CICM Second Part Exam Practice SAQs 12122019

Status epilepticus is continuous seizure activity >10 minutes, or repeat seizure without full recovery; it is a life-threatening emergency. (Definition is controversial!)

•  longer a seizure lasts the more likely it is to become refractory or recur.
• High mortality and risk of incomplete neurological recovery if >20-30min

Pharmacological therapy includes:

• First line benzodiazepine
  • General
    • modulation of the GABA A receptor, which opens the chloride channel and hyperpolarises the cell, leading to postsynaptic inhibition
    • Adverse effects are similar for all benzodiazepines and include sedation, dizziness, weakness, unsteadiness, respiratory depression, and hypotension. There are additive effects when several benzodiazepines are co-administered
    • Cochrane review shows no clear benefit for one agent over another (midazolam, diazepam, lorazepam) https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29320603/
  • My preference is midazolam 5 to 10 mg (child: 0.2 mg/kg) IV, IM, buccally or intranasally, repeat once 15 minutes later if status epilepticus continues.
    • multiple routes including intramuscular, buccal or intranasal administration if no IV access
    • short elimination half-life
    • may accumulate in patients with renal impairment
    • Familiar
    • Readily available
    • No propylene glycol toxicity
  • diazepam 10 to 20 mg IV, not exceeding 2 to 5 mg/min; repeat once 15 minutes later if status epilepticus continues (child: 0.1 to 0.25 mg/kg IV, over 2 to 5 minutes)
    • Long half life but rapid redistribution from CNS (20-30 min)
    • is diluted with sodium chloride 0.9% before administration, a fine white precipitate may form
    • Propylene glycol diluent – toxicity in high dose
    • Not IM route
    • Can be given via rectal route
  • clonazepam 1 to 2 mg IV, not exceeding 0.5 mg/min; repeat once 15 minutes later if status epilepticus continues (child: 0.25 to 0.5 mg IV, over 2 to 5 minutes)
  • Lorazepam 0.1 mg/kg (4-8mg) IV
    • Longer DOA but shorter half- life than diazepam
    • slower onset of action
• First line antiepiletpic drug (AED)
  • General
    • Longer acting, so more sustained effect
    • However, typically have slow onset – increasing practice of rapid transition to an induction agent and intubation
    • ESSET trial https://www.nejm.org/doi/10.1056/NEJMoa1905795
      • 384 children with refractory SE
      • Fosphenytoin, levitiracetam, and sodium valproate all were ~45-47% effective (resolved seizure and improvement at 60 mins)
      • No difference in safety (but not powered to detect uncommon events)
      • I.e. current algorithm is not very successful
  • Levetiracetam: 60 mg/kg to 4000 mg over 5–15 min; additional dose 1500–3000 mg
    • Less SE than phenytoin
  • Phenytoin 15 to 20 mg/kg IV, not exceeding 50 mg/min (or 25 mg/min in high-risk patients) (child: 20 mg/kg IV, not exceeding 25 mg/min). Continuous monitoring of the electrocardiogram and blood pressure is essential.
    • Familiar
    • Risk of toxicity if on phenytoin already
    • Drug interactions
    • Propylene glycol toxicity if administered too rapidly
    • Phenytoin has membrane-stabilizing activity and slows inward Na+ and Ca2+  flux during depolarization in excitable tissue; it also delays outward K+ ux.
    • irritant/ tissue damage if IM or extravasates
  • sodium valproate 400 to 800 mg depending on body weight (up to 10 mg/kg) by slow IV injection over 3 to 5 minutes, usually followed by continuous infusion of 1 to 2 mg/kg/hour up to a maximum of 2500 mg/day, according to the patient’s clinical response
    • GABA-ergic inhibition; sodium valproate increases brain GABA levels by inhibition of succinic semialdehyde dehydrogenase in the GABA shunt. Alternatively, it may: 1. mimic the action of GABA at post-synaptic receptors and 2. reduce excitatory inhibition (especially that due to aspartate).
• Second/ third line agents
  • Alternative first line AED (see above)
  • Induction/ general anaesthetic agents
    • Require intubation due to respiratory depression
    • Short-acting unless infusion
    • Physiologically make most sense for rapid termination of seizures
    • Generally lacking evidence (e.g. animal models, case series)
    • Refractory SE requires cEEG monitoring
  • Barbiturate e.g. Thiopental: loading dose of 2–7 mg/kg (infused at a rate <50 mg/min), with additional doses of 1–2 mg/kg as needed, followed by a continuous infusion at a rate of 0.5–5 mg/kg/h.
    • Rapid acting 
    • GABA receptors on RAS
    • Issues: CVS effects, porphyria, extravasation, intra-arterial toxicity
    • RCT in south Africa favoured phenobarbitone over phenytoin
  • Benzodiazepine infusion (e.g. midazolam, clonazepam)
  • propofol 1.5-2mg/kg IV then 20-200mcg/kg/min
  • Ketamine: loading doses 1–2 mg/kg, every 3–5 min until seizure stop (max 4.5 mg/kg) followed by continuous infusion ranging from 1 to 10 mg/kg/h.
  • Inhalational anaesthetic (e.g. isoflurane)
• Specific therapies for specific underlying causes
  • magnesium 4 grams IV if eclampsia
  • Pyridoxine for isoniazid toxicity
  • Phenytoin not useful for tox causes
  • Hypertonic saline for hyponatremia
  • NaHCO3 for TCA/ sodium channel blockade
  • Immunosuppressants (eg. methylpred, IV IgG, Rituximab) for autoimmune causes/ NORSE
  • antibiotics/ antivirals

Critical illness polyneuropathy (CIP) nerve conduction studies shows sensorimotor axonopathy with:

decreased compound muscle action potentials (CMAP) and sensory-nerve action potentials

preserved conduction velocities (CV)

if also present, critical illness myopathy (CIM) shows reduced amplitude and increased duration of CMAPs

GBS CSF

• elevated protein (only after 5-7 days of disease)
  • sometimes termed ‘cytoalbuminological dissociation’: increased CSF protein in the absence of increased WBCs
    • absence does not rule out GBS or make the diagnosis less likely
  • some patients have oligoclonal banding
  • ~5% of GBS patients have a mild increase in CSF cell count (5–50 cells per μL)

CT brain of hyperacute MCA occlusion

• The earliest finding of MCA occlusion is hyperdense middle cerebral artery sign – direct visualization of the thromboembolism.
  • Early parenchymal signs include subtle blurring, decreased attenuation and swelling of the grey-white matter junction
  • deep grey matter structures are affected before the cortex (lenticulostriate arteries are end arteries so cytotoxic edema occurs earlier)
    • lentiform nucleus; caudate nucleus
    • insular ribbon
    • surface cortex, including peri-rolandic cortex (usually not evident by 3 h)
  • With time the hypo-attenuation and swelling become more marked, leading to mass effect; before gradually reducing over days

Acute traumatic central cord syndrome

Osseous imaging may be

• Normal
• show spondylosis
• acquired/congenital canal stenosis, or
• fracture

The presence of an extension teardrop fracture should be a warning sign