Status Epilepticus; what’s the rush?

Fitting is a really common reason to attend the Emergency Department. In the vast majority of cases the seizure has terminated before the patient arrives in the ED. But in some cases it’s still on going and by virtue of the length of time it takes for a patient to arrive in your ED that means they will have been fitting for quite some time when they pitch up in your Resus room.

5-10% of epileptics will have intractable epilepsy despite compliance with pharmacological treatment. In 50% of cases however status epilepticus will occur in patients without a diagnosis of epilepsy and the range of causes are pretty broad stretching from electrolyte imbalance, CVA, poor medication compliance, intra cerebral tumours, CNS infections, hypoxic brain injury, renal failure etc, etc…. So having a broad range of differentials in your armoury is essential as well as knowing the treatment for these. But of course you are going to need to treat the seizure itself as well.

So what actually is status epilepticus?

Generalised convulsive (tonic-clonic) status epilepticus is defined as a generalised convulsion lasting 30 minutes or longer, or repeated tonic-clonic convulsions occurring over a 30 minute period without recover of consciousness between each convulsion - NICE

It is important to recognise that status is a retrospective diagnosis and you don’t wait for the 30 minutes duration (if that is the definition you use) to start treatment due to the nature of the beast.

Practice hasn’t always been hugely prescriptive or seemed that time critical. A survey published in Anaesthesia in 1995 by Walker, Smith and Shorvon looked to benchmark the treatment of convulsive status epilepticus in the UK. This questionnaire showed a significant variety in the initial management from benzodiazepine infusion to anaesthetic induction agents with only 12 % of respondents (from this ITU based sample) being aware of a protocol for the management of status.

Things have moved on a fair bit since then though. The resuscitation council has some really useful algorithms for the management of fitting, no doubt they’ll be engrained on the back of your mind for not only your practice but also they’re a favourite for exam questions! But when it comes to the latter part of the algorithms and you’re thinking about the  prospect of intubating the patient to control the seizures have you ever wondered if this is overkill or even if this comes too late down the line? What is the evidence base to support it?

We should also mention that epilepsy comes in a variety of forms and the treatment for these is different. Status epilepticus is broken down into convulsive and non-convulsive status (depending on the presence or absence of rhythmical jerking).

Most clinicians follow the guidance set out by NICE on status epilepticus which can be found here. The algorithm for the treatment of status in adults is below (published in 2004)

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hyperlink to the document

Similarly the algorithm for the treatment of status in children is here (published in 2011);

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hyperlink to the document here

So in effect that means if the seizure is continuing for longer than 5 minutes then the patient gets benzodiazepines to help terminate the seizure. If this doesn’t work 10 minutes later then it’s another dose of benzo’s. Wait a further 10 minutes and it’s on to phenytoin or phenobarbitol (which tends to be less commonly used as an agent, certainly in the UK – which is a little odd when you consider some of the evidence we’ll touch on in a bit) and if the seizure still hasn’t ceased after 20 minutes then it’s time for an RSI with thiopentone (or a few other pharmacological agents to chose from in adults) as the final step of the status epilepticus algorithm.

Interestingly the document states that the treatment on con-convulsive status is less urgent;

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In 1998 in the NEJM Treiman and colleagues looked to find the most effective anticonvulsant for terminating status epilepticus. They compared i.v. treatments with diazepam (0.15 mg/kg) followed by phenytoin (18 mg/kg), lorazepam (0.1 mg/kg), phenobarbital (15 mg/kg), and phenytoin (18 mg/kg). They divided patients into 2 categories, those with overt generalised status (easily visible convulsions) or those with subtle status epilepticus (those indicated by coma and octal discharges on EEG with or without subtle convulsive movements e.g. rhythmic muscle twitches to tonic eye deviation).  The anti epileptics were produced to look identical to each other and require the same administration rate and that enabled the trial to be double blinded and randomisation of the treatment.

The headline findings from the study was that for generalised convulsive status lorazepam was most successful at terminating seizures (65%), then phenobarbital (58%), next diazepam and phenytoin (56%) and finally phenytoin alone (44%) in the 384 patients in this category. In the group with subtle generalised convulsive status there were no significant difference in success rates.

So why are we so bothered about getting control of generalised tonic clonic seizures so urgently, what harm do these patients actually come to long after they leave the emergency department?

Well there is significant morbidity and mortality associated with convulsive status at 12.5% and 2.5 % which may be higher than you’d thought. It has also been shown to be associated with a significant neuronal loss in the hippocampus. So getting on top of the seizure as quickly as possible and ensuring its termination occurs as soon as possible is critical for good patient outcomes.

And how exactly is it that seizures cause this morbidity and mortality? Well animal models in status can help us understand a little bit more; it was described by Lothman in 2 phases; in phase 1 there is increased cerebral metabolic demand which is caused by abnormally discharging cerebral cells but that this is met by an increase in cerebral blood flow, autonomic activity, arterial blood pressure, increased glycemic levels and hyperpyrexia and hyper salivation. After approximately 30 minutes phase 2 begins which is where the systems begin to fail with impaired cerebral autoregualtion, decreased cerebral blood flow and systemic hypotension which leads to a decrease in cerebral perfusion pressure. Interestingly at this stage the cerebral oxygen delivery can’t meet demand and electromechanical dissociation may occurr in which cerebral seizure activity continues but the clinical manifestations may be restricted to minor twitching. For this reason, presumably, the diagnosis of status includes not just the patient witnessed still to be fitting but those who have not returned to a normal neurological baseline as well. Arrhythmias are common in up to 60% of status. Metabolic derangement may also contribute to neuronal damage.

So for these reasons and specifically the cerebral metabolic decompensation occurring in phase 2 around 30 minutes of status rapid and effective treatment of seizures is required.

But once the convulsion has stopped then you can stop and give yourself a high five, fist bump, or whatever celebration tickles your fancy right? Well sadly not. You need to observe for a resolution to a normal neurological state and if that hasn’t happened within 20-60 minutes you need to be considering non convulsive status (or subtle status). This again is important; Pang reported in Neurology 2005 that there have been several case reports of non-convulsive status that have resulted in permanent neurological damage

So that’s it in a nutshell. Status is a common presentation, it can occur in pretty much any patient and commonly in the non-epileptic. It’s important to know the algorithms of treatment and the options that we have for the presentation and it’s also important to appreciate that it perhaps has a higher morbidity and mortality than we may have expected.

Swift and effective treatment of status saves neurones and saves lives!

Simon

 References

  1. Pang T, Hirsch LJ. Treatment of Convulsive and Nonconvulsive Status Epilepticus. Curr Treat Options Neurol. 2005 Jul. 7(4):247-259.
  2. Aminoff M J, Simon R P. Status epilepticus: causes, clinical features and consequences in 98 patients. American Journal of Medicine 1980; 6 9 657-66.
  3. Walker MC, Smith SJ, Shorvon SD. The intensive care treatment of convulsive status epilepticus in the UK. Anaesthesia. 1995 Feb 1;50(2):130-5.
  4. A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group. Treiman DM. N Engl J Med. 1998 Sep 17;339(12):792-8.
  5. Chapman MG, Smith M, Hirsch NP. Status epilepticus. Anaesthesia. 2001 Jul 1;56(7):648-59.
  6. NICE guidelines; Status Epilepticus

 

 

 

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