Neurocritical Care

, Volume 12, Issue 3, pp 430–437 | Cite as

The Effect of Increased Inspired Fraction of Oxygen on Brain Tissue Oxygen Tension in Children with Severe Traumatic Brain Injury

  • Anthony A. Figaji
  • Eugene Zwane
  • A. Graham Fieggen
  • Andrew C. Argent
  • Peter D. Le Roux
  • Jonathan C. Peter
Original Article



This study examines the effect of an increase in the inspired fraction of oxygen (FiO2) on brain tissue oxygen (PbO2) in children with severe traumatic brain injury (TBI).


A prospective observational study of patients who underwent PbO2 monitoring and an oxygen challenge test (temporary increase of FiO2 for 15 min) was undertaken. Pre- and post-test values for arterial partial pressure of oxygen (PaO2), PbO2, and arterial oxygen content (CaO2) were examined while controlling for any changes in arterial carbon dioxide tension and cerebral perfusion pressure during the test. Baseline transcranial Doppler studies were done. Outcome was assessed at 6 months.


A total of 43 tests were performed in 28 patients. In 35 tests in 24 patients, the PbO2 monitor was in normal-appearing white matter and in eight tests in four patients, the monitor was in a pericontusional location. When catheters were pericontusional or in normal white matter the baseline PbO2/PaO2 ratio was similar. PaO2 (P < 0.0001) and PbO2 (P < 0.0001) significantly increased when FiO2 was increased. The magnitude of the PbO2 response (∆PbO2) was correlated with ∆PaO2 (P < 0.0001, R2 = 0.37) and ∆CaO2 (P = 0.001, R2 = 0.23). The ∆PbO2/∆PaO2 ratio (oxygen reactivity) varied between patients, was related to the baseline PbO2 (P = 0.001, r = 0.54) and was inversely related to outcome (P = 0.02, confidence interval 0.03–0.78).


Normobaric hyperoxia increases PbO2 in children with severe TBI, but the response is variable. The magnitude of this response is related to the change in PaO2 and the baseline PbO2. A greater response appears to be associated with worse outcome.


Brain tissue oxygen tension Arterial oxygen tension Children Traumatic brain injury Outcome 


  1. 1.
    Stiefel MF, Spiotta A, Gracias VH, et al. Reduced mortality rate in patients with severe traumatic brain injury treated with brain tissue oxygen monitoring. J Neurosurg. 2005;103:805–11.CrossRefPubMedGoogle Scholar
  2. 2.
    Meixensberger J, Jaeger M, Vath A, Dings J, Kunze E, Roosen K. Brain tissue oxygen guided treatment supplementing ICP/CPP therapy after traumatic brain injury. J Neurol Neurosurg Psychiatry. 2003;74:760–4.CrossRefPubMedGoogle Scholar
  3. 3.
    Valadka AB, Gopinath SP, Contant CF, Uzura M, Robertson CS. Relationship of brain tissue PO2 to outcome after severe head injury. Crit Care Med. 1998;26:1576–81.CrossRefPubMedGoogle Scholar
  4. 4.
    Figaji AA, Zwane E, Thompson C, et al. Brain tissue oxygen tension monitoring in pediatric severe traumatic brain injury: Part 1: Relationship with outcome. Childs Nerv Syst. 2009;25(10):1325–33.CrossRefPubMedGoogle Scholar
  5. 5.
    van den Brink WA, van Santbrink H, Steyerberg EW, et al. Brain oxygen tension in severe head injury. Neurosurgery 2000;46:868–76. discussion 876–878.CrossRefPubMedGoogle Scholar
  6. 6.
    Figaji AA, Fieggen AG, Argent AC, Leroux PD, Peter JC. Does adherence to treatment targets in children with severe traumatic brain injury avoid brain hypoxia? A brain tissue oxygenation study. Neurosurgery. 2008;63:83–91, discussion 91–92.CrossRefPubMedGoogle Scholar
  7. 7.
    Figaji AA, Zwane E, Thompson C, et al. Brain tissue oxygen tension monitoring in pediatric severe traumatic brain injury: Part 2: Relationship with clinical, physiological, and treatment factors. Childs Nerv Syst. 2009;25(10):1335–43.CrossRefPubMedGoogle Scholar
  8. 8.
    Rosenthal G, Hemphill JC III, Sorani M, et al. Brain tissue oxygen tension is more indicative of oxygen diffusion than oxygen delivery and metabolism in patients with traumatic brain injury. Crit Care Med. 2008;36:1917–24.CrossRefPubMedGoogle Scholar
  9. 9.
    Doppenberg EM, Zauner A, Bullock R, Ward JD, Fatouros PP, Young HF. Correlations between brain tissue oxygen tension, carbon dioxide tension, pH, and cerebral blood flow—a better way of monitoring the severely injured brain? Surg Neurol. 1998;49:650–4.CrossRefPubMedGoogle Scholar
  10. 10.
    Doppenberg EM, Zauner A, Watson JC, Bullock R. Determination of the ischemic threshold for brain oxygen tension. Acta Neurochir Suppl. 1998;71:166–9.PubMedGoogle Scholar
  11. 11.
    Jaeger M, Soehle M, Schuhmann MU, Winkler D, Meixensberger J. Correlation of continuously monitored regional cerebral blood flow and brain tissue oxygen. Acta Neurochir (Wien). 2005;147:51–6, discussion 56.CrossRefGoogle Scholar
  12. 12.
    Valadka AB, Hlatky R, Furuya Y, Robertson CS. Brain tissue PO2: correlation with cerebral blood flow. Acta Neurochir Suppl. 2002;81:299–301.PubMedGoogle Scholar
  13. 13.
    Zauner A, Bullock R, Di X, Young HF. Brain oxygen, CO2, pH, and temperature monitoring: evaluation in the feline brain. Neurosurgery. 1995;37:1168–76, discussion 1176–1177.CrossRefPubMedGoogle Scholar
  14. 14.
    Hemphill JC III, Smith WS, Sonne DC, Morabito D, Manley GT. Relationship between brain tissue oxygen tension and CT perfusion: feasibility and initial results. AJNR Am J Neuroradiol. 2005;26:1095–100.PubMedGoogle Scholar
  15. 15.
    Gupta AK, Hutchinson PJ, Fryer T, et al. Measurement of brain tissue oxygenation performed using positron emission tomography scanning to validate a novel monitoring method. J Neurosurg. 2002;96:263–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Scheufler KM, Lehnert A, Rohrborn HJ, Nadstawek J, Thees C. Individual value of brain tissue oxygen pressure, microvascular oxygen saturation, cytochrome redox level, and energy metabolites in detecting critically reduced cerebral energy state during acute changes in global cerebral perfusion. J Neurosurg Anesthesiol. 2004;16:210–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Magnoni S, Ghisoni L, Locatelli M, et al. Lack of improvement in cerebral metabolism after hyperoxia in severe head injury: a microdialysis study. J Neurosurg. 2003;98:952–8.CrossRefPubMedGoogle Scholar
  18. 18.
    Tolias CM, Reinert M, Seiler R, Gilman C, Scharf A, Bullock MR. Normobaric hyperoxia-induced improvement in cerebral metabolism and reduction in intracranial pressure in patients with severe head injury: a prospective historical cohort-matched study. J Neurosurg. 2004;101:435–44.CrossRefPubMedGoogle Scholar
  19. 19.
    Nortje J, Coles JP, Timofeev I, et al. Effect of hyperoxia on regional oxygenation and metabolism after severe traumatic brain injury: Preliminary findings. Crit Care Med. 2008;36:273–81.CrossRefPubMedGoogle Scholar
  20. 20.
    Diringer MN, Aiyagari V, Zazulia AR, Videen TO, Powers WJ. Effect of hyperoxia on cerebral metabolic rate for oxygen measured using positron emission tomography in patients with acute severe head injury. J Neurosurg. 2007;106:526–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Pagano A, Barazzone-Argiroffo C. Alveolar cell death in hyperoxia-induced lung injury. Ann N Y Acad Sci. 2003;1010:405–16.CrossRefPubMedGoogle Scholar
  22. 22.
    Clark JM, Lambertsen CJ. Pulmonary oxygen toxicity: a review. Pharmacol Rev. 1971;23:37–133.PubMedGoogle Scholar
  23. 23.
    Nakajima S, Meyer JS, Amano T, Shaw T, Okabe T, Mortel KF. Cerebral vasomotor responsiveness during 100% oxygen inhalation in cerebral ischemia. Arch Neurol. 1983;40:271–6.PubMedGoogle Scholar
  24. 24.
    Floyd TF, Clark JM, Gelfand R, et al. Independent cerebral vasoconstrictive effects of hyperoxia and accompanying arterial hypocapnia at 1 ATA. J Appl Physiol. 2003;95:2453–61.PubMedGoogle Scholar
  25. 25.
    Adelson PD, Bratton SL, Carney NA, et al. Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents. Chapter 17. Critical pathway for the treatment of established intracranial hypertension in pediatric traumatic brain injury. Pediatr Crit Care Med. 2003;4:S65–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Adelson PD, Bratton SL, Carney NA, et al. Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents. Chapter 6. Threshold for treatment of intracranial hypertension. Pediatr Crit Care Med. 2003;4:S25–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Steiner LA, Coles JP, Johnston AJ, et al. Assessment of cerebrovascular autoregulation in head-injured patients: a validation study. Stroke. 2003;34:2404–9.CrossRefPubMedGoogle Scholar
  28. 28.
    Bishop CC, Powell S, Rutt D, Browse NL. Transcranial Doppler measurement of middle cerebral artery blood flow velocity: a validation study. Stroke. 1986;17:913–5.PubMedGoogle Scholar
  29. 29.
    Rosenthal G, Hemphill JC, Sorani M, et al. The role of lung function in brain tissue oxygenation following traumatic brain injury. J Neurosurg. 2008;108:59–65.CrossRefPubMedGoogle Scholar
  30. 30.
    Menon DK, Coles JP, Gupta AK, et al. Diffusion limited oxygen delivery following head injury. Crit Care Med. 2004;32:1384–90.CrossRefPubMedGoogle Scholar
  31. 31.
    Bullock MR. Hyperoxia: good or bad? J Neurosurg. 2003;98:943–4, discussion 944.CrossRefPubMedGoogle Scholar
  32. 32.
    Hlatky R, Valadka AB, Gopinath SP, Robertson CS. Brain tissue oxygen tension response to induced hyperoxia reduced in hypoperfused brain. J Neurosurg. 2008;108:53–8.CrossRefPubMedGoogle Scholar
  33. 33.
    Longhi L, Valeriani V, Rossi S, De Marchi M, Egidi M, Stocchetti N. Effects of hyperoxia on brain tissue oxygen tension in cerebral focal lesions. Acta Neurochir Suppl. 2002;81:315–7.PubMedGoogle Scholar
  34. 34.
    Nishimura N, Iwasaki K, Ogawa Y, Shibata S. Oxygen administration, cerebral blood flow velocity, and dynamic cerebral autoregulation. Aviat Space Environ Med. 2007;78:1121–7.CrossRefPubMedGoogle Scholar
  35. 35.
    Shin HK, Dunn AK, Jones PB, et al. Normobaric hyperoxia improves cerebral blood flow and oxygenation, and inhibits peri-infarct depolarizations in experimental focal ischaemia. Brain. 2007;130:1631–42.CrossRefPubMedGoogle Scholar
  36. 36.
    Dings J, Meixensberger J, Amschler J, Hamelbeck B, Roosen K. Brain tissue pO2 in relation to cerebral perfusion pressure, TCD findings and TCD-CO2-reactivity after severe head injury. Acta Neurochir (Wien). 1996;138:425–34.CrossRefGoogle Scholar
  37. 37.
    Gupta AK, Hutchinson PJ, Al-Rawi P, et al. Measuring brain tissue oxygenation compared with jugular venous oxygen saturation for monitoring cerebral oxygenation after traumatic brain injury. Anesth Analg. 1999;88:549–53.CrossRefPubMedGoogle Scholar
  38. 38.
    van Santbrink H, vd Brink WA, Steyerberg EW, Carmona Suazo JA, Avezaat CJ, Maas AI. Brain tissue oxygen response in severe traumatic brain injury. Acta Neurochir (Wien). 2003;145:429–38. discussion 438.Google Scholar
  39. 39.
    Maloney-Wilensky E, Gracias V, Itkin A, et al. Brain tissue oxygen and outcome after severe traumatic brain injury: a systematic review. Crit Care Med. 2009;37:2057–63.CrossRefPubMedGoogle Scholar
  40. 40.
    Shah CV, Localio AR, Lanken PN, et al. The impact of development of acute lung injury on hospital mortality in critically ill trauma patients. Crit Care Med. 2008;36:2309–15.CrossRefPubMedGoogle Scholar
  41. 41.
    Doppenberg EM, Rice MR, Di X, Young HF, Woodward JJ, Bullock R. Increased free radical production due to subdural hematoma in the rat: effect of increased inspired oxygen fraction. J Neurotrauma. 1998;15:337–47.CrossRefPubMedGoogle Scholar
  42. 42.
    Puccio AM, Hoffman LA, Bayir H, et al. Effect of short periods of normobaric hyperoxia on local brain tissue oxygenation and cerebrospinal fluid oxidative stress markers in severe traumatic brain injury. J Neurotrauma. 2009. doi:10.1089/neu.2008-0624.
  43. 43.
    Reinert M, Barth A, Rothen HU, Schaller B, Takala J, Seiler RW. Effects of cerebral perfusion pressure and increased fraction of inspired oxygen on brain tissue oxygen, lactate and glucose in patients with severe head injury. Acta Neurochir (Wien). 2003;145:341–9. discussion 349–350.Google Scholar
  44. 44.
    Reinert M, Schaller B, Widmer HR, Seiler R, Bullock R. Influence of oxygen therapy on glucose-lactate metabolism after diffuse brain injury. J Neurosurg. 2004;101:323–9.CrossRefPubMedGoogle Scholar
  45. 45.
    Liu S, Liu W, Ding W, Miyake M, Rosenberg GA, Liu KJ. Electron paramagnetic resonance-guided normobaric hyperoxia treatment protects the brain by maintaining penumbral oxygenation in a rat model of transient focal cerebral ischemia. J Cereb Blood Flow Metab. 2006;26:1274–84.CrossRefPubMedGoogle Scholar
  46. 46.
    Vereczki V, Martin E, Rosenthal RE, Hof PR, Hoffman GE, Fiskum G. Normoxic resuscitation after cardiac arrest protects against hippocampal oxidative stress, metabolic dysfunction, and neuronal death. J Cereb Blood Flow Metab. 2006;26:821–35.CrossRefPubMedGoogle Scholar
  47. 47.
    Rossi S, Stocchetti N, Longhi L, et al. Brain oxygen tension, oxygen supply, and oxygen consumption during arterial hyperoxia in a model of progressive cerebral ischemia. J Neurotrauma. 2001;18:163–74.CrossRefPubMedGoogle Scholar
  48. 48.
    Scheufler KM, Rohrborn HJ, Zentner J. Does tissue oxygen-tension reliably reflect cerebral oxygen delivery and consumption? Anesth Analg. 2002;95:1042–8.CrossRefPubMedGoogle Scholar
  49. 49.
    Suttner S, Piper SN, Kumle B, et al. The influence of allogeneic red blood cell transfusion compared with 100% oxygen ventilation on systemic oxygen transport and skeletal muscle oxygen tension after cardiac surgery. Anesth Analg. 2004;99:2–11.CrossRefPubMedGoogle Scholar
  50. 50.
    Habler OP, Kleen MS, Hutter JW, et al. Effects of hyperoxic ventilation on hemodilution-induced changes in anesthetized dogs. Transfusion. 1998;38:135–44.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Anthony A. Figaji
    • 1
    • 5
  • Eugene Zwane
    • 2
  • A. Graham Fieggen
    • 1
  • Andrew C. Argent
    • 3
  • Peter D. Le Roux
    • 4
  • Jonathan C. Peter
    • 1
  1. 1.Division of Neurosurgery, School of Child and Adolescent HealthUniversity of Cape Town, Red Cross Children’s HospitalCape TownSouth Africa
  2. 2.Infectious Disease Epidemiology Unit (Biostatistics), School of Public Health and Family Medicine, Falmouth BuildingUniversity of Cape TownCape TownSouth Africa
  3. 3.Pediatric Critical Care, School of Child and Adolescent HealthUniversity of Cape Town, Red Cross Children’s HospitalCape TownSouth Africa
  4. 4.Department of NeurosurgeryHospital of the University of PennsylvaniaPhiladelphiaUSA
  5. 5.617 Institute for Child Health, Red Cross War Memorial Children’s HospitalCape TownSouth Africa

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