Targeted treatment in severe traumatic brain injury in the age of precision medicine

Abstract

In recent years, much progress has been made in our understanding of traumatic brain injury (TBI). Clinical outcomes have progressively improved, but evidence-based guidelines for how we manage patients remain surprisingly weak. The problem is that the many interventions and strategies that have been investigated in randomized controlled trials have all disappointed. These include many concepts that had become standard care in TBI. And that is just for adult TBI; in children, the situation is even worse. Not only is pediatric care more difficult than adult care because physiological norms change with age, but also there is less evidence for clinical practice. In this article, we discuss the heterogeneity inherent in TBI and why so many clinical trials have failed. We submit that a key goal for the future is to appreciate important clinical differences between patients in their pathophysiology and their responses to treatment. The challenge that faces us is how to rationally apply therapies based on the specific needs of an individual patient. In doing so, we may be able to apply the principles of precision medicine approaches to the patients we treat.

Anatomical and Physiological Differences between Children and Adults Relevant to Traumatic Brain Injury and the Implications for Clinical Assessment and Care

“…This phenomenon, along with age- and cause-specific differences, produces heterogeneity and explains the observation that the relationship between ICP and brain oxygenation is weak when pooled across all patients, even though they may be tightly linked in episodes in individual patients ( 92 ). Indeed, this may represent part of the interindividual variability that confounds many of our treatments and leads to negative studies, in large part because not all patients respond the same to treatments, or in fact need that particular treatment at all ( 100 ). This raises several questions: should the threshold for ICP treatment be different if the cause of increased ICP is increased blood flow, i.e., if perfusion is not compromised can we be permissive about ICP higher than our traditional target?…”

Approaches to Multimodality Monitoring in Pediatric Traumatic Brain Injury

“…Current literature also indicates that TD values below 15 mL/100 g/min are associated with CVS in adult patients after aneurysmal subarachnoid hemorrhage (43). While these techniques are utilized in children with TBI in select centers (44), there is a lack of literature describing their findings.…”

Therapeutic hypothermia and targeted temperature management for traumatic brain injury: Experimental and clinical experience

“…Because TBI is also a very heterogeneous patient population, it will be important in future studies to develop diagnostic strategies including imaging and surrogate protein biomarker approaches to better select appropriate patients and to monitor temperature-sensitive injury cascades. [ 89 90 ] Such an approach would allow physicians to vary therapeutic treatments based on an individual's specific status. Furthermore, because many patients have focal lesions that can be identified with high-resolution computed tomography or magnetic resonance imaging, it might be important in future investigations to consider more focal-cooling strategies for these patients.…”