Pathway for the Pharmacological Management of Status Epilepticus in Pediatric Patients

Additional Info

• Audio File:uab/ua177.mp3
• Doctors:Rashid, Salman
• Featured Speaker:Salman Rashid, MD
• CME Series:Quality and Outcomes
• Post Test URL:https://cmecourses.som.uab.edu/mod/quiz/view.php?id=4440
• Guest Bio:Salman Rashid, MD specializes in Pediatric Neurology, Pediatrics. 
  
  Learn more about Salman Rashid, MD 
  
  Release Date: December 23, 2020
  Expiration Date: December 23, 2023
  
  Disclosure Information:
  
  Planners:
  Ronan O’Beirne, EdD, MBA
  Director, UAB Continuing Medical Education
  
  Katelyn Hiden
  Physician Marketing Manager, UAB Health System
  
  The planners have no commercial affiliations to disclose.
  
  Faculty:
  Salman Rashid, MD
  Associate Professor, Pediatric Neurology & Pediatrics
  
  Dr. Rashid has no financial relationships related to the content of this activity to disclose.
  
  There is no commercial support for this activity.
• Transcription:Introduction: UAB MedCast is an ongoing medical education podcast. The UAB division of continuing education designates that each episode of this enduring material is worth a maximum of 0.25 AMA PRA category one credit to collect credit, please visit UABmedicine.org/medcast, and complete the episodes Post-Test. Welcome to UAB MedCast, a continuing education podcast for medical professionals, bringing knowledge to your world. Here's Melanie Cole.
  
  Melanie Cole: Welcome to UAB MedCast. I'm Melanie Cole, and today I invite you to listen in, as we discuss the pathway for the pharmacological management of status epilepticus in pediatric patients. Joining me is Dr. Salman Rashid. He's a Pediatric Neurologist and an Assistant Professor at UAB Medicine. Dr. Rashid, it's a pleasure to have you join us today. Terminology used to describe different seizure stages phases, reflect the complex and nuanced definition of status epilepticus. Tell us what it is, what's the prevalence and the different types that you see?
  
  Dr. Rashid: So, status epilepticus is a condition which results from either the failure of mechanisms, responsible for seizure termination or from initiation of mechanisms, which lead to abnormally prolonged seizures after a time point, which is termed as T1. It is a condition that can have long-term consequences if it continues for a long time. And the time point named at that point is T2. The long-term consequences could include neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type of duration type and duration of seizure. So for example, for a generalized tonicclonic seizure, T1 is thought to be five minutes and T2 is thought to be 30 minutes. In practical terms, it is thought that at point T1, the treatment of a seizure should begin. And by the time two status epilepticus should have been controlled. Now, there are a few more things in terms of the definitions, because conventionally, it was thought that if seizure lasts for less than five minutes, it would be termed as brief seizure.
  
  If the seizure would last between five to 30 minutes, it would be termed as prolonged seizure. And if it would last beyond 30 minutes, it would be termed as status epilepticus. Now it could just be a single seizure, or it could be more than two seizures without full recovery of consciousness between the seizures. Now, since majority of the seizures are brief and once a seizure lasts more than five minutes, it is likely to be prolonged. Therefore, most of the treatment pathways like ours adhere to a five minute definition for decision management. This approach may reduce the risk for prolonged seizures without management and the adverse outcomes associated with unnecessarily terminating intervening on brief self limited seizures. A couple of other definitions to be discussed here would be a refractory status epilepticus. If the status epilepticus fails to respond to therapy with two antiepileptic medication, one of them being a benzodiazepine class of medication, it is termed as refractory status epilepticus.
  
  But if the status epilepticus has failed to resolve or reoccurs within 24 hours or more despite therapy that includes a continuous infusion such as midazolam or pentobarbital infusion, then it is termed a super refractory status epilepticus. In terms of the prevalence of status epilepticus in children, it is estimated that around 17 to 23 of hundred thousand children experienced status epilepticus every year with the highest incidence in children less than one year of age. And one of the studies from United Kingdom, the overall incidence of status epilepticus was around 14.5 in a hundred thousand pediatric patients. The incidence was the highest in children, younger than one, which was around 51 in a hundred thousand. And then it progressively decreased to the point that it was around two in a hundred thousand in kids who were 10 to 15 years of age. It is also important to mention that there is some literature that suggests that social economic deprivation is associated with increased incidence of convulsive status epilepticus in children, although it needs to be studied in more details.
  
  Host: What does it represent? Is this an exacerbation of a preexisting seizure disorder doctor or an initial manifestation of one, or can it represent an insult that something other than a seizure disorder? How does it present?
  
  Dr. Rashid: Yeah, that's a very good question. Status epilepticus could be the initial presentation of a patient who does not have a diagnosis of epilepsy. And when that happens, you have to look into what may be causing such a prolonged seizure. It could also happen in patients with already existing diagnosis of epilepsy. And when that happens again, you have to look at what may be causing it. One of the common cause may be, for example, not taking the antiepileptic medications as prescribed or inappropriate amounts. In those scenarios, obviously you have to make a clinical judgment in terms of what may be the underlying reason for status epilepticus in those patients.
  
  Host: So how emergent is this condition what's important to note in supportive care for these children in the prehospital setting? And why is this vital that EMS know what's going on?
  
  Dr. Rashid: As the literature supports, if the seizures last too long, at a certain point, there comes a time when there is irreversible loss of brain structure and function, and it can lead to neuronal death, neuronal injury, and alteration of neuronal networks. So that is why it is extremely important for the primary care providers and also the first responders to be well aware of this situation, and to be well aware of some of the seizure abortive medication that can be administered for the seizure to stop before it gets too long. One often common medication that is used in pediatric population is Diastat, which is usually prescribed by the primary care practitioners after the kid had a seizure that lasted for more than five minutes. And similarly, some parents that are apprehensive on administration of Diastat because of the fear side effect of respiratory depression, and if the kid is having a seizure, they're talking to 911 or the first responders, and usually feel comfortable in administering that when the 911 is on their way.
  
  Host: So then based on that doctor, I'd like you to talk about the treatment pathway and the route of administration. Is this usually in the ER, is this a planned treatment path?
  
  Dr. Rashid: The treatment pathway that we proposed is basically for the patients who have seizures within the hospital. And obviously there are other situations. And as I mentioned, if the seizure happens outside the hospital or in the field, usually the first step is to give a medication that is called a seizure abortive medication in a hope to prevent the seizure from lasting too long. So in general treatment pathways are likely to be more helpful when evidence-based guidelines are combined with the cultural practices. Our status epilepticus pathway is largely based on 2016 guidelines for the American Epilepsy Society. We utilize a quality improvement type of approach to synchronize our local practices with guidelines. Our team included a group of pediatric neurology providers, pediatric critical care providers, as well as pharmacy and nursing staff, including nurse educators. It also involves looking at our local resources, cultures, and practices. For example, we carefully looked at our medications suggested in the pathway available within the desired time window.
  
  Where are these medications located? For example, are they located in the Pyxis machine? What is the desired dilution for the medication? And what is the rate of administration? Through tabletop simulations, we also looked at the common problems encountered by the healthcare providers while managing status epilepticus and try to account for all these scenarios in our pathways. It is also important to remember that this pathway is for the management of status epilepticus in non neonatal pediatric age group. It is designed to assist clinicians for treating patients with status epilepticus. It is not intended to establish a standard of care or replace a clinical judgment or establish a protocol for all patients. Therefore, other approaches that are not covered within this pathway may also be appropriate for management.
  
  Host: Well, then please speak about that. Speak to us about the first-line medications, second line, and some of the other treatment options in patients who are refractory to the first and second line medications?
  
  Dr. Rashid: So, the initial phase of the management of a seizure is stabilization of the patient. Look at their airway, breathing, circulation, do a neurological exam if you can. Time the seizure, monitor vital signs, and assess their cardio-respiratory status. And if it is nearing five minutes, obtain an IV access. One of the lap tests that is very important to be obtained urgently is a point of care blood glucose, because if status epilepticus or seizure is due to hypoglycemia, it is less likely to respond to other medications, and can lead to brain damage relatively quickly. So in essence, the first five minutes is basically stabilizing patient and evaluating for urgent causes for seizures. Now, if the seizure is prolonged beyond the first five minutes, the first-line medication is usually a benzodiazepine. And the choice depends upon whether the patient has an IV access or does not have an IV access.
  
  If the patient has an IV access, we recommend using lorazepam 0.1 milligrams per kilograms, up to the maximum dose of four milligrams. But if the patient does not have an IV access, there could be multiple medications that could be used. But for this pathway, we have recommended intramuscular midazolam. If the patient is between 13 to 40 kilograms, the dose would be five milligrams. And if the patient is more than 40 kilograms, the dose would be 10 milligrams. Now, if the seizure continues, then repeat these benzodiazepine, class of medication can be administered. If it is IV lorazepam. Again, the dose would be 0.1 milligrams per kilogram with the maximum dose of four milligrams. But at the same time, the staff should also get ready in preparing for second line medications. Now, if the seizure is prolonged and lasts beyond 20 minutes, then the second line medication should be used.
  
   
  
  If the patient has no known diagnosis of epilepsy or is not on anti-epileptic medications, in those scenarios, we recommend three medications and one of them can be used for the management. These medication are suggested based on their safety, tolerability and efficacy profile. The first medication that we recommend would be intravenous alazopram. The loading dose of the medication is 60 milligrams per kilogram with a maximum dose of 4,500 milligrams. If the patient is allergic to, for example to the lorazepam, or if there are other contraindications, then intravenous Fosphenytoin can be used. The loading dose is 20 milligram PE per kilogram, the maximum dose of 1500 milligrams, PE per dose. And if both these medications cannot be used, then phenobarbital can be used. If the patient is not intubated, we suggest using a dose of 15 milligrams per kilogram.
  
  This dose is in accordance with what is suggested by the American Epilepsy Society guideline from 2016. If the patient is on anti-epileptic medications already, then we suggest that initial presentation lab values of those medications, that the patient is on should be obtained. And neurology should actually be contacted before 20 minutes to guide management for the second line medication, if the seizure lasts that long. Now this is the treatment up to 40 minutes from the onset of seizure. In scenarios where the seizure lasts beyond that, for example, more than 40 minutes, or if the patient has more than two seizures and does not gain awareness between the seizures, then unfortunately we do not have evidence-based guidelines for guiding therapy. But what is usually suggested is that you can repeat the second line therapy, or you can go to the next step of anesthetic doses of medications, for example, midazolam or pentobarbital. In such scenarios. EG also becomes very important.
  
  Host: That is such an interesting topic. And you gave such a great description of the first and second line and whether or not those don't even work at that point. So what would you like other providers to know as the take home points from this discussion and when you feel that it's important that they refer their patients with status epilepticus?
  
  Dr. Rashid: So, the take home points I would like to mention are that number one, it is to be remembered that this pathway is for pharmacological management of status epilepticus in children, and does not take into account individual patients’ scenarios. For example, does the patient need urgent intubation? So while managing the patient pharmacologically, it is extremely necessary to think why the patient is suffering from status epilepticus, therefore diagnostic workup, including labs and imaging should be completed as soon as possible and occur simultaneously, and in parallel with the treatment. Number two, when establishing disease management pathways, it is important to analyze and find ways to synchronize evidence-based medicine with local resources, cultures, and practices. Now, what we have presented in this pathway is based on the best evidence and then our culture, but the management of seizures and status epilepticus pathway is likely to change in coming times.
  
  And we should all keep our eyes open for the new literature and new evidence that is coming in. I think that if the patient has status epilepticus, whether it is a febrile status epilepticus or not, usually those patients present to the emergency room. And in those scenarios, on-call neurology is usually involved and they guide management based on a patient's presentation. So most in most of these scenarios, the neurologists are already involved in care. And my experience has been that with patients with prolonged seizures, most of the pediatricians do refer them for further management. Now whether the treatment for epilepsy is required or not, that would be a different topic and will be covered in the upcoming talks.
  
  Host: Thank you so much, Dr. Rashid and I invite you to come on with updates as we learn more. Thank you again for joining us. And a community physician can refer a patient to UAB Medicine by calling the MIST line at 1-800-UAB-MIST. That concludes this episode of UAB MedCast, to refer your patients, or for more information on resources available at UAB Medicine, please visit our website at UABmedicine.org/physician. Please also remember to subscribe, rate, and review this podcast and all the other UAB Medicine podcasts. I'm Melanie Cole.
• Hosts:Melanie Cole, MS