Monitoring patients with severe traumatic brain injury
Authors: Ramon Diaz-Arrastia, Francis Bernard, Lori Shutter, William Barsan, Robert Silbergleit
Journal: The Lancet Neurology (2024)

We read with interest the Article by Jean-Francois Payen and colleagues, reporting findings of the OXY-TC trial.1Payen J-F Launey Y Chabanne R et al.Intracranial pressure monitoring with and without brain tissue oxygen pressure monitoring for severe traumatic brain injury in France (OXY-TC): an open-label, randomised controlled superiority trial.Lancet Neurol. 2023; 22: 1005-1014Summary Full Text Full Text PDF PubMed Scopus (10) Google Scholar The study is the first of three randomised trials assessing brain tissue pressure (PbtO2) monitoring after traumatic brain injury, with BOOST3 (NCT03754114) and BONANZA-GT (ACTRN12619001328167) still recruiting. Although the results of OXY-TC showed no difference in outcome at 6 months between groups managed with either intracranial pressure monitoring alone or dual monitoring of intracranial pressure and PbtO2, significant improvement in neurological outcomes were noted in a subgroup of patients with elevated intracranial pressure at the start of monitoring. Furthermore, differences were observed that might have been clinically significant if more patients would have been enrolled, considering the shifts towards favourable outcome in the intracranial pressure and PbtO2 group. We would like to highlight several important differences in study design between OXY-TC and BOOST3 that suggest there is still equipoise regarding the value of managing patients through PbtO2 and intracranial pressure monitoring. First, OXY-TC was designed to show a 30% improvement in favourable outcomes, but BOOST3 is powered to detect an absolute increase in favourable outcomes of 7%, with a sliding dichotomy based on the International Mission For Prognosis and Analysis of Clinical Trials score for this heterogeneous population.2Bernard F Barsan W Diaz-Arrastia R Merck LH Yeatts S Shutter LA Brain Oxygen Optimization in Severe Traumatic Brain Injury (BOOST-3): a multicentre, randomised, blinded-endpoint, comparative effectiveness study of brain tissue oxygen and intracranial pressure monitoring versus intracranial pressure alone.BMJ Open. 2022; 12e060188Crossref Scopus (33) Google Scholar Second, BOOST3 uses continuous monitoring of intracranial pressure and PbtO2 in both groups (blinded in the intracranial pressure-only arm) rather than hourly measurements in OXY-TC. Continuous monitoring allows for calculation of ischaemic burden, provides evidence that PbtO2-directed treatment lowers the burden of brain tissue hypoxia, and facilitates rapid recognition and intervention to correct abnormal PbtO2 values. Our experience in BOOST2,3Okonkwo DO Shutter LA Moore C et al.Brain oxygen optimization in severe traumatic brain injury phase-II: a phase II randomized trial.Crit Care Med. 2017; 45: 1907-1914Crossref PubMed Scopus (287) Google Scholar and so far in BOOST3, is that the availability of continuous high-resolution physiological data are crucial to facilitate timely implementation of therapeutic strategies to reverse brain tissue hypoxia. Third, OXY-TC allowed enrolment up to 16 h after injury (vs 6 h in BOOST3), with a low initial mean PbtO2 of 14 mm Hg. Substantial cumulative early ischaemic burden could have occurred during those extra 10 h in OXY-TC. Fourth, management of low PbtO2 can vary substantially between centres. BOOST3 uses a complex treatment protocol supported by a bedside clinical decision-making aid.2Bernard F Barsan W Diaz-Arrastia R Merck LH Yeatts S Shutter LA Brain Oxygen Optimization in Severe Traumatic Brain Injury (BOOST-3): a multicentre, randomised, blinded-endpoint, comparative effectiveness study of brain tissue oxygen and intracranial pressure monitoring versus intracranial pressure alone.BMJ Open. 2022; 12e060188Crossref Scopus (33) Google Scholar The BOOST3 decision-making algorithm emphasises correction of cerebral blood flow before increasing the fraction of inspired oxygen (FiO2), which can normalise PbtO2 despite low blood flow.4Hlatky R Valadka AB Gopinath SP Robertson CS Brain tissue oxygen tension response to induced hyperoxia reduced in hypoperfused brain.J Neurosurg. 2008; 108: 53-58Crossref PubMed Scopus (74) Google Scholar OXY-TC used increased FiO2 as the initial treatment. These important differences between OXY-TC and the ongoing BOOST3 trial show that there is equipoise regarding the potential benefit of PbtO2-guided therapy. The findings of OXY-TC support further study. RD-A declares grant funding from the National Institutes of Health (NIH). WB declares grant funding from the National Institute of Neurological Disorders and Stroke (NINDS). RS declares funding to his institution from the NIH and NINDS to conduct a clinical trial on the same intervention studied in the Article being discussed. FB and LS declare no competing interests. Intracranial pressure monitoring with and without brain tissue oxygen pressure monitoring for severe traumatic brain injury in France (OXY-TC): an open-label, randomised controlled superiority trialAfter severe non-penetrating traumatic brain injury, intracranial pressure and PbtO2 monitoring did not reduce the proportion of patients with poor neurological outcome at 6 months. Technical failures related to intracerebral catheter and intracerebral haematoma were more frequent in the intracranial pressure and PbtO2 group. Further research is needed to assess whether a targeted approach to multimodal brain monitoring could be useful in subgroups of patients with severe traumatic brain injury–eg, those with high intracranial pressure on admission. Full-Text PDF Monitoring patients with severe traumatic brain injury – Authors' replyWe fully agree with Randall M Chestnut and colleagues' comments and thank them for underlining important considerations. The findings from OXY-TC trial1 do raise questions on the heterogeneity of patients with severe traumatic brain injury despite comparable Glasgow Coma Scale scores at baseline. Pooled data from the trials OXY-TC, BOOST3, and BONANZA might provide sufficiently robust evidence to identify the patients who most likely benefit from multimodal invasive brain monitoring. Full-Text PDF