Objective A relationship between reduced brain tissue oxygenation (PbtO2) and poor outcome following severe traumatic brain injury (TBI) has been reported in observational studies. We designed a Phase II trial to assess whether a neurocritical care management protocol could improve PbtO2 levels in patients with severe TBI and the feasibility of a Phase III efficacy study. Design Randomized prospective clinical trial Setting Ten ICUs in the United States Patients One hundred nineteen severe TBI patients Interventions Patients were randomized to treatment protocol based on intracranial pressure (ICP) plus PbtO2 monitoring versus ICP monitoring alone. PbtO2 data were recorded in the ICP-only group in blinded fashion. Tiered interventions in each arm were specified and impact on ICP and PbtO2 measured. Monitors were removed if values were normal for 48 hours consecutively, or after 5 days. Outcome was measured at 6 months using the Glasgow Outcome Scale–Extended. Measurements and Main Results A management protocol based on PbtO2 and ICP monitoring reduced the proportion of time with brain tissue hypoxia after severe TBI (0.45 in ICP-only group, 0.16 in ICP+PbtO2 group; p<0.0001). ICP control was similar in both groups. Safety and feasibility of the tiered treatment protocol was confirmed. There were no procedure related complications. Treatment of secondary injury after severe TBI based on PbtO2 and ICP values was consistent with reduced mortality and increased proportions of patients with good recovery compared to ICP-only management; however, the study was not powered for clinical efficacy. Conclusions Management of severe TBI informed by multimodal ICP and PbtO2 monitoring reduced brain tissue hypoxia with a trend towards lower mortality and more favorable outcomes than ICP-only treatment. A Phase III randomized trial to assess impact on neurologic outcome of ICP plus PbtO2-directed treatment of severe TBI is warranted.

Adverse impacts of chronic or intermittent hypoxia on development, behavior, and academic achievement have been reported in many well-designed and controlled studies in children with CHD and SDB as well as in a variety of experimental studies in adults. This should be taken into account in any situation that may expose children to hypoxia. Because adverse effects have been noted at even mild levels of oxygen desaturation, future research should include precisely defined data on exposure to all levels of desaturation.

Traumatic cerebral vascular injury (TCVI) is a very frequent, if not universal, feature after traumatic brain injury (TBI). It is likely responsible, at least in part, for functional deficits and TBI-related chronic disability. Because there are multiple pharmacologic and non-pharmacologic therapies that promote vascular health, TCVI is an attractive target for therapeutic intervention after TBI. The cerebral microvasculature is a component of the neurovascular unit (NVU) coupling neuronal metabolism with local cerebral blood flow. The NVU participates in the pathogenesis of TBI, either directly from physical trauma or as part of the cascade of secondary injury that occurs after TBI. Pathologically, there is extensive cerebral microvascular injury in humans and experimental animal, identified with either conventional light microscopy or ultrastructural examination. It is seen in acute and chronic TBI, and even described in chronic traumatic encephalopathy (CTE). Non-invasive, physiologic measures of cerebral microvascular function show dysfunction after TBI in humans and experimental animal models of TBI. These include imaging sequences (MRI-ASL), Transcranial Doppler (TCD), and Near InfraRed Spectroscopy (NIRS). Understanding the pathophysiology of TCVI, a relatively under-studied component of TBI, has promise for the development of novel therapies for TBI.