Neurosurgery notes/Functional/Seizure/Status epilepticus (SE)

Status epilepticus (SE)

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Seizure

Definition

  • Status Epilepticus
    • A seizure lasting > 5minutes or persistent seizure activity after sequential administration of appropriate first and second-line AEDs. OR
    • Recurrent seizure activity without recovery (To baseline) between seizures
  • Refractory SE
    • SE which is refractory to two intravenous AEDs, one of which is a benzodiazepine.
  • Generalized Convulsive Status
    • Convulsions that are associated with rhythmic jerking of the extremities.
  • Non-convulsive Status
    • Seizure activity seen on EEG without clinical findings associated with GCSE.

Numbers

  • 61% of seizures that persist > 5mins will continue > 1 hour
  • Incidence: 150,000 new cases/year
  • Children (73% of cases in <5 yrs) > Elderly > Adults
  • 50% SE was the patients first seizure
  • 1/6 of patients presenting with 1st time seizure will present as SE

Types

  • By types of seizure
    • Generalized status
      • Convulsive (tonic-clonic, tonic-clonic-tonic, or clonic):
        • Generalized convulsive tonic-clonic status epilepticus (SE) is the most frequent type.
        • A medical emergency
      • Absence
        • (In status, this may present in twilight state)
        • Characterized by confusion or diminished responsiveness, with occasional blinking or twitching, lasting hours to days, with generalized spike and slow wave discharges on the EEG
      • Secondarily generalized
        • Accounts for 75% of generalized SE, esp in adults
        • Myoclonic
        • Atonic (drop attack): especially in Lennox-Gastaut syndrome
    • Partial status (usually related to an anatomic abnormality)
      • Simple (AKA epilepsy partialis continua)
      • Complex
        • In status, this may present in twilight state
          • Most often from frontal lobe focus.
        • Urgent treatment is required (several case reports of permanent deficits following this)
      • Secondarily generalized
    • Non-convulsive SE
      • Benign variants (typical absence SE, complex partial SE)
      • Electrical SE during sleep
      • Atypical absence SE
      • Tonic SE (associated with learning disability in children), SE in coma
  • By clinical signs
    • With prominent motor effects
    • Without prominent motor effects
    • Boundary syndromes (syndromes which combine encephalopathy, behavioural disturbances, delirium, or psychosis with SE-like EEG findings)

Causes

  • Known
    • Low level of AED (34%)
      • Due to
        • Non-compliance
        • Intercurrent infection preventing PO intake of meds
        • Drug-drug interactions → lowering effectiveness of AEDs
      • Precipitous drug withdrawal: barbiturates, benzodiazepines, alcohol, or narcotics
    • Remote symptomatic cause (24%)
      • Tumor
    • Cerebrovascular accident (22%)
      • Common in elderly
    • Metabolic disturbances (15%)
      • Electrolyte imbalance
        • Hyponatremia (most common in children, usually due to water intoxication),
        • Hypoglycemia,
        • Hypocalcemia,
        • Uremia,
        • Hypomagnesemia
      • Illicit drug intoxication: especially cocaine, amphetamines
    • Hypoxia (13%)
    • Eclampsia
    • Less common
      • Proconvulsant drugs, including: β-lactam antibiotics (penicillin, cephalosporins), certain antidepressants (bupropion), clonazapine, bronchodilators, immunosuppressants
      • Traumatic brain injury: acute as well as old
  • Unknown: idiopathic (1/3 cases)
    • Febrile seizures: a common precipitator in young patients. 5–6% of patients presenting with SE have a history of prior febrile seizures
  • Age associated causes
    • Children <1 yr of age (Phillips 1989)
      • 75% had an acute cause:
        • 28% were secondary to CNS infection,
        • 30% due to electrolyte disorders,
        • 19% associated with fever
    • Adults
      • Unknown sz pt: Structural cause
      • Known Sz pt: low AED levels

Morbidity and mortality from SE

  • Related to
    • Underlying cause
      • Mortality: < 10–12%,
        • 2% is directly due to SE or its complications;
        • Rest are due to the underlying process producing the SE
    • Duration of SE
      • Mean duration of SE in patients without neurologic sequelae is 1.5 hrs (therefore, proceed to pentobarbital anaesthesia before ≈ 1 hour of SE)
  • Mortality
    • 1% die during the episode
    • Long-term outcome of patients who suffer from prolonged refractory status epilepticus:
      • 50% mortality
      • Of the patients surviving, only about 50% will have functional cognitive status.
    • Lowest in
      • Children 6%
      • Subtherapeutic AED
      • Patients with unprovoked SE
    • Highest in
      • Elderly patients and those with SE resulting from anoxia or stroke.
  • Mechanism
    • CNS injury from repetitive electric discharges:
      • 20 mins irreversible changes appear in neurons
      • 60 mins Cell death
    • SUDEP
    • CNS damage by the acute insult that provoked the SE

Management

  • Emergent initial therapy → Urgent control therapy → Refractory status therapy

Treatment

  • See Glauser 2016

      • Stage 1 (0-5mins) management

      • Immediate Measures
        • Secure airway
        • Give oxygen
        • Check temperature
        • Assess cardiac and respiratory function
        • Secure IV access in large veins
        • Time seizure from onset
      • Determine aetiology
        • Any suggestion of alcohol abuse or impaired nutritional status: give thiamine IV (as 2 pairs of Pabrinex® ampoules)
        • Any suggestion of hypoglycaemia: give 100ml of glucose 20% IV. If no IV access 1mg IM glucagon. Check blood glucose again after 10 mins
        • Give usual antiepileptic drug(AED) treatment if not already given – can be given via nasogastric tube if airway secured
        • Consider appropriate antibiotic/antiviral if any concern about CNS infection
      • Bloods
        • U+Es, LFTs, FBC, coagulation screen, glucose, CK, calcium, magnesium, blood culture, blood gas, alcohol and toxicology screen, AED levels
          • How does magnesium prevent excitotoxicity in brain injury?
            • Magnesium readily crosses the blood–brain barrier (BBB) and blocks various subtypes of calcium and N-methyl-d-aspartate (NMDA) channels

      Stage 2 (>5mins) management

      • Give ONE of the following drugs:
        • Midazolam 10 mg buccally, intranasally* or intramuscularly. Give 5mg of Midazolam in the elderly or patients less than 50kg OR
            • *Intranasal midazolam: Use the midazolam buccal preparation. Half the dose in each nostril.
        • Lorazepam up to 4mg IV if midazolam not available, given as 2mg IV over 1 min, if seizure not terminating give a further 2mg IV after 2-3 minutes. OR
        • Diazepam 10 mg IV or rectally if midazolam and lorazepam not available. Risk of respiratory depression (maximum rate 5mg/min). Give 5mg of Diazepam in the elderly or patients less than 50kg.
      • Administer a repeat dose of benzodiazepine at 10 minutes if there is no response
      • Emergent initial therapy of 3 different benzodiazepine
          • Drug
          Evidence
          Considerations
          Lorazepam (IV)
          I, Level A
          Respiratory depression (RD), small volume of distribution
          Midazolam (IV, IM, buccal)
          I, Level A
          RD, short acting
          Diazepam (IV, rectal)
          IIa, Level A
          RD, short acting
        • RCT: BZD vs placebo
          • Respiratory depression was seen less frequently in those treated with benzodiazepines for GCSE than for those who received placebo (Alldredge et al 2001)

      Stage 3 (10–30mins) management

      • If status persists, give ONE of the following AED loading doses:
        • Intravenous sodium valproate 25mg/kg, max: 2500mg/dose (contraindicated in women of child bearing age) OR
        • Intravenous phenytoin 18mg /kg, max: 1800mg/dose OR
        • Intravenous levetiracetam 60mg/kg, max: 4500mg/dose
      • Call ICU to inform them of the patient
      • If seizures continue or reoccur in patients who are haemodynamically stable then consider another stage 3 AED.
      • Refractory SE therapy
        • Determined by cEEG and clinical exam
            • Drug
            Evidence
            Considerations (RD, hypotension)
            Midazolam
            Insuff data
            Tachyphylaxis with prolonged use
            Propofol
            Insuff data
            Cardiac failure, rhabdomyolisis, metabolic acidosis, PRIS
            Thiopental
            Insuff data
            Cardiac depression, metabolised to pentobarbital (paralytic ileus, withdrawal seizures)
        • Alternatives
          • Ketamine
          • IVIg/PE
          • Steroids
          • Hypothermia
          • Ketogenic diet
          • Vagal nerve stimulator
      • Result?
        • Established status epilepticus treatment trial (ESETT)
            • notion image
            Outcome
            Levetiracetam (N=150)
            Fosphenytoin (N=125)
            Valproate (N=125)
            Life-threatening hypotension within 60 min
            1 (0.7%)
            4 (3.2%)
            2 (1.6%)
            Life-threatening cardiac arrhythmia within 60 min
            1 (0.7%)
            0
            0
            Endotracheal intubation within 60 min
            30 (20.0%)
            33 (26.4%)
            21 (16.8%)
            Acute seizure recurrence 60 min to 12 hr
            16 (10.7%)
            14 (11.2%)
            14 (11.2%)
            Acute anaphylaxis
            0
            0
            0
            Acute respiratory depression
            12 (8.0%)
            16 (12.8%)
            10 (8.0%)
            Hepatic aminotransferase or ammonia elevations
            1 (0.7%)
            0
            1 (0.8%)
            Purple glove syndrome
            0
            0
            0
            Death
            7 (4.7%)
            3 (2.4%)
            2 (1.6%)
          • See Kapur 2019
      notion image
    • Paralytics
      • Stop the visible manifestations of the seizure
        • Do not stop the abnormal electrical brain activity → neurological damage
      • Useful for intubation and obtaining head imaging;
    • Pentobarbital (5mg/kg IV → 1–5mg/kg/hr) is often reserved for SE that is refractory to all of the above interventions.

Patient with/o seizure history

  • Dx/Tx underlying disease which is the cause of the cortical irritation or injury
    • Hypoglycaemia
      • In patients with poor nutrition (e.g. alcoholics):
        • Giving glucose in thiamine deficiency can precipitate Wernicke’s encephalopathy → prior to glucose bolus give thiamine 50– 100mg IV
      • If no fingerstick glucose can be done:
        • Give 25–50ml of D50 IV push for adults (2 ml/kg of 25% glucose for peds).
        • If at all possible, draw blood for definitive serum glucose first
    • Electrolytes, FBC, LFTs, Mg++,Ca++ , AED levels, ABG
    • Head CT (usually without contrast)
    • CNS infection
      • LP
        • Especially for febrile children
        • WBC pleocytosis up to 80 × 106/L (bacterial meningitis can raise it to 1000 × 106/L) can occur following SE (benign postictal pleocytosis), and these patients should be treated with antibiotics until infection can be ruled out by negative cultures
    • Drug overdose
      • Naloxone (Narcan®) 0.4mg IVP (in case of narcotics)
    • ± Bicarbonate to counter acidosis (1–2 amps depending on length of seizure)
    • For neonate <2 years: consider pyridoxine 100mg IV push (pyridoxine-dependent seizures constitute a rare autosomal recessive condition that generally presents in the early neonatal period)

Patient with seizure history

  • Treatment with a bolus of maintenance AED a relapse of seizure in a patient with a known seizure disorder and subtherapeutic AED levels usually responds to a bolus of the maintenance AEDs.
    • However, SE should be treated by the standard protocol
  • Magnesium for eclampsia
  • Alcohol withdrawal:
    • Benzo
    • Thiamine

Medications to avoid in status epilepticus

  • Opiates
  • Phenothiazines (antipsychotics): including promethazine (treatment of allergies)
  • Neuromuscular blocking agents in the absence of AED therapy: seizures may continue and cause neurologic injury but would not be clinically evident

Success

  • Determinant
    • Dose
    • Starting treatment in <30 min (60% aborted-Lowenstein 2006)
    • Does not matter what type of AED is used
  • 2/3 will respond to therapy
  • 1/3 progress to refractory SE

Experimental interventions include

  • Lidocaine infusion,
  • Inhalational anaesthesia,
  • Direct brain stimulation,
  • Transcranial magnetic stimulation,
  • Electroconvulsive therapy (shock therapy),
  • Surgical intervention if a seizure focus is identified

Treatment of other subtypes of SE

  • Myoclonic status
    • Valproic acid (drug of choice).
      • Place NG, give 20mg/kg per NG loading dose. Maintenance: 40mg/kg/d divided.
    • Can add lorazepam or clonazepam to help with acute control.
  • Absence status epilepticus
    • Responds to diazepam.

For refractory status epilepticus

  • Dbs to centromedian nucleus

Rapid Anticonvulsant Medication Prior to Arrival Trial 2011 (RAMPART)

  • IM Midazolam (10 mg) v IV Lorazepam (4 mg) in the prehospital status epilepticus setting
  • Lower rate of endotracheal intubation and recurrent seizures with IM midazolam administered through an autoinjector compared to IV lorazepam