Pediatric Traumatic Brain Injury, Seizure Prophylaxis, and Opining for Integration of Pediatric EEG
Ethan Sanford MD, Justin L. Lockman MD MSEd, and Shawn Jackson MD PhD
In the 1970s it was widely known that adult, acute MI patients who developed arrythmias had worse outcomes than those who didn’t. Logically, if we prophylactically treated these patients with lidocaine infusions to prevent the arrythmias during the initial treatment the acute MI outcomes would be better. Unfortunately, it actually increased mortality!1 In today’s PAAD and accompanying editorial2, the authors knew that patients who seize after a traumatic brain injury did worse than those who didn’t. This isn’t a surprising idea, because seizures are associated with a greater burden of neurologic injury and, even worse, subsequently increase neuronal metabolic demand, which can result in cerebral hypoxia, hyperemia leading to increased intracranial pressure (ICP), and the release of damaging inflammatory and excitotoxic neurotransmitters. It turns out, just like with the lidocaine story it, prophylactic anti-convulsant therapy with either Levetiracetam or Phenytoin reduced status epilepticus in TBI patients, but did it affect mortality? Further, did the choice of anticonvulsant make a difference? The results surprised us. Myron Yaster MD
Original article
Ahmed N, Russo L, Kuo YH. Levetiracetam or Phenytoin as Prophylaxis for Status Epilepticus: Secondary Analysis of the "Approaches and Decisions in Acute Pediatric Traumatic Brain Injury Trial" (ADAPT) Dataset, 2014-2017. Pediatr Crit Care Med. 2024 Aug 1;25(8):710-719. doi: 10.1097/PCC.0000000000003526. Epub 2024 May 8. PMID: 38717237.
Editorial
Lacoul A, Kirschen MP. You Say Potato, I Say Potatoe: Seizure Prophylaxis After Pediatric Traumatic Brain Injury. Pediatr Crit Care Med. 2024 Aug 1;25(8):764-766. doi: 10.1097/PCC.0000000000003543. Epub 2024 Aug 5. PMID: 39101802.
Today’s PAAD3 and accompanying editorial2 offers insight into current practices of prophylactic antiseizure medications in children who have suffered traumatic brain injury (TBI). At a recent teaching conference, a senior ICU attending exclaimed to me (ES) that anyone who tells you they can predict the ultimate outcome or recovery after pediatric TBI is likely lying or foolish. Most experienced ICU attendings have all cared for children whom we thought would not survive with a “good” quality of life who are now speaking, eating and proving us wrong. While seeking to provide frank, honest information when children suffer brain injuries, we are now more cognizant of delineating the type of brain injury (hypoxic/ischemic, thromboembolic, traumatic, etc) and explaining the anticipated prognosis – or rather our lack of certainty about prognosis for most of these patients.
In considering the complexities of pediatric TBI and the role of anesthesiologist, we must consider the complexities of using multiple sedative-hypnotic medications in a heterogenous population, the role of intracranial hypertension management, the mechanism of injury, and the prevention and management of seizures, among other things. Drs. Jerry Chao and Ian Yuan recently summarized current knowledge and practice of electroencephalography (EEG) for pediatric anesthesia4 and pointed out how imperfect we are at optimizing sedation and states of consciousness.
But in addition to dynamic EEG monitors of consciousness, software now exists that allows analyzing EEG signals for pathologic states. We should expect that in the coming decade, advances in this frontier will push us towards improved care. Of course, as with cerebral oximetry, the incorporation of new technologies is likely to meet resistance due to lacking definitive data supporting improved outcomes, discomfort with learning a new tool, and cost. We would like to remind PAAD readers that a Cochrane review in 20145 showed no effect of pulse oximetry on cognitive function, complications, or death after anesthesia – but we doubt any readers would argue against its use nevertheless. Certain knowledge of whether a new tool is of value can be hard to come by without a willingness to try it.
In today’s PAAD, Ahmed et al. seek to better inform our practices surrounding seizure prophylaxis and how these practices may impact outcomes. Seizure after TBI is common (~25% for clinical seizures, likely higher for subclinical seizures detected on EEG), and approximately 10% of severe TBI patients will develop early status epilepticus, which has been associated with worse outcomes. Therefore, appropriate guidelines for seizure prophylaxis are critical. Over time, levetiracetam has gained increased utilization because of its better side effect profile compared to phenytoin. The authors compared these two seizure regimens for occurrence of status epilepticus and mortality. The study benefits from application of the Approaches and Decisions in Acute Pediatric Traumatic Brain Injury Trial (ADAPT). ADAPT is a multicenter observational cohort study of children with TBI requiring an ICP monitor. These large collaborations provide evidence to guide practice and, hopefully, guide prospective interventional trials.
Before propensity matching of the cohorts based on demographic and clinical variables, the authors found an association of levetiracetam with increased seizure, greater ICU days, and worsened 6-month functional neurologic outcome, and even increased 60-day mortality. Only differences in the functional neurologic score (GOS-E 6 months after injury) and median number of ICU days remained significant after propensity matching. After evaluating confidence intervals, the authors state “We are unable to exclude the possibility that selecting levetiracetam rather than phenytoin for prophylaxis was associated with greater prevalence of seizure and mortality.” We were somewhat surprised and concerned about the results of this study. Currently, common practice is to start prophylactic levetiracetam for severe TBI. This study draws attention to more carefully considering these medications. Importantly, this should drive further studies which will hopefully guide us towards optimal practice. And as Dr. Jim DiNardo always reminds us, association is not the same thing as causation.
Do you routinely give prophylactic seizure medications in the OR for a patient with acute TBI? If so, which one(s)? Do you use EEG in your ICU and/or OR for the acute care of these patients? Will we all be using EEG in 10 years?
Email your thoughts to Myron (myasterster@gmail.com) who will post in a Friday Reader Response.
References
1. Sadowski ZP, Alexander JH, Skrabucha B, et al. Multicenter randomized trial and a systematic overview of lidocaine in acute myocardial infarction. American heart journal 1999;137(5):792-798. DOI: https://doi.org/10.1016/S0002-8703(99)70401-1.
2. Lacoul A, Kirschen MP. You Say Potato, I Say Potatoe: Seizure Prophylaxis After Pediatric Traumatic Brain Injury. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies 2024;25(8):764-766. (In eng). DOI: 10.1097/pcc.0000000000003543.
3. Ahmed N, Russo L, Kuo YH. Levetiracetam or Phenytoin as Prophylaxis for Status Epilepticus: Secondary Analysis of the "Approaches and Decisions in Acute Pediatric Traumatic Brain Injury Trial" (ADAPT) Dataset, 2014-2017. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies 2024;25(8):710-719. (In eng). DOI: 10.1097/pcc.0000000000003526.
4. Yuan I, Bong CL, Chao JY. Intraoperative pediatric electroencephalography monitoring: an updated review. Korean J Anesthesiol 2024;77(3):289-305. (In eng). DOI: 10.4097/kja.23843.
5. Pedersen T, Nicholson A, Hovhannisyan K, Møller AM, Smith AF, Lewis SR. Pulse oximetry for perioperative monitoring. The Cochrane database of systematic reviews 2014;2014(3):Cd002013. (In eng). DOI: 10.1002/14651858.CD002013.pub3.