Pediatric Small Talk – Pediatric Status Epilepticus: The Chess Game of the ED

Welcome back to Small Talk.  Every first Wednesday of the month we will release high yield PEM content written by PEM talent from around the country.  We hope you enjoy these reviews. Comments, questions, accolades or concerns: feel free to reach out to Joe Ravera, MD (pemgemspod@gmail.com).

Author: Joe Ravera MD (@pemuvm1, Director of Pediatric Emergency Medicine, Assistant Professor of Surgery, Division of Emergency Medicine, University of Vermont Medical Center) // Reviewed by: Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

Case

The paramedics radio in that they are coming in with a 4-year-old actively seizing.  The patient has a history of Lennox-Gastaut syndrome and severe seizures in the past.  They are unable to establish an IV and are 5 minutes out.

Background Demographics, Definitions, and Setting Up the Chess Board

Seizures are a common presentation to the emergency department.  While most seizures are self-terminating, a small subset of patients may present in status epilepticus which is a seizure lasting longer than 5 minutes or multiple seizures without return to baseline.  Fortunately, for EM physicians, the care of status has become algorithmic and there are multiple available flowcharts (e.g. https://www.chop.edu/clinical-pathway/status-epilepticus-clinical-pathway) for the escalation of anticonvulsant therapy. However just like chess grandmasters, we are more than just an algorithm and by thinking moves ahead as opposed to reacting and reading an algorithm we can improve the care for children presenting in status epilepticus.

The Opening

A child who arrives actively seizing this can be a chaotic environment.  Furthermore, status epilepticus is a like a ball rolling down hill and, particularly with children with severe seizure disorders, the longer they seize the harder it may be to terminate the seizure.  There are several priorities from the start.

Establish a weight or color on length-based resuscitation: As discussed in my piece on pediatric cardiac arrest (http://www.emdocs.net/pediatric-small-talk-the-135-approach-to-pediatric-cardiac-arrest/) every medication you administer will based on either an accurate weight or an estimated weight, so get this first.   If possible, get report form the paramedics and have medications predawn and ready to go.

Establish access: These kids, particularly those that are still actively seizing on arrival to the ED, will likely require multiple medications for seizure termination.  If you are unable to establish IV access quickly, move to interosseous (IO) access.  In my practice I typically will place an IO if not IV access is established in the first minuet.

 Eliminate two etiologies: Although rare, hypoglycemia and hyponatremia change the management of a child in status.  A POCT blood glucose and i-STAT for sodium should be obtained as soon as possible.

Administer a dose of benzodiazepine: Often times these children will have received a dose from EMS and if they are still seizing on arrival or start to seize again the first line agent is an IV benzodiazepine. Recent literature would support the use of IV, IM or IO Midazolam (0.1-0.2mg/kg) or Lorazepam (0.1mg/kg) with Diazepam being a less desirable but a semi effective choice if it is all that is available.  In the absence of IV or IO access or while it is being established consider an alternate route such as PR diazepam or even buccal or intranasal midazolam (0.3mg/kg).¹ Benzodiazepines can be repeated every 3-5 minuets in a patient who is actively seizing.

These are the opening steps to status epilepticus and often time a child’s seizure will terminate with the initial dose of benzodiazepine, however for the cases when the child is still seizing or the seizures return, we enter what I have coined “the middle game” or the next phase of status epilepticus.  As a generally principle, just like a chess grandmaster, you want to think moves ahead.   A mantra I use for status epilepticus is when one medication goes in, call for the next medication.

The Middle Game  

Ideally as the benzodiazepine is being administered the next medication is being drawn up to cut down on lag time in administration.  There are several second line choices for antiepileptic medication, and in the last 10 years there have been several studies that compared them head-to-head in the pediatric population. The take-home point of all the studies was that there was no difference in seizure control with fosphenytoin (20 mg/kg) vs. levetiracetam (40-60 mg/kg) vs. valproic acid (40 mg/kg).  It should be noted that only one study included valproic acid, as such there is more robust data in levetiracetam and fosphenytoin.^2,3,4  Translating this research in to practice, this author recommends whatever you can get in fastest would likely provide the optimal care with a preference for either fosphenytoin or levetiracetam.  Also, following up on the core mantra of managing status epilepticus I would have the other second line medication drawn up and ready to go as the first one is infusing.  If it’s not needed then it can be returned but again, if the second line agent fails to control the seizure, this will cut down on lag time for additional medication administration.

In addition to treatment, the second consideration in the middle game is the underlying etiology of the seizure.  If the child has a known seizure disorder or an underlying syndrome with predisposition for seizures consideration should be towards medication noncompliance or an underlying infectious or metabolic etiology.  It should also be noted that some children may have underlying syndromes that predispose them to prolonged seizures without a clear underlying trigger.  In the absence of an underlying syndrome or known seizure disorder EM providers need careful consideration of the possible trigger.  The most common thing would be a complex febrile seizure, if it fits the right age group and clinical picture.  Absent this, and based on the clinical scenario, strong consideration should be given to a CNS infection, toxicologic ingestion, or trauma (including non-accidental trauma).

The End Game

After one or possibly two second line medications, children who are still seizing can be extremely challenging. Based on data from one of the above-mentioned trials approximately 70% of children will have their seizures controlled with a second line agent, meaning up to 30% may continue to seize and be considered refractory status epilepticus. In this case a third line administration of phenobarbital (20 mg/kg) should be considered.  Ideally this would be drawn up and ready to go as the second-line agent is infusing.  Given the critical nature of these kids, if not already in process, arrangements should be made for PICU admission.

Most children who are in refractory status epilepticus will require airway management. The exact timing of when to intubate children in status epilepticus depends largely on the clinical scenario.  In this authors opinion any child that has not terminated with one second line agent merits strong consideration for intubation as they will likely need multiple medications and possibly intravenous sedative anesthetics such as propofol or even, in rare cases, inhaled anesthetics.  Once a child is intubated and paralyzed the physical exam and clinical signs of convulsive status are lost.  Arrangements should be made to place an EEG as soon as possible for titration of medication.

If timing of intubation in status the timing of intubation in the exact postictal period is near impossible.  Apnea post termination of seizures is not uncommon and often multifactorial from the post ictal state, sedative properties of anticonvulsants and underlying disease. The period of apnea is varied and unpredictable, thus leading providers to move quickly to endotracheal intubation particularly in settings where transport is necessary. However, if resources allow, and the child is stable, this author recommends a brief period (5-10 minutes) of assisted ventilation with BVM in an attempt to give the child time to recover and become alert enough to oxygenate, ventilate, and maintain their airway.

Pearls and Pitfalls

• Get a weight or length-based resuscitation and establish IV or IO early in resuscitation of status epilepticus.
• When one medication goes in, call for and prepare the next medication.
• Consider the underlying etiology particularly in a child without a history of seizures who requires second-line medications.
• Timing of intubation is challenging both in status and in post-ictal apnea. Consider a brief period of BVM in the post-ictal phase to allow the child to recover and avoid intubation.

Case Conclusion

The child arrives still actively seizing.  He is blue on the Broselow and has an estimated weight 20 kg. An IO is quickly established, and a weight-based dose of midazolam is administered while a weight-based dose of levetiracetam is drawn up.  The child has a normal glucose and sodium.  The child continues to seize, and a repeat dose of midazolam is given followed by the levetiracetam.  fosphenytoin is drawn up but thankfully not needed as the child’s seizure terminates.  The child briefly becomes apneic and desaturates in the post ictal phase.  The child is successfully assisted with a BVM for 2 minutes and regains adequate ventilation and oxygenation.

References

1. Zhao ZY, Wang HY, Wen B, Yang ZB, Feng K, Fan JC. A Comparison of Midazolam, Lorazepam, and Diazepam for the Treatment of Status Epilepticus in Children: A Network Meta-analysis. J Child Neurol. 2016 Aug;31(9):1093-107.
2. Lyttle MD, Rainford NEA, Gamble C, Messahel S, Humphreys A, Hickey H, Woolfall K, Roper L, Noblet J, Lee ED, Potter S, Tate P, Iyer A, Evans V, Appleton RE; Paediatric Emergency Research in the United Kingdom & Ireland (PERUKI) collaborative. 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. doi: 10.1016/S0140-6736(19)30724-X. Epub 2019 Apr 17.
3. Dalziel SR, Borland ML, Furyk J, Bonisch M, Neutze J, Donath S, Francis KL, Sharpe C, Harvey AS, Davidson A, Craig S, Phillips N, George S, Rao A, Cheng N, Zhang M, Kochar A, Brabyn C, Oakley E, Babl FE; PREDICT research network. 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.
4. Chamberlain JM, Kapur J, Shinnar S, Elm J, Holsti M, Babcock L, Rogers A, Barsan W, Cloyd J, Lowenstein D, Bleck TP, Conwit R, Meinzer C, Cock H, Fountain NB, Underwood E, Connor JT, Silbergleit R; Neurological Emergencies Treatment Trials; Pediatric Emergency Care Applied Research Network investigators. Efficacy of levetiracetam, fosphenytoin, and valproate for established status epilepticus by age group (ESETT): a double-blind, responsive-adaptive, randomised controlled trial. Lancet. 2020 Apr 11;395(10231):1217-1224.