J Neurosurg 74:407-414, 1991
Acute regional cerebral blood flow changes caused by severe head injuries DONALD W. MARION, M.D., JOSEPH DARBY, M.D., AND HOWARD YONAS, M.D.
Departments of Neurological Surgery and Anesthesiology/Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania ~" To evaluate the changes in cerebral blood flow (CBF) that occur immediately after head injury and the effects of different posttraumatic lesions on CBF, 6 l CBF studies were obtained using the xenon-computerized tomography method in 32 severely head-injured adults (Glasgow Coma Scale score (GCS) 9 vol%). 24a7'32 However, the oxygen content in blood samples from one internal jugular vein may not accurately represent the oxygen content throughout the brain, and such misrepresentation is even more likely when there is structural brain injury.'~ Robertson, etal., 35 recently demonstrated that arteriovenous difference in oxygen content is variable in patients with cerebral ischemia and found that the lactateoxygen index is a much better predictor of ischemia. In addition, many reports on CBF following head injury have combined blood flow data obtained for up to 7 days after the injury or values from patients with various types of traumatic brain lesions. 2'24'27"29"32 We demonstrated considerable inhomogeneity in CBF among patients with surgical intracranial mass lesions as compared to those with nonsurgical injuries. We also found a marked increase in CBF 24 hours after the injury in groups that initially had low flows. By averaging combined CBF data obtained at various times or from patients with different types of lesions, many previous studies may have masked early ischemia by higher flows occurring either later or in association with surgical intracranial mass lesions. Effect of Posttraumatic Lesions on Regional CBF Victims of severe head injuries who develop focal mass lesions have been shown to have a higher CBF in the hemisphere with the mass) 2 This suggests that local hyperemia is caused by the mass or the underlying brain-tissue injury. We also observed this effect with 412
acute subdural hematomas but not with focal contusions (Table 1). The double CBF studies we obtained with CO2 manipulation provided some insight into the etiology of these focal blood flow changes. We found that CO2 vasoresponsivity was markedly increased in four patients with acute subdural hematomas, particularly on the side of the lesion. This appears to indicate that the cerebral vasculature underlying the clot is hypersensitive to changes in pCO2 and/or changes in pH. If such hypersensivity caused the unusually low CBF observed when we reduced pCO2 in our double studies, it also might cause abnormally high flows at a higher pCO2. The mean CBF34 values we found in the hemispheres ipsilateral to acute subdural hematomas were higher than those for any other posttraumatic lesion. In one patient with diffuse contusions, CBF changed less than was expected following the decrease in pCO2, possibly representing a partial loss of CO2 vasoresponsivity. Reduction in CO2 vasoresponsivity has been associated with low CBF, 2~ and our patients with diffuse contusions had lower CBF than those with any other lesion. Three patients with epidural hematomas had nearly intact vasoresponsivity to CO2; these were among the patients who had similar CBF in both hemispheres.
Implications for the Management of Severe Head Injury Abnormal CO2 vasoresponsivity has several important implications for the management of intracranial hypertension. Hyperventilation can cause blood from high-resistance, maximally constricted vessels with intact or supersensitive CO2 vasoresponsivity to be shunted into low-resistance, maximally dilated vessels that have lost CO2 vasoresponsivity (inverse steal effect). In a recent review of the 3- and 6-month outcome in 114 patients with severe head injuries, Ward, el a/., 37 found that the subgroup of patients in whom the arterial pCO2 was routinely kept at 24 _+ 2 mm Hg had significantly worse outcomes than those in whom the arterial pCO2 was kept at 35 _+2 mm Hg. The use of hyperventilation in patients with critically ischemic brain regions might well be expected to cause infarcts in those regions, perhaps because of the inverse steal effect. Nordstrrm and coworkers 28 suggested that the beneficial effects of barbiturates in head injury are influenced by the integrity of CO2 vasoresponsivity and also found that outcome was better in the group with intact vasoresponsivity. We and others 2.24 have found that it is not possible to predict which patients have critically low CBF or abnormal CO2 vaseresponsivity on the basis of clinical examinations or CT findings. Rather than the broad application of hyperventilation, mannitol, or barbiturates, we advocate a plan of initial management individualized for each patient and based on the severity of neurological injury, direct measurements of ICP, CT findings, and serial measurements of regional CBF. J. Neurosurg. / Volume 74/March, 1991
Acute rCBF changes in severe head injury' Patients who do not have a surgical intracranial mass lesion can undergo a Xe/CT CBF study immediately after the initial CT scan. Those who require emergency surgery should have their initial blood flow study as soon as possible after the operation. With early CBF information, management of elevated ICP can be designed not only to treat the ICP, but also to enhance blood flow to regions of the brain in which flow is deficient or to reduce CBF when there is global hyperemia. If cerebral ischemia is t11e principal cause of secondary brain injury, as Miller2~ has suggested, the management of intracranial hypertension based in part on serial measurements of regional CBF may be expected to reduce the incidence of uncontrollable or prolonged inlracranial hypertension and may lead to improved outcome. Acknowledgments The authors gratefully acknowledge Dr. J. Paul Muizelaar for his critical review of the manuscript and Helene Marion for editing it. References 1. Barclay L, Zemcov A, Reichen W, et al: Cerebral blood flow decrements in chronic head injury syndrome. Biol Psychiatry 20:146-157, 1985 2. Bruce DA, Langfitt TW, Miller JD, et al: Regional cerebral blood flow, intracranial pressure, and brain metabolism in comatose patients. J Neurosurg 38:131-144, 1973 3. Busija DW: Unilateral and bilaleral sympathetic effects on cerebral blood flow during normocapnia. Am J Physiol 250:H498-H502, 1986 4. Cold GE, Jensen FT, Malmros R: The effects of PaCO: reduction on regional cerebral blood flow in the acute phase of brain injury'. Acta Anaesthesiol Stand 21: 359-367, 1977 5. Darby JM, Yonas H, Moossy JJ, et al: Effect of stable xenon inhalation on ICP in head injury, in Hoff JT, Betz AL (eds): Intracranial Pressure VII. Berlin: SpringerVerlag, 1989, pp 643-645 6. Enevoldsen EM, Cold G, Jensen FT, et al: Dynamic changes in regional CBF, intraventricular pressure, CSF pH and lactate levels during the acute phase of head injury. J Neurosurg 44:191-214, 1976 7. Enevoldsen EM, Jensen FT: Autoregulation and CO2 responses of cerebral blood flow in patients with acute severe head injury'. J Neurosnrg 48:689-703, 1978 8. Faden AI, Jacobs TP, Smith MT, et al: Comparison of thyrotropin-releasing hormone (TRH), naloxone, and dexamethasone treatments in experimental spinal injury,. Neurology 33:673-678, 1983 9. Fehlings MG, Tator CH, Linden RD: The relationships among the severity of spinal cord injury, motor and somatosensory evoked potentials and spinal cord blood flow. Electroencephalogr Clin Neurophysiol 74:241-259, 1989 10. Gibbs EL, Lennox WG, Gibbs FA: Bilateral internal jugular blood. Comparison of A-V differences, oxygendextrose ratios and respiratory quotients. Am J Psychiatry 102:184-190, 1945 11. Graham DI, Adams JH, Doyle D: Ischemic brain damage in fatal non-missile head injuries. J Neurol Sci 39: 213-234, 1978 J. Neurosurg. / Volume 74~March, 1991
12. Gur D, Good WF, Wolfson SK Jr, et al: In viw) mapping of local cerebral blood flow by xenon-enhanced computed tomography. Science 215:1267-1268, 1982 13. Gur D, Herron JM. Molter BS, et al: Simultaneous mass spectrometry and thermoconductivity measurements of end-tidal xenon concentrations: a comparison. Med Phys 11:209-212, 1984 14. Gur D, Wolfson SK Jr, Yonas H, et al: Progress in cerebrovascular disease: local cerebral blood flow by xenon enhanced CT. Stroke 13:750-758, 1982 15. Harrington TR, Manwaring K, Hodak J: Local basal ganglia and brain stem blood flow in the head injured patient using stable xenon enhanced CT scanning, in Miller JD, Teasdale GM, Rowan JO, et al (eds): Intracranial Pressure Vl. Berlin: Springer-Verlag, 1986, pp 680-686 16. Hellman RS, Collier BD. Tikofsky RS, et al: Comparison of single-photon emission computed tomography with rt2-~%doamphetamineand xenon-enhanced computed tomography for assessing regional cerebral blood flow. J Cereb Blood Flow Metab 6:747-755, 1986 17. Holl K, Nemati N, Kohmura E, et al: Stable-xenon-CT: effects of xenon inhalation on EEG and cardio-respiratory parameters in the human. Acta Neurochir 87:129-133, 1987 18. Jaggi JL, Obrist WD, Gennarelli TA, et al: Relationship of early cerebral blood flow and metabolism to outcome in acute head injur,,-.J Neurosurg 72:176-182, 1990 19. Kearfott KJ, Lu HC, Rottenberg DA, et al: The effects of CT drift on xenon/CT measurement of regional cerebral blood flow. Med Phys 11:686-689, 1984 20. Kendall BE, Moseley IF: Xenon as a contrast agent for computed tomography. Principles and current applications. J Neuroradiol 8:3-12, 1981 21. Lassen NA: The luxury-perfusion syndrome and its possible relation to acute metabolic acidosis localized within the brain. Lancet 2:1113-1115, 1966 22. Latchaw RE, Yonas H, Pentheny SL, et al: Adverse reactions to xenon-enhanced CT cerebral blood flow determination. Radiology 163:251-254, 1987 23. Lobato RD, Sarabia R, Cordobes F, et al: Posltraumatic cerebral hemispheric swelling. Analysis of 55 cases studied with computerized tomography. J Neurosurg 68: 417-423, 1988 24. Mendlelow AD, Teasdale GM, Russell T, et al: Effect of mannitol on cerebral blood flow and cerebral perfusion pressure in human head injury. J Neurosurg 63:43-48, 1985 25. Meyer JS, Hayman LA, Yamamoto M, et al: Local cerebral blood flow measured by CT after stable xenon inhalation. AJR 135:239-251, 1980 26. Miller JD: Head injury and brain ischaemia - - implicalions for therapy. Br J Anaesth 57:120-129, 1985 27. Muizelaar .IP, Marmarou A, DeSalles AAF, et al: Cerebral blood flow and metabolism in severely head-injured children. Part 1: Relationship with GCS score, outcome, ICP, and PVI. J Neurosurg 71:63-71, 1989 28. Nordstr6m CH, Messeter K, SundNirg G, et al: Cerebral blood flow, vasoreactivity, and oxygen consumption during barbiturate therapy in severe traumatic brain lesions. J Neurosurg 68:424-431, 1988 29. Obrist WD, Gennarelli TA, Segawa H, el al: Relation of cerebral blood flow to neurological status and outcome in head-injured patients. J Neurosurg 51:292-300, 1979 30. Obrist WD, Jaggi JL, Harel D, et al: Effect of stable xenon inhalation on human CBF. J Cereb Blood Flow Metab 5: 557-558, 1985 31. Obrist WD, Langfltt TW, Dolinskas CA, et al: Factors 413
D. W. Marion, J. Darby, and H. Yonas
32.
33.
34.
35.
414
relating to intracranial hypertension in acute head inju~', in Ishii S, Nagai H, Brock M (eds): lntracranial Pressure V. Berlin: Springer-Verlag, 1983, pp 491-494 Obrist WD, Langfitt TW, Jaggi Jk, et al: Cerebral blood flow and metabolism in comatose patients with acute head injury. Relationship to intracranial hypertension. J Neurosnrg 61:241-253, 1984 Osterholm JL, Mathews G J: Altered norepinephrine mctabolism following experimental spinal cord injury. Part 2: Protection against traumatic spinal cord hemorrhagic necrosis by norepinephrine synthesis blockade with alpha methyl tyrosine. J Neurosurg 36:395-401, 1972 Overgaard J, Mosdal C, Tweed WA: Cerebral circulation after head injury. Part 3: Does reduced regional cerebral blood flow determine recovery of brain function after blunt head injury? J Neurosurg 55:63-74, 1981 Robertson CS, Narayan RK, Gokaslan ZL, el al: Cerebral
arteriovenous oxygen difference as an estimate of cerebral blood flow in comatose patients. J Nenrosurg 70: 222-230, 1989 36. Rosner M J, Newsome HH, Becket DP: Mechanical brain inju~': the sympathoadrenal response. ,I Neurosurg 61: 76-86, 1984 37. Ward JD, Choi S, Marmarou A, et al: Effect of prophylactic hyperventilation on outcome in patients with severe head injury, in HoffJT, Betz AL (eds): Intracranial Pressure VII. Berlin: Springer-Verlag, 1989, pp 630-633 Manuscript received March 9, 1990. Accepted in final form September 14, 1990. Address reprint requests to: Donald W. Marion, M.D., Department of Neurosurgery, Room 9402, Presbyterian-University Hospital, 230 Lothrop Street, Pittsburgh, Pennsylvania 15213.
Z Neurosurg. / Volume 74/March, 1991
Acute regional cerebral blood flow changes caused by severe head injuries DONALD W. MARION, M.D., JOSEPH DARBY, M.D., AND HOWARD YONAS, M.D.
Departments of Neurological Surgery and Anesthesiology/Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania ~" To evaluate the changes in cerebral blood flow (CBF) that occur immediately after head injury and the effects of different posttraumatic lesions on CBF, 6 l CBF studies were obtained using the xenon-computerized tomography method in 32 severely head-injured adults (Glasgow Coma Scale score (GCS) 9 vol%). 24a7'32 However, the oxygen content in blood samples from one internal jugular vein may not accurately represent the oxygen content throughout the brain, and such misrepresentation is even more likely when there is structural brain injury.'~ Robertson, etal., 35 recently demonstrated that arteriovenous difference in oxygen content is variable in patients with cerebral ischemia and found that the lactateoxygen index is a much better predictor of ischemia. In addition, many reports on CBF following head injury have combined blood flow data obtained for up to 7 days after the injury or values from patients with various types of traumatic brain lesions. 2'24'27"29"32 We demonstrated considerable inhomogeneity in CBF among patients with surgical intracranial mass lesions as compared to those with nonsurgical injuries. We also found a marked increase in CBF 24 hours after the injury in groups that initially had low flows. By averaging combined CBF data obtained at various times or from patients with different types of lesions, many previous studies may have masked early ischemia by higher flows occurring either later or in association with surgical intracranial mass lesions. Effect of Posttraumatic Lesions on Regional CBF Victims of severe head injuries who develop focal mass lesions have been shown to have a higher CBF in the hemisphere with the mass) 2 This suggests that local hyperemia is caused by the mass or the underlying brain-tissue injury. We also observed this effect with 412
acute subdural hematomas but not with focal contusions (Table 1). The double CBF studies we obtained with CO2 manipulation provided some insight into the etiology of these focal blood flow changes. We found that CO2 vasoresponsivity was markedly increased in four patients with acute subdural hematomas, particularly on the side of the lesion. This appears to indicate that the cerebral vasculature underlying the clot is hypersensitive to changes in pCO2 and/or changes in pH. If such hypersensivity caused the unusually low CBF observed when we reduced pCO2 in our double studies, it also might cause abnormally high flows at a higher pCO2. The mean CBF34 values we found in the hemispheres ipsilateral to acute subdural hematomas were higher than those for any other posttraumatic lesion. In one patient with diffuse contusions, CBF changed less than was expected following the decrease in pCO2, possibly representing a partial loss of CO2 vasoresponsivity. Reduction in CO2 vasoresponsivity has been associated with low CBF, 2~ and our patients with diffuse contusions had lower CBF than those with any other lesion. Three patients with epidural hematomas had nearly intact vasoresponsivity to CO2; these were among the patients who had similar CBF in both hemispheres.
Implications for the Management of Severe Head Injury Abnormal CO2 vasoresponsivity has several important implications for the management of intracranial hypertension. Hyperventilation can cause blood from high-resistance, maximally constricted vessels with intact or supersensitive CO2 vasoresponsivity to be shunted into low-resistance, maximally dilated vessels that have lost CO2 vasoresponsivity (inverse steal effect). In a recent review of the 3- and 6-month outcome in 114 patients with severe head injuries, Ward, el a/., 37 found that the subgroup of patients in whom the arterial pCO2 was routinely kept at 24 _+ 2 mm Hg had significantly worse outcomes than those in whom the arterial pCO2 was kept at 35 _+2 mm Hg. The use of hyperventilation in patients with critically ischemic brain regions might well be expected to cause infarcts in those regions, perhaps because of the inverse steal effect. Nordstrrm and coworkers 28 suggested that the beneficial effects of barbiturates in head injury are influenced by the integrity of CO2 vasoresponsivity and also found that outcome was better in the group with intact vasoresponsivity. We and others 2.24 have found that it is not possible to predict which patients have critically low CBF or abnormal CO2 vaseresponsivity on the basis of clinical examinations or CT findings. Rather than the broad application of hyperventilation, mannitol, or barbiturates, we advocate a plan of initial management individualized for each patient and based on the severity of neurological injury, direct measurements of ICP, CT findings, and serial measurements of regional CBF. J. Neurosurg. / Volume 74/March, 1991
Acute rCBF changes in severe head injury' Patients who do not have a surgical intracranial mass lesion can undergo a Xe/CT CBF study immediately after the initial CT scan. Those who require emergency surgery should have their initial blood flow study as soon as possible after the operation. With early CBF information, management of elevated ICP can be designed not only to treat the ICP, but also to enhance blood flow to regions of the brain in which flow is deficient or to reduce CBF when there is global hyperemia. If cerebral ischemia is t11e principal cause of secondary brain injury, as Miller2~ has suggested, the management of intracranial hypertension based in part on serial measurements of regional CBF may be expected to reduce the incidence of uncontrollable or prolonged inlracranial hypertension and may lead to improved outcome. Acknowledgments The authors gratefully acknowledge Dr. J. Paul Muizelaar for his critical review of the manuscript and Helene Marion for editing it. References 1. Barclay L, Zemcov A, Reichen W, et al: Cerebral blood flow decrements in chronic head injury syndrome. Biol Psychiatry 20:146-157, 1985 2. Bruce DA, Langfitt TW, Miller JD, et al: Regional cerebral blood flow, intracranial pressure, and brain metabolism in comatose patients. J Neurosurg 38:131-144, 1973 3. Busija DW: Unilateral and bilaleral sympathetic effects on cerebral blood flow during normocapnia. Am J Physiol 250:H498-H502, 1986 4. Cold GE, Jensen FT, Malmros R: The effects of PaCO: reduction on regional cerebral blood flow in the acute phase of brain injury'. Acta Anaesthesiol Stand 21: 359-367, 1977 5. Darby JM, Yonas H, Moossy JJ, et al: Effect of stable xenon inhalation on ICP in head injury, in Hoff JT, Betz AL (eds): Intracranial Pressure VII. Berlin: SpringerVerlag, 1989, pp 643-645 6. Enevoldsen EM, Cold G, Jensen FT, et al: Dynamic changes in regional CBF, intraventricular pressure, CSF pH and lactate levels during the acute phase of head injury. J Neurosurg 44:191-214, 1976 7. Enevoldsen EM, Jensen FT: Autoregulation and CO2 responses of cerebral blood flow in patients with acute severe head injury'. J Neurosnrg 48:689-703, 1978 8. Faden AI, Jacobs TP, Smith MT, et al: Comparison of thyrotropin-releasing hormone (TRH), naloxone, and dexamethasone treatments in experimental spinal injury,. Neurology 33:673-678, 1983 9. Fehlings MG, Tator CH, Linden RD: The relationships among the severity of spinal cord injury, motor and somatosensory evoked potentials and spinal cord blood flow. Electroencephalogr Clin Neurophysiol 74:241-259, 1989 10. Gibbs EL, Lennox WG, Gibbs FA: Bilateral internal jugular blood. Comparison of A-V differences, oxygendextrose ratios and respiratory quotients. Am J Psychiatry 102:184-190, 1945 11. Graham DI, Adams JH, Doyle D: Ischemic brain damage in fatal non-missile head injuries. J Neurol Sci 39: 213-234, 1978 J. Neurosurg. / Volume 74~March, 1991
12. Gur D, Good WF, Wolfson SK Jr, et al: In viw) mapping of local cerebral blood flow by xenon-enhanced computed tomography. Science 215:1267-1268, 1982 13. Gur D, Herron JM. Molter BS, et al: Simultaneous mass spectrometry and thermoconductivity measurements of end-tidal xenon concentrations: a comparison. Med Phys 11:209-212, 1984 14. Gur D, Wolfson SK Jr, Yonas H, et al: Progress in cerebrovascular disease: local cerebral blood flow by xenon enhanced CT. Stroke 13:750-758, 1982 15. Harrington TR, Manwaring K, Hodak J: Local basal ganglia and brain stem blood flow in the head injured patient using stable xenon enhanced CT scanning, in Miller JD, Teasdale GM, Rowan JO, et al (eds): Intracranial Pressure Vl. Berlin: Springer-Verlag, 1986, pp 680-686 16. Hellman RS, Collier BD. Tikofsky RS, et al: Comparison of single-photon emission computed tomography with rt2-~%doamphetamineand xenon-enhanced computed tomography for assessing regional cerebral blood flow. J Cereb Blood Flow Metab 6:747-755, 1986 17. Holl K, Nemati N, Kohmura E, et al: Stable-xenon-CT: effects of xenon inhalation on EEG and cardio-respiratory parameters in the human. Acta Neurochir 87:129-133, 1987 18. Jaggi JL, Obrist WD, Gennarelli TA, et al: Relationship of early cerebral blood flow and metabolism to outcome in acute head injur,,-.J Neurosurg 72:176-182, 1990 19. Kearfott KJ, Lu HC, Rottenberg DA, et al: The effects of CT drift on xenon/CT measurement of regional cerebral blood flow. Med Phys 11:686-689, 1984 20. Kendall BE, Moseley IF: Xenon as a contrast agent for computed tomography. Principles and current applications. J Neuroradiol 8:3-12, 1981 21. Lassen NA: The luxury-perfusion syndrome and its possible relation to acute metabolic acidosis localized within the brain. Lancet 2:1113-1115, 1966 22. Latchaw RE, Yonas H, Pentheny SL, et al: Adverse reactions to xenon-enhanced CT cerebral blood flow determination. Radiology 163:251-254, 1987 23. Lobato RD, Sarabia R, Cordobes F, et al: Posltraumatic cerebral hemispheric swelling. Analysis of 55 cases studied with computerized tomography. J Neurosurg 68: 417-423, 1988 24. Mendlelow AD, Teasdale GM, Russell T, et al: Effect of mannitol on cerebral blood flow and cerebral perfusion pressure in human head injury. J Neurosurg 63:43-48, 1985 25. Meyer JS, Hayman LA, Yamamoto M, et al: Local cerebral blood flow measured by CT after stable xenon inhalation. AJR 135:239-251, 1980 26. Miller JD: Head injury and brain ischaemia - - implicalions for therapy. Br J Anaesth 57:120-129, 1985 27. Muizelaar .IP, Marmarou A, DeSalles AAF, et al: Cerebral blood flow and metabolism in severely head-injured children. Part 1: Relationship with GCS score, outcome, ICP, and PVI. J Neurosurg 71:63-71, 1989 28. Nordstr6m CH, Messeter K, SundNirg G, et al: Cerebral blood flow, vasoreactivity, and oxygen consumption during barbiturate therapy in severe traumatic brain lesions. J Neurosurg 68:424-431, 1988 29. Obrist WD, Gennarelli TA, Segawa H, el al: Relation of cerebral blood flow to neurological status and outcome in head-injured patients. J Neurosurg 51:292-300, 1979 30. Obrist WD, Jaggi JL, Harel D, et al: Effect of stable xenon inhalation on human CBF. J Cereb Blood Flow Metab 5: 557-558, 1985 31. Obrist WD, Langfltt TW, Dolinskas CA, et al: Factors 413
D. W. Marion, J. Darby, and H. Yonas
32.
33.
34.
35.
414
relating to intracranial hypertension in acute head inju~', in Ishii S, Nagai H, Brock M (eds): lntracranial Pressure V. Berlin: Springer-Verlag, 1983, pp 491-494 Obrist WD, Langfitt TW, Jaggi Jk, et al: Cerebral blood flow and metabolism in comatose patients with acute head injury. Relationship to intracranial hypertension. J Neurosnrg 61:241-253, 1984 Osterholm JL, Mathews G J: Altered norepinephrine mctabolism following experimental spinal cord injury. Part 2: Protection against traumatic spinal cord hemorrhagic necrosis by norepinephrine synthesis blockade with alpha methyl tyrosine. J Neurosurg 36:395-401, 1972 Overgaard J, Mosdal C, Tweed WA: Cerebral circulation after head injury. Part 3: Does reduced regional cerebral blood flow determine recovery of brain function after blunt head injury? J Neurosurg 55:63-74, 1981 Robertson CS, Narayan RK, Gokaslan ZL, el al: Cerebral
arteriovenous oxygen difference as an estimate of cerebral blood flow in comatose patients. J Nenrosurg 70: 222-230, 1989 36. Rosner M J, Newsome HH, Becket DP: Mechanical brain inju~': the sympathoadrenal response. ,I Neurosurg 61: 76-86, 1984 37. Ward JD, Choi S, Marmarou A, et al: Effect of prophylactic hyperventilation on outcome in patients with severe head injury, in HoffJT, Betz AL (eds): Intracranial Pressure VII. Berlin: Springer-Verlag, 1989, pp 630-633 Manuscript received March 9, 1990. Accepted in final form September 14, 1990. Address reprint requests to: Donald W. Marion, M.D., Department of Neurosurgery, Room 9402, Presbyterian-University Hospital, 230 Lothrop Street, Pittsburgh, Pennsylvania 15213.
Z Neurosurg. / Volume 74/March, 1991
