Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial

J. Paul MuizelaarDivision of Neurological Surgery, Medical College of Virginia, Richmond, Virginia

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Anthony MarmarouDivision of Neurological Surgery, Medical College of Virginia, Richmond, Virginia

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John D. WardDivision of Neurological Surgery, Medical College of Virginia, Richmond, Virginia

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Hermes A. KontosDivision of Neurological Surgery, Medical College of Virginia, Richmond, Virginia

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Sung C. ChoiDivision of Neurological Surgery, Medical College of Virginia, Richmond, Virginia

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Donald P. BeckerDivision of Neurological Surgery, Medical College of Virginia, Richmond, Virginia

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Hans GruemerDivision of Neurological Surgery, Medical College of Virginia, Richmond, Virginia

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Harold F. YoungDivision of Neurological Surgery, Medical College of Virginia, Richmond, Virginia

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✓ There is still controversy over whether or not patients should be hyperventilated after traumatic brain injury, and a randomized trial has never been conducted. The theoretical advantages of hyperventilation are cerebral vasoconstriction for intracranial pressure (ICP) control and reversal of brain and cerebrospinal fluid (CSF) acidosis. Possible disadvantages include cerebral vasoconstriction to such an extent that cerebral ischemia ensues, and only a short-lived effect on CSF pH with a loss of HCO3 buffer from CSF. The latter disadvantage might be overcome by the addition of the buffer tromethamine (THAM), which has shown some promise in experimental and clinical use. Accordingly, a trial was performed with patients randomly assigned to receive normal ventilation (PaCO2 35 ± 2 mm Hg (mean ± standard deviation): control group), hyperventilation (PaCO2 25 ± 2 mm Hg: HV group), or hyperventilation plus THAM (PaCO2 25 ± 2 mm Hg: HV + THAM group). Stratification into subgroups of patients with motor scores of 1–3 and 4–5 took place. Outcome was assessed according to the Glasgow Outcome Scale at 3, 6, and 12 months. There were 41 patients in the control group, 36 in the HV group, and 36 in the HV + THAM group. The mean Glasgow Coma Scale score for each group was 5.7 ± 1.7, 5.6 ± 1.7, and 5.9 ± 1.7, respectively; this score and other indicators of severity of injury were not significantly different. A 100% follow-up review was obtained. At 3 and 6 months after injury the number of patients with a favorable outcome (good or moderately disabled) was significantly (p < 0.05) lower in the hyperventilated patients than in the control and HV + THAM groups. This occurred only in patients with a motor score of 4–5. At 12 months posttrauma this difference was not significant (p = 0.13). Biochemical data indicated that hyperventilation could not sustain alkalinization in the CSF, although THAM could. Accordingly, cerebral blood flow (CBF) was lower in the HV + THAM group than in the control and HV groups, but neither CBF nor arteriovenous difference of oxygen data indicated the occurrence of cerebral ischemia in any of the three groups. Although mean ICP could be kept well below 25 mm Hg in all three groups, the course of ICP was most stable in the HV + THAM group. It is concluded that prophylactic hyperventilation is deleterious in head-injured patients with motor scores of 4–5. When sustained hyperventilation becomes necessary for ICP control, its deleterious effect may be overcome by the addition of THAM.

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  • 1.

    Akioka T, , Ota K, & Matsumoto A, et al: The effect of THAM on acute intracranial hypertension. An experimental and clinical study, in Beks JWF, , Bosch DA, & Brock M (eds): Intracranial Pressure III. Berlin: Springer-Verlag, 1976, pp 219223 Akioka T, Ota K, Matsumoto A, et al: The effect of THAM on acute intracranial hypertension. An experimental and clinical study, in Beks JWF, Bosch DA, Brock M (eds): Intracranial Pressure III. Berlin: Springer-Verlag, 1976, pp 219–223

    • Search Google Scholar
    • Export Citation
  • 2.

    Becker DP, & Gardner S: Intensive management of head injury, in Wilkins RH, & Rengachary SS (eds): Neurosurgery. New York: McGraw-Hill, 1985, Vol 2, pp 15931599 Becker DP, Gardner S: Intensive management of head injury, in Wilkins RH, Rengachary SS (eds): Neurosurgery. New York: McGraw-Hill, 1985, Vol 2, pp 1593–1599

    • Search Google Scholar
    • Export Citation
  • 3.

    Bruce D: Clinical care of the severely head injured child, in Shapiro K (ed): Pediatric Head Trauma. Mt Kisco, NY: Futura, 1983, pp 3140 Bruce D: Clinical care of the severely head injured child, in Shapiro K (ed): Pediatric Head Trauma. Mt Kisco, NY: Futura, 1983, pp 31–40

    • Search Google Scholar
    • Export Citation
  • 4.

    Choi SC, , Muizelaar JP, & Barnes TY, et al: Prediction tree for severely head-injured patients. J Neurosurg 75:251255, 1991 Choi SC, Muizelaar JP, Barnes TY, et al: Prediction tree for severely head-injured patients. J Neurosurg 75:251–255, 1991

    • Search Google Scholar
    • Export Citation
  • 5.

    Christensen MS: Prolonged artificial hyperventilation in cerebral apoplexy. Acta Anaesthesiol Scand Suppl 62:724, 1976 Christensen MS: Prolonged artificial hyperventilation in cerebral apoplexy. Acta Anaesthesiol Scand Suppl 62:7–24, 1976

    • Search Google Scholar
    • Export Citation
  • 6.

    Cold G, , Enevoldsen E, & Malmros R: Ventricular fluid lactate, pyruvate, bicarbonate, and pH in unconscious brain-injured patients subjected to controlled ventilation. Acta Neurol Scand 52:187195, 1975 Cold G, Enevoldsen E, Malmros R: Ventricular fluid lactate, pyruvate, bicarbonate, and pH in unconscious brain-injured patients subjected to controlled ventilation. Acta Neurol Scand 52:187–195, 1975

    • Search Google Scholar
    • Export Citation
  • 7.

    DeSalles AAF, , Kontos HA, & Becker DP, et al: Prognostic significance of ventricular CSF lactic acidosis in severe head injury. J Neurosurg 65:615624, 1986 DeSalles AAF, Kontos HA, Becker DP, et al: Prognostic significance of ventricular CSF lactic acidosis in severe head injury. J Neurosurg 65:615–624, 1986

    • Search Google Scholar
    • Export Citation
  • 8.

    DeSalles AAF, , Muizelaar JP, & Young HF: Hyperglycemia, cerebrospinal fluid lactic acidosis and cerebral blood flow in severely head-injured patients. Neurosurgery 21:4550, 1987 DeSalles AAF, Muizelaar JP, Young HF: Hyperglycemia, cerebrospinal fluid lactic acidosis and cerebral blood flow in severely head-injured patients. Neurosurgery 21:45–50, 1987

    • Search Google Scholar
    • Export Citation
  • 9.

    Gaab M, , Knoblich OE, & Spohr A, et al: Effect of THAM on ICP, EEG, and tissue edema parameters in experimental and clinical brain edema, in Shulman K, , Marmarou A, & Miller JD, et al (eds): Intracranial Pressure IV. Berlin: Springer-Verlag, 1980, pp 664668 Gaab M, Knoblich OE, Spohr A, et al: Effect of THAM on ICP, EEG, and tissue edema parameters in experimental and clinical brain edema, in Shulman K, Marmarou A, Miller JD, et al (eds): Intracranial Pressure IV. Berlin: Springer-Verlag, 1980, pp 664–668

    • Search Google Scholar
    • Export Citation
  • 10.

    Gordon E: Non-operative treatment of acute head injuries: the Karolinska experience. Int Anesthesiol Clin 17:181199, 1979 Gordon E: Non-operative treatment of acute head injuries: the Karolinska experience. Int Anesthesiol Clin 17:181–199, 1979

    • Search Google Scholar
    • Export Citation
  • 11.

    Gordon E, & Rossanda M: Further studies on cerebrospinal fluid acid-base status in patients with brain lesions. Acta Anaesthesiol Scand 14:97109, 1970 Gordon E, Rossanda M: Further studies on cerebrospinal fluid acid-base status in patients with brain lesions. Acta Anaesthesiol Scand 14:97–109, 1970

    • Search Google Scholar
    • Export Citation
  • 12.

    Harrell FE, , Lee KL, & Califf RM, et al: Regression modelling strategies for improved prognostic prediction. Stat Med 3:143152, 1984 Harrell FE, Lee KL, Califf RM, et al: Regression modelling strategies for improved prognostic prediction. Stat Med 3:143–152, 1984

    • Search Google Scholar
    • Export Citation
  • 13.

    Hinds CJ: Intensive Care. A Concise Textbook. London: Bailliere Tindall, 1987, p 284 Hinds CJ: Intensive Care. A Concise Textbook. London: Bailliere Tindall, 1987, p 284

    • Search Google Scholar
    • Export Citation
  • 14.

    Jennett B, & Bond M: Assessment of outcome after severe brain damage. A practical scale. Lancet 1:480484, 1975 Jennett B, Bond M: Assessment of outcome after severe brain damage. A practical scale. Lancet 1:480–484, 1975

    • Search Google Scholar
    • Export Citation
  • 15.

    Jennett B, & Teasdale G: Management of Head Injuries. Philadelphia: FA Davis, 1981, p 255 Jennett B, Teasdale G: Management of Head Injuries. Philadelphia: FA Davis, 1981, p 255

    • Search Google Scholar
    • Export Citation
  • 16.

    Levasseur JE, , Wei EP, & Kontos HA, et al: Responses of pial arterioles after prolonged hypercapnia and hypoxia in the awake rabbit. J Appl Physiol 46:8995, 1979 Levasseur JE, Wei EP, Kontos HA, et al: Responses of pial arterioles after prolonged hypercapnia and hypoxia in the awake rabbit. J Appl Physiol 46:89–95, 1979

    • Search Google Scholar
    • Export Citation
  • 17.

    Marmarou A, , Anderson R, & Ward JD, et al: The Traumatic Coma Data Bank: monitoring of ICP, in Hoff JT, & Betz AL (eds): Intracranial Pressure VII. Berlin: Springer-Verlag, 1989, pp 549551 Marmarou A, Anderson R, Ward JD, et al: The Traumatic Coma Data Bank: monitoring of ICP, in Hoff JT, Betz AL (eds): Intracranial Pressure VII. Berlin: Springer-Verlag, 1989, pp 549–551

    • Search Google Scholar
    • Export Citation
  • 18.

    Marmarou A, , Shulman K, & Rosende RM: A nonlinear analysis of the cerebrospinal fluid system and intracranial pressure dynamics. J Neurosurg 48:332344, 1978 Marmarou A, Shulman K, Rosende RM: A nonlinear analysis of the cerebrospinal fluid system and intracranial pressure dynamics. J Neurosurg 48:332–344, 1978

    • Search Google Scholar
    • Export Citation
  • 19.

    Marshall LF, & Marshall SB: Medical management of intracranial pressure, in Cooper PR (ed): Head Injury, ed 2. Baltimore: Williams & Wilkins, 1987, pp 177196 Marshall LF, Marshall SB: Medical management of intracranial pressure, in Cooper PR (ed): Head Injury, ed 2. Baltimore: Williams & Wilkins, 1987, pp 177–196

    • Search Google Scholar
    • Export Citation
  • 20.

    Maset AL, , Marmarou A, & Ward JD, et al: Pressure-volume index in head injury. J Neurosurg 67:832840, 1987 Maset AL, Marmarou A, Ward JD, et al: Pressure-volume index in head injury. J Neurosurg 67:832–840, 1987

    • Search Google Scholar
    • Export Citation
  • 21.

    Muizelaar JP, & Obrist WD: Cerebral blood flow and blood metabolism with brain injury, in Becker DP, & Povlishock JT (eds): Central Nervous System Trauma: Status Report. Washington, DC: National Institutes of Health, 1985, pp 123137 Muizelaar JP, Obrist WD: Cerebral blood flow and blood metabolism with brain injury, in Becker DP, Povlishock JT (eds): Central Nervous System Trauma: Status Report. Washington, DC: National Institutes of Health, 1985, pp 123–137

    • Search Google Scholar
    • Export Citation
  • 22.

    Muizelaar JP, , van der Poel HG, & Li ZC, et al: Pial arteriolar vessel diameter and CO2 reactivity during prolonged hyperventilation in the rabbit. J Neurosurg 69:923927, 1988 Muizelaar JP, van der Poel HG, Li ZC, et al: Pial arteriolar vessel diameter and CO2 reactivity during prolonged hyperventilation in the rabbit. J Neurosurg 69:923–927, 1988

    • Search Google Scholar
    • Export Citation
  • 23.

    Obrist WD, , Langfitt TW, & Jaggi JL, et al: Cerebral blood flow and metabolism in comatose patients with acute head injury. Relationship to intracranial hypertension. J Neurosurg 61:241253, 1984 Obrist WD, Langfitt TW, Jaggi JL, et al: Cerebral blood flow and metabolism in comatose patients with acute head injury. Relationship to intracranial hypertension. J Neurosurg 61:241–253, 1984

    • Search Google Scholar
    • Export Citation
  • 24.

    Rosner MJ, & Becker DP: Experimental brain injury: successful therapy with the weak base, tromethamine. With an overview of CNS acidosis. J Neurosurg 60:961971, 1984 Rosner MJ, Becker DP: Experimental brain injury: successful therapy with the weak base, tromethamine. With an overview of CNS acidosis. J Neurosurg 60:961–971, 1984

    • Search Google Scholar
    • Export Citation
  • 25.

    Rossanda M, & Selenativ VL: Role of automatic ventilation in treatment of severe head injuries. J Neurosurg Sci 17:265270, 1973 Rossanda M, Selenativ VL: Role of automatic ventilation in treatment of severe head injuries. J Neurosurg Sci 17:265–270, 1973

    • Search Google Scholar
    • Export Citation
  • 26.

    Saul TG: Acute head injuries in adults, in Rakel RE (ed): Conn's Current Therapy. Philadelphia: WB Saunders, 1987, pp 776781 Saul TG: Acute head injuries in adults, in Rakel RE (ed): Conn's Current Therapy. Philadelphia: WB Saunders, 1987, pp 776–781

    • Search Google Scholar
    • Export Citation
  • 27.

    Schindler U, , Betz EE, & Pfeiffer H, et al: Cortical metabolites during constant high CO2 concentrations and changes during pH variation. Eur Neurol 6:8387, 1971 Schindler U, Betz EE, Pfeiffer H, et al: Cortical metabolites during constant high CO2 concentrations and changes during pH variation. Eur Neurol 6:83–87, 1971

    • Search Google Scholar
    • Export Citation
  • 28.

    Schwartz D, & Lellouch J: Explanatory and pragmatic attitudes in therapeutic trials. J Chronic Dis 20:637648, 1967 Schwartz D, Lellouch J: Explanatory and pragmatic attitudes in therapeutic trials. J Chronic Dis 20:637–648, 1967

    • Search Google Scholar
    • Export Citation
  • 29.

    Teasdale G, & Jennett B: Assessment of coma and impaired consciousness. A practical scale. Lancet 2:8184, 1974 Teasdale G, Jennett B: Assessment of coma and impaired consciousness. A practical scale. Lancet 2:81–84, 1974

    • Search Google Scholar
    • Export Citation
  • 30.

    Toutant SM, , Klauber MR, & Marshall LF, et al: Absent or compressed basal cisterns on first CT scan: ominous predictors of outcome in severe head injury. J Neurosurg 61:691694, 1984 Toutant SM, Klauber MR, Marshall LF, et al: Absent or compressed basal cisterns on first CT scan: ominous predictors of outcome in severe head injury. J Neurosurg 61:691–694, 1984

    • Search Google Scholar
    • Export Citation
  • 31.

    Yoshida K, & Marmarou A: Effects of tromethamine and hyperventilation on brain injury in the cat. J Neurosurg 74:8796, 1991 Yoshida K, Marmarou A: Effects of tromethamine and hyperventilation on brain injury in the cat. J Neurosurg 74:87–96, 1991

    • Search Google Scholar
    • Export Citation

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