OUR CASE
Sharon is brought to ICU intubated and ventilated on a propofol and midazolam infusion for ongoing management.
Her CT brain looks normal.
CSF from her LP is also normal.
Her initial ABG showed a severe lactic acidosis, but this has rapidly normalised.
The rest of her bloods are also essentially normal.
Her blood alcohol level was slightly elevated.
PRIORITIES IN ICU
> Ongoing supportive care maintaining adequate oxygenation and cardiovascular stability
> Monitor for and treat ongoing seizures
> Find and treat the cause
> In super-refractory status epilepticus, escalate treatment and investigations
> Always balance treatments with their consequences
The EEG is critical in determining the next steps.
If there is ongoing non-convulsive seizure activity it will affect which drugs are stopped and which are introduced.
> Continuous EEG may be preferable in this context, if available
If there is no clinical seizure activity, ideally stop general anaesthesia with EEG monitoring
For example stop the midazolam long enough prior to the EEG and stop the propofol with while EEG monitoring on.
If there is still possible clinical seizure activity obviously don’t stop medications.
> Target normoxia
> Target normocapnia
> Avoid hypotension
> Look for and manage EICP
> Usual ICU housekeeping:
Art line & CVC in intubated
NGT & Start enteral feeding
IDC & monitor urine output
VTE prophylaxis is no contraindication e.g. enoxaparin 40 mg OD
Stress ulcer prophylaxis if intubated
Aim BGL 6-10 mmol/L
Keep in mind the broad differential of the potential causes
The initial investigations reveal the cause in the majority of cases
History
If the cause is uncertain, getting more history is often invaluable.
> Contact different sources e.g. GP, psychiatrist, other hospitals they have presented to
MRI
If the bloods, LP and CT haven’t given a cause, consider an LP. This may reveal:
> PRES
> CNS vasculitis
> Tumour or scarring from a previous CVA not appreciated on CT
Refractory Status Epilepticus (RSE)
An acute convulsive seizure that fails to respond to two or more anti-seizure medications including at least one non-benzodiazepine drug.
i.e. Seizures despite Tier 2 therapy e.g. midazolam and levetiracetam
Super-refractory status epilepticus (SRSE)
Status epilepticus that continues for ≥24 hours despite anesthetic treatment, or recurs on an attempted wean of the anesthetic regimen.
i.e. Seizures despite Tier 3 therapy e.g. midazolam and levetiracetam, intubated, seizures controlled with propofol and midazolam infusion but when these are reduced, seizures start again.
NORSE and FIRES
> NORSE: New onset of refractory SE without a clear acute or active structural, toxic, or metabolic cause in a patient without active epilepsy or other pre-existing relevant neurological disorder.
A clinical presentation, not a specific diagnosis.
> FIRES: NORSE with a prior febrile infection between 2 weeks and 24 hours prior to onset of refractory SE, with or without fever at the actual onset of SE.
It is a subcategory of NORSE.
A work up for SRSE
As you can see, the list of potential causes is massive.
If a driving cause can be found, the refractory seizures may stop and a good neurological outcome may be achieved e.g. Anti-NMDA receptor encephalitis causing SRSE, driven by an ovarian tumour, resolving after the tumour is resected
These patients may be in the ICU for months.
> Here are some of the tests that are often ordered in the work-up
Bloods
Blood cultures: bacterial and fungal cultures, RPR-VDRL, and HIV-1/2 immunoassay with confirmatory viral load if appropriate
Toxin screen
Levels of anti-seizure medication
Ammonia, lactate, pyruvate, acylcarnitine profile, plasma amino acids, urine organic acids (IEMs)
C3, C4, serum cryoglobulins, serum immune electrophoresis, quantitative Ig levels
Chromosomal microarray and epilepsy next-generation sequencing panel (genetic causes)
CRP, ANA and other antibodies (Ro/SSA, La/SSB, Sm, RNP, dsDNA, anti-phospholipid, ANCA)
Serum paraneoplastic / cancer serum markers
Autoimmune epilepsy antibody panel
Metabolic screen: LDH and ammonia; consider vitamin B1 level, B12 level, folate, lactate, pyruvate, CPK, and troponin;
Mitochondrial disorder screen: lactate and pyruvate, serum triglycerides
MRI / MRA
Cerebrovascular diseases
Tumors
Malformations of cortical development
TBI
HIE
Autoimmune encephalitis – limbic encephalitis may have mesial temporal or hippocampal signal changes
MR angiography (could do CTA or DSA as alternatives) looking for vasculitis, vascular malformations
CSF
Biochemistry
Microscopy
Culture
Viral studies
Bacterial and fungal stains and cultures
VDRL, PCR for HSV1, HSV2, VZV, EBV, HIV, and Mycobacterium tuberculosis
Autoimmune encephalitis panel
CSF paraneoplastic screen including CSF cytology, flow cytometry
Autoimmune epilepsy CSF antibody panel (see above)
Other imaging
CT chest/abdomen/pelvis (paraneoplastic cause)
Scrotal ultrasound (testicular tumours)
Mammogram (breast tumour)
Pelvic MRI (e.g. for ovarian tumours)
Whole-body PET-CT (paraneoplastic cause)
Tissue Biopsies
Specialized muscle or liver tissue studies (suspected mitochondrial disorders)
Bone marrow biopsy (paraneoplastic screen)
Brain biopsy
If Immunocompromised:
Serologic: IgG Cryptococcus species, IgM and IgG Histoplasma capsulatum, and IgG Toxoplasma gondii
Sputum: Mycobacterium tuberculosis GeneXpert
Serum and CSF: Toxoplasma IgG
CSF: eosinophils, silver stain for CNS fungi, PCR for JC virus, CMV, HHV6, EEE, Enterovirus, influenza A/B, WNV, Parvovirus, Listeria Ab, and measles (rubeola)
Stool: adenovirus PCR and Enterovirus PCR
As you saw in the ASM section, all these medications carry the risk of adverse effects
Using just enough ASM to control seizures is critical
cEEG can be helpful in titrating ASMs to electrographic evidence of seizures
For patients with SRSE, complications to watch for include:
> Cardiac arrhythmias e.g. from autonomic instability or relating to potassium shifts with thiopentone administration
> Hypotension with vasopressor requirement (from ASM’s, autonomic involvement, sepsis), need for central access and complications of this
> Venous thromboembolism (common, despite prophylaxis); regular screening recommended.
> Infections (line, LRTI, UTI); higher risk if immunosuppression treatment used
> Critical illness associated weakness (common, slows recovery)
The ICU resident contacts Sharon’s GP and gets some more history. She has recently been seeing him for anxiety and depression; her regular temazepam had been increased and there was suspicion she was using a higher dose than that prescribed.
On contacting Sharon’s pharmacist, it became clear she probably ran out of benzodiazepines 3 days ago.
Sharon’s friend visits the ICU and gives further history: she has been drinking more than usual recently and the day before she came to hospital she had drunk two bottles of wine, much more than usual for her.
What’s the likely cause of her seizure?
After 3 hours in ICU, the midazolam is stopped and an EEG performed.
There is no seizure activity, just diffuse slowing.
While the EEG is performed the propofol is also stopped, and there is still no electrographic evidence of seizures.
Sharon wakes and is successfully extubated.
Has she had SE, RSE, SRSE, NORSE or FIRES?