general anesthesia in status epilepticus presented by r2 簡維宏 / vs 黃謙琳
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General Anesthesia in Status Epilepticus
Presented by R2 簡維宏 / VS 黃謙琳
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
Definition (I)
• In 1962, Marseilles conference described status epilepticus as “enduring epileptic state”
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
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
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
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
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
Etiology (I)• Acute process
1. Electrolyte imbalance2. Cerebrovascular accident3. Cerebral trauma4. Drug toxicity5. Cerebral anoxic/hypoxic damage6. CNS infection7. Renal failure8. Sepsis syndrome
~Anaestthesia 2001;56: 648-659
Etiology (II)
• Chronic process1. 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
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
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
Management (I)
• Initial care includes standard measures applicable to any acute medical emergency
• See Figure1.
~NEJM 1998; 338(14):970-976
Management (II)
• Treatment should proceed of four fronts1. 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
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
Principles of Drug Treatment (II)
Successful rate:
Overt SE Subtle SE
Lorazepam 64.9% 17.9%
Phenobarbital 58.2% 24.2%
Diazepam and Phenytoin
55.8% 8.3%
Phenytoin only 43.6% 7.7%
~NEJM 1998; 339(12): 792-798
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
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
Treatment of Refractory Status Epilepticus (II)
• Continuous EEG monitor should be available
• Electrophysiological end-point1. burst suppression
2. isoelectric patterns
~Quarterly Journal of Medicine 1996;89:913-920
Treatment of Refractory Status Epilepticus (III)
• Long acting anti-epileptic drug therapy should be maintained at the upper limit of the normal range
• Anesthetized duration1. 24 to 96 hours
2. Gradually tapering and if seizure recur, then re-anesthetized
~current treatment options in neurology 1999;1:359-69
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
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
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
Inhalation Anesthetic Gases
• Drugs of choice : Isoflurane• N2O: 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
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
Isoflurane (II)
1. A clinical series result (nine patient)
2. Isoflurane administrated for 1-55 hours
3. 8 of 11 occasions, seizures resumed upon discontinuation of isoflurane
4. 6 of 9 patients died
~Anesthesiology, 1989; 71(5): 653-659
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
Isoflurane (IV)
1. Earlier use of isoflurane, within 60 minutes “therapeutic window” proposed by Delgado-Esceuta et al.
2. Early role of isoflurane
3. Advantage: Titratablility and reversibility
4. Lack of prospective study
~NEJM 1982; 306: 1337-1340
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
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
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
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