPokdiEpilepsi


2/83

Neuro-Emergency

Update

Imam rusdi, Neuro-Emergency Update,FK UGM/RS Dr Sardjito, 26-27 Maret 2011

2

Status Epilepticus in Children Adult Pregnancy

Childbearing


3/83

Status Epilepticus (SE) The term status epilepticus may be used to describe any

continuing type of seizure.

Status epilepticus is a common, life-threatening

neurologic disorder. It is essentially an acute, prolongedepileptic crisis.

In early studies, SE was defined by its duration, that is,as continuous seizures occurring for longer than 1 hour .

Clinical and animal experiences later showed thatpathologic changes and prognostic implications occurredwhen SE persisted for 30 minutes. Therefore, the timefor the definition was shortened.

EFNS guideline on the management of status epilepticus in adultsEuropean Journal of Neurology 2010, 17: 348 355 3


4/83

More than 30 minutes of continuous seizureactivity ortwo or more sequential seizureswithout full recovery of consciousness between

seizures. More recently, SE be defined as any seizure

lasting longer than 5 minutes based on naturalhistory data that show typical generalizedconvulsive seizures that resolve spontaneouslyafter 3-5 minutes.

Status Epilepticus (SE)-cont

4


5/83

Diagnosis Children (%) Adults (%)Stroke 3 25

Drug change/noncompliance 20 20

Alcohol/other drugs 2 15CNS infection 5 10

Hypoxia 5 10

Metabolic 10 10

Tumor


6/83

o Low blood concentrations of AED (34%)o Remote symptomatic causes (24%)o Cerebrovascular accidents (22%)o Anoxia or hypoxia (10%)o Metabolic causes (10%)o Alcohol and drug withdrawal (10%)

6

Causes of SE


7/83

SE Classification

Generalized convulsive SE (GCSE)Subtle SE

Non-Convulsive SE (NCSE) Absence SE Complex partial SE

Simple Partial SE

7


8/83

Non ColvulsiveStatus Epilepticus

NCSE refers to continuous seizure activitywithout predominant motor activity.

This should not be confused with subtlestatus epileptics which refers to GCSE inwhich the motor findings have diminished

either through high doses of administeredmedications or from muscular fatigue dueto prolonged seizure activity

8


9/83


10/83

Aktifitas serangan yang berlangsung terus akanmengurangi secara bertahap reseptor2 GABA Apada synaptic membrane diikuti denganinternalisasi reseptor ke dalam vesikel2endositotik dan degradasi berikutnya.

Proses ini berakibat pada erosi endogen GABA

ergic inhibisi yang akan meningkatkann aktifitasepileptic berkepanjangan.

10

Patomekanisme Status Epilepticuscont.


11/83

Hilangnya reseptor GABA A post sinaptikmerupakan factor patofisiologik yg relevansehingga terjadi farmakoresisten terhadap obat2seperti benzodiazepine, barbiturate dan propofol.

Sebaliknya, selama aktifitas epileptic berlangsung,reseptor NMDA secara progresif berpindah kesynaptic membrane, sehingga menambahreseptor NMDA exitatorik presynaps. Proses inimemudahkan exitabilitas neuron dan berikutnyamemperpanjang SE.

11



12/83

Namun sebaliknya, meningkatnya expressireseptor Glutamat dapat merupakan target yang

dipakai pada farmakological management dariSE advanced stage. Absance SE with 3-Hz spike wave discharge

akan menginduksi dengan excessive inhibition.Bentuk SE spt ini tdk menyebabkan neuronalinjury dengan excitasi yang excessive.

12



13/83

Seizures produce a number ofphysiologic consequences.

During a generalized convulsion transientapnea and hypoxia .

Initially, brain compensatory mechanisms mayprevent neuronal injury from seizures hypertension with increased cerebral blood flow.Normal physiological response includes anincrease in body temperature with up to 43%

Temperature >100 F

13


14/83

Glucose levels also increase, and lactic acidosis(occurs within 60 seconds of a convulsive event and

normalizes within one hour after ictus). A rise in the peripheral white blood cell count withoutan increase in bands is often seen.

If the seizure persists, at approximately 30 minutesthe homeostatic mechanisms begin to deteriorate.

14

Seizures produce a number ofphysiologic consequences. Cont.


15/83

Animal models suggest that, even if systemic factors,such as acidosis and hypoxia are controlled,prolonged status epilepticus results in direct neuronaldamage from neurotoxic amino acids and calciuminflux.

15

Seizures produce a number ofphysiologic consequences. Cont.


16/83


17/83

Management ofStatus Epilepticus

17

o Prehospital Concernso Emergency Departemento

ICU


18/83

Prehospital Concerns

Managing the airwayMaintainingoxygenationObtainingIntra Venous accessProtecting the patient from injury.(The use of a padded tongue blade

is contraindicated since it may induceemesis or break a tooth )

18


19/83


20/83

When IV access is not immediately available, rectaldiazepam is an option.One prospective study reported that there were no

significant differences betweenrectal andintravenous diazepam therapy with regard to SEduration, intubation, or recurrent seizures in theemergency department (ED).

These data suggest that prehospital administrationof diazepam may shorten the duration of SE inchildren and simplify the subsequent management.

20

Prehospital Concerns cont..


21/83

In a retrospective study on prehospital seizuremanagement in children, rectal diazepam (5 mg/kg),was compared to IM midazolam(15 mg /kg).

Over the 4 year study period,2566 children presented with seizures and107 children were eligible for entry into the study.Of these 107 patients received diazepamand 45 received midazolam.

21



22/83

Both drugs were effective in stopping seizures within5 minutes of drug administration; however, fewerpatients in the midazolam group suffered apnea.

In a study comparing IV diazepam to IM midazolam,Chamberlain et al concluded that IM midazolam isan effective anticonvulsant for children with motor

seizures and an important alternative when IVaccess is not easily available.

22



23/83

Vilke et al compared IM to IV midazolam andreported that IV delivery was more effective:47/49 in the IV group vs 20/25 with IM

administration (p less than 0.05).Four patients (three treated IM and one IV) hadrespiratory compromise necessitating field airwaymanagement. In light of the Chamberlain and Vilke

studies, some experts recommend IV midazolam asthe agent of choice in the prehospital managementof seizures.

23



24/83

Tests include a determination of :serum glucose

electrolytesurea nitrogen, creatininemagnesium, phosphate, calciumcomplete blood count

pregnancy testsanti-epileptic drug levelsliver function testsdrugs of abuse screening.

24

Diagnostic TestingLaboratory


25/83

Status EpilepticusClinical manifestations

Convulsive SERelated to acutely elevated serumcatecholamine levelsRespiratory interferenceCardiovascular system adversely affected

Acidosis and rhabdomyolysis Hyperkalemia Myoglobinuria

25


26/83

Status EpilepticusClinical manifestations

Nonconvulsive SE (10-15%) Obtundation

underlying systemic or neurological disorder sedating or paralyzing medication

Alterations in behavior Slow mentation

Confusion Stupor coma Unexplained, prolonged coma

26


27/83


28/83

Protocol for Convulsive SEMinutes 0-5

100% O2 by mask or canulaHead position for airway patency

Assist ventilation if necessaryCardiac monitoringRecord vital signs: BP, temperature, etc.Check glucose

Establish IVDraw blood for glucose, chemistry, CBC, toxicology,antiseizure medication level, etc.

28


29/83

Protocol for Convulsive SE Minutes 5-15

Thiamine 100 mg IV and 50 ml D50W if indicated Sedatives

Lorazepam (ativan) 0.1 mg/kg IV, 2 mg/min, OR

Diazepam (valium) 0.2 mg/kg IV, 5 mg/min, OR Diazepam (valium) 0.5 mg/kg per rectum (if no IV) Anticonvulsant

Fosphenytoin 15-20 mg/kg IV, 150 mg/min, OR Phenytoin (dilantin) 15-20 mg/kg IV, 50 mg/min, OR Valproic acid (depakin) 800 mg IV

Monitor BP and cardiac rhythm Do not infuse phenytoin through a line containing

glucose

29


30/83

Protocol for Convulsive SE Minutes 15-30

Repeat lorazepam or diazepam if seizure continues Additional fosphenytoin or phenyoin in increments dose of

5 mg/kg to total 30 mg/kg

Minutes 30-60 Monitor respirations because patient may require assistedventilation (intubation). Monitor EEG.

If status persists, give phenobarbital 20 mg/kg, 100 mg/min Midazolam (dormicum) IV infusion (0.2 mg/kg slow bolus;

0.1-2.0 mg/kg/hr) Propofol 1-5 mg/kg bolus over 5 min, then 2-4 mg/kg/hr

Minutes 60 or more If status remains refractory, consider pentobarbital 5 mg/kg

load, then 1-4 mg/kg/h infusion30


31/83


32/83

Seizures continuing stage ofRefractory Status Epilepticus

General anesthesia should be induced Propofol : 2mg/kg IV bolus, Repeat if necessary, followed byinfusion (5mg/kg/hr)

Thiopental : 100-250mg IV bolus over 20 sec. with further50mg bolus every 2-3 min.until seizure control followed by IVinfusion(3-5mg/kg/hr) Midazolam : 0.1-0.3mg/kg IV bolus dose at the rate of 4mg/minfollowed by infusion(0.05-0.4mg/kg/hr) If seizures have been controlled for 12hrs., reduce the doseover further 12hrs. If seizure recurs again GA agent should be given


33/83

Lancet Neurol 2006; 5: 252

Diff ti l Di i Of Alt d


34/83

Differential Diagnosis Of AlteredMental Status In The Patient

Who Has Seized

Post-ictal state

NCSE or subtle convulsive status

Hypoglycemia

CNS infection

CNS vascular event

Drug toxicity

Psychiatric disorder

34


35/83

NonconvulsiveStatus Epilepticus (NCSE)

NCSE, like convulsive status epilepticus, is a state ofcontinuous or intermittent seizure activity lasting morethan thirty minutes without a return to baseline function.

NCSE can be either a primary generalized process(absence status) or secondary generalized (complexpartial status).

35


36/83

NCSEThough the distinction is not clear in theliterature, NCSE in general should bedistinguished from subtle GCSE, which is the

end stage of GCSE, associated with anoxicbrain injury, and has a very poor prognosis.

36


37/83


38/83

Special Situations Alcohol Withdrawal Seizures (AWS)

Of special concern to any emergency physician is the relationof alcohol to seizures. Twenty to 40% of seizure patientspresenting to an ED will have their seizures related to

alcohol abuse, and alcohol is reported as a causative factorin 15 to 24% of patients with status epilepticus.

Diagnostic yield for CT after first alcohol related seizure is high,mainly because patients who overuse alcohol have a high

incidence of structural intracranial lesions, such as subduralhematomas or other intracranial hemorrhages.


39/83

EclampsiaEclampsia is the major consideration in pregnantpatients of more than 20-week gestation and up to23 days postpartum who present with new onsetseizures . Magnesium has been demonstrated tobe the therapy of choice in the treatment of acuteeclamptic seizures and for prevention of recurrenteclamptic seizures. A systematic review of fourgood quality trials involving 823 women found

magnesium sulfate to be substantially moreeffective than phenytoin with regards to recurrenceof convulsions and maternal death.

39


40/83

Complications, such as respiratory depressionand pneumonia, were also less for magnesiumthan for phenytoin.

Magnesium showed a trend towards increasedincidence of renal failure when compared tophenytoin; however, this was not statisticallysignificant. Magnesium sulfate was alsoassociated with benefits for the baby, includingfewer admissions to the NICU.

40

Eclampsia


41/83


42/83


43/83

Ten to 50% of cases of status epilepticus in childrenare associated with febrile seizures; status in thisgroup is a consistent predictor of increased risk forsubsequent seizures.Simple febrile seizures are a benign process.When they occur in children older than 18 monthswho have not been on antibiotics, they do notrequire any particular diagnostic work-up, even for afirst time event. Management focuses on a carefulhistory and physical, and on parental education.

43

Febrile Seizures


44/83

Two to four percent of all children will have a simplefebrile seizure. Children who have had a febrile seizurehave a 25 to 50% chance of having a second event,usually within a year. Children at highest risk forrecurrence are those with a first degree relative who hashad a febrile seizure, complex first febrile seizure, or ageyounger that one year when the first event occurred.There is an increased incidence of developing epilepsy inchildren who have had a simple febrile seizure (2.4%versus a .4% incidence in the general population).

44

Febrile Seizures


45/83

Patients with simple febrile seizures require no specialworkup or treatment. Reassuring the parents is often themost Herculean task. Nearly half of parents think thattheir child is dying during the seizure. Such concernsneed to be addressed; simply suggesting the child bedischarged on acetaminophen is not appropriate.

45

Febrile Seizures


46/83


47/83

S E il i


48/83

Both phenytoin and phenobarbital are often effective inpediatric status if a bolus administration of a benzodiazepinefails. However, as in adults, continuous infusion ofbenzodiazepines have been reported as successful. Infection

has been reported as a more common cause of status inchildren than in adults. Therefore, many physicians willempirically cover such children with broad-spectrumantibiotics, usually ceftriaxone (or the combination of

ceftriaxone and amoxicillin in neonates). The routine use ofempiric acyclovir to treat presumed herpes encephalitis in theneonate remains unstudied.

48

Status Epilepticusin Children


49/83


50/83

50

Causes

Fever Medicationchange. 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


51/83

51

Drugs which can cause seizures

Antibiotics Penicillins Isoniazid Metronidazole

Anesthetics, narcotics Halothane, enflurane Cocaine, fentanyl Ketamine

Psychopharmaceuticals Antihistamines Antidepressants Antipsychotics Phencyclidine Tricyclic antidepressants


52/83


53/83


54/83

54

Respiratory Hypoxia and hypercarbia

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


55/83

55

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


56/83

56

Neurogenic pulmonary edema

Rare complicationLikely occurs as

consequence of markedincrease of pulmonaryvascular pressure

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


57/83

57

Acidosis

Respiratory

Lactic Impaired tissue oxygenation Increased energy expenditure


58/83

58

Hemodynamics

Sympathetic overdrive Massive catecholamine /

autonomic discharge Hypertension Tachycardia High CVP

0 min 60 min

Exhaustion Hypotension hypoperfusion

Cerebral blood flow


59/83

59

Cerebral blood flow Cerebral O2 requirement

Blood pressure

Blood flow

O2 requirement

Seizure duration

Hyperdynamic phase CBF meets CMRO2

Exhaustion phase CBF drops as

Hypotension sets in Autoregulation

exhausted Neuronal demage

ensue


60/83

60

Glucose

G l u c o s e

Seizure duration

30 min

SE

SE + hypoxia


61/83

61

Hyperpyrexia

Hyperpyrexia may develop during protractedSE, and aggravate possible mismatch ofcerebral metabolic requirement and substratedelivery

Treat hyperpyrexia aggressively Antipyretics, external cooling Consider intubation, relaxation, ventilation


62/83


63/83


64/83


65/83

65

Initial investigations

Labs Na, Ca, Mg, PO 4 , glucose

CBC Liver function tests, ammonia Anticonvulsant level

Toxicology


66/83

66

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


67/83


68/83

68

Treatment

Hyponatremia: Give 5 cc/kg of 3% (hypertonic saline)

Hypocalcemia: Give 20-25 mg/kg of Calcium Chloride


69/83

69

Treatment

The longer you wait with anticonvulsant, themore anticonvulsant you will need to stop SE

Most common mistake is ineffective dose


70/83

70

Anticonvulsants

Rapid acting

plus

Long acting


71/83

71

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


72/83

72

Benzodiazepines

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

Midazolam May be given i.m.


73/83


74/83

74

Anticonvulsants - Long acting

Phenobarbital 20 mg/k g i.v. over 10 - 15 min

Onset 15-30 min May cause hypotension, respiratory depression

Initial choice of long acting


75/83

75

Initial choice of long actinganticonvulsants in SE

Is patient an infant?Is patient already receiving phenytoin?

Yes No

At high risk for extravasation?

(small vein, difficult access etc.)?

Phenobarbital

YesNo

Phenytoin Fosphenytoin


76/83


77/83

77

NCSE?

Neurologic signs after terminationof SE are common: Pupillary changes Abnormal tone Babinski Posturing

Clonus May be asymmetrical


78/83

78

NCSE?

Up to 20% of children with SE have

NCSE after GCSE


79/83

Management of a pregnant


80/83

Management of a pregnantpatient in status epilepticus

Establish the ABCs, and check vital signs, includingoxygenation. Assess the fetal heart rate or fetal status.Rule out eclampsia.

Administer a bolus of lorazepam (0.1 mg/kg, ie, 5-10 mg) atno faster than 2 mg/min.Load phenytoin (20 mg/kg, ie, 1-2 g) at no faster than 50mg/min, with cardiac monitoring.If this is not successful, load phenobarbital

(20 mg/kg, ie, 1-2 g) at no faster than 100 mg/min.Check laboratory findings, including electrolytes, AED levels,glucose, and toxicology screen.If fetal testing results are nonreassuring, move to emergentdelivery.

80


81/83

81


82/83


83/83

Alhamdulillahirobbilalamin

Semoga bermanfaat

Documents

1 - Status Epilepticus