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Pediatric Status Epilepticus

Ilene Claudius, MD, Al Sacchetti, MD, and Anand Swaminathan, MD FAAEM
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Nurses Edition Commentary

Kathy Garvin, RN and Lisa Chavez, RN
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EM:RAP 2019 July Written Summary 289 KB - PDF

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Ian L., Dr -

What happens re breathing with the treatment and what airway management has been found safe and efficacious ?

Alfred S., M.D. -

Airway management remains the same in these patients. If the anti-epileptic medications produce respiratory depression to the point of hypoventilation, then they require endotracheal intubation. Occasionally you may find that immediately after a bolus of a benzodiazepine there is transient hypoventilation that can be managed simply with bag valve mask ventilations.

ilene c. -

Agree entirely- nothing in your normal toolbox is contraindicated, though some steer clear of etomidate due to the myoclonus being confused with seizure activity. I usually use a benzo for intubation as a sedative. Old school and the residents laugh at me, but why not when it will help with the seizure? Rarely end up intubating. I do alot of BVM (2-3 minutes) following meds and often drop an NGT to empty out the stomach from the BVM. Kids rarely aspirate with NGT placement and can get hard to bag due to stomach distension from introduced air.

Alfred S., M.D. -

Perfect, I follow Ilene’s lead on this. Definitely avoid etomidate. In addition myoclonus, it will lower the seizure threshold.

Al

prestwig1 -

When I absolutely positively want a child to stop seizing. RIGHT NOW. PHENOBARBITAL. binds to sites in the membrane-spanning the transmembrane regions of the 5 subunits of the GABA receptor (two alphas two bets and a gamma) The Benzodiazepine binding site is only at the interface between the alpha and gamma subunits. Phenobarbital also reduces glutamate-mediated currents. Ketamine? Propofol? Mechanistically, neither seem to offer an advantage over Phenobarbital. Although Ketamine is an NMDA-R antagonist. I submit that early use of Barbituates would obviate the need for its favorable properties. My question to Dr. Saccheti. WHY NOT PHENOBARBITAL??

prestwig1 -

PS to Dr Saccheti Phenobarbital has AMPA activity as well. Also Propofol is 2,6 Diisopropyl Phenol effectively a tri-alcohol. The alcohols act at sites in the same transmembrane region (of the GABA receptor) similar to Phenobarbital. I really don't see what it adds.

Alfred S., M.D. -

Your pharmacology is excellent. In fact, back in the day we used pentobarbital rather than phenobarbital because of it's faster onset, although shorter duration of action.

Here is the problem, the barbiturates work on the GABA receptor, but in status epilepticus the GABA receptors are lost. The neurons actively remove and lyse these receptors. So although phenobarbital is an effective agent, it has no site to operate upon.

prestwig1 -

Dr. Saccheti I agree. In late-stage Status. This is true. I am just a simple country doctor. As I understand this process...the is a regression of Gaba receptors.. Externalization of AMPA receptors..then externalization and increase expression of NMDA receptors late in the process. I once read an article which divided Status into two phases. The stage of compensation marked by increased cerebral blood flow < 30 min and a stage of decompensation >30 min ... and marked by loss of cerebral autoregulation. I may not be accurate in my thinking but I have always thought of stage one as the GABA phase and Stage 2 as the NMDA phase. Phenobarbital acts potently at the GABA receptor...also at the AMPA receptor. Time is brain. So if benzos have been given in the field. I might give one dose of benzo and I call for the phenobarbital EARLY. So early administration of potent GABA and AMPA. Given the pathophysiology, early aggressive treatment always seemed indicated. In my simple way of thinking phenobarbital early obviates the need for Ketamine and Propofol (my GOD!) late. My concern in all this is that once a drug because cheap and generic. First comes commercial abandonment. No one has a financial interest in promoting the drug. Then disturbingly comes scientific abandonment. We in the profession abandon the drug for the shiny, the new, the unexplored. New is not always better. Sometimes old still works. Recently, there was a study regarding the utility of Phenobarbital for alcohol withdrawal. I laughed hysterically! Thank for your feedback.

Alfred S., M.D. -

I do not differentiate between different stages of status epilepticus, since there is frequently no way to really tell exactly when a seizure began. If the seizure activity responds to a GABA agent then it is likely early on and there is no need for another class of anti-epileptic agents. If it doesn't respond then you need to move on to an agent with a different mechanism of action.

If you prefer to use a barbiturate as the first line agent instead of a benzodiazepine you have a strong argument. However, the cost of the barbiturates has skyrocketed recently so you may have difficulty getting them, I know we can no longer get pentobarbital for this reason.

prestwig1 -

Thank you for your feedback. It is much appreciated. We met once at an ATLS course in Atlantic City. Back when the hair on both of our heads was much darker (and I had more of it) Thanks again. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2824929/#CIT27

Alfred S., M.D. -

Enjoyed the conversation as well. Take care.

Roy C. -

Our organization is developing a process to administer Levetiracetam 60mg/kg as the second line agent for children > 2 months old. Anyone else using Levetiracetam? How does that look in practice? What forms are available? Are you using the 1G in 100cc bags? How fast can you or should you give it? What about dose loss in the IV set, how are you addressing that? We don't have an ED pharmacist (yet). Do you have any protocols you're able to share? Are you mixing and administering via syringe pump?

Alfred S., M.D. -

Can't really help you on that Roy. We use ketamine as our second line medication. Big advantage is that it can be given as an IV push. We usually use the Levetiracetam as an infusion over 30 minutes in non-status cases.

ilene c. -

Hey Roy- there were 2 articles out in 2019 comparing phenytoin with levetiracetam as second line post benzos. They used 40mg/kg and at least 1 of them administered over 5 minutes. Definitiely not saying 60 is wrong- many of us use that dose- these are just the trials I am familiar with. Trial names CONSEPT and ECLIPSE (below). We put in small bag and run via pump after priming. It looks like the commercial vials come at a concentration of 500 mg/5mL per their website. We don't have a protocol per say, but LMK if I didn't fully address your questions and I can check with our pharmacist.

Dalziel SR. Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (ConSEPT): an open-label, multicentre, randomised controlled trial. Lancet. 2019 May 25;393(10186):2135-2145.
AND
Lyttle MD. Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial. Lancet. 2019 May 25;393(10186):2125-2134.

Roy C. -

ilene- thank you so much for your rapid and complete response. This was just the information I needed! Our policy is still a work in progress...

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