1. General Anesthesia in Status Epilepticus Presented by R2 簡維宏 / VS 黃謙琳

2. Status Epilepticus continuous and rapidly repeating seizures medical emergency 102,000 to 152,000 cases per year in US and roughly 55,000 deaths associated with status epilepticus annually ~NEJM 1998; 338(14):970-976

3. Definition (I) In 1962, Marseilles conference described status epilepticus as “enduring epileptic state”

4. Definition (II) In 1981, the International League against Epilepsy defined status epilepticus as a seizure that “persists for a sufficient length of time or is repeated frequently enough that recovery between attacks does not occur” ~Epilepsia 1981;22:489-501

5. Definition (III) Status epilepticus as seizures that persist for 20 to 30 minutes, which is an estimate of the duration necessary to cause injury to central nervous system ~JAMA 1993;270:854-9

6. Definition (IV) Either continuous seizures lasting at least five minutes or two or more discrete seizures between which there is incomplete recovery of consciousness ~NEJM 1998; 338(14):970-976

7. Clinical features (I) Loss of consciousness Clinically obvious seizures Duration Differential diagnosis with rigor due to sepsis, myoclonic jerking, generalized dystonia, and pseudostatus epilepticus ~NEJM 1998; 338(14):970-976

8. Clinical features (II) Clinical manifestation often become subtle with time Electrographic status epilepticus: no observable, repetitive motor activity, and the detection of ongoing seizures requires electroencephalography Still at risk for CNS injury and require prompt treatment ~NEJM 1998; 338(14):970-976

9. Etiology (I) Acute process 1. Electrolyte imbalance 2. Cerebrovascular accident 3. Cerebral trauma 4. Drug toxicity 5. Cerebral anoxic/hypoxic damage 6. CNS infection 7. Renal failure 8. Sepsis syndrome ~Anaestthesia 2001;56: 648-659

10. Etiology (II) Chronic process 1. Pre-existing epilepsy 2. Poor anticonvulsant drug compliance or change of anticonvulsant therapy 3. Chronic alcoholism 4. Cerebral tumors or other space- occupying lesion ~Anaestthesia 2001;56: 648-659

11. Pathophysiology (I) Failure of mechanism that normally abort an isolated seizure Arise from abnormally persistent, excessive excitation or ineffective recruitment of inhibition ??? ~NEJM 1998; 338(14):970-976

12. Pathophysiology (II) Status epilepticus lasting for 30-45 minutes can cause cerebral damage Glutamate-mediated excitotoxicity Superimposition of systemic stress exacerbating the degree of neuronal injury e.g. hyperthermia, hypotension, hypoxia ~Arch Neurol 1973; 29: 82-7

13. Management (I) Initial care includes standard measures applicable to any acute medical emergency See Figure1. ~NEJM 1998; 338(14):970-976

15. Management (II) Treatment should proceed of four fronts 1. Termination of status epilepticus 2. Prevention of recurrence 3. Management of potential precipitating causes 4. Management of complications and underlying conditions ~Epilepsia 1999; 40(suppl.1): s59-63

16. Principles of Drug Treatment (I) Drug of choice: Lorazepam (0.1mg/kg) Other drugs: 1. Phenobarbital (15mg/kg) 2. Diazepam (0.15mg/kg) and Phenytoin (18mg/kg) 3. Phenytoin (18mg/kg) only ~NEJM 1998; 339(12): 792-798

17. Principles of Drug Treatment (II) Successful rate: Overt SESubtle SE Lorazepam64.9%17.9% Phenobarbital58.2%24.2% Diazepam and Phenytoin 55.8%8.3% Phenytoin only43.6%7.7% ~NEJM 1998; 339(12): 792-798

18. Principles of Drug Treatment (III) Patients who did not respond to first-line agents 1. Response rate to second-line agents: 7% 2. Response rate to third-line agents: 2.3% Status epilepticus that does not respond to a benzodiazepine, phenytoin, or Phenobarbital is considered refractory and required more aggressive treatment

20. Treatment of Refractory Status Epilepticus (I) Continuous intravenous infusions with anesthetic doses of midazolam, propofol, or barbiturates Inhalation anesthetic gases ~Anaesthesia, 2001; 56: 648-659

21. Treatment of Refractory Status Epilepticus (II) Continuous EEG monitor should be available Electrophysiological end-point 1. burst suppression 2. isoelectric patterns ~Quarterly Journal of Medicine 1996;89:913-920

22. Treatment of Refractory Status Epilepticus (III) Long acting anti-epileptic drug therapy should be maintained at the upper limit of the normal range Anesthetized duration 1. 24 to 96 hours 2. Gradually tapering and if seizure recur, then re- anesthetized ~current treatment options in neurology 1999;1:359-69

23. IV General anesthesia (I) Propofol 1-2mg/kg bolus followed 2-10mg/kg/hr Barbiturate-like and benzodiazepine-like effect at the GABA receptor and a potent anticonvulsant action at clinical dose Rapid clearance Metabolic acidosis and lipidemia Avoid rapid discontinuation ~Anaesthesia, 2001; 56: 648-659

24. IV General Anesthesia (II) Midazolam 0.2mg/kg bolus followed 0.75-10 µg/kg/min Rapid clearance and less hypotensive effect than barbiturates Tachyphylaxis ~Anaesthesia, 2001; 56: 648-659

25. IV General Anesthesia (III) Barbiturates (Thiopental) 3-5mg/kg bolus followed 3-5mg/kg/hr Potential cerebral protective effects Accumulates in lipoid tissues during prolong infusions, resulting in delay recovery Severe hypotension requiring vasopressor therapy Potently immunosuppressive and prolonged use increase the risk of nosocomial infection ~Anaesthesia, 2001; 56: 648-659

26. Inhalation Anesthetic Gases Drugs of choice : Isoflurane N 2 O: single use can’t achieve enough anesthetic level and long term use causing bone marrow suppression Enflurane: lowering seizure activity Halothane: High anesthetic gas concentration is need and resulting in hemodynamic unstable and potential organ toxicity

27. Isoflurane (I) An effective, rapidly titratable anticonvulsant Invasive monitors such as: A-line, CVP Usually necessitates hemodynamic support with fluids and/or vasopressors ~Anesthesiology, 1989; 71(5): 653-659

28. Isoflurane (II) A clinical series result (nine patient) 1.Isoflurane administrated for 1-55 hours 2.8 of 11 occasions, seizures resumed upon discontinuation of isoflurane 3.6 of 9 patients died ~Anesthesiology, 1989; 71(5): 653-659

29. Isoflurane (III) Effects on pathogenetic process 1. Can isoflurane “control” seizures permanently or alter a seizure focus? 2. Temporarily attenuate activity of epileptic neural generators 3. No evidence that adverse neuropathologic processes were stopped ~Anesthesiology 1989; 71(5): 653-659 ~Anesthesiology 1987; 67: A390

30. Isoflurane (IV) Earlier use of isoflurane, within 60 minutes “therapeutic window” proposed by Delgado-Esceuta et al. Early role of isoflurane 1.Advantage: Titratablility and reversibility 2.Lack of prospective study ~NEJM 1982; 306: 1337-1340

31. Outcomes (I) Overall mortality: approximately 20~25% Higher mortality rate group: 1.age over 60 year-old 2.patient with ECG change 3.more severe underlying brain damage and underlying disease ~Epilepsia 1992; 33 (suppl.4):s15-25

32. Outcome (II) 90% of patients with status epilepticus secondary to anti-epileptic drug withdrawal, alcohol or trauma have good outcomes 33% 0f patients with status epilepticus secondary to stoke or hypoxia have good outcome

33. Outcome (III) Uncontrolled status epilepticus lasting more than 1 hour  mortality rate 34.8% Seizures were terminated within 30 minutes  mortality rate 3.7% It is not clear whether the success of treatment was the cause or the effect of the better prognosis, or a combination of both ~Epilepsia 1992; 33 (suppl.4):s15-25