Status epilepticus kong kiat
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    Status epilepticus kong kiat Status epilepticus kong kiat Presentation Transcript

    • Status Epilepticus Time is brain! Kongkiat Kulkantrakorn, M.D. Associate ProfessorNeurology division, Department of Internal Medicine Faculty of Medicine , Thammasat University 1
    • Status Epilepticus: Operational Definition• Generalized, convulsive status epilepticus in adults and older children (>5 years old) refers to at least 5 min of – (a) continuous seizures or – (b) two or discrete seizures between which there is incomplete recovery of consciousness 2
    • Types of Seizure Emergencies• Convulsive status epilepticus (CSE)• Nonconvulsive status epilepticus (NCSE)• Acute repetitive seizures or clusters 3
    • Generalized Convulsive Status Epilepticus (GCSE): Characteristics• Broad spectrum of clinical presentations – Tonic-clonic motor activity – Impaired consciousness – Ictal discharges• Subtle GSCE – Continuous subtle motor phenomena – Generalized ictal discharges – Profound coma• Other types – Myoclonic – Focal 4
    • Status epilepticus• Incidence: – 27/100,000 in young adult » with 14% mortality rate – 86/100,000 in elderly » with 38% mortality rate• Number of cases: – 65,000- 150,000 cases per year in USA 5
    • Mortality in Status Epilepticus by Age Group Among 546 patients with status epilepticus in Richmond, Virginia, from 1982 to 1989. % Mortalitiy 60 50 40 30 20 10 0 0–1 2–4 5–9 10–19 20–39 40–59 60–79 80+ Age Group 6DeLorenzo RJ, et al. Epilepsia. 1992;33(suppl 4):515-525.
    • Survival in Status Epilepticus by Duration of Seizure Survival curves for prolonged (solid line) and nonprolonged (dashed line) seizure duration. The data are presented as percent survival based on a 30-day follow-up period. % Survival 100 90 Length of Seizure >1 h 80 <1 h 70 60 0 5 10 15 20 25 30 Days 7DeLorenzo RJ, et al. Epilepsia. 1992;33(suppl 4):515-525.
    • Main causes of status epilepticus• Low AED level patients with epilepsy (34%)• Remote symptomatic causes (24%)• Cerebrovascular accidents (22%)• Anoxia or hypoxia (~10%)• Metabolic causes (~10%)• Alcohol and drug withdrawal (~10%) 8
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    • Generalized convulsive status epilepticus after nontraumatic subarachnoid hemorrhage: the nationwide inpatient sample.• Nationwide Inpatient Sample, a database of admissions to nonfederal United States hospitals between 1994 and 2002• Among the 29,998 patients hospitalized with nontraumatic SAH, GCSE was reported to occur in 0.2% of patients (N = 73 patients).• GCSE risks: the youngest tertiale 49 years old or younger; OR ( 2.0-5.1), those with renal disease OR 4.8 ( 2.6-8.8), and those who did not undergo a neurosurgical procedure involving a craniotomy ; OR 2.2 (1.3-3.8). Claassen J, et al. Neurosurgery 2007 ;61:60-4. 10
    • Generalized convulsive status epilepticus afternontraumatic subarachnoid hemorrhage: the nationwide inpatient sample. • GCSE : higher in-hospital mortality (48% versus 33% of patients; OR 2.1 (1.3-3.4; P = 0.002) and longer (9 versus 7 days; P = 0.016) and more expensive (US $39,677 versus US $26,686; P = 0.007) hospitalizations. • CONCLUSION: GCSE rarely complicates SAH; however, it is associated with increased patient mortality, length of hospital stay, and cost. GCSE occurs more frequently in young patients, those with a history of renal disease, and patients who do not undergo a craniotomy 11
    • Nonconvulsive electrographic seizures after traumatic brain injury result in a delayed, prolonged increase in intracranial pressure and metabolic crisis.• 20 moderate to severe TBI (Glasgow Coma Score 3- 13) : continuous EEG and cerebral microdiablysis for 7 days after injury.• Ten patients had seizures , matched with control TBI. SE in 7 patients• Using a within-subject design, post-traumatic seizures resulted in episodic increases in intracranial pressure (22.4 +/- 7 vs. 12.8 +/- 4.3 mm Hg; p < .001) and an episodic increase in lactate/pyruvate ratio (49.4 +/- 16 vs. 23.8 +/- 7.6; p < .001) in the seizure group. • . Vespa PM, et al. Crit Care Med. 2007 Dec;35(12):2830-6 12
    • • Using a between-subjects comparison, the seizure group demonstrated a higher mean intracranial pressure (17.6 +/- 6.5 vs. 12.2 +/- 4.2 mm Hg; p < .001), a higher mean lactate/pyruvate ratio (38.6 +/- 18 vs. 27 +/- 9; p < .001) compared with nonseizure patients.• The intracranial pressure and lactate/pyruvate ratio remained elevated beyond postinjury hour 100 in the seizure group but not the nonseizure group (p < .02).• CONCLUSION: Post-traumatic seizures result in episodic as well as long-lasting increases in intracranial pressure and microdialysis lactate/pyruvate ratio. These data suggest that post-traumatic seizures represent a therapeutic target for patients with traumatic brain injury. 13
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    • Management of Status Epilepticus:General Principlesn Medical emergencyn Prolonged electrical seizure activity causes neuronal damagen EEG monitoring essentialn Systemic factors exacerbate SE-induced neuronal damagen The longer the duration, the later the EEG stage, and the more subtle the motor manifestations, the harder SE is to stopn A predetermined Rx protocol more effective 18
    • Schematic Approach of Status EpilepticusLowensteinD, Alldredge B. NEJM. 1998; 338:970-976. 19
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    • 1. Assess and control airway 2. Monitor vital signs ( including temperature ) 3. Conduct pulse oximetry and monitor cardiac function 4. Perform rapid blood glucose assay Start intravenous infusion Administer thiamine ( 100 mg ) and glucose ( 50 ml of 50 percent dextrose )LowensteinD, Alldredge B. NEJM. 1998; 338:970-976. 21
    • Investigation•Antiepileptic drug level•Septic work up•CBC, UA•Blood sugar•BUN, Cr•Liver function test•Electrolyte•Calcium, Magnesium,Phosphorous•Toxicology•Lumbar puncture•CT brain•MRI brain 22
    • Start anticonvulsant therapyTake focused Hx and examine patient Perform laboratory studiesPerform laboratory studies Complete blood countKnown seizure disorder or other Serum electrolytes and calcium illnesses ? Arterial - blood gasTrauma ? Liver functionFocal neurologic signs ? Renal functionSigns of medical illnesses ( e.g., Toxicology infection, hepatic or renal Serum AEDs concentrations disease, substance abuse ) ? Undertake further work-up to define cause Manage other medical problems 23
    • Schematic Approach of Status EpilepticusAntiepileptic Drug Therapy • Begin with Lorazepam 4mg • (0.1 mg/kg ) at 2 mg/min i.v. • or Diazepam 10-20 mg • (0.3 mg/kg ) at 2 mg/min i.v. LowensteinD, Alldredge B. NEJM.1998; 338:970-976. 24
    • Seizures continuing at 5 minPhenytoin (20 mg/kg IV at 50 mg/min) orFosphenytoin(20 mg/kg IV PE at 150 mg/min) Seizures continuing at 20 - 25 minPhenytoin or Fosphenytoin (additional 5 - 10 mg/kg or 5 - 10 mg/kg PE)LowensteinD, Alldredge B. NEJM.1998; 338:970-976. 25
    • Seizures continuing at 30 - 35 min Phenobarbital ( 20 mg/kg IV at 50 - 75 mg/min ) Seizures continuing at 50 - 55 min Phenobarbital ( additional 5 - 10 mg/kg )LowensteinD, Alldredge B. NEJM.1998; 338:970-976. 26
    • Seizures continuing at 60 - 65 min Anesthesia with IV midazolam , pentobarbital or propofolLowensteinD, Alldredge B. NEJM.1998; 338:970-976. 27
    • EFNS guideline on the management of status epilepticus in adults.• The preferred treatment pathway for generalised convulsive status epilepticus (GCSE) is• Intravenous (i.v.) administration of 4-8 mg lorazepam or 10 mg diazepam directly followed by 18 mg/kg phenytoin.• If seizures continue more than 10 min after first injection, another 4 mg lorazepam or 10 mg diazepam is recommended. Eur J Neurol. 2009 Dec 30. [Epub ahead of print]
    • EFNS guideline on the management of status epilepticus in adults.• The initial therapy of non-convulsive SE depends on type and cause. Complex partial SE is initially treated in the same manner as GCSE.• However, if it turns out to be refractory, further non- anaesthetising i.v. substances such levetiracetam, phenobarbital or valproic acid should be given instead of anaesthetics.• In subtle SE, in refractory GCSE is treated by anaesthetic doses of barbiturates, midazolam or propofol; the anaesthetics are titrated against an electroencephalogram burst suppression pattern for at least 24 h. Most patients, i.v. anaesthesia is required. Eur J Neurol. 2009 Dec 30. [Epub ahead of print]
    • Evidence based review Comparison of 2 drugs• Benzodiazepine: – no difference among lorazepam, diazepam, midazolam• Hydantoin: – Fosphenytoin: less pain and phlebitis at injection side – Faster infusion rate in fos-PHT with 10-15 min dephosphorylation » Save 19 min on 150mg/kg vs 50 mg/kg in 70 kg patient » Advantage: displace PHT form albumin binding site in chronic PHT treatment, rapidly increase free PHT 30
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    • Pharmacology of AED 37
    • Diazepam Peak brain levels in 5 minutes by IVDosage : I.V. : 0.15-0.25 mg/kg.IV rate : No faster than 5 mg/minEffective level : more than 0.2-0.8 mcg/dlTime to stop Sz : 1 - 3 minutesEffective duration : 15-30 minutesHalf-life : 30 hr, rapid redistribution to fat/muscleVolume of distribution : 1-2 L/kgAdvantage : rapid action, can be given rectallyDisadvantages : hypotension, respiratory depression
    • Phenobarbital Peak brain levels in 20-60 minutes by IVDosage : I.V. : 20 mg/kg.IV rate : No faster than 100 mg/minEffective level : more than 20 mcg/dlTime to stop Sz : 20 - 30 minutes, 60-70% effectiveEffective duration : > 24 hoursHalf-life : 4-6 daysVolume of distribution : 0.7 L/kgAdvantage : Long lasting therapeutic effortDisadvantages : Hypotension, Respiration depression Sensorial depression, Consider intubation when used after diazepam administration
    • Phenytoin Peak brain levels in 15 minutes by IVDosage : I.V. : 20 mg/kg.IV rate : No faster than 50 mg/minEffective level : more than 25-35 mcg/dlTime to stop Sz : 10 - 30 minEffective duration : > 24 hr, 50% effective after failing BDZHalf-life : varies, around 24 hoursVolume of distribution : 0.5-0.8 L/kgAdvantage : No sedation, less respiratory depressionDisadvantages : hypotension, cardiac arrhythmia need ECG monitoring, purple glove syndrome, cannot mix with glucose
    • Fosphenytoin Fosphenytoin PhenytoinAll Fosphenyoin dosing is expressed in phenytoin equivalents (PE) (1mg PE Fosphenytoin = 1 mg IV phenytoin)
    • Phenytoin vs Fosphenytoin Phenytoin FosphenytoinVehicle Propylene glycol & ethanol Water, TRISpH 12 8.6 - 9Maximuminfusion rate 50 mg/min 150 mg PE/minAdmixtures No Saline, dextrose
    • Fosphenytoin IV administration-events at maximum dose and rate IV Fosphenytoin (n=90) IV Phenytoin (n=22)Percentage of patients Nystagmus Dizziness Pruritus Ataxia Somnolence Hypotension Headache
    • Summary—Fosphenytoin benefits (rapid administration)• Rapidly and completely converted to phenytoin after IV and IM dosing• Completely converted regardless of dose, rate, or route• Bioequivalent to phenytoin when infused at 150 mg PE/min• Therapeutic phenytoin levels rapidly achieved — Within 7 minutes with IV infusion at 150 mg PE/min — Within 30 minutes with IM injection
    • Summary—Fosphenytoin benefits (tolerability)• Better tolerated at injection site than IV phenytoin• Improved flexibility of IM administration• CNS adverse events similar to phenytoin• Transient paresthesia and pruritus with IV infusion• Fewer reductions in IV rates and site changes than IV phenytoin• IV loading dose-special populations
    • Recommended doses and rates
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    • •32 cases diagnosed as SE with VPAiv treatment; 12 and 20 patientsreceived VPAiv as the first- and second-line therapy, (15-20 mg/kg).•SE ceased in 7/12 patients (75%) and in 7/20 (35%) patients•Hypotension and leucocytosis associated with death•Mortality 54.8% 48
    • • Thirty-two patients (15 female) were treated with i.v. LEV for SE (median age 71 years).• SE was generalized convulsive in five, nonconvulsive in 20, and simple focal in seven patients.• Etiology was acute 13 times and remote symptomatic 16 times; three SE were of unknown etiology.• Therapy was initiated within a median time of 3 h and• LEV i.v. was applied within a median time of 6 h. Median LEV bolus was 2,000 mg; median total dose on day 1 was 3500 mg• Benzodiazepines plus i.v. LEV terminated SE in 23 patients without application of additional anticonvulsants, 10 within 30 min.• LEV could not terminate SE in seven patients.
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    • Admixture and Administration of Injectable AEDs AED Dosage/Rate of Infusion Loading Dose: 15-20 mg/kg; up to 25 mg/kg has been used clinically. Maintenance Dose: 300 mg/day or 5-6 mg/kg/day in 3 divided doses,IM not Phenytoin recommended; Dilute in NS or LR, DO NOT MIX WITH DEXTROSE, do not (Dilantin®) refrigerate, use within 4 hrs. Use inline 0.22-5 micron filter Infusion Rate: Should not exceed 50 mg/min; elderly/debilitated should not exceed 20 mg/min Status epilepticus: Loading Dose: 15-20 mg PE/kg IVFosphenytoin Non-emergent: Loading Dose: 10-20 mg PE/kg IV or IM; MD: 4-6 mg PE/kg/day IV (Cereneu®) or IM Infusion Rate: Should not exceed 150 mg PE/minute Loading : 15-20/kgValproic acid No Loading Dose; 1000-2500 mg/day in 1-3 divided doses(Depakine®) Admin over 60 min (<= 20 mg/min); rapid infusion over 5-10 min as 1.5-3 mg/kg/min >16 y/o. No loading dose. 1000 mg/day (500 MG BID). Dose can be increased byLevetiracetam 1000 mg/day ever 2 weeks up to a maximum dose of 3000 mg/day Rate: Dilute in 100ml of normal saline (NS), lactated ringers (LR) or dextrose 5% (Keppra®) and infuse over 15 minutes
    • Special group of status epilepticus 55
    • SE in children• Young children: More febrile seizures and acute causes, infection in etiology than older children• Generalized SE, less NCSE• Similar treatment protocol as in adult• May use IV or rectal diazepam or buccal /intranasal midazolam as initial treatment• Should not use valproate if below 2 years old or propofol• Midazolam IV infusion in refractory cases 56
    • Relationship between depth of coma (x-axis), prognosis (x-axis),degree of structural brain damage (red y-axis) and epileptic brain dysfunction (blue y-axis) due to status epilepticus.
    • Refractory Status epilepticus• Definition: failure to stop after 2 drugs• Slow taper of continuous infusion at least over 24 hours after seizure control• Possible benefit of more intensity of burst suppression• Recurrence: 25% in acute or remote symptomatic and idiopathic cases• Role of neuroprotection ??? 58
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    • Status epilepticusTiming is everything Save the brain! 63