Effect of hyperoxia on regional oxygenation and metabolism after severe traumatic brain injury: Preliminary findings*

Objective:To determine the effect of normobaric hyperoxia on cerebral metabolism in patients with severe traumatic brain injury. Design:Prospective clinical investigation. Setting:Neurosciences critical care unit of a university hospital. Patients:Eleven patients with severe traumatic brain injury. Interventions:Cerebral microdialysis, brain tissue oximetry (Pbo2), and oxygen-15 positron emission tomography (15O-PET) were undertaken at normoxia and repeated at hyperoxia (Fio2 increase of between 0.35 and 0.50). Measurements and Main Results:Established models were used to image cerebral blood flow, blood volume, oxygen metabolism, and oxygen extraction fraction. Physiology was characterized in a focal region of interest (surrounding the microdialysis catheter) and correlated with microdialysis and oximetry. Physiology was also characterized in a global region of interest (including the whole brain), and a physiologic region of interest (defined using a critical cerebral metabolic rate of oxygen threshold). Hyperoxia increased mean ± sd Pbo2 from 28 ± 21 mm Hg to 57 ± 47 mm Hg (p = .015). Microdialysate lactate and pyruvate were unchanged, but the lactate/pyruvate ratio showed a statistically significant reduction across the study population (34.1 ± 9.5 vs. 32.5 ± 9.0, p = .018). However, the magnitude of reduction was small, and its clinical significance doubtful. The focal region of interest and global 15O-PET variables were unchanged. “At-risk” tissue defined by the physiologic region of interest, however, showed a universal increase in cerebral metabolic rate of oxygen from a median (interquartile range) of 23 (22–25) &mgr;mol·100 mL−1·min−1 to 30 (28–36) &mgr;mol·100 mL−1·min−1 (p < .01). Conclusions:In severe traumatic brain injury, hyperoxia increases Pbo2 with a variable effect on lactate and lactate/pyruvate ratio. Microdialysis does not, however, predict the universal increases in cerebral metabolic rate of oxygen in at-risk tissue, which imply preferential metabolic benefit with hyperoxia.

[1]  John D Pickard,et al.  Defining Ischemic Burden after Traumatic Brain Injury Using 15O PET Imaging of Cerebral Physiology , 2004, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[2]  Foss Mv.  MANAGEMENT OF VIRUS HEPATITIS. , 1964 .

[3]  S. Moncada,et al.  Nitric oxide from inflammatory‐activated glia synergizes with hypoxia to induce neuronal death , 2005, Journal of neuroscience research.

[4]  J. Haddad,et al.  A non‐hypoxic, ROS‐sensitive pathway mediates TNF‐α‐dependent regulation of HIF‐1α , 2001 .

[5]  J. Pickard,et al.  Integrated Image Analysis Solutions for PET Datasets in Damaged Brain , 2002, Journal of Clinical Monitoring and Computing.

[6]  P. Enblad,et al.  Outcome after traumatic brain injury improved by an organized secondary insult program and standardized neurointensive care* , 2002, Critical care medicine.

[7]  B. Jennett,et al.  ASSESSMENT OF OUTCOME AFTER SEVERE BRAIN DAMAGE A Practical Scale , 1975, The Lancet.

[8]  The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on Neurotrauma and Critical Care. Intracranial pressure treatment threshold. , 2000, Journal of neurotrauma.

[9]  G. Hedenstierna,et al.  Prevention of atelectasis during general anaesthesia , 1995, The Lancet.

[10]  Guy B. Williams,et al.  Incidence and Mechanisms of Cerebral Ischemia in Early Clinical Head Injury , 2004, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[11]  E. Draper,et al.  APACHE II: A severity of disease classification system , 1985, Critical care medicine.

[12]  D. Menon.  Cerebral protection in severe brain injury: physiological determinants of outcome and their optimisation. , 1999, British medical bulletin.

[13]  G. Semenza,et al.  Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1. , 1994, The Journal of biological chemistry.

[14]  J. Adams,et al.  Ischaemic brain damage is still common in fatal non-missile head injury. , 1989, Journal of neurology, neurosurgery, and psychiatry.

[15]  N. Chandel,et al.  Reactive Oxygen Species Generated at Mitochondrial Complex III Stabilize Hypoxia-inducible Factor-1α during Hypoxia , 2000, The Journal of Biological Chemistry.

[16]  Jong-Wan Park,et al.  Early Expression of Myocardial HIF-1&agr; in Response to Mechanical Stresses: Regulation by Stretch-Activated Channels and the Phosphatidylinositol 3-Kinase Signaling Pathway , 2002, Circulation research.

[17]  Marvin Bergsneider,et al.  Metabolic Crisis without Brain Ischemia is Common after Traumatic Brain Injury: A Combined Microdialysis and Positron Emission Tomography Study , 2005, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[18]  N. Nakayama,et al.  Evidence for white matter disruption in traumatic brain injury without macroscopic lesions , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[19]  J. Povlishock,et al.  Intracranial pressure treatment threshold , 1996 .

[20]  Oscar D. Guillamondegui,et al.  Reduced mortality rate in patients with severe traumatic brain injury treated with brain tissue oxygen monitoring. , 2005, Journal of neurosurgery.

[21]  A. Rodríguez-Baeza,et al.  Morphological features in human cortical brain microvessels after head injury: a three-dimensional and immunocytochemical study. , 2003, The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology.

[22]  Guy B. Williams,et al.  Does induced hypertension reduce cerebral ischaemia within the traumatized human brain? , 2004, Brain : a journal of neurology.

[23]  J. Meixensberger,et al.  Brain tissue oxygen guided treatment supplementing ICP/CPP therapy after traumatic brain injury , 2003, Journal of neurology, neurosurgery, and psychiatry.

[24]  B. Jennett,et al.  Assessment of coma and impaired consciousness. A practical scale. , 1974, Lancet.

[25]  Guy C. Brown.  Nitric oxide regulates mitochondrial respiration and cell functions by inhibiting cytochrome oxidase , 1995, FEBS letters.

[26]  J. Povlishock,et al.  Guidelines for cerebral perfusion pressure , 1996 .

[27]  K. Ikoma,et al.  Loss of neuronal integrity: a cause of hypometabolism in patients with traumatic brain injury without MRI abnormality in the chronic stage , 2006, European Journal of Nuclear Medicine and Molecular Imaging.

[28]  L. Hillered,et al.  Chemical monitoring of neurosurgical intensive care patients using intracerebral microdialysis. , 1992, Journal of neurosurgery.

[29]  D. Spahn,et al.  New concepts of atelectasis during general anaesthesia. , 2003, British journal of anaesthesia.

[30]  A. Blamire,et al.  Early proton magnetic resonance spectroscopy in normal-appearing brain correlates with outcome in patients following traumatic brain injury. , 2000, Brain : a journal of neurology.

[31]  G. Antoni,et al.  Journal of Cerebral Blood Flow and Metabolism Simultaneous Intracerebral Microdialysis and Positron Emission Tomography in the Detection of Ischemia in Patients with Subarachnoid Hemorrhage , 2022 .

[32]  G. Johnson,et al.  Diffuse axonal injury in mild traumatic brain injury: a diffusion tensor imaging study. , 2005, Journal of neurosurgery.

[33]  R. Bullock,et al.  Evidence for time-dependent glutamate-mediated glycolysis in head-injured patients: a microdialysis study. , 1999, Acta neurochirurgica. Supplement.

[34]  M. Bullock,et al.  Normobaric hyperoxia--induced improvement in cerebral metabolism and reduction in intracranial pressure in patients with severe head injury: a prospective historical cohort-matched study. , 2004, Journal of neurosurgery.

[35]  T. Carpenter,et al.  Diffusion limited oxygen delivery following head injury* , 2004, Critical care medicine.

[36]  D. Weisdorf,et al.  Granulocytes utilize different energy sources for movement and phagocytosis , 1982, Inflammation.

[37]  R. Bullock,et al.  Influence of oxygen therapy on glucose-lactate metabolism after diffuse brain injury. , 2004, Journal of neurosurgery.

[38]  R. Nelson,et al.  Reduction in mortality from severe head injury following introduction of a protocol for intensive care management. , 2004, British journal of anaesthesia.

[39]  R. Crystal,et al.  Oxidant injury of lung parenchymal cells. , 1981, The Journal of clinical investigation.

[40]  A. Sorensen,et al.  Diffusion tensor imaging as potential biomarker of white matter injury in diffuse axonal injury. , 2004, AJNR. American journal of neuroradiology.

[41]  M E Phelps,et al.  Cerebral hyperglycolysis following severe traumatic brain injury in humans: a positron emission tomography study. , 1997, Journal of neurosurgery.

[42]  M A Foulkes,et al.  The diagnosis of head injury requires a classification based on computed axial tomography. , 1992, Journal of neurotrauma.

[43]  P. London.  Injury , 1969, Definitions.

[44]  Yasuyoshi Watanabe,et al.  Middle Cerebral Artery Occlusion and Reperfusion in Primates Monitored by Microdialysis and Sequential Positron Emission Tomography , 2001, Stroke.

[45]  K. Utsumi,et al.  Oxygen-dependent regulation of mitochondrial energy metabolism by nitric oxide. , 1995, Archives of biochemistry and biophysics.

[46]  B Jennett,et al.  Assessment of outcome after severe brain damage. , 1975, Lancet.

[47]  N. Stocchetti,et al.  Lack of improvement in cerebral metabolism after hyperoxia in severe head injury: a microdialysis study. , 2003, Journal of neurosurgery.

[48]  J. Eaton,et al.  Mitochondrial metabolism underlies hyperoxic cell damage. , 2004, Free radical biology & medicine.

[49]  R. Bullock,et al.  Increased inspired oxygen concentration as a factor in improved brain tissue oxygenation and tissue lactate levels after severe human head injury. , 1999, Journal of neurosurgery.

[50]  P. Magistretti,et al.  Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging. , 1999, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[51]  R. Bullock,et al.  Substrate delivery and ionic balance disturbance after severe human head injury. , 2000, Acta neurochirurgica. Supplement.

[52]  The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on Neurotrauma and Critical Care. Guidelines for cerebral perfusion pressure. , 2000, Journal of neurotrauma.

[53]  Marvin Bergsneider,et al.  Subcortical White Matter Metabolic Changes Remote from Focal Hemorrhagic Lesions Suggest Diffuse Injury after Human Traumatic Brain Injury , 2004, Neurosurgery.

[54]  J. Adams,et al.  Ischaemic brain damage in fatal head injuries. , 1971, Lancet.

[55]  D. Graham,et al.  Association between Intravascular Microthrombosis and Cerebral Ischemia in Traumatic Brain Injury , 2004, Neurosurgery.

[56]  J. Takala,et al.  Effects of cerebral perfusion pressure and increased fraction of inspired oxygen on brain tissue oxygen, lactate and glucose in patients with severe head injury , 2003, Acta Neurochirurgica.

[57]  Patti,et al.  Impaired cerebral mitochondrial function after traumatic brain injury in humans. , 2000, Journal of neurosurgery.

[58]  The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on Neurotrauma and Critical Care. Resuscitation of blood pressure and oxygenation. , 2000, Journal of neurotrauma.

[59]  G. Hedenstierna,et al.  Lung aeration. The effect of pre-oxygenation and hyperoxygenation during total intravenous anaesthesia. , 1996, Anaesthesia.

[60]  R. Schmidt-Kastner,et al.  Hypoxia and hypoxia-inducible factor modulated gene expression in brain: involvement in neuroprotection and cell death , 2001, European Archives of Psychiatry and Clinical Neuroscience.

[61]  Peter J. Kirkpatrick,et al.  Specialist neurocritical care and outcome from head injury , 2002, Intensive Care Medicine.

[62]  A. Blamire,et al.  Evidence for cellular damage in normal-appearing white matter correlates with injury severity in patients following traumatic brain injury: A magnetic resonance spectroscopy study. , 2000, Brain : a journal of neurology.

[63]  C. Richter,et al.  Nitric oxide potently and reversibly deenergizes mitochondria at low oxygen tension. , 1994, Biochemical and biophysical research communications.

[64]  J. Haddad,et al.  A non-hypoxic, ROS-sensitive pathway mediates TNF-alpha-dependent regulation of HIF-1alpha. , 2001, FEBS letters.

[65]  J D Pickard,et al.  Physiological thresholds for irreversible tissue damage in contusional regions following traumatic brain injury. , 2005, Brain : a journal of neurology.