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