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  1. Focus on Status Epilepticus Joseph I. Sirven, MD On behalf of the American Epilepsy Society Resident, Medical Student, Nursing and Pharmacology Education Committee

  2. History of Status Epilepticus • Xth Marseilles Colloquium (1962) • Development of modern conceptual basis of status epilepticus (SE) • First meeting devoted to SE • Gastaut

  3. History of Status Epilepticus • Definition • “ a term used whenever a seizure persists for a sufficient length of time or is repeated frequently enough to produce a fixed or enduring epileptic condition.” • … “The fixed and enduring epileptic condition should last at least 30-60 minutes in order to qualify as SE.”

  4. Status Epilepticus  Definition • More than 10 minutes of continuous seizure activity or • Two ormore sequential seizures spanning this period without full recovery between seizures

  5. Physiological Consequences of Status Epilepticus

  6. Physiological Changes in GCSE-Compensation

  7. Physiological Changes in GCSE-Decompensation

  8. ImagingEvidence of SE Damage

  9. Epidemiological Factors that Impact Outcome/Therapy • Duration of SE = Rapid ID and Treatment • Etiology = Prevention/Neuroprotection • Age = Neuroprotection

  10. Principles of Pharmacologic Therapy

  11. Ideal Antiepileptic Drug • Intravenous routes • Few adverse effects • High CNS penetrance • Easy pharmacokinetics • Rapid efficacy

  12. General Measures in SE Management • Maintenance of oxygenation and circulation • Assessment of etiology and lab evaluations • Obtaining intravenous access and initiation of therapy

  13. AEDs for Status epilepticus • Benzodiazepines • Diazepam • Lorazepam • Midazolam • Phenytoin ( Fosphenytoin) • Valproic acid • Phenobarbital

  14. Benzodiazepines • Diazepam (Valium, Diastat) • Lorazepam (Ativan) • Midazolam (Versed)

  15. Diazepam • High lipid solubility • Fast redistribution: 15- 20 minutes • T1/2 elimination: 24 hours • Adverse effects: • respiratory depression • Hypotension • Dose 5-10 mg

  16. Midazolam • Highest lipid solubility • Fast redistribution: 15 minutes • T1/2: 2 hours • Adverse effects: • respiratory depression • Hypotension • Dose:5-10 mg

  17. Lorazepam • Less lipid solubility than Diazepam • Redistribution: 2-3 hours • T1/2 elimination: 6-12 hours • Adverse effects: • respiratory depression • Hypotension • Dose: 4-8 mg

  18. Fosphenytoin • Formulated • Water soluble prodrug • 150 mg/min • IV or IM

  19. Parenteral Valproic Acid • Dose ( Under investigation) • 25 mg/kg dose yields a level 100-150 mg/L in 2-4 hours • Adverse effects • Local irritation • GI distress • Lethargy

  20. Phenobarbital • Dose: 20 mg/kg • Infusion: 100 mg/min • Time to halt seizure: 20-30 min • Duration of action > 48 hours • T ½: 100 hours • AE: sedation, respiratory depression, hypotension

  21. SE TrialsEvidence to Support Medication Choices

  22. Prehospital Treatment of Status Epilepticus 205 patients enrolled Patient seizing for 5 minutes 3 treatment arms 5 mg valium 2 mg lorazepam 1 ml of propylene glycol/9% NACL Administered by paramedics (after consent from the base hospital)

  23. Prehospital Treatment of Status Epilepticus • Conclusions • Treatment of SE with benzos outside of the hospital are feasible • Lorazepam is likely more effective than diazepam • Lorazepam requires refrigeration

  24. Diazepam vs. Lorazepam • Leppik et. al. 1983 • 78 patients • 10 mg Diazepam vs. 4 mg Lorazepam • Initial Seizure Termination • 58% Diazepam • 78% Lorazepam • P=NS

  25. VA Cooperative Study • Treiman et. al., 1998 • Randomized double blind trial • Four regimens • 0.1 mg/kg lorazepam • 15 mg/kg phenobarbital • 0.15 mg/kg diazepam • 18 mg/kg phenytoin

  26. VA Cooperative Study • 570 patients enrolled • 395 overt • 175 subtle • Primary endpoint: Complete cessation of all seizures within 20 minutes

  27. VA Cooperative Study • Conclusions • Lorazepam is more effective than phenytoin as initial intravenous treatment for overt generalized convulsive SE • Equal efficacy between lorazepam, phenobarbital, diazepam with phenytoin

  28. Protocol for SE Management

  29. Status Epilepticus Treatment Time post onsetTreatment Onset Ensure adequate ventilation/O2 2-3 min. IV line with NS, rapid assessment, blood draw 4-5 min. Lorazepam 4 mg (0.1 mg/kg) or diazepam 10 mg (0.2 mg/kg) over 2 minutes via second IV line or rectal diazepam 7-8 min. Thiamine 100 mg, 50% glucose 25 mg IV Phenytoin or fosphenytoin 20 mg/kg IV (phenytoin PE) at  50 mg/per minute phenytoin or 150 mg per minute fosphenytoin ( 0.75 mg/kg/min) Pyridoxine 100-200 mg IV in children under 18 mo.

  30. Status Epilepticus Treatment (cont.) Time post onsetTreatment 10 min. Can repeat lorazepam or diazepam if seizures ongoing 30-60 min. EEG monitoring unless status ended and patient waking up 40 min. Phenobarbital 20 mg/kg at  5 mg per minute (0.75 mg/kg per minute) continued Reference: Lowenstein DH, Alldredge BK, Status Epilepticus. NEJM 1998; 338: 970-976.

  31. Status Epilepticus Treatment (cont.) Time post onsetTreatment 70 min. Pentobarbital 3-5 mg/kg load, 1 mg/kg per hour infusion, increase to burst- suppression OR Propofol 3-5 mg/kg load, 5-10 mg/kg/hr initial infusion then 103 mg/kg/hr OR Midazolam 0.2 mg/kg load, .25-2 mg/kg infusion Reference: Lowenstein DH, Alldredge BK, Status Epilepticus. NEJM 1998; 338: 970-976.

  32. Medical Student Cases  Case 4: A 62 yo male with Continuous Seizures

  33. Case Study 4  A 62 y/o male without significant previous history of seizures presents to the E R following one generalized tonic-clonic seizure.  Initial assessment after the first seizure revealed poorly reactive pupils, no papilledema or retinal hemorrhages and a supple neck.

  34. Case Study 4  Oculocephalic reflex is intact.  Respirations are rapid at 22/min and regular, heart rate is 105 with a temperature of 101.  As you are leaving the room, the patient had another seizure.

  35. Case Study 4  What should the initial management be?  What initial investigations should be performed in this setting?  What is the appropriate management with continued seizures if initial therapy does not terminate the seizures?

  36. Case Study 4  Creatinine- 1.0  Mg 1.0  Na- 132  K- 4.5  Ca- 9.0  Glucose- 90  Laboratory study results: CBC  WBC- 13.1  HGB 11  Plt 200,000

  37. Case Study 4 What are indications for lumbar puncture in this case?  CSF color- clear  Cell count tube # 1 – 500 RBC/ 35 WBC- 100% Neutrophils  Tube # 3 - 100 RBC/ 11 WBC  Protein 65  Glucose 60

  38. Case Study 4  Urinalysis- (+) ketones  No White Blood Cells or bacteria  Tox screen: negative for alcohol positive for benzodiazepines

  39. Case Study 4 You obtain an MRI of the brain with the following images

  40. Case Study 4

  41. Case Study 4  Which of the above studies helps to explain the current seizures?  Would you ask for other studies?  What are the CSF findings during repeated convulsions?

  42. Case Study 4: Questions to Answer  Define Status Epilepticus.  Describe the systemic manifestations of status epilepticus.  What causes status epilepticus?  What is the role of EEG in status epilepticus management?

  43. Key Points

  44. First AidTonic-Clonic Seizure  Turn person on side with face turned toward ground to keep airway clear, protect from nearby hazards  Transfer to hospital needed for: • Multiple seizures or status epilepticus • Person is pregnant, injured, diabetic • New onset seizures  DO NOT put any object in mouth or restrain

  45. Status Epilepticus  A medical emergency • Adverse consequences can include hypoxia, hypotension, acidosis and hyperthermia • Know the recommended sequential protocol for treatment with benzodiazepines, phenytoin, and barbiturates. • Goal: stop seizures as soon as possible