STATUS EPILEPTICUS

Classification of status epilepticus: Focal status epilepticus (Focal SE): Focal motor manifestations EEG pattern: Focal Typical setting: Focal brain lesion Prognosis: variable but usually poor Non convulsive SE Complex partial
Complex partial or generalized without tonic-clonic activity

Recurrent or continuous changes in mental status Focal EEG pattern History of seizures or focal brain lesion Prognosis is good

Generalized without tonic-clonic activity: Coma with subtle or no motor manifestations Generalized EEG pattern Seen in Severe diffuse brain insult Variable prognosis depending on underlying aetiology

Often requires EEG to differentiate it from other causes of unresponsiveness (postictal state, underlying neurologic disease) Subtle nonconvulsive status Similar to nonconvulsive status Except that there is subtle face, eyelid, or eye twitching Generalized convulsive status may be 10 or 20 generalized High mortality (20%) B/L tonic clonic activity EEG pattern: Generalized or burst suppression History of seizures with AED, noncompliance, meningitis, encephalitis, electrolyte imbalance, or toxicity Poor prognosis Absence status Benign Brain damage is unlikely Responds to low-dose benzodiazepines
1 Prolonged change of consciousness or behavioural function>30min 2 Generalized 3 Hz slow spike wave EEG abnormality 3 Prompt clinical as well as EEG response to IV AED

Myoclonic status: Usually indicates severe neurologic injury (e.g., anoxic, degenerative) Treatment response and prognosis are poor Etiologies Idiopathic: one-third of cases of SE Most common cause: AED noncompliance most common in adults In children: febrile seizures and meningitis (especially Haemophilus influenzae and Streptococcus pneumoniae) are common Electrolyte imbalance (especially hyponatremia) Drug intoxication (especially cocaine) or drug withdrawal Systemic effects of convulsive SE Cyanotic appearance tonic contraction, desaturation of hemoglobin, or impedance of venous return due to increased intrathoracic pressure Cardiovascular system: Tachycardia is invariable Bradycardia due to vagal tone modulation by the CNS hyperkalemia may cause arrhythmia BP initially increases in phase I and later on in phase II BP normalizes or hypotension develops Endocrine Increase in Prolactin, glucagon, growth hormone, and corticotropin Serum glucose may initially increase to 200250 mg/dL, but, if seizure activity is persistent, hypoglycemia may develop Rhabdomyolysis Metabolic-biochemical complications: respiratory and metabolic acidosis, hypokalemia, and hyponatremia Autonomic disturbance: excessive sweating, hyperpyrexia, and salivary and tracheobronchial hypersecretion Cerebrospinal fluid may demonstrate pleocytosis Definition: Q Q Old Definition: 30 minutes of continuous seizure activity or two or more seizures in 30 minutes without recovery of consciousness New definition: more than 5 minutes of seizure activity or two or more seizures without recovery of consciousness

Most generalized seizures are self-limited to 23 minutes. If seizure activity extends beyond 45 minutes will usually progress to SE New definition neuronal damage begins after 30 minutes In any case begin treatment if seizure activity extends beyond 45 minutes

Prolonged seizures are more difficult to stop and can cause neuronal injury within 20 to 30 minutes, leading to mesial temporal sclerosis and epilepsy

Mean duration of SE without neurologic sequelae is 1.5 hours (i.e., must institute barbiturate coma by approximately 1 hour of onset). 10% of patients with epilepsy go into SE at some point in their lives SE most common among children <5 y/o (~74% of cases) Approximately 3050% of cases of SE are the patients first seizures Treatment of SE Pharmacologic management: overview First-line agent: benzodiazepines Second-line agent: phenytoin Third-line agent: phenobarbital vs. anesthetic agent (midazolam, propofol) If refractory to midazolam or propofol, consider inhalent anesthetic (isoflurane is the first choice)
Time (mins) Basic life support Pharmacologic treatment

0-3 min

1. ABCs (airway, breathing, and circulation); evaluate respiration and give 24 L oxygen per nasal cannula (intubate if needed) 2. i.v. access: Thiamine, 100 mg intravenously followed by 50 cc 50% dextrose in water intravenously and continue normal saline or 5% dextrose in water 3. Draw blood for electrolytes, metabolic profile, complete blood cell count, toxicology, arterial blood gas, and AED levels Lorazepam: preferred BZD onset of action as fast as that of diazepam but also a longer duration of action (24 hours vs. 30 minutes) Dose: 0.1 mg/kg intravenously at 1 mg/min (410mg) Diazepam: risk of recurrent seizure because of short duration of action

5min

8-10min

1015min 30-45min

60min

Dose: 0.2 mg/kg intravenously at 2 mg/min Adverse effects: respiratory depression, hypotension, decreased level of consciousness Maximum dose= 10 to 15 mg of diazepam Lorazepam8-12mg Monitor electrocardiography Phenytoin: 20 mg/kg intravenously at 50 mg/min and blood pressure during May repeat an additional 10 mg/kg if seizures PHT administration continue Fosphenytoin: 20 mg/kg phenytoin equivalents intravenously at 150 mg/min Valproate: may be used as an alternative to PHT specially in cardiac and old patients, or in patients taking valproate Dose: 15 to 20 mg/kg (over 5 minutes) Efficacy? but side effects less specially hemodynamically unstable patients Start continuous EEG Benzodiazepine may be repeated once up to max monitoring doses CT, LP Valproate: 15-25mg/kg@20-50mg/min( in 5min) if not given earlier Phenobarbital: 20mg/kg intravenously at 50 mg/min May repeat Phenobarbital10mg/kg@50mg/min if the seizure persists for Prepare for GA: >30 minutes, the patient Midazolam: 0.10.3 mg/kg bolus continuous should be transferred to infusion at 0.05 mg/kg/hr and increasing by an intensive care unit for 0.05 mg/kg/hr q15mins up to 1-2 mg/kg/hr probable intubation Propofol: 3 to 5 mg/kg load (intubate), then 1 to 15 (likely secondary to decreased respiratory rate mg/kg per hour associated with advantages: short onset and offset, effective barbiturate Disadvantages: bradycardia, hypotension administration) Propofol infusion syndrome: severe hypotension, lipidemia, and metabolic acidosis Common in children but rarely may occur in adults Diazepam: 0.2 mg/mL at 0.5 mg/kg/hr up to 40 mg/hr to get a level of 0.20.8 mg/L Pentobarbital: load with 35 mg/kg given over 35 mins followed by continuous infusion at 1 mg/kg/hr and increase continuous infusion at 1 mg/kg/hr with additional smaller loading doses until EEG shows burst suppression

Or old age, cardiac patients, hemodynamically unstable

Approximately 80% of prolonged seizures are brought under control with the combination of a benzodiazepine and PHT Typical reasons why seizures persist after load of Fosphenytoin: Inadequate Fosphenytoin loading dose Structural brain lesion Metabolic derangement The use of phenobarbital as a third-line agent in status epilepticus (before anesthetics such as midazolam and propofol) is controversial because of the long half-life and the risks of hypotension and decreased cardiac contractility If on PHT, VA, or PB, give appropriate i.v. dose to achieve high or supratherapeutic serum level: Bolus dose = [(VD) (body weight) (desired serum concentration current serum concentration)] VD= PHT = 0.6 L/kg, PB = 0.6 L/kg, VPA = 0.10.3 L/kg

Comparison of commonly used AEDs in SE: Time To reach brain To peak brain concentration To stop SE Half-life Diazepam 10 secs <5 mins 1 min 15 mins Lorazepam 2 mins 30 mins <5 mins 6 hrs PHT 1 min 1530 mins 1530 mins >22 hrs PB 20 mins 30 mins 20 mins 50 hrs

Depolarizing neuromuscular blocking agents (e.g., succinylcholine) are contraindicated in patients with generalized convulsive status epilepticus because of the risk of hyperkalemia and arrhythmias EEG: initially EEG shows discrete seizures with interictal slowingseizures wax and waneeventually evolving into continuous ictal dischargesif seizures persist, ictal discharges are interrupted by flat periodsfinally paroxysmal bursts of epileptiform discharges arise from a flat background If seizures persist for >1 hour, then motor activity may diminish, although EEG activity continues The MRI during and for days after a bout of status epilepticus may show signal abnormalities in the region of a focal seizure or in the hippocampi, most often reversible Neurogenic pulmonary edema is encountered during or just after the convulsions, and some patients may become extremely hypertensive, making it difficult to distinguish the syndrome from hypertensive encephalopathy