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Neurocritical Care

, Volume 25, Issue 2, pp 205–214 | Cite as

Controlled Hypercapnia Enhances Cerebral Blood Flow and Brain Tissue Oxygenation After Aneurysmal Subarachnoid Hemorrhage: Results of a Phase 1 Study

  • Thomas WestermaierEmail author
  • Christian Stetter
  • Ekkehard Kunze
  • Nadine Willner
  • Judith Holzmeier
  • Judith Weiland
  • Stefan Koehler
  • Christopher Lotz
  • Christian Kilgenstein
  • Ralf-Ingo Ernestus
  • Norbert Roewer
  • Ralf Michael Muellenbach
Original Article

Abstract

Background

This study investigated if cerebral blood flow (CBF) regulation by changes of the arterial partial pressure of carbon dioxide (PaCO2) can be used therapeutically to increase CBF and improve neurological outcome after subarachnoid hemorrhage (SAH).

Methods

In 12 mechanically ventilated poor-grade SAH-patients, a daily trial intervention was performed between day 4 and 14. During this intervention, PaCO2 was decreased to 30 mmHg and then gradually increased to 40, 50, and 60 mmHg in 15-min intervals by modifications of the respiratory minute volume. CBF and brain tissue oxygen saturation (StiO2) were the primary and secondary endpoints. Intracranial pressure was controlled by an external ventricular drainage.

Results

CBF reproducibly decreased during hyperventilation and increased to a maximum of 141 ± 53 % of baseline during hypercapnia (PaCO2 60 mmHg) on all days between day 4 and 14 after SAH. Similarly, StiO2 increased during hypercapnia. CBF remained elevated within the first hour after resetting ventilation to baseline parameters and no rebound effect was observed within this time-span. PaCO2-reactivities of CBF and StiO2 were highest between 30 and 50 mmHg and slightly decreased at higher levels.

Conclusion

CBF and StiO2 reproducibly increased by controlled hypercapnia of up to 60 mmHg even during the period of the maximum expected vasospasm. The absence of a rebound effect within the first hour after hypercapnia indicates that an improvement of the protocol is possible. The intervention may yield a therapeutic potential to prevent ischemic deficits after aneurysmal SAH.

Keywords

Subarachnoid hemorrhage Vasospasm Delayed cerebral infarction Ischemia DCI Hypercapnia CO2-reactivity 

Notes

Acknowledgments

The study was supported by the Else-Kröner-Fresenius Stiftung (2013_A171).

Compliance with Ethical Standards

Conflict of Interest

None of the authors has a conflict of interest to declare.

References

  1. 1.
    Diringer MN, Kirsch JR, Hanley DF, Traystman RJ. Altered cerebrovascular CO2 reactivity following subarachnoid hemorrhage in cats. J Neurosurg. 1993;78(6):915–21.PubMedCrossRefGoogle Scholar
  2. 2.
    Schmieder K, Jarus-Dziedzic K, Wronski J, Harders A. CO2 reactivity in patients after subarachnoid haemorrhage. Acta Neurochir (Wien). 1997;139(11):1038–41.CrossRefGoogle Scholar
  3. 3.
    Hassler W, Chioffi F. CO2 reactivity of cerebral vasospasm after aneurysmal subarachnoid haemorrhage. Acta Neurochir (Wien). 1989;98(3–4):167–75.CrossRefGoogle Scholar
  4. 4.
    Carrera E, Schmidt JM, Fernandez L, et al. Spontaneous hyperventilation and brain tissue hypoxia in patients with severe brain injury. J Neurol Neurosurg Psychiatry. 2010;81(7):793–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Yamamoto M, Meyer J, Naritomi H, Sakai F, Yamaguchi F, Shaw T. Noninvasive measurement of cerebral vasospasm in patients with subarachnoid hemorrhage. J Neurol Sci. 1979;43(2):301–15.PubMedCrossRefGoogle Scholar
  6. 6.
    Curley G, Kavanagh BP, Laffey JG. Hypocapnia and the injured brain: more harm than benefit. Crit Care Med. 2010;38(5):1348–59.PubMedCrossRefGoogle Scholar
  7. 7.
    Carrera E, Kurtz P, Badjatia N, et al. Cerebrovascular carbon dioxide reactivity and delayed cerebral ischemia after subarachnoid hemorrhage. Arch Neurol. 2010;67(4):434–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Westermaier T, Stetter C, Kunze E, et al. Controlled transient hypercapnia: a novel approach for the treatment of delayed cerebral ischemia after subarachnoid hemorrhage? J Neurosurg. 2014;121(5):1056–62.PubMedCrossRefGoogle Scholar
  9. 9.
    von Kummer R, Holle R, Gizyska U, et al. Interobserver agreement in assessing early CT signs of middle cerebral artery infarction. AJNR Am J Neuroradiol. 1996;17(9):1743–8.Google Scholar
  10. 10.
    Cross DT, Tirschwell DL, Clark MA, et al. Mortality rates after subarachnoid hemorrhage: variations according to hospital case volume in 18 states. J Neurosurg. 2003;99(5):810–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Rivero-Arias O, Gray A, Wolstenholme J. Burden of disease and costs of aneurysmal subarachnoid haemorrhage (aSAH) in the United Kingdom. Cost Eff Resour Alloc. 2010;8(6):6.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Frontera JA, Fernandez A, Schmidt JM, et al. Defining vasospasm after subarachnoid hemorrhage: what is the most clinically relevant definition? Stroke. 2009;40(6):1963–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Petridis AK, Doukas A, Kienke S, et al. The effect of lung-protective permissive hypercapnia in intracerebral pressure in patients with subarachnoid haemorrhage and ARDS: a retrospective study. Acta Neurochir (Wien). 2010;152(12):2143–5. doi: 10.1007/s00701-010-0761-z.CrossRefGoogle Scholar
  14. 14.
    Claassen J, Carhuapoma JR, Kreiter KT, Du EY, Connolly ES, Mayer SA. Global cerebral edema after subarachnoid hemorrhage: frequency, predictors, and impact on outcome. Stroke. 2002;33(5):1225–32.PubMedCrossRefGoogle Scholar
  15. 15.
    Stengl M, Ledvinova L, Chvojka J, et al. Effects of clinically relevant acute hypercapnic and metabolic acidosis on the cardiovascular system: an experimental porcine study. Crit Care. 2013;17(6):R303.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Chuang IC, Dong HP, Yang RC, et al. Effect of carbon dioxide on pulmonary vascular tone at various pulmonary arterial pressure levels induced by endothelin-1. Lung. 2010;188(3):199–207.PubMedCrossRefGoogle Scholar
  17. 17.
    Karlsson T, Stjernstrom EL, Stjernstrom H, Norlen K, Wiklund L. Central and regional blood flow during hyperventilation: an experimental study in the pig. Acta Anaesthesiol Scand. 1994;38(2):180–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Macdonald RL. Delayed neurological deterioration after subarachnoid haemorrhage. Nat Rev Neurol. 2014;10(1):44–58.PubMedCrossRefGoogle Scholar
  19. 19.
    Diringer MN, Kirsch JR, Traystman RJ. Reduced cerebral blood flow but intact reactivity to hypercarbia and hypoxia following subarachnoid hemorrhage in rabbits. J Cereb Blood Flow Metab. 1994;14(1):59–63.PubMedCrossRefGoogle Scholar
  20. 20.
    Ma XD, Hauerberg J, Pedersen DB, Juhler M. Effects of morphine on cerebral blood flow autoregulation CO2-reactivity in experimental subarachnoid hemorrhage. J Neurosurg Anesthesiol. 1999;11(4):264–72.PubMedCrossRefGoogle Scholar
  21. 21.
    Dernbach PD, Little JR, Jones SC, Ebrahim ZY. Altered cerebral autoregulation and CO2 reactivity after aneurysmal subarachnoid hemorrhage. Neurosurgery. 1988;22(5):822–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Poulin MJ, Liang PJ, Robbins PA. Fast and slow components of cerebral blood flow response to step decreases in end-tidal PCO2 in humans. J Appl Physiol. 1998;85(2):388–97.PubMedGoogle Scholar
  23. 23.
    Komori M, Takada K, Tomizawa Y, Nishiyama K, Kawamata M, Ozaki M. Permissive range of hypercapnia for improved peripheral microcirculation and cardiac output in rabbits. Crit Care Med. 2007;35(9):2171–5.PubMedCrossRefGoogle Scholar
  24. 24.
    Hickling KG, Joyce C. Permissive hypercapnia in ARDS and its effect on tissue oxygenation. Acta Anaesthesiol Scand Suppl. 1995;107:201–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Rabinstein AA, Friedman JA, Weigand SD, et al. Predictors of cerebral infarction in aneurysmal subarachnoid hemorrhage. Stroke. 2004;35(8):1862–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Westermaier T, Pham M, Stetter C, et al. Value of transcranial Doppler, perfusion-CT and neurological evaluation to forecast secondary ischemia after aneurysmal SAH. Neurocrit Care. 2014;20(3):406–12.PubMedCrossRefGoogle Scholar
  27. 27.
    Agnoli A. Adaptation of CBF during induced chronic normooxic respiratory acidosis. Scand J Clin Lab Investig Suppl. 1968;102:VIII.Google Scholar
  28. 28.
    Fencl V, Vale JR, Broch JA. Respiration and cerebral blood flow in metabolic acidosis and alkalosis in humans. J Appl Physiol. 1969;27(1):67–76.PubMedGoogle Scholar
  29. 29.
    Skinhoj E. CBF adaption in man to chronic hypo- and hypercapnia and its relation to CSF pH. Scand J Clin Lab Investig Suppl. 1968;102:8.Google Scholar
  30. 30.
    Jones TH, Morawetz RB, Crowell RM, et al. Thresholds of focal cerebral ischemia in awake monkeys. J Neurosurg. 1981;54(6):773–82.PubMedCrossRefGoogle Scholar
  31. 31.
    Raichle ME, Posner JB, Plum F. Cerebral blood flow during and after hyperventilation. Arch Neurol. 1970;23(5):394–403.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Thomas Westermaier
    • 1
    Email author
  • Christian Stetter
    • 1
  • Ekkehard Kunze
    • 1
  • Nadine Willner
    • 1
  • Judith Holzmeier
    • 1
  • Judith Weiland
    • 1
  • Stefan Koehler
    • 1
  • Christopher Lotz
    • 2
  • Christian Kilgenstein
    • 2
  • Ralf-Ingo Ernestus
    • 1
  • Norbert Roewer
    • 2
  • Ralf Michael Muellenbach
    • 2
  1. 1.Department of NeurosurgeryUniversity Hospital WuerzburgWürzburgGermany
  2. 2.Department of Anesthesia and Critical CareUniversity Hospital WuerzburgWürzburgGermany

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