David Chin-Sing Wang MD, PhD
Department of Neurological Surgery, Medical College of Georgia at Georgia Health Sciences University, Augusta, GA 30912
Journal Club Article: Oddo M, Levine J, Mackenzie L, et al. Brain hypoxia is associated with short-term outcome after severe traumatic brain injury independently of intracranial hypertension and low cerebral perfusion pressure. Neurosurgery. 2011;69:1037-1045
Significance/context and importance of the study
Traumatic brain injury is a leading cause of death and disability of young people that robs the future productivity of its victims. The neurological exam in severe brain injury is difficult to assess clinically, and may be delayed, so invasive monitoring is imperative to optimize the potential for recovery after injury. Invasive physiological monitoring of intracranial pressures have been recommended by brain trauma foundation guidelines for brain injury with GCS <91 and is rapidly becoming standard of care that is proving to be cost effective in treatment of severe TBI.2
Originality of work
Oddo et al. reports a retrospective study to assess invasive monitoring of brain tissue oxygen pressure (PbtO2) in severe TBI and report a correlation of low PbtO2 monitoring with poor neurological outcomes. The authors work suggests that PbtO2 measures in conjunction with intracerebral pressure (ICP) and cerebral perfusion pressures (CPP) measures enhance the ability to predict poor neurologic outcome. While similar studies have evaluated outcome measures with such monitoring, this study appears to be the first of its kind in predicting poor outcome.
Appropriateness of the study design or experimental approach
The authors present a retrospective study of 103 patients with severe brain injury (GCS <9) from non-penetrating trauma where periods of hypoxia (PbtO2 <15mm Hg), intracranial hypertension (ICP >20 mm Hg) and poor perfusion (CPP<60 mmHg) were correlated to poor neurological outcome. Results from this study suggest an association of poor neurological outcome with low PbtO2 that is independent of ICP and CPP. These conclusions were based upon univariate analysis of age, admission glascow coma scale (GCS), Marshall CT classification, APACHE II score, duration of hypoxia, elevated ICP, and low CPP to affect the dependent variable: neurological outcome, as measured by glascow outcome score (GOS). GOS of 4 or 5 were considered favorable outcomes while GOS scores of 1-3 were considered unfavorable.
Adequacy of experimental technique
The authors show that low PtO2 correlates with poor outcome and that low PtO2 led to aggressive treatment, but treatment given and response thereof is ill defined. It remains unclear whether trauma patients benefitted from PtO2 monitoring in this cohort as has been previously demonstrated3. While invasive monitoring with ICP and CPP monitoring has been shown to be a cost effective method of reducing morbidity and mortality associated with severe TBI2, PtO2 measures has not. Studies assessing outcomes in PbtO2 after severe TBI report decreased mortality and improved outcomes in six month follow up, but this study was retrospective and based upon historic controls3.
Soundness of conclusions and interpretation
As one might expect, younger patients with better initial GCS, less severe CT scans, and lower APACHE II scores correlated with better outcomes, while patients with prolonged elevations in ICP and hypoxia correlated with poor outcomes. Patients with prolonged hypoxia proved to be ‘more significant’ then elevations in ICP in correlating to poor outcomes while low CPP would significantly correlate to a poor outcome only when the parameter of low PbtO2 was added to the analysis. These results suggest that the correlation of brain hypoxia to poor outcome is less likely to be the result of a random event as other variables such as elevated ICP. These significant factors identified in univariate analysis were then back-fitted to see if each ‘variable’ could affect outcome independently. Admission GCS, CT classification, APACHE II score, and brain hypoxia was found to be significant ‘independent’ correlating variables in outcome. Elevated ICPs was not found to be significant as an independent correlating variable. Furthermore, the authors report that hypoxia when coupled with elevated ICP or low CPP significant increases the chance of having a less favorable outcome. The authors draw 2 implications from their findings: low PbtO2 as a measure of brain hypoxia is a superior marker of TBI compared to ICP and CPP and that low CPP by itself does not correlate with poor neurological outcome.
Relevance of discussion
This work is relevant since early detection of worsening severe traumatic brain injury may lead to early treatment. The authors make a valiant effort to identify specific measured factors that are linked to poor neurological outcomes however the statistics in this case focus upon assessing correlations that does not necessarily imply causality.
Clarity of writing, strength and organization of the paper/Economy of words
Overall, the article is well written. The authors choice of word is concise with a paucity of words.
Relevance, accuracy and completeness of bibliography
The authors provide an accurate and complete bibliography of use of PtO2 monitoring in the context of traumatic brain injury.
Number and quality of figures, tables and illustrations
Overall, authors provided an appropriate number and quality of figures, tables, and illustrations. Reporting treatment modalities administered and therapeutic intensity in patients experiencing brain hypoxia and whether treatment was successful would be helpful. This would address the question of whether PtBO2 monitoring was useful in guiding clinical decisions regarding treatment of severe TBI that improved patient outcomes.
Overall, the authors report a study that adds to the growing body of evidence that PbtO2 may have a role in early detection of neurological decline in severe TBI and thus may improve outcome. The data presented is class II evidence, and has observer bias. This data with historical data3 may be used as a launching point upon which power analysis may be performed for sample sizes needed for future studies. Many trauma centers do not routinely use brain tissue perfusion as an invasive measure to monitor worsening severe brain injury; these centers may serve as an effective control for outcomes comparing to centers using PtO2 monitoring. To assess clinical outcome in trauma patients is a daunting task since head injury typically does not happen in isolation. Subtle differences between treatment patterns of neurosurgeons at different institutions may introduce enough variability in treatment and outcome to render any attempts to discern the benefits of PtO2 measures very difficult. Future studies will likely seek to assess: 1, the efficacy of PbtO2 measurements in reducing morbidity and mortality in severe TBI and 2, assessing the cost effectiveness of this therapy given current treatment options.
Bratton SL, Chestnut RM, Ghajar J, McConnell Hammond FF, Harris OA, Hartl R, Manley GT, Nemecek A, Newell DW, Rosenthal G, Schouten J, Shutter L, Timmons SD, Ullman JS, Videtta W, Wilberger JE, Wright DW. Guidelines for the management of severe traumatic brain injury. VIII. Intracranial pressure thresholds. Brain Trauma Foundation; American Association of Neurological Surgeons; Congress of Neurological Surgeons; Joint Section on Neurotrauma and Critical Care, AANS/CNS,J Neurotrauma. 2007;24 Suppl 1:S55-8. No abstract available. Erratum in: J Neurotrauma. 2008 Mar;25(3):276-8.
Whitmore RG, Thawani JP, Grady MS, Levine JM, Sanborn MR, Stein SC. Is aggressive treatment of traumatic brain injury cost-effective? J Neurosurg. 2012 Mar 6.
Narotam PK, Morrison JF, Nathoo N. Brain tissue oxygen monitoring in traumatic brain injury and major trauma: outcome analysis of a brain tissue oxygen-directed therapy. J Neurosurg. 2009 Oct;111(4):672-82.