SOAP – Status Epilepticus

Definition

A.Five minutes or more of continuous clinical and /or electrographic seizure activity or recurrent seizure activity without return to baseline between seizures.

B.Classification of the type of status epilepticus (SE) based on semiology, duration, and underlying etiology.

1.Convulsive SE: Associated with generalized tonic-clonic movements of extremities and mental status impairment; a life-threatening medical emergency.

2.Nonconvulsive status epilepticus (NCSE): Seizure activity only seen on EEG without any correlating clinical findings; requires emergent treatment to prevent cortical neuronal damage.

3.Refractory SE: Clinical or electrographic seizures that do not respond to adequate doses of initial benzodiazepines, followed by a second antiepileptic drug (AED) agent.

Incidence

A.Annual incidence of SE is 100,000 to 200,000 cases in the United States.

B.Refractory SE occurs in up to 43% of patients with SE.

C.Up to a third of neuro ICU patients have NCSE.

D.10% of medical ICU patients develop NCSE.

Pathogenesis

A.SE results from a neuronal imbalance between excitatory and inhibitory neurotransmitters (gamma-aminobutyric acid [GABA], N-methyl-D-aspartate [NMDA], glutamate) within the central nervous system (CNS).

B.Prolonged epileptic seizures result in lack of oxygen and glucose in brain cells, stimulating the release of excessive amounts of glutamate. Glutamate alters membrane channels, leading to an influx of calcium, which in turn triggers oxygen free radicals. These make brain cells electrically stable and cause cell injury.

Predisposing Factors

A.Acute processes.

1.Traumatic brain injury.

2.Metabolic disturbances: Electrolyte abnormalities, hypoglycemia, and renal failure.

3.CNS infections.

4.Cerebrovascular pathology: Ischemic stroke, hemorrhage, cerebral sinus thrombosis, and hypertensive encephalopathy.

5.Autoimmune encephalitis, paraneoplastic syndromes.

6.Sepsis.

7.Drugs: Toxicity; noncompliance with AEDs; and withdrawal from opioids, benzodiazepine, barbiturates, or alcohol.

8.Anoxic brain injury.

B.Chronic processes.

1.Preexisting epilepsy.

2.CNS tumors.

3.History of CNS pathology (traumatic brain injury, abscess, stroke).

4.Chronic ethanol abuse.

Subjective Data

A.Common complaints/symptoms.

1.Generalized convulsive status epilepticus (GCSE): Tonic extension of trunk and extremities, followed by clonic extension. Consciousness is usually lost.

2.Myoclonic SE: Bursts of brief myoclonic jerks, which increase in intensity until a convulsion occurs. This condition is seen mostly in anoxic encephalopathy or metabolic disturbances, particularly renal failure.

3.NCSE: Absence of awakening or returning to baseline even after 20 minutes of successful termination of clinical seizures. Symptoms may include coma, confusion, aphasia, staring, automatisms, facial twitching, eye deviation, and agitation.

B.Common/typical scenario.

1.GCSE usually presents with the classic full body convulsions and the patient is not aware of the occurrence.

2.Myoclonic SE typically is seen in what people describe as limb shaking or twitching. Patients are awake and are able to describe the sensation.

3.In NCSE, patients do not have any signs of twitching or abnormal movements. The only clue to lead to NCSE is the absence of the patient waking up or returning to baseline after an event such as cardiac arrest, intracranial hemorrhage, or any surgery.

C.Family and social history.

1.Most common cause of SE is a prior history of epilepsy.

2.Ask about changes in antiepileptic medications.

3.Alcohol and drug use can lower the seizure threshold in patients with a history of epilepsy.

D.Review of systems.

1.In patients with GCSE or NCSE, a review of systems is generally not possible to the altered level of consciousness.

Physical Examination

A.Neurological examination.

1.Assess for any sensory or motor deficits in all limbs.

2.Assess for any speech, memory, or language impairment.

3.Assess for cranial nerve palsies.

4.Assess level of consciousness and response to stimuli.

Diagnostic Tests

A.Workup should occur simultaneously and in parallel with treatment.

1.Finger stick glucose.

2.Complete blood count (CBC), comprehensive metabolic panel (CMP), drug screen, AED levels, alcohol levels, arterial blood gas (ABG), serum magnesium, and calcium (total and ionized).

3.CT of brain to rule out intracranial pathology.

4.Continuous EEG monitoring: 24-hour EEG is the gold standard. Most typical pattern in SE is

rhythmic high frequency (>12 hz) activity that increases in amplitude and decreases in frequency, finally terminating abruptly and leaving postictal low amplitude slowing.

5.Brain MRI: Seizure focus may show up as a bright signal on diffusion weighted imaging (DWI) and dark signal on apparent diffusion coefficient (ADC) imaging in a nonvascular territory possibly with leptomeningeal enhancement.

6.Lumbar puncture and cerebrospinal fluid (CSF) studies.

7.Toxicology panel: Check for toxins that frequently cause seizures (i.e., isoniazid, tricyclic antidepressants (TCAs), antidepressants, theophylline, cocaine, sympathomimetic, organophosphates, and cyclosporine).

Differential Diagnosis

A.Movement disorders.

B.Herniation syndromes (decerebrate /decorticate posturing).

C.Psychiatric disorders: Psychogenic nonepileptic seizures, conversion disorder, acute psychosis, or catatonia.

Evaluation and Management Plan

A.General plan.

1.Treatment of SE should occur rapidly and continue sequentially until clinical and electrographic seizures are stopped.

2.Simultaneous assessment and management of airway, breathing, and circulation should be performed.

3.Do not withhold seizure medications because of fear of respiratory compromise.

4.Definitive control of SE should be established within 60 minutes of onset.

5.Emergent treatment.

a.Stabilize patient (airway, breathing, circulation).

b.Perform cardiac monitoring.

c.Consider intubation as needed.

d.Use nutritional resuscitation with 100 mg of thiamine IV followed by 50 mL of 50% dextrose IV push.

e.Lorazepam (drug of choice for intravenous administration): 0.1 mg/kg IV at the rate of 2 mg/min (max 4 mg per dose); max total dose 8 mg.

f.Midazolam is preferred for IM. 0.2 mg/kg IM; max dose 10 mg.

g.Diazepam (preferred for rectal administration): One time dose of 10 mg per rectum.

6.Urgent treatment.

a.Recommended AEDs include intravenous fosphenytoin or phenytoin (PHT), valproic acid, levetiracetam, and lacosamide. Initial total levels should be drawn after 2 hours of intravenous loading dose to determine maintenance dose and need to reload.

i.Load with fosphenytoin 20 mg phenytoin sodium equivalent (PE)/kg at the rate of 150 mg/min. If using phenytoin, the rate should not be more than 50 mg/min. Cardiac monitoring should occur during infusion due to increased risk of QT prolongation and cardiac arrhythmia. An additional 10 mg/kg IV can be given if seizures persist. The maintenance dose is phenytoin 100 mg q8h. The target free phenytoin level is 2 to 3 mcg/mL. Check serum levels daily.

ii.Valproic acid: Load with 20 mg/kg (max 2,000 mg) at a rate of 3 to 6 mg/kg/min. If seizure persists, additional 20 mg/kg can be given. Maintenance dose is 30 to 60 mg/kg/d in divided doses. Serum valproic goal is 70 to 100 mcg/mL. Check levels daily.

iii.Levetiracetam is usually loaded with 1,000 mg. Maintenance dosing is 1,000 to 1,500 mg q12. Blood levels are not monitored.

iv.Lacosamide: Load with 400 mg. Maintenance dosing is 100 to 200 mg twice daily. Max dose is 400 mg daily. Blood levels are not monitored.

7.Refractory therapy.

a.If seizures persist, consider continuous infusion of AEDs. The most recommended are midazolam, propofol, and pentobarbital. Dosing of continuous infusion of AEDs should be titrated to cessation of electrographic seizures or burst suppression.

b.A period of 24 to 48 hours of electrographic seizure control is recommended prior to slow withdrawal of continuous infusion of AEDs. It is recommended that EEG findings, not serum drug levels, guide therapy.

i.Midazolam infusion: Load with 0.2 mg/kg, at an infusion rate of 2 mg/min. Begin continuous infusion: 0.05 to 2 mg/kg/hr. For breakthrough seizures: Give 0.1 to 0.2 mg/kg bolus and increase infusion by 0.05 to 0.1 mg/kg/hr every 3 to 4 hours.

ii.Propofol infusion: Load with 1 to 2 mg/kg, infused over 1 minute. Begin continuous infusion at 20 to 200 mcg/kg/min. Use caution when administering high doses (>80 mcg/kg/min) for extended periods of time (>48 hours) to avert risk of propofol infusion syndrome. For breakthrough seizures: Increase infusion rate by 5 to 10 mcg/kg/min every 5 minutes until seizure cessation.

iii.Pentobarbital infusion: Load with 3 to 5 mg/kg IVPB over 10 to 30 minutes. Begin continuous infusion at 0.5 to 5 mg/kg/hr. For breakthrough seizures: Titrate 1 mg/kg/hr every 10 minutes to continuous EEG of 4 to 6 bursts/minute.

Follow-Up

A.Patients will need to follow-up with an epileptologist to monitor and control the antiepileptic medications that will be required.

Consultation/Referral

A.A neurologist must be consulted on cases of SE. A neurologist with continuous EEG training and specialty training in epileptology is preferred.

B.Centers without the ability to perform or interpret continuous EEG in patients with SE or NCSE should consider rapid transfer to a higher level of care.

Special/Geriatric Considerations

A.Pregnancy: Lorazepam and fosphenytoin are recommended as initial and urgent therapy. Levetiracetam has shown to be safe in recent studies.

1.Eclampsia must be considered in patients with SE in pregnancy; delivering the fetus is the best therapy in this situation.

2.Also, magnesium sulfate is proved to be superior to AEDs in pregnant women with seizures and eclampsia.

B.Anoxic brain injury: Prognosis of SE after hypoxic or anoxic brain injury is really poor.