Welcome to the 51st Critical Care Congress. I would like to thank the planning committee for the invitation to present this session as part of a larger discussion on comparing pediatric and adult biologic responses to critical illness. I am very pleased to present on the topic of pediatric traumatic brain injury. My name is Dr. Karen Ritter-Rice, and it is a pleasure to be here with you. I have no conflicts. The objectives include to discuss the contrast between pediatric and adult patients with traumatic brain injury in several aspects of critical illness, specifically as it relates to basic science, and then to describe pediatric versus adult differences in anatomy, cerebral blood flow, cerebral blood flow monitoring, and current guidelines for management. And this is where the majority of my session will focus. Adult versus pediatric neurotrauma are magnified by the following differences. There are a number of controversies and uncertainties, specifically lack of normative data for children, scarcity of pediatric studies, and inappropriate generalization from adult studies. There are a number of childhood differences that you can appreciate on this slide. Additionally, the head and the brain of children are fundamentally different to adults, both physiologically and anatomically. In the newborn and infant, the head is disproportionately large and gradually assumes the head-body ratio of an adult over several years. At birth, the brain is about 25% of the adult size, even though the body weight is about 5%. About half of the postnatal growth of the brain occurs within the first one to two years of life. The ratio of head and neck length to body length, about 25% in infants, is almost double that of adults. The disproportionately greater weight of the head also affects the movement of the head when a child falls or is struck by a moving object. Fontanelles and sutures close at different times. So at two months of age, the posterior fontanelle is usually closed, and by 12 to 18 months, the anterior fontanelle is closed. Open sutures and fontanelles allow some buffering of ICP, especially if the intracranial volume increases slowly, but only to some extent. Intracranial ICP in the very young is considerably lower than in adults, as is blood pressure. So small increases in ICP may have significant adverse effects. There are also appreciable differences in cerebral blood flow in children. Resting and activated metabolic rates change across the childhood age range before settling into reasonably stable patterns in adulthood, as does cerebral blood flow and its response to injury. The same is true for blood pressure, and so uncertainty about optimal cerebral perfusion pressure thresholds is even greater. In children, the debate about thresholds for intracranial pressure treatments are aggravated by the fact that normative values for ICP in children are not well-established and depend on age. As I indicated on the earlier slide, brain metabolism in children changes with advancing age. This depends on progressive myelination and synaptogenesis and drives the substantial changes in cerebral blood flow, especially in the first eight years of life. Cerebral metabolism of glucose starts at low rates of around 60% of adult values at birth, but rapidly accelerates to over 200% of adult values by age 5, before slowly decreasing to adult levels through adolescence. Assessing cerebral metabolism in children using microdialysis, a technique that allows for direct sampling of the chemical constituents in the extracellular space of various tissues through a fine probe, has not achieved widespread utilization as a clinical tool. To date, there have been little data on imaging metabolism in children, in part limited by the snapshot methodology, the need to move unstable patients, and radiation exposure in children. It remains a valuable tool in research-led environments, but wider adoption is likely limited to costs and effort required to run an effective program in which catheters are placed, vials are changed regularly by the bedside and analyzed, and clinical decision made on the basis of chemical changes. While there has been little published data, there is a nice study by Tolius and his team who reported a small series of children with severe TBI who underwent microdialysis monitoring. As you can see here on the slide, the monitoring was primarily concentrated on glutamate. The preliminary metabolic data from the microdialysis is fairly much in keeping with the adult data. And as you can see in this cohort, elevated lactate pyruvate ratio was associated with mortality, poor clinical outcome, and low brain oxygen, as well as glucose decreased at lower cerebral perfusion pressures. Understanding cerebral blood flow is more challenging in pediatric TBI and in children in general, in part because in pediatric TBI, hyperemia is reported to be a frequent cause of raised ICP, and because normal cerebral blood flow varies with age. As you can see here on the slide, there are three different studies using different techniques trying to equate how much cerebral blood flow there is at the time of a three-year-old, which is 700 milliliters per minute, than a newborn, which is 70 milliliters per minute. Here's another example of a table illustrating bilateral blood flow volumes in extracranial arteries and total cerebral blood flow volume in different age groups. Measuring cerebral blood flow in children is not as easy as it is in adults. We heavily depend on the use of transcranial Doppler ultrasound-based techniques, MRI, and PET scans. The conditions under which these studies are performed also markedly can affect the outcome. These are often difficult in children, such as MRIs and PET scans, so sedation and anesthesia are used, both of which, of course, affect cerebral blood flow. There's also cerebral compliance, which is affected by cerebral blood flow and volume and the ratio of cerebral spinal fluid to brain, all of which are age-dependent. So you can see here there's a PET study of children where they found the regional cerebral blood flow was about 140 to 175% of adult values for children between the ages of three and seven. And they also determined that their metabolic rates were less different. When normalized for brain volume, you can see here that at three to four years of age, there's a peak of the volume, and it's about two and a half times that of adults. Cerebral monitoring in adults is much more common than it is in children, and it's not actually even used all that much in pediatric TBI, in large part because the tools aren't well-developed or the techniques that have been developed in adults don't always apply in children. There are often challenges with the dynamic nature of pediatric cerebral hemodynamics. As well, catheter-based monitoring has good temporal resolution, excuse me, but poor spatial resolution. But importantly, there's still a lot of discussion around what the normative values, ICP values for children are. You know, there's really surprisingly very little data. Much of the existing knowledge derives from examination of CSF, opening pressures from lumbar punctures. There's still really no general agreement that it accurately reflects ICP, specifically in disease states. So there is a team, Cartwright and his team, who studied 12 children, average age of about eight and a half years, where they monitored the intracranial pressure using a Camino, and the children also underwent a lumbar puncture. And it was really interesting because they had significant discrepancies. The mean ICP using the Camino monitor was 7.8 millimeters of mercury as compared to the lumbar puncture, which was 22.4 millimeters of mercury. And so I think it's important to realize that, you know, CSF opening pressures may overestimate true ICP. Also that, you know, lumbar punctures aren't really the best measure because, you know, there's a lot of technical factors such as positioning and sedation, as well as pathology-related factors. So a once-off determination of ICP doesn't reflect compliance, dynamic ICP changes or ICP behavior after stimulation. And then also I think ICP tolerated in normal physiologic state may not be tolerated if there already are factors reducing tissue perfusion or if physiologic mechanisms such as pressure autoregulation and flow metabolism coupling are impaired. So really, we are still in our field struggling to very accurately assess what are normal ICP values. And I think one other caveat I'd like to add is that, you know, ICP treatment thresholds in children are complicated also because we're trying to assess cerebral perfusion pressure, which heavily relies on blood pressure. And blood pressure changes across the age range in children, and there are a number of complexities with pressure autoregulation. And so it appears reasonable that adequate CPP should be age-based, but really at this point there's no recommendations that exist for that. And also that ideal normative blood pressure range, sex, and height should be considered, but they rarely are as well. And so ICP really still to this day in children has some ranges, but it is not as definitively clear as we would like to suggest it is in adults. One tool that's gaining traction in pediatric TBI is the use of transcranial Doppler, which measures flow velocity in the basilar vessels. It's noninvasive. It's portable. It can determine flow changes, both autoregulation tests, detect vasospasm, embolic vents. The nice thing about it is you can have it at the bedside. You can measure continuously or periodically. There are some limitations to it, of course, and that is that it's operator-dependent. Long-term monitoring is a little more difficult because changes in incination angle affect the recorded values. There's some published reference values now by O'Brien and team looking at critically ill and sedated children, so we do have some normative values in them. And there's more work that's being conducted both by Dr. O'Brien and others, including myself, in the use of transcranial Doppler as a more prevalent tool to assess the cerebral vasculature. So the importance around the use of transcranial Doppler and, more importantly, assessing what are normative values really lends itself to the fact that children's TCD values don't represent adult values, specifically because of age. And so when we use TCD in pediatrics, we're really looking at age-based values. Importantly, why this is different is because there are standardized measurements for cerebral vasospasm, both by measuring the middle cerebral artery in adults and then also then using the Lindegaard ratio. In pediatrics, we adjust our middle cerebral artery values based on age, and we still are using the Lindegaard ratio to assess for vasospasm. But another component of this work really was a consortium of experts that came together to really assess the use of TCD in pediatric TBI and other children who may be at risk for a neurologic injury in the ICU setting to come to some kind of consensus and have some practice recommendations about the use of TCD. And you can see here that this is actually a published recommendation. And why that's important is because being able to better assess whether or not you're truly evaluating a patient for hyperemia versus vasospasm matters. It's important, too, as a measure of, do we have any dysfunctional autoregulation? And so I think that having some criteria around how to conduct TCDs in children, as well as what might those appreciative values be, are important going forward in the field of traumatic brain injury. So just briefly, just a little historical context, how we came up with these practice recommendations really are born out of the PNCRG, which is a pediatric neurocritical care research group. There was a subgroup who used primarily transcranial Doppler in critically ill children. And it was this group that came together to really develop the recommendations going forward. You can find those recommendations along with accompanying tools and templates for use if you log into this site. I think one of the other really important pieces to this is it allows for us to have more standardized measures to start looking at the type of data we want to collect, the kind of data we'd like to report out in our research studies, so that we can actually get a little closer to what normative looks like in critically ill children. And now just to wrap up the last couple of slides of this presentation to talk about the management of children with severe traumatic brain injury, in 2019, I was privileged to be part of a group of authors who reexamined the current evidence and then made recommendations for the third edition of the guidelines. As you can see on this slide, it's a little bit of a busy algorithm, but once you actually drill down into it, you can see where it is that you want to go next once you have a child who presents with severe TBI. I think what's important here is that there are definitely pathways for intracranial pressure management as well as what kind of monitoring we should be conducting within these children who present with severe TBI. I think, too, the other component of this is the fact that there are a number of pathway options here that support both the medical and surgical management of children with traumatic brain injury. And so the second component of these therapies, the previous slide was Tier 1, and now we're moving into Tier 2, is really appreciating that in the addition of the third practice management guidelines, you now see TCD as being something worth consideration for advanced neuromonitoring. And I think this is born out of the work of many of us who really feel that this type of evaluation of the cerebral blood flow is inherently important and is a nice companion to ICP measure as well as cerebral perfusion measurement. So, in summary, children aren't small adults, and it's particularly true in children with traumatic brain injury. We know that cerebral metabolism and blood flow are unique based on age, anatomy, and physiology. We can appreciate that monitoring and management are evolving and are informed really by prospective pediatric TBI studies and also some of our retrospective studies that we have. We have new recommendations for the use of TCD in pediatric TBI and other children at risk for neurologic injury, and I've provided you a link to that as well as the PubMed link. There are new 2019 pediatric TBI guidelines for severe TBI, and I think if you're not familiar with these and you have the opportunity to care for these children, it's really worth a thorough read. There's both an executive summary and then there are the algorithm pathways for management. And then, importantly, that we need more research to measure and report cerebral blood flow, both differences and responses, both after injury and then, of course, in response to therapies. And we need well-designed clinical trials. We need consortium trials where we are really truly examining a large group of children with, you know, using the technologies that we have available to better provide new standard values but also to better inform practice as to how we use this monitoring well, but then also what does it mean when we get the values we get using the monitoring? How do we appropriately treat? And so, with that, I will close and say thank you. It's been a pleasure having the opportunity to share this session with you. I hope if you have any questions that you will reach out to me. I've provided a number of references throughout the slide deck as PMIDs, but you'll also find those referenced here throughout all of these slides. And you will also find some links that you can link into. And I wish you a very good Congress.

pediatric traumatic brain injury

anatomy

cerebral blood flow

management guidelines

physiological differences