A 53-year-old male presents to the Emergency Department with headache and vomiting. He has a left hemiparesis and has a Glasgow Coma Scale score of 5. Soon after presentation he is seen to have a tonic clonic seizure.

a) Outline your priorities for the management of this seizure. Include approximate dosing for any drugs you might use.

After 30 minutes the seizure is terminated and the patient is intubated and paralysed and sent for CT brain that confirms high-grade sub-arachnoid haemorrhage. On return to ICU the neurosurgeon asks you to “lighten” the patient for assessment. On reducing sedation, further seizure activity is noticed. This happens on 3 occasions.

b) Describe your approach to this problem.

c) Describe when and how you would cease sedation in this patient.

d) Using the information given above, give an assessment of this patient’s prognosis.

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College Answer

a)
1. ABC+monitoring; BSL; Thiamine;
2. Cease the seizure

i. Clonazepam 0.01–0.02 mg/kg

ii. Midazolam 0.1 mg/kg or 2-5 mg boluses

iii. Or similar/reasonable alternative

3. Prevent further seizures

iv. Phenytoin 20 mg/kg @ max 50 mg/min

v. Valproate: 15–20 mg/kg IV

vi. Levetiracetam: 500–2000 mg depending on renal function

vii. Or other reasonable choice

b)
Should recognize this is status epilepticus: defined as a continuous state of seizures, or multiple
seizures, without return to baseline, resulting in observable or even subjectively perceived sensory,
motor, and/or cognitive dysfunction for at least 30 minutes. Other definitions exist so whatever is
reasonable.
Involvement with neurosurgeons for reversible factors.
Further benzodiazepine or similar → infusion
Propofol IV: loading dose: 1–5 mg/kg; infusion rate: 1–15 mg/kg/hr
Other agents – e.g. barbiturates if available
Early EEG monitoring to clarify seizure and confirm cessation (i.e. that a non-convulsive state is not
present).
Avoid muscle relaxants.


c)
Reduction of sedative medication needs to be discussed as a potentially difficult situation.
Balance of determining neurological function against the return of a convulsive or non-convulsive
state.
Continuous EEG monitoring should be discussed in this patient due to the prolonged, difficult to
control and recurrent seizures.
Timings and how medications are reduced needs to be logically explained and must be gradual.
Therapeutic drug monitoring to confirm phenytoin levels are in the therapeutic range

d)
Outcome after status epilepticus is determined primarily by the aetiology.
Relating to the Sub-arachnoid haemorrhage: High grade sub-arachnoid haemorrhage based on
Hunt & Hess; World federation of neurosurgeons & Fisher grading scales.
Relating to the fitting: status epilepticus secondary to the SAH infers a poorer prognosis. Various
series quote 20-35% “all comers” in this age group. A discussion should include the contribution and guarded prognosis from the SAH and coupled with this the status epilepticus prognosis.

Discussion

This question on status epilepticus differs from the others by its request for some information about prognosis. Status epilepticus is discussed elsewhere, both as a brief summary and as an extensive digression. From those chapters, the tabulated summary of management can be cut-and-pasted:

Management of Status Epilepticus 
From the 2012 "Guidelines for the evaluation and management of status epilepticus"
as well as the review of "Super-refractory status epilepticus"  (2011)

First line therapy

  • Benzodiazepines: boluses every 2-5 minutes (lorazepam apparently superior)
  • Earlier is better (late benzodiazepine therapy is less effective)
  • Phenytoin: 20mg/kg loading dose

Second line therapy

  • Midazolam infusion
  • More phenytoin
  • Phenobarbital/thiopentone, and levetiracetam

Refractory status

  • Propofol infusion, or midazolam infusion, or thiopentone infusion.
    • No real way to discriminate between them all in terms of efficacy
  • Continuous EEG monitoring
  • Probably no benefit from adding any more traditional antiepileptic drugs once burst suppression is achieved
  • Once the seizures resolve, it is recommended you wait for 12 hours before weaning the infusion of anaesthetic drugs.

The college expects the trainees to recognise that this is status epilepticus; the definition they offer is slightly different to the recent Neurocritical Care Society Guidelines definition
("5 minutes or more of continuous seizure activity, or two seizures with no intervening recovery of consciousness").

But they do allow "whatever's reasonable", so that is ok.

Weaning sedation in status epilepticus

The reduction in sedation (presumably a sedating infusion) in this patient will be coming on the coat-tails of three previous such attempts, which were unsuccessful. Thinking seriously about this, one would have to come to the conclusion that there is some sort of decreased seizure threshold here, which the patient crosses in the course of surfacing from anaesthesia. The solution to this could include the following measures:

  • Continuous EEG monitoring to commence while still sedated.
  • Confirmation of appropriate therapeutic drug levels
  • Confirmation of unchanged CT appearance (is there some sort of new pathology?)
  • Consultation with neurology specialist, and commencement of synergistic antiepileptics
  • Then, when everything is ready, a gradual decrease of sedation can be commenced.
  • With continuous EEG monitoring, antiepileptic therapy and sedation can be cross-titrated until the patient is only on anti-epileptics, and all the sedation is ceased.

Outcomes of status epilepticus

As the college politely point out, the outcome is strongly related to the aetiological cause. For instance, the glioblastoma multiforme has a very diffent prognosis to the viral meningoencephalitis. That said, status epilepticus has a certain pathophysiological influence on the outcome, as it too is associated with some neurological damage.

The following table is an abridgement of the far better table available in the 2012 Guidelines for Management of Status Epilepticus.

Status Epilepticus

Mortality:

  • At hospital discharge: 9–21 %
  • At 30 days: 19–27 % 
  • At 90 days: 19 %
  • Older age
  • Unconsciousness
  • Duration of seizures,
  • Focal neurological signs
  • Medical complications

Non-convulsive status

Mortality:

  • At hospital discharge: 18-52%
  • At 30 days: 65%

Time-critical diagnosis:

  • Diagnosis within 30 min of seizure onset:
    mortality 36 %
  • Diagnosed 24 hr after seizure onset:
    mortality 75 %

Features associated with poor outcome:

  • Severe mental status impairment
  • Unknown cause
  • Longer seizure duration
    • Less than 10hrs:
      10% mortality
    • More than 20hrs:
      85% mortality

Refractory status

Mortality:

  • At hospital discharge: 23–61 % 
  • At 3 months: 39 %

Features associated with poor outcome:

  • Older age (e.g., >50 years)
  • long seizure duration
  • high APACHE-2 scale scores
Outcome Statistics for Status Epilepticus

References

References

Oh's Intensive Care manual:

Chapter 49   (pp. 549) Disorders  of  consciousness  by Balasubramanian  Venkatesh

Chapter   50   (pp. 560) Status  epilepticus  by Helen  I  Opdam

Tan, R. Y. L., A. Neligan, and S. D. Shorvon. "The uncommon causes of status epilepticus: a systematic review." Epilepsy research 91.2 (2010): 111-122.

Brophy, Gretchen M., et al. "Guidelines for the evaluation and management of status epilepticus." Neurocritical care 17.1 (2012): 3-23.

Chen, James WY, and Claude G. Wasterlain. "Status epilepticus: pathophysiology and management in adults." The Lancet Neurology 5.3 (2006): 246-256.

Treiman, David M., et al. "A comparison of four treatments for generalized convulsive status epilepticus." New England Journal of Medicine 339.12 (1998): 792-798.

Meierkord, Hartmut, and Martin Holtkamp. "Non-convulsive status epilepticus in adults: clinical forms and treatment." The Lancet Neurology 6.4 (2007): 329-339.

Corry, Jesse J., et al. "Hypothermia for refractory status epilepticus."Neurocritical care 9.2 (2008): 189-197.

Brophy, Gretchen M., et al. "Guidelines for the evaluation and management of status epilepticus." Neurocritical care 17.1 (2012): 3-23.