- Email: [email protected]
Correlations Between Brain Tissue Oxygen Tension, Carbon Dioxide Tension, pH, and Cerebral Blood Flow—A Better Way of Monitoring The Severely Injured Brain?
Technology
Correlations Between Brain Tissue Oxygen Tension, Carbon Dioxide Tension, pH, and Cerebral Blood Flow—A Better Way of Monitoring The Severely Injured Brain? Egon M.R. Doppenberg, M.D., Alois Zauner, M.D., Ross Bullock, M.D., Ph.D., John D. Ward, M.D., Panos P. Fatouros, Ph.D., and Harold F. Young, M.D. Division of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia
Doppenberg EMR, 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. BACKGROUND
The ideal method for monitoring the acutely injured brain would measure substrate delivery and brain function continuously, quantitatively, and sensitively. We have tested the hypothesis that brain pO2, pCO2, and pH, which can now be measured continuously using a single sensor, are valid indicators of regional cerebral blood flow (CBF) and oxidative metabolism, by measuring its product, brain pCO2. METHODS
Twenty-five patients (Glasgow Coma Score # 8) were studied. A Clark electrode, combined with a fiber optic system (Paratrend 7, Biomedical Sensors, Malvern, PA) was used to measure intraparenchymal brain pO2, pCO2, and pH. Data were averaged over a 1-h period before and after CBF studies. Regional CBF was measured around the probe, using stable xenon computed tomography. Regression analyses and Spearman Rank tests were used for data analysis. RESULTS
Regional CBF and mean brain pO2 were strongly correlated (r 5 0.74, p 5 0.0001). CBF values , 18 mL/100 g/min were all accompanied by brain pO2 # 26 mm Hg. The four patients with a brain pO2 , 18 mm Hg died. Brain pCO2 and pH, however, were not correlated with CBF (r 5 0.36, p 5 0.24 and r 5 0.30, p 5 0.43, respectively). CONCLUSIONS
Until recently, substrate supply to the severely injured brain could only be intermittently estimated by measuring CBF. The excellent intra-regional correlation between
Address reprint requests to: Dr. E.M.R. Doppenberg, Division of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, P.O. Box 980631, Richmond, VA 23298. Received December 4, 1996; accepted May 30, 1997. 0090-3019/98/$19.00 PII S0090-3019(97)00355-8
CBF and brain pO2, suggests that this method does allow continuous monitoring of true substrate delivery, and offers the prospect that measures to increase O2 delivery (e.g., increasing CBF, CPP, perfluorocarbons etc.) can be reliably tested by brain pO2 monitoring. © 1997 by Elsevier Science Inc. KEY WORDS
Brain tissue oxygenation, regional cerebral blood flow, severe head injury.
schemic brain damage is extremely common after severe head injury. Eighty to ninety percent of the patients who die show ischemia on brain histopathological examination [2]. However, the exact mechanisms of derangement in substrate delivery and brain metabolism after trauma remain poorly understood. The cerebral metabolic rate probably increases transiently and therefore substrate demand may vary over time, being highest early after trauma, which makes an increase in substrate delivery (cerebral blood flow (CBF)) necessary [1,3,5, 6,9 –12,14]. Nonetheless, in about one-third of the patients, CBF is low in the early phase after traumatic brain injury [4]. Early “flow/metabolism mismatch,” well demonstrated in animal models, may cause secondary damage to neurons, yet its exact mechanism and controlling factors remain poorly understood. We therefore studied local brain tissue oxygen tension (brain pO2), brain tissue carbon dioxide tension (brain pCO2), and brain pH in a group of 25 consecutive patients with severe traumatic brain injury, and we correlated these findings with regional CBF measurements.
I
© 1998 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
Brain pO2, pCO2, pH, and CBF in Severe Human Head Injury
Surg Neurol 651 1998;49:650 –4
(A) CT scan showing the multiparameter sensor next to the standard ventriculostomy catheter. (B) Xenon flow image corresponding with Figure 1A, showing the region of interest drawn immediately next to the multiparameter sensor.
1
Methods These studies were approved by the Committee for Conduct of Human Research, at the Virginia Commonwealth University. Twenty-five patients admitted to the Neuroscience Intensive Care Unit (NSICU) at the Medical College of Virginia (MCV), older than 16 years, with severe head injury and a Glasgow Coma Score of 8 or less, were studied. All patients received intensive ICP-directed management, according to a standard protocol at MCV. A multiparameter, minimally invasive (0.5 3 3.5 mm) sensor (Paratrend 7, Biomedical Sensors, Malvern, PA) was used for continuous measurements of brain pO2, pCO2, and brain pH. Brain temperature was measured with this sensor at the same time; these data are under analysis and will be reported separately. The sensor, originally developed for intra-arterial applications, was supplied as a sterile, single-use, disposable unit. The device consists of two modified optical fibers for pH and pCO2 measurements, and a miniaturized Clark electrode for pO2 measurement. Before insertion into the patient, the sensor was calibrated with sterile, precision gases bubbled in sequence through the tonometer under microprocessor control. The accuracy and precision of the sensor have been vali-
dated before intracranial human use, both in vitro and in vivo, in our previous studies [15–17]. The sensor data were digitally transferred from the host computer to a Macintosh computer (Apple Computers, Cuppertino, CA). The multiparameter sensor was inserted either on arrival in the NSICU or in the operating room after evacuation of a hematoma. Data collection started 1 h before CBF measurements until 1 h after. The multiparameter sensor was placed in the right frontal cortex (together with a standard ventriculostomy catheter and a microdialysis probe), through a specially designed triple lumen bolt for rigid skull fixation. Stable (nonradioactive) xenon-enhanced computed tomography (CT) was used for measuring CBF. This was performed by repeated CT scanning during the inhalation of a gas mixture containing 30% xenon, 30 –50% oxygen, and room air. Regional CBF was calculated using a 20 –30 mm2 region of interest at the site where the multiparameter probe was placed (Figure 1A, B). One CBF measurement was performed in each patient. The mean time 6 SD between injury and performance of the CBF measurement was 27 6 28 h, with a range of 3–96 h. Regression analyses and non-parametric tests (Spearman Rank) were used for data analysis (Statview).
652 Surg Neurol 1998;49:650 –4
Doppenberg et al
Regression plot showing the relationship between brain pO2 and regional CBF (r 5 0.74, p 5 0.0001).
2
Results BRAIN TISSUE OXYGEN TENSION In these 25 patients the brain pO2 was closely and linearly related to the regional CBF (r 5 0.74, p 5 0.0001). Patients with a higher brain pO2 also showed a higher CBF. CBF levels below the ischemic threshold of 18 mL/100 g/min (n 5 6) were associated with brain pO2 of 26 mm Hg or less. The four patients with a brain pO2 below 20 mm Hg all died. Patients with a CBF above 40 mL/100 g/min
Regression plot showing the poor correlation between brain pCO2 and regional CBF (r 5 0.36, p 5 0.24).
3
(n 5 3) had brain pO2 levels above 30 mm Hg (Figure 2). BRAIN TISSUE CARBON DIOXIDE TENSION AND PH No correlation could be found for measured brain pCO2 and CBF (r 5 0.36, p 5 0.24). The one patient with an extremely high brain pCO2 (112 mm Hg), a concomitant brain pH of 5.99 and CBF close to zero, was declared brain dead shortly after the study. Brain pH did not correlate with CBF (r 5 0.30, p 5
Brain pO2, pCO2, pH, and CBF in Severe Human Head Injury
Surg Neurol 653 1998;49:650 –4
Regression plot showing the poor relationship between brain pH and regional CBF (r 5 0.30, p 5 0.43).
4
0.43). No clear trends could be found for brain pCO2 or brain pH during hyperemic or ischemic episodes (Figures 3 and 4).
Discussion Brain pO2 is a measure of the tissue oxygenation status. The excellent correlation between regional CBF and brain pO2 indicates that monitoring brain pO2 measures true substrate delivery and represents regional CBF. This apparent close correlation between regional CBF and brain oxygen has several important implications. First, continuous brain pO2 monitoring using this method provides an apparently reliable, continuous, relatively minimally invasive technique to assess true substrate delivery. Second, low brain tissue oxygen tension was never seen without flow reduction, suggesting that at least for oxygen metabolism by the brain, CBF, or substrate delivery, is the major limiting factor, rather than substrate use, as might be expected if mitochondrial oxidative phosphorylation were increased after trauma. The increased “metabolism” shown by several other authors and ourselves, in both humans after severe head injury and in animal trauma models has been for glucose use only. Brain tissue hypermetabolism does not lead to hypoxia during normal CBF. Thus, our data leads us to postulate that the apparent flow-metabolism mismatch seen in these autoradiographic and PET studies has been for anaero-
bic glycolysis only [1,8,10]. This accords with the very high levels of extracellular fluid (ECF) dialysate brain lactate and very low ECF brain glucose levels which we and other authors have found in both humans [unpublished data] and animal models after trauma and ischemia [10 –14]. It is surprising that brain pCO2 did not correlate with CBF, because CO2 is accepted to be the most potent vasoregulator of the cerebral microcirculation through extracellular pH changes as shown by Harper et al. These authors showed in 1965 that arterial pCO2, and CBF are tightly, linearly correlated in normal mammals [7]. We speculate that local brain metabolism regulates brain pCO2 (and therefore pH) and that this may not be the same as the arterial pCO2. Another explanation could be that in this group of severely head injured patients the CO2-vasoregulation is impaired. In this group of severely head injured patients, we also found a tight link between brain pO2 and outcome. All patients with a brain pO2 below 25 mm Hg did poorly; they all died or remained vegetative. At the same time, the patients with a brain pO2 above 35 mm Hg did well [18]. Clearly, more studies are needed to better understand the inter-relationships between substrates and products of cerebral metabolism after severe head injury. We are currently analyzing brain lactate and glucose data obtained through microdialysis in the same region of the brain, in the same patient population. This combined “multimodality cerebral metabolism monitoring” should give us a
654 Surg Neurol 1998;49:650 –4
Doppenberg et al
fuller understanding of the mechanisms that play a role in the derangement of cerebral metabolism after traumatic brain injury. Finally, threshold analysis is needed to establish the ischemic threshold for brain tissue oxygen tension to make this technique clinically useful for both nurses and medical staff.
9.
10.
These studies were supported by NIH Grant NS12587. 11.
REFERENCES 1. Ackermann RF, Lear JL. Glycolysis-induced discordance between glucose metabolic rates measured with radio-labeled fluorodeoxyglucose and glucose. J Cereb Blood Flow Metab 1989;9:774 – 85. 2. Adams JH, Graham DI, Gennarelli TA. Head injury in man and experimental animals: neuropathology. Acta Neurochir Suppl 1983;32:S15–30. 3. Andersen BJ, Marmarou A. Isolated stimulation of glycolysis following traumatic brain injury. In: Hoff JT, Betz AL, eds. Intracranial pressure VII. Berlin: Springer-Verlag, 1989:575– 80. 4. Bouma GJ, Muizelaar JP, Stringer WA, Choi SC, Fatouros PP, Young HF. Ultra-early evaluation of regional cerebral blood flow in severely head-injured patients using xenon-enhanced computerized tomography. J Neurosurg 1992;77:360 – 8. 5. Duckrow RB, LaManna JC, Rosenthal M. Oxidative metabolic activity of cerebral cortex after fluidpercussion injury in the cat. J Neurosurg 1986;54:607– 14. 6. Edvinsson L, MacKenzie ET, McCulloch J. Energy generation in the central nervous system. In: Cerebral Blood Flow and Metabolism. New York: Raven Press, 1993:153– 8. 7. Harper AM. Physiology of cerebral blood flow. Brit J Anaesth 1965;37:225–35. 8. Hovda DA, Lee SM, Smith ML, Von Stuck S, Bergsneider M, Kelly D, Shalmon E, Martin N, Caron M, Mazziotta J, Phelps M, Becker DP. The neurochemical and metabolic cascade following brain injury: moving
T
12.
13.
14.
15. 16. 17. 18.
from animal models to man. J Neurotrauma 1995;12: 903– 6. Inglis FM, Bullock R, Chen MH, Graham DI, Miller JD, McCulloch J. Ischaemic brain damage associated with tissue hypermetabolism in acute subdural haematoma: reduction by a glutamate antagonist. Acta Neurochir 1990;51:277–9. Kawamata T, Katayama Y, Hovda DA. Administration of excitatory amino acid antagonists via microdialysis attenuates the increase in glucose utilization seen following concussive brain injury. J Cereb Blood Flow Metab 1992;12:12–24. Kawamata T, Katayama Y, Hovda DA, Yoshino A, Becker DP. Lactate accumulation following concussive brain injury: the role of ion fluxes induced by excitatory amino acids. Brain Res 1995;674:196 –204. Kuroda Y, Inglis FM, Miller JD, McCulloch J, Graham DI, Path FRC, Bullock R. Transient glucose hypermetabolism after acute subdural hematoma in the rat. J Neurosurg 1992;76:471–7. Pellerin L, Magistretti PJ. Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci USA 1994;91:10625–9. Yoshino A, Hovda DA, Kawamata T, Katayama Y, Becker DP. Dynamic changes in local glucose utilization following cerebral concussion in rats: evidence of a hyper and subsequent hypometabolic state. Brain Res 1991;561:106 –19. Zauner A, Bullock R, Di X, Young HF. Brain oxygen, C02, pH, and temperature monitoring: evaluation in the feline brain. Neurosurgery 1995;37:1168 –77. Zauner A, Bullock R, Young HF. Continuous brain oxygen, C02, pH and temperature monitoring in neurosurgical patients. Neurosurgery 1995;37:570. Zauner A, Bullock R, Young HF. Continuous monitoring of oxygen, C02, pH and temperature in brain tissue using a single sensor. J Neurotrauma 1995;12:468. Zauner A, Doppenberg EMR, Woodward JJ, Choi SC, Young HF, Bullock R. Continuous multiparameter monitoring of substrate delivery and brain metabolism: initial experience in 24 patients with severe acute brain injury. Neurosurgery 1997;41:1082–91.
he more you sweat in Peacetime, the less you bleed during War. —Chinese proverb
Correlations Between Brain Tissue Oxygen Tension, Carbon Dioxide Tension, pH, and Cerebral Blood Flow—A Better Way of Monitoring The Severely Injured Brain? Egon M.R. Doppenberg, M.D., Alois Zauner, M.D., Ross Bullock, M.D., Ph.D., John D. Ward, M.D., Panos P. Fatouros, Ph.D., and Harold F. Young, M.D. Division of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia
Doppenberg EMR, 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. BACKGROUND
The ideal method for monitoring the acutely injured brain would measure substrate delivery and brain function continuously, quantitatively, and sensitively. We have tested the hypothesis that brain pO2, pCO2, and pH, which can now be measured continuously using a single sensor, are valid indicators of regional cerebral blood flow (CBF) and oxidative metabolism, by measuring its product, brain pCO2. METHODS
Twenty-five patients (Glasgow Coma Score # 8) were studied. A Clark electrode, combined with a fiber optic system (Paratrend 7, Biomedical Sensors, Malvern, PA) was used to measure intraparenchymal brain pO2, pCO2, and pH. Data were averaged over a 1-h period before and after CBF studies. Regional CBF was measured around the probe, using stable xenon computed tomography. Regression analyses and Spearman Rank tests were used for data analysis. RESULTS
Regional CBF and mean brain pO2 were strongly correlated (r 5 0.74, p 5 0.0001). CBF values , 18 mL/100 g/min were all accompanied by brain pO2 # 26 mm Hg. The four patients with a brain pO2 , 18 mm Hg died. Brain pCO2 and pH, however, were not correlated with CBF (r 5 0.36, p 5 0.24 and r 5 0.30, p 5 0.43, respectively). CONCLUSIONS
Until recently, substrate supply to the severely injured brain could only be intermittently estimated by measuring CBF. The excellent intra-regional correlation between
Address reprint requests to: Dr. E.M.R. Doppenberg, Division of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, P.O. Box 980631, Richmond, VA 23298. Received December 4, 1996; accepted May 30, 1997. 0090-3019/98/$19.00 PII S0090-3019(97)00355-8
CBF and brain pO2, suggests that this method does allow continuous monitoring of true substrate delivery, and offers the prospect that measures to increase O2 delivery (e.g., increasing CBF, CPP, perfluorocarbons etc.) can be reliably tested by brain pO2 monitoring. © 1997 by Elsevier Science Inc. KEY WORDS
Brain tissue oxygenation, regional cerebral blood flow, severe head injury.
schemic brain damage is extremely common after severe head injury. Eighty to ninety percent of the patients who die show ischemia on brain histopathological examination [2]. However, the exact mechanisms of derangement in substrate delivery and brain metabolism after trauma remain poorly understood. The cerebral metabolic rate probably increases transiently and therefore substrate demand may vary over time, being highest early after trauma, which makes an increase in substrate delivery (cerebral blood flow (CBF)) necessary [1,3,5, 6,9 –12,14]. Nonetheless, in about one-third of the patients, CBF is low in the early phase after traumatic brain injury [4]. Early “flow/metabolism mismatch,” well demonstrated in animal models, may cause secondary damage to neurons, yet its exact mechanism and controlling factors remain poorly understood. We therefore studied local brain tissue oxygen tension (brain pO2), brain tissue carbon dioxide tension (brain pCO2), and brain pH in a group of 25 consecutive patients with severe traumatic brain injury, and we correlated these findings with regional CBF measurements.
I
© 1998 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
Brain pO2, pCO2, pH, and CBF in Severe Human Head Injury
Surg Neurol 651 1998;49:650 –4
(A) CT scan showing the multiparameter sensor next to the standard ventriculostomy catheter. (B) Xenon flow image corresponding with Figure 1A, showing the region of interest drawn immediately next to the multiparameter sensor.
1
Methods These studies were approved by the Committee for Conduct of Human Research, at the Virginia Commonwealth University. Twenty-five patients admitted to the Neuroscience Intensive Care Unit (NSICU) at the Medical College of Virginia (MCV), older than 16 years, with severe head injury and a Glasgow Coma Score of 8 or less, were studied. All patients received intensive ICP-directed management, according to a standard protocol at MCV. A multiparameter, minimally invasive (0.5 3 3.5 mm) sensor (Paratrend 7, Biomedical Sensors, Malvern, PA) was used for continuous measurements of brain pO2, pCO2, and brain pH. Brain temperature was measured with this sensor at the same time; these data are under analysis and will be reported separately. The sensor, originally developed for intra-arterial applications, was supplied as a sterile, single-use, disposable unit. The device consists of two modified optical fibers for pH and pCO2 measurements, and a miniaturized Clark electrode for pO2 measurement. Before insertion into the patient, the sensor was calibrated with sterile, precision gases bubbled in sequence through the tonometer under microprocessor control. The accuracy and precision of the sensor have been vali-
dated before intracranial human use, both in vitro and in vivo, in our previous studies [15–17]. The sensor data were digitally transferred from the host computer to a Macintosh computer (Apple Computers, Cuppertino, CA). The multiparameter sensor was inserted either on arrival in the NSICU or in the operating room after evacuation of a hematoma. Data collection started 1 h before CBF measurements until 1 h after. The multiparameter sensor was placed in the right frontal cortex (together with a standard ventriculostomy catheter and a microdialysis probe), through a specially designed triple lumen bolt for rigid skull fixation. Stable (nonradioactive) xenon-enhanced computed tomography (CT) was used for measuring CBF. This was performed by repeated CT scanning during the inhalation of a gas mixture containing 30% xenon, 30 –50% oxygen, and room air. Regional CBF was calculated using a 20 –30 mm2 region of interest at the site where the multiparameter probe was placed (Figure 1A, B). One CBF measurement was performed in each patient. The mean time 6 SD between injury and performance of the CBF measurement was 27 6 28 h, with a range of 3–96 h. Regression analyses and non-parametric tests (Spearman Rank) were used for data analysis (Statview).
652 Surg Neurol 1998;49:650 –4
Doppenberg et al
Regression plot showing the relationship between brain pO2 and regional CBF (r 5 0.74, p 5 0.0001).
2
Results BRAIN TISSUE OXYGEN TENSION In these 25 patients the brain pO2 was closely and linearly related to the regional CBF (r 5 0.74, p 5 0.0001). Patients with a higher brain pO2 also showed a higher CBF. CBF levels below the ischemic threshold of 18 mL/100 g/min (n 5 6) were associated with brain pO2 of 26 mm Hg or less. The four patients with a brain pO2 below 20 mm Hg all died. Patients with a CBF above 40 mL/100 g/min
Regression plot showing the poor correlation between brain pCO2 and regional CBF (r 5 0.36, p 5 0.24).
3
(n 5 3) had brain pO2 levels above 30 mm Hg (Figure 2). BRAIN TISSUE CARBON DIOXIDE TENSION AND PH No correlation could be found for measured brain pCO2 and CBF (r 5 0.36, p 5 0.24). The one patient with an extremely high brain pCO2 (112 mm Hg), a concomitant brain pH of 5.99 and CBF close to zero, was declared brain dead shortly after the study. Brain pH did not correlate with CBF (r 5 0.30, p 5
Brain pO2, pCO2, pH, and CBF in Severe Human Head Injury
Surg Neurol 653 1998;49:650 –4
Regression plot showing the poor relationship between brain pH and regional CBF (r 5 0.30, p 5 0.43).
4
0.43). No clear trends could be found for brain pCO2 or brain pH during hyperemic or ischemic episodes (Figures 3 and 4).
Discussion Brain pO2 is a measure of the tissue oxygenation status. The excellent correlation between regional CBF and brain pO2 indicates that monitoring brain pO2 measures true substrate delivery and represents regional CBF. This apparent close correlation between regional CBF and brain oxygen has several important implications. First, continuous brain pO2 monitoring using this method provides an apparently reliable, continuous, relatively minimally invasive technique to assess true substrate delivery. Second, low brain tissue oxygen tension was never seen without flow reduction, suggesting that at least for oxygen metabolism by the brain, CBF, or substrate delivery, is the major limiting factor, rather than substrate use, as might be expected if mitochondrial oxidative phosphorylation were increased after trauma. The increased “metabolism” shown by several other authors and ourselves, in both humans after severe head injury and in animal trauma models has been for glucose use only. Brain tissue hypermetabolism does not lead to hypoxia during normal CBF. Thus, our data leads us to postulate that the apparent flow-metabolism mismatch seen in these autoradiographic and PET studies has been for anaero-
bic glycolysis only [1,8,10]. This accords with the very high levels of extracellular fluid (ECF) dialysate brain lactate and very low ECF brain glucose levels which we and other authors have found in both humans [unpublished data] and animal models after trauma and ischemia [10 –14]. It is surprising that brain pCO2 did not correlate with CBF, because CO2 is accepted to be the most potent vasoregulator of the cerebral microcirculation through extracellular pH changes as shown by Harper et al. These authors showed in 1965 that arterial pCO2, and CBF are tightly, linearly correlated in normal mammals [7]. We speculate that local brain metabolism regulates brain pCO2 (and therefore pH) and that this may not be the same as the arterial pCO2. Another explanation could be that in this group of severely head injured patients the CO2-vasoregulation is impaired. In this group of severely head injured patients, we also found a tight link between brain pO2 and outcome. All patients with a brain pO2 below 25 mm Hg did poorly; they all died or remained vegetative. At the same time, the patients with a brain pO2 above 35 mm Hg did well [18]. Clearly, more studies are needed to better understand the inter-relationships between substrates and products of cerebral metabolism after severe head injury. We are currently analyzing brain lactate and glucose data obtained through microdialysis in the same region of the brain, in the same patient population. This combined “multimodality cerebral metabolism monitoring” should give us a
654 Surg Neurol 1998;49:650 –4
Doppenberg et al
fuller understanding of the mechanisms that play a role in the derangement of cerebral metabolism after traumatic brain injury. Finally, threshold analysis is needed to establish the ischemic threshold for brain tissue oxygen tension to make this technique clinically useful for both nurses and medical staff.
9.
10.
These studies were supported by NIH Grant NS12587. 11.
REFERENCES 1. Ackermann RF, Lear JL. Glycolysis-induced discordance between glucose metabolic rates measured with radio-labeled fluorodeoxyglucose and glucose. J Cereb Blood Flow Metab 1989;9:774 – 85. 2. Adams JH, Graham DI, Gennarelli TA. Head injury in man and experimental animals: neuropathology. Acta Neurochir Suppl 1983;32:S15–30. 3. Andersen BJ, Marmarou A. Isolated stimulation of glycolysis following traumatic brain injury. In: Hoff JT, Betz AL, eds. Intracranial pressure VII. Berlin: Springer-Verlag, 1989:575– 80. 4. Bouma GJ, Muizelaar JP, Stringer WA, Choi SC, Fatouros PP, Young HF. Ultra-early evaluation of regional cerebral blood flow in severely head-injured patients using xenon-enhanced computerized tomography. J Neurosurg 1992;77:360 – 8. 5. Duckrow RB, LaManna JC, Rosenthal M. Oxidative metabolic activity of cerebral cortex after fluidpercussion injury in the cat. J Neurosurg 1986;54:607– 14. 6. Edvinsson L, MacKenzie ET, McCulloch J. Energy generation in the central nervous system. In: Cerebral Blood Flow and Metabolism. New York: Raven Press, 1993:153– 8. 7. Harper AM. Physiology of cerebral blood flow. Brit J Anaesth 1965;37:225–35. 8. Hovda DA, Lee SM, Smith ML, Von Stuck S, Bergsneider M, Kelly D, Shalmon E, Martin N, Caron M, Mazziotta J, Phelps M, Becker DP. The neurochemical and metabolic cascade following brain injury: moving
T
12.
13.
14.
15. 16. 17. 18.
from animal models to man. J Neurotrauma 1995;12: 903– 6. Inglis FM, Bullock R, Chen MH, Graham DI, Miller JD, McCulloch J. Ischaemic brain damage associated with tissue hypermetabolism in acute subdural haematoma: reduction by a glutamate antagonist. Acta Neurochir 1990;51:277–9. Kawamata T, Katayama Y, Hovda DA. Administration of excitatory amino acid antagonists via microdialysis attenuates the increase in glucose utilization seen following concussive brain injury. J Cereb Blood Flow Metab 1992;12:12–24. Kawamata T, Katayama Y, Hovda DA, Yoshino A, Becker DP. Lactate accumulation following concussive brain injury: the role of ion fluxes induced by excitatory amino acids. Brain Res 1995;674:196 –204. Kuroda Y, Inglis FM, Miller JD, McCulloch J, Graham DI, Path FRC, Bullock R. Transient glucose hypermetabolism after acute subdural hematoma in the rat. J Neurosurg 1992;76:471–7. Pellerin L, Magistretti PJ. Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci USA 1994;91:10625–9. Yoshino A, Hovda DA, Kawamata T, Katayama Y, Becker DP. Dynamic changes in local glucose utilization following cerebral concussion in rats: evidence of a hyper and subsequent hypometabolic state. Brain Res 1991;561:106 –19. Zauner A, Bullock R, Di X, Young HF. Brain oxygen, C02, pH, and temperature monitoring: evaluation in the feline brain. Neurosurgery 1995;37:1168 –77. Zauner A, Bullock R, Young HF. Continuous brain oxygen, C02, pH and temperature monitoring in neurosurgical patients. Neurosurgery 1995;37:570. Zauner A, Bullock R, Young HF. Continuous monitoring of oxygen, C02, pH and temperature in brain tissue using a single sensor. J Neurotrauma 1995;12:468. Zauner A, Doppenberg EMR, Woodward JJ, Choi SC, Young HF, Bullock R. Continuous multiparameter monitoring of substrate delivery and brain metabolism: initial experience in 24 patients with severe acute brain injury. Neurosurgery 1997;41:1082–91.
he more you sweat in Peacetime, the less you bleed during War. —Chinese proverb