Seizures

Seizures are the clinical manifestation of an abnormal and excessive discharge of neurones, with alterations of consciousness, motor, sensory, or autonomic function. Seizures are classified into:

Covers emergency management of seizures, including status epilepticus. Other seizure disorders include:

Status Epilepticus is:

  • A medical emergency
  • Defined as either:
    • Continuous seizure activity for 5 minutes without return of consciousness
    • Recurrent seizure activity over 30 minutes, between which consciousness is not regained

  • Refractory status epilepticus are seizures non-responsive to first and second line agents
  • Super-refractory status epilepticus are seizures continuing despite general anaesthesia

Epidemiology and Risk Factors

Pathophysiology

Physiological changes occur in two stages:

  • First stage
    • ↑ Cerebral metabolism
    • ↑ CBF
    • ↑ BSL and lactate
    • ↑↑ Catecholamine release
      • ↑ HR/CVP
        Compensation reduces cerebral damage in first 30-60 minutes.
    • ↑ Temperature
      Only partially obviated by muscle relaxation, as partially driven by ↑ sympathetic drive.
    • Normal termination mechanisms fail
      • Internalisation of GABA receptors
        Accounts for ↓ response to benzodiazepines with ↑ seizure duration.
  • Second stage
    Compensatory mechanisms exhausted.
    • Cerebral damage may occur
    • Failure of cerebral autoregulation
      • Hypoxia
      • ↓ BSL
      • Cerebral oedema
        ↑ ICP.
    • ↑ Catecholamines
      Cessation may precipitate hypotension and hypoglycaemia following seizure resolution.

Aetiology

Causes may be multifactorial, as multiple insults may ↓ seizure threshold:

  • B
    • Hypoxia
  • C
    • Hypertensive encephalopathy
      • Eclampsia
        Aggressive control of seizures in pregnancy is required for good foetal outcome.
      • PRES
  • D
    • CVA
    • Tumour
    • Degenerative
      • Dementia
      • Alzheimer’s Disease
    • Post-syncope
    • Chronic epilepsy
  • F
    • Hypo/hypernatraemia
    • Hypo/hypercalcaemia
    • Hypo/hypermagnesaemia
    • Hypoglycaemia
    • Uraemia
  • G
    • Hepatic encephalopathy
  • Immune
    • Multiple sclerosis
    • Autoimmune encephalitis
      • anti-NMDA receptor antibodies
      • anti-VGKC receptor antibodies
      • Paraneoplastic
  • Traumatic
    Post-traumatic epilepsy associated with:
    • Early seizures
    • Depressed skull fractures
    • ICH
    • TBI
  • Infective
    • Meningitis
    • Encephalitis
  • Toxin/Drug
    • Low antiepileptic drug levels
    • Toxicity
      • Antibiotics
        • Cephalosporins
        • Isoniazid
      • Immunosuppression
        • Tacrolimus
      • TXA
      • Recreational
        • Alcohol
          Toxicity and withdrawal.
        • Cocaine
        • Amphetamines

Clinical Manifestations

  • Most convulsive seizures cease within 2-3 minutes
  • Any seizure continuing ⩾5 minutes is unlikely to resolve spontaneously
  • All seizures lasting ⩾2 minutes longer than the patients usual seizure should be treated
  • Rapid control ↓ brain injury
  • ↑ Seizure duration associated with:
    • ↓ Response to treatment
    • ↑ Risk of refractory status epilepticus

Seizures affect:

  • Consciousness
  • Motor function
    • Tonic-clonic (sustained-interrupted) seizures
    • May begin generalised or with focal onset, evolving into bilateral convulsive SE
  • Autonomic function
    • Urinary incontinence
  • Sensory function

History should cover:

  • Seizure
    • Time of onset
    • Time of offset
    • Prodromal symptoms
    • Manifestations
      Sequence of involvement/evolution.
  • Past or family history of epilepsy
  • Medications taken
    • Compliance
    • New medications
    • Recreational drug use
  • Other precipitants
    • Drug withdrawal

Diagnostic Approach and DDx

Include:

Determination of pseudo-seizures can be difficult and is best confirmed with EEG.

  • Psychogenic non-epileptic seizures (pseudoseizures)
    • Variable manifestations from event to event
    • Non-sustained convulsions
    • ↑ Movement with restraint
    • Suggestible movements
    • Resistance to eye opening
    • Absence of pupillary dilatation
    • Normal tendon reflexes post-convulsion
    • Paucity of metabolic consequences
  • Syncope

Jerking and tonic posturing is common in syncope. The 10/20 rule states:

  • <10 jerks is likely secondary to syncope
  • >20 jerks is a convulsive seizure

Investigations

Bedside:

  • ABG
    • Lactate
    • BSL

Laboratory:

  • Blood
    • FBE/Coagulation assay
    • UEC
    • CMP
    • LFTs
    • TFTs
    • Porphyrins
    • Drug levels
      • Antiepileptic
      • Alcohol
      • Benzodiazepines
  • LP
    If consideration of:
    • Infection
    • Autoimmune encephalitis

Imaging:

  • CXR
    Aspiration.
  • CTB
    Investigation of structural cause.

Other:

  • EEG
    • Diagnostic
    • Required following resolution without improvement in conscious state
      15% of this group have NCSE.
    • Changing appearance over time
      • Initially discrete seizure activity
      • Continuous monomorphic discharges
      • Periodic epileptiform discharges
    • Continuous EEG required for refractory status, ideally with video monitoring if available

Management

Principles:

  • Seizure termination
    Early benzodiazepines. Definitive control should occur within 60 minutes of onset.
  • Prevent secondary brain injury
  • Treat underlying cause
  • Prevent recurrence

The more the seizure is disturbing consciousness, the greater the risk of brain injury to the patient therefore there is strong justification to escalate treatment.

Resuscitation:

  • A
    • Airway protection
      If intubation is required, consider suxamethonium so seizure recurrence can be rapidly identified.
  • B
    • Supplemental oxygenation
  • C
    • IV access
  • D
    • 50% Dextrose 50mL IV with thiamine 100mg IV
      Low threshold if ↓ BSL is a possibility.
    • Seizure termination
      See below.

Specific therapy:

Interestingly, patients convulsive status are unlikely to get respiratory depression following benzodiazepines.

  • Pharmacological
    • Seizure termination
    Choice depends on timing, IV access, and drug availability. * Premonitory * 10mg SL or IN midazolam * 10-20mg PR diazepam * Emergent initial therapy (1st line)
    Benzodiazepines Q2-5 minutely: * Lorazepam 0.1mg/kg IV
    Preferred IV option, if available. * Diazepam 0.1mg/kg IV * Midazolam 0.1mg/kg IV/0.2mg/kg IM
    Preferred IM option, if available. * Urgent control therapy (2nd line)
    One of: * Levetiracetam 60mg/kg up to 4.5g * No levels required * Phenytoin 20mg/kg IV load, given at 50mg/min, up to 1.5g
    Always should be combined with a benzodiazepine for seizure termination. * Valproate 40mg/kg IV load up to 3g * Level 2-4 hours following load * Midazolam infusion at 0.05-0.4mg/kg/hr
    Phenobarbital (below) can be used as an alternative. * Refractory therapy (3rd line)
    * Transition to continuous infusions * Duration of therapy usually dictated by EEG * Consideration of: * Anaesthetic agents
    Continue infusions for 12-48 hours before attempting to wean therapy. Options include: * Thiopental 100-250mg IV * Propofol 2mg/kg IV, then infusion at 5-10mg/kg/hr * Phenobarbital 10-15mg/kg IV, given at 100mg/min * Ketogenic diet
    Considered dual 3rd line in some institutions.
    • Maintenance antiepileptic
      All have demonstrated equivalence, but levetiracetam is the most logistically convenient.
      • Levetiracetam
        • 60mg/kg IV load
      • Phenytoin
        • 20mg/kg IV load
        • Wait 2 hours before checking levels following loading dose
        • May precipitate hypotension
        • Avoid if usually on phenytoin
        • Avoid if drug induced seizures
      • Valproate
        • 40mg/kg IV load
        • Non-sedating
        • Levels can be checked immediately
  • Procedural
    Last-line therapy for refractory status may include:
    • Deep brain stimulation
    • Surgical resection
      • Callostomy

Disposition:

Anaesthetic Considerations

Marginal and Ineffective Therapies

  • Hypothermia
    Theorised to be neuroprotective in setting of seizures.
  • Muscle relaxation
    Prevent the metabolic cost of seizures, however renders it unclear if fitting has ceased.

Complications

  • Death
    10-20% of status epilepticus.
  • B
    • Aspiration pneumonitis
    • Neurogenic pulmonary oedema
  • D
    • Permanent neurological deficit
      • Primary injury
        Neuronal cell death occurs after ~30 minutes of status. Occurs in 10-16% of status.
      • Secondary injury
        • Hypoxia
        • Hyperthermia
        • Hypotension
    • Focal epilepsy
    • Todd’s Paresis
      Transient (hours-days) focal weakness following seizure activity in that limb.
  • E
    • Rhabdomyolysis
    • Hyperthermia
  • F
    • Glucose derangements
      • Hyperglycaemia
        Early, due to catecholamine release.
      • Hypoglycaemia
        Late, due to catecholamine tachyphylaxis.
      • Lactic acidosis

Prognosis

Poor prognostic signs include:

  • Age
  • Aetiology
    • CNS infection
    • HIE
      Usually fatal.
  • Degree of impaired consciousness
  • Refractory status
    ↑ Mortality and ↓ chance of returning to functional baseline.

Good prognostic signs include:

  • Aetiology
    • Drug withdrawal
    • Drug induced
    • Systemic infection

Key Studies

  • ESETT (2019)
    • Americans >2 years old with convulsive status epilepticus unresponsive to benzodiazepines, without another precipitant of seizure
    • Investigator-initiated, blinded, adaptive trial
    • Comparison of levetiracetam, fosphenytoin, and valproate
    • Absence of clinically apparent seizures and improving responsiveness after 60 minutes from trial drug delivery
    • Stopped early for futility, with no significant difference in ICU admission or safety outcomes)
    • Demonstrates the superiority of levetiracetam, as it avoids the complexities of dosing and monitoring valproate and fosphenytoin

References

  1. Gratrix AP, Enright SM. Epilepsy in anaesthesia and intensive care. Continuing Education in Anaesthesia Critical Care & Pain. 2005 Aug;5(4):118–21.
  2. Perks A, Cheema S, Mohanraj R. Anaesthesia and epilepsy. Br J Anaesth. 2012 Apr 1;108(4):562–71.
  3. Bersten, A. D., & Handy, J. M. (2018). Oh’s Intensive Care Manual. Elsevier Gezondheidszorg.
  4. Neurocritical Care Society Status Epilepticus Guideline Writing Committee et al. Guidelines for the Evaluation and Management of Status Epilepticus. Neurocritical Care 17, no. 1 (August 2012): 3–23.
  5. Kapur J, Elm J, Chamberlain JM, et al. Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus. New England Journal of Medicine. 2019;381(22):2103-2113. doi:10.1056/NEJMoa1905795
  6. Shmuely S, Bauer PR, van Zwet EW, van Dijk JG, Thijs RD. Differentiating motor phenomena in tilt-induced syncope and convulsive seizures. Neurology. 2018 Apr 10;90(15):e1339–46.