Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Clinical relevance of cerebral autoregulation following subarachnoid haemorrhage

Nature Reviews Neurology volume 9, pages 152–163 (2013)Cite this article

Subjects

Abstract

Subarachnoid haemorrhage (SAH) is a form of stroke that is associated with substantial morbidity, often as a result of cerebral ischaemia that occurs in the following days. These delayed deficits in blood flow have been traditionally attributed to cerebral vasospasm (the narrowing of large arteries), which can lead to cerebral infarction and poor neurological outcome. Data from recent studies, however, show that treatment of vasospasm in patients with SAH, using targeted medication, does not translate to better neurological outcomes, and argue against vasospasm being the sole cause of the delayed ischaemic complications. Cerebral autoregulation—a mechanism that maintains stability of cerebral blood flow in response to changes in cerebral perfusion pressure—has been reported to fail after SAH, often before vasospasm becomes apparent. Failure of autoregulation, therefore, has been implicated in development of delayed cerebral ischaemia. In this Review, we summarize current knowledge about the clinical effect of disturbed cerebral autoregulation following aneurysmal SAH, with emphasis on development of delayed cerebral ischaemia and clinical outcome, and provide a critical assessment of studies of cerebral autoregulation in SAH with respect to the method of blood-flow measurement. Better understanding of cerebral autoregulation following SAH could reveal mechanisms of blood-flow regulation that could be therapeutically targeted to improve patient outcome.

Key Points

  • Failure of cerebral autoregulation following subarachnoid haemorrhage (SAH) is common, with the severity of dysautoregulation directly linked to the severity of the initial ictus

  • Patients with cerebral dysautoregulation are at high risk of developing delayed cerebral ischaemia, particularly when concomitant cerebral vasospasm is present

  • In some studies, impaired autoregulation has been associated with poor outcome, but this relationship must be further investigated in a large cohort of patients with SAH

  • The exact temporal profile of cerebral autoregulatory failure and its relationship with cerebral vasospasm are poorly defined

  • Randomized controlled trials in SAH that used cerebral autoregulation indices as an end point suggest that the duration of dysautoregulation has clinical relevance

  • A need exists for prospective studies in SAH that use clearly defined, widely accepted, and comparable methodologies to target and monitor cerebral autoregulatory parameters

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Dissociation between cerebral vasospasm and perfusion deficits.
Figure 2: Cerebral autoregulation.
Figure 3: Static rate of autoregulation.
Figure 4: Dynamic autoregulation with blood pressure stimulus.
Figure 5: Dynamic autoregulation based on spontaneous fluctuations of blood pressure.
Figure 6: Pathways of pathophysiology of cerebral autoregulation following early brain injury and SAH.

Similar content being viewed by others

References

  1. Hop, J. W., Rinkel, G. J., Algra, A. & van Gijn, J. Case-fatality rates and functional outcome after subarachnoid hemorrhage: a systematic review. Stroke 28, 660–664 (1997).

    Article  CAS  PubMed  Google Scholar 

  2. Ecker, A. & Riemenschneider, P. A. Arteriographic demonstration of spasm of the intracranial arteries, with special reference to saccular arterial aneurysms. J. Neurosurg. 8, 660–667 (1951).

    Article  CAS  PubMed  Google Scholar 

  3. Harders, A. G. & Gilsbach, J. M. Time course of blood velocity changes related to vasospasm in the circle of Willis measured by transcranial Doppler ultrasound. J. Neurosurg. 66, 718–728 (1987).

    Article  CAS  PubMed  Google Scholar 

  4. Etminan, N., Vergouwen, M. D., Ilodigwe, D. & Macdonald, R. L. Effect of pharmaceutical treatment on vasospasm, delayed cerebral ischemia, and clinical outcome in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. J. Cereb. Blood Flow Metab. 31, 1443–1451 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Macdonald, R. L. Clazosentan: an endothelin receptor antagonist for treatment of vasospasm after subarachnoid hemorrhage. Expert Opin. Investig. Drugs 17, 1761–1767 (2008).

    Article  CAS  PubMed  Google Scholar 

  6. Macdonald, R. L. et al. Clazosentan, an endothelin receptor antagonist, in patients with aneurysmal subarachnoid haemorrhage undergoing surgical clipping: a randomised, double-blind, placebo-controlled phase 3 trial (CONSCIOUS-2). Lancet Neurol. 10, 618–625 (2011).

    Article  CAS  PubMed  Google Scholar 

  7. Petruk, K. C. et al. Nimodipine treatment in poor-grade aneurysm patients. Results of a multicenter double-blind placebo-controlled trial. J. Neurosurg. 68, 505–517 (1988).

    Article  CAS  PubMed  Google Scholar 

  8. Pickard, J. D. et al. Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial. BMJ 298, 636–642 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Minhas, P. S. et al. Positron emission tomographic cerebral perfusion disturbances and transcranial Doppler findings among patients with neurological deterioration after subarachnoid hemorrhage. Neurosurgery 52, 1017–1022 (2003).

    PubMed  Google Scholar 

  10. Dhar, R. et al. Relationship between angiographic vasospasm and regional hypoperfusion in aneurysmal subarachnoid hemorrhage. Stroke 43, 1788–1794 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Macdonald, R. L., Pluta, R. M. & Zhang, J. H. Cerebral vasospasm after subarachnoid hemorrhage: the emerging revolution. Nat. Clin. Pract. Neurol. 3, 256–263 (2007).

    Article  CAS  PubMed  Google Scholar 

  12. Rasmussen, G., Hauerberg, J., Waldemar, G., Gjerris, F. & Juhler, M. Cerebral blood flow autoregulation in experimental subarachnoid haemorrhage in rat. Acta Neurochir. (Wien) 119, 128–133 (1992).

    Article  CAS  Google Scholar 

  13. Harper, A. M., Deshmukh, V. D., Sengupta, D., Rowan, J. O. & Jennett, W. B. The effect of experimental spasm on the CO2 response of cerebral bloodflow in primates. Neuroradiology 3, 134–136 (1972).

    Article  CAS  PubMed  Google Scholar 

  14. Harper, A. M. & Glass, H. I. Effect of alterations in the arterial carbon dioxide tension on the blood flow through the cerebral cortex at normal and low arterial blood pressures. J. Neurol. Neurosurg. Psychiatry 28, 449–452 (1965).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Fitch, W., Ferguson, G. G., Sengupta, D., Garibi, J. & Harper, A. M. Autoregulation of cerebral blood flow during controlled hypotension in baboons. J. Neurol. Neurosurg. Psychiatry 39, 1014–1022 (1976).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Eide, P. K. et al. Pressure-derived versus pressure wave amplitude-derived indices of cerebrovascular pressure reactivity in relation to early clinical state and 12-month outcome following aneurysmal subarachnoid hemorrhage. J. Neurosurg. 116, 961–971 (2012).

    Article  PubMed  Google Scholar 

  17. Lam, J. M., Smielewski, P., Czosnyka, M., Pickard, J. D. & Kirkpatrick, P. J. Predicting delayed ischemic deficits after aneurysmal subarachnoid hemorrhage using a transient hyperemic response test of cerebral autoregulation. Neurosurgery 47, 819–825 (2000).

    Article  CAS  PubMed  Google Scholar 

  18. Jaeger, M., Soehle, M., Schuhmann, M. U. & Meixensberger, J. Clinical significance of impaired cerebrovascular autoregulation after severe aneurysmal subarachnoid hemorrhage. Stroke 43, 2097–2101 (2012).

    Article  PubMed  Google Scholar 

  19. Jaeger, M., Schuhmann, M. U., Soehle, M., Nagel, C. & Meixensberger, J. Continuous monitoring of cerebrovascular autoregulation after subarachnoid hemorrhage by brain tissue oxygen pressure reactivity and its relation to delayed cerebral infarction. Stroke 38, 981–986 (2007).

    Article  PubMed  Google Scholar 

  20. Lassen, N. A. Cerebral blood flow and oxygen consumption in man. Physiol. Rev. 39, 183–238 (1959).

    Article  CAS  PubMed  Google Scholar 

  21. Fog, M. The relationship between the blood pressure and the tonic regulation of the pial arteries. J. Neurol. Psychiatry 1, 187–197 (1938).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kontos, H. A. et al. Responses of cerebral arteries and arterioles to acute hypotension and hypertension. Am. J. Physiol. 234, H371–H383 (1978).

    CAS  PubMed  Google Scholar 

  23. Symon, L., Held, K. & Dorsch, N. W. A study of regional autoregulation in the cerebral circulation to increased perfusion pressure in normocapnia and hypercapnia. Stroke 4, 139–147 (1973).

    Article  CAS  PubMed  Google Scholar 

  24. Andresen, J., Shafi, N. I. & Bryan, R. M. Jr. Endothelial influences on cerebrovascular tone. J. Appl. Physiol. 100, 318–327 (2006).

    Article  CAS  PubMed  Google Scholar 

  25. Bayliss, W. M. On the local reactions of the arterial wall to changes of internal pressure. J. Physiol. 28, 220–231 (1902).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kontos, H. A. et al. Role of tissue hypoxia in local regulation of cerebral microcirculation. Am. J. Physiol. 234, H582–H591 (1978).

    CAS  PubMed  Google Scholar 

  27. Paulson, O. B., Strandgaard, S. & Edvinsson, L. Cerebral autoregulation. Cerebrovasc. Brain Metab. Rev. 2, 161–192 (1990).

    CAS  PubMed  Google Scholar 

  28. Symon, L., Held, K. & Dorsch, N. W. On the myogenic nature of the autoregulatory mechanism in the cerebral circulation. Eur. Neurol. 6, 11–18 (1971).

    Article  PubMed  Google Scholar 

  29. Wang, Q., Pelligrino, D. A., Baughman, V. L., Koenig, H. M. & Albrecht, R. F. The role of neuronal nitric oxide synthase in regulation of cerebral blood flow in normocapnia and hypercapnia in rats. J. Cereb. Blood Flow Metab. 15, 774–778 (1995).

    Article  CAS  PubMed  Google Scholar 

  30. Baron, J. C. et al. Local interrelationships of cerebral oxygen consumption and glucose utilization in normal subjects and in ischemic stroke patients: a positron tomography study. J. Cereb. Blood Flow Metab. 4, 140–149 (1984).

    Article  CAS  PubMed  Google Scholar 

  31. Lundar, T. et al. Dissociation between cerebral autoregulation and carbon dioxide reactivity during nonpulsatile cardiopulmonary bypass. Ann. Thorac. Surg. 40, 582–587 (1985).

    Article  CAS  PubMed  Google Scholar 

  32. Gordon, E. & Bergvall, U. The effect of controlled hyperventilation on cerebral blood flow and oxygen uptake in patients with brain lesions. Acta Anaesthesiol. Scand. 17, 63–69 (1973).

    Article  CAS  PubMed  Google Scholar 

  33. Kontos, H. A., Raper, A. J. & Patterson, J. L. Jr. Mechanisms of action of CO2 on pial precapillary vessels. Eur. Neurol. 6, 114–118 (1971).

    Article  CAS  PubMed  Google Scholar 

  34. Panerai, R. B. Cerebral autoregulation: from models to clinical applications. Cardiovasc. Eng. 8, 42–59 (2008).

    Article  PubMed  Google Scholar 

  35. van Beek, A. H., Claassen, J. A., Rikkert, M. G. & Jansen, R. W. Cerebral autoregulation: an overview of current concepts and methodology with special focus on the elderly. J. Cereb. Blood Flow Metab. 28, 1071–1085 (2008).

    Article  PubMed  Google Scholar 

  36. Giller, C. A. A bedside test for cerebral autoregulation using transcranial Doppler ultrasound. Acta Neurochir. (Wien) 108, 7–14 (1991).

    Article  CAS  Google Scholar 

  37. Aaslid, R., Lindegaard, K. F., Sorteberg, W. & Nornes, H. Cerebral autoregulation dynamics in humans. Stroke 20, 45–52 (1989).

    Article  CAS  PubMed  Google Scholar 

  38. Czosnyka, M. et al. Continuous assessment of the cerebral vasomotor reactivity in head injury. Neurosurgery 41, 11–17 (1997).

    Article  CAS  PubMed  Google Scholar 

  39. Czosnyka, M., Smielewski, P., Kirkpatrick, P., Menon, D. K. & Pickard, J. D. Monitoring of cerebral autoregulation in head-injured patients. Stroke 27, 1829–1834 (1996).

    Article  CAS  PubMed  Google Scholar 

  40. Zhang, R., Zuckerman, J. H., Giller, C. A. & Levine, B. D. Transfer function analysis of dynamic cerebral autoregulation in humans. Am. J. Physiol. 274, H233–H241 (1998).

    CAS  PubMed  Google Scholar 

  41. Larsen, F. S., Olsen, K. S., Hansen, B. A., Paulson, O. B. & Knudsen, G. M. Transcranial Doppler is valid for determination of the lower limit of cerebral blood flow autoregulation. Stroke 25, 1985–1988 (1994).

    Article  CAS  PubMed  Google Scholar 

  42. Newell, D. W., Aaslid, R., Lam, A., Mayberg, T. S. & Winn, H. R. Comparison of flow and velocity during dynamic autoregulation testing in humans. Stroke 25, 793–797 (1994).

    Article  CAS  PubMed  Google Scholar 

  43. Lang, E. W., Mehdorn, H. M., Dorsch, N. W. & Czosnyka, M. Continuous monitoring of cerebrovascular autoregulation: a validation study. J. Neurol. Neurosurg. Psychiatry 72, 583–586 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Steiner, L. A. et al. Assessment of cerebrovascular autoregulation in head-injured patients: a validation study. Stroke 34, 2404–2409 (2003).

    Article  PubMed  Google Scholar 

  45. Al-Rawi, P. G. & Kirkpatrick, P. J. Tissue oxygen index: thresholds for cerebral ischemia using near-infrared spectroscopy. Stroke 37, 2720–2725 (2006).

    Article  PubMed  Google Scholar 

  46. Al-Rawi, P. G., Smielewski, P. & Kirkpatrick, P. J. Evaluation of a near-infrared spectrometer (NIRO 300) for the detection of intracranial oxygenation changes in the adult head. Stroke 32, 2492–2500 (2001).

    Article  CAS  PubMed  Google Scholar 

  47. Kirkpatrick, P. J., Lam, J., Al-Rawi, P., Smielewski, P. & Czosnyka, M. Defining thresholds for critical ischemia by using near-infrared spectroscopy in the adult brain. J. Neurosurg. 89, 389–394 (1998).

    Article  CAS  PubMed  Google Scholar 

  48. Budohoski, K. P. et al. Impairment of cerebral autoregulation predicts delayed cerebral ischemia after subarachnoid hemorrhage: a prospective observational study. Stroke 43, 3230–3237 (2012).

    Article  PubMed  Google Scholar 

  49. Lam, J. M. et al. Internal and external carotid contributions to near-infrared spectroscopy during carotid endarterectomy. Stroke 28, 906–911 (1997).

    Article  CAS  PubMed  Google Scholar 

  50. Jobsis, F. F. Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. Science 198, 1264–1267 (1977).

    Article  CAS  PubMed  Google Scholar 

  51. Matcher, S. J. & Cooper, C. E. Absolute quantification of deoxyhaemoglobin concentration in tissue near infrared spectroscopy. Phys. Med. Biol. 39, 1295–1312 (1994).

    Article  CAS  PubMed  Google Scholar 

  52. Brady, K. M. et al. Continuous measurement of autoregulation by spontaneous fluctuations in cerebral perfusion pressure: comparison of 3 methods. Stroke 39, 2531–2537 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  53. Brady, K. M. et al. Continuous time-domain analysis of cerebrovascular autoregulation using near-infrared spectroscopy. Stroke 38, 2818–2825 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  54. Brady, K. M. et al. Noninvasive autoregulation monitoring with and without intracranial pressure in the naive piglet brain. Anesth. Analg. 111, 191–195 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Zweifel, C. et al. Continuous assessment of cerebral autoregulation with near-infrared spectroscopy in adults after subarachnoid hemorrhage. Stroke 41, 1963–1968 (2010).

    Article  PubMed  Google Scholar 

  56. Budohoski, K. P. et al. Cerebral autoregulation after subarachnoid hemorrhage: comparison of three methods. J. Cereb. Blood Flow Metab. http://dx.doi.org/10.1038/jcbfm.2012.189.

  57. Zweifel, C. et al. Noninvasive monitoring of cerebrovascular reactivity with near infrared spectroscopy in head-injured patients. J. Neurotrauma 27, 1951–1958 (2010).

    Article  PubMed  Google Scholar 

  58. Steiner, L. A. et al. Near-infrared spectroscopy can monitor dynamic cerebral autoregulation in adults. Neurocrit. Care 10, 122–128 (2009).

    Article  PubMed  Google Scholar 

  59. Brady, K. M. et al. Monitoring cerebral blood flow pressure autoregulation in pediatric patients during cardiac surgery. Stroke 41, 1957–1962 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  60. Nornes, H. The role of intracranial pressure in the arrest of hemorrhage in patients with ruptured intracranial aneurysm. J. Neurosurg. 39, 226–234 (1973).

    Article  CAS  PubMed  Google Scholar 

  61. Nornes, H. Cerebral arterial flow dynamics during aneurysm haemorrhage. Acta Neurochir. (Wien) 41, 39–48 (1978).

    Article  CAS  Google Scholar 

  62. Wartenberg, K. E. et al. Acute ischemic injury on diffusion-weighted magnetic resonance imaging after poor grade subarachnoid hemorrhage. Neurocrit. Care 14, 407–415 (2011).

    Article  PubMed  Google Scholar 

  63. Cahill, J., Calvert, J. W. & Zhang, J. H. Mechanisms of early brain injury after subarachnoid hemorrhage. J. Cereb. Blood Flow Metab. 26, 1341–1353 (2006).

    Article  CAS  PubMed  Google Scholar 

  64. Cho, H. G., Shin, H. K., Shin, Y. W., Lee, J. H. & Hong, K. W. Role of nitric oxide in the CBF autoregulation during acute stage after subarachnoid haemorrhage in rat pial artery. Fundam. Clin. Pharmacol. 17, 563–573 (2003).

    Article  CAS  PubMed  Google Scholar 

  65. Shin, H. K. et al. Impairment of autoregulatory vasodilation by NAD(P)H oxidase-dependent superoxide generation during acute stage of subarachnoid hemorrhage in rat pial artery. J. Cereb. Blood Flow Metab. 22, 869–877 (2002).

    Article  CAS  PubMed  Google Scholar 

  66. Gaetani, P., Rodriguez y Baena, R., Silvani, V., Rainoldi, F. & Paoletti, P. Prostacyclin and vasospasm in subarachnoid hemorrhage from ruptured intracranial aneurysm. A preliminary clinical study. Acta Neurol. Scand. 73, 33–38 (1986).

    Article  CAS  PubMed  Google Scholar 

  67. Pickard, J. D., MacDonell, L. A., MacKenzie, E. T. & Harper, A. M. Response of the cerebral circulation in baboons to changing perfusion pressure after indomethacin. Circ. Res. 40, 198–203 (1977).

    Article  CAS  PubMed  Google Scholar 

  68. Shohami, E. & Sidi, A. Accumulation of prostacyclin in rat brain during haemorrhagic hypotension—possible role of PGI2 in autoregulation. J. Cereb. Blood Flow Metab. 4, 107–109 (1984).

    Article  CAS  PubMed  Google Scholar 

  69. Dreier, J. P. et al. Delayed ischaemic neurological deficits after subarachnoid haemorrhage are associated with clusters of spreading depolarizations. Brain 129, 3224–3237 (2006).

    Article  PubMed  Google Scholar 

  70. Bosche, B. et al. Recurrent spreading depolarizations after subarachnoid hemorrhage decreases oxygen availability in human cerebral cortex. Ann. Neurol. 67, 607–617 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Romano, J. G. et al. Microemboli in aneurysmal subarachnoid hemorrhage. J. Neuroimaging 18, 396–401 (2008).

    Article  PubMed  Google Scholar 

  72. Stein, S. C., Browne, K. D., Chen, X. H., Smith, D. H. & Graham, D. I. Thromboembolism and delayed cerebral ischemia after subarachnoid hemorrhage: an autopsy study. Neurosurgery 59, 781–787 (2006).

    Article  PubMed  Google Scholar 

  73. Friedrich, B., Muller, F., Feiler, S., Scholler, K. & Plesnila, N. Experimental subarachnoid hemorrhage causes early and long-lasting microarterial constriction and microthrombosis: an in-vivo microscopy study. J. Cereb. Blood Flow Metab. 32, 447–455 (2012).

    Article  CAS  PubMed  Google Scholar 

  74. Park, K. W., Metais, C., Dai, H. B., Comunale, M. E. & Sellke, F. W. Microvascular endothelial dysfunction and its mechanism in a rat model of subarachnoid hemorrhage. Anesth. Analg. 92, 990–996 (2001).

    Article  CAS  PubMed  Google Scholar 

  75. Herz, D. A., Baez, S. & Shulman, K. Pial microcirculation in subarachnoid hemorrhage. Stroke 6, 417–424 (1975).

    Article  CAS  PubMed  Google Scholar 

  76. Woitzik, J. et al. Delayed cerebral ischemia and spreading depolarization in absence of angiographic vasospasm after subarachnoid hemorrhage. J. Cereb. Blood Flow Metab. 32, 203–212 (2012).

    Article  PubMed  Google Scholar 

  77. Griffiths, D. P. et al. Cerebral blood flow and metabolism during hypotension induced with sodium nitroprusside. Br. J. Anaesth. 46, 671–679 (1974).

    Article  CAS  PubMed  Google Scholar 

  78. Hattingen, E. et al. Perfusion-weighted MRI to evaluate cerebral autoregulation in aneurysmal subarachnoid haemorrhage. Neuroradiology 50, 929–938 (2008).

    Article  PubMed  Google Scholar 

  79. Heilbrun, M. P., Olesen, J. & Lassen, N. A. Regional cerebral blood flow studies in subarachnoid hemorrhage. J. Neurosurg. 37, 36–44 (1972).

    Article  CAS  PubMed  Google Scholar 

  80. Ishii, R. Regional cerebral blood flow in patients with ruptured intracranial aneurysms. J. Neurosurg. 50, 587–594 (1979).

    Article  CAS  PubMed  Google Scholar 

  81. Nornes, H., Knutzen, H. B. & Wikeby, P. Cerebral arterial blood flow and aneurysm surgery. Part 2: induced hypotension and autoregulatory capacity. J. Neurosurg. 47, 819–827 (1977).

    Article  CAS  PubMed  Google Scholar 

  82. Pickard, J. D., Matheson, M., Patterson, J. & Wyper, D. Prediction of late ischemic complications after cerebral aneurysm surgery by the intraoperative measurement of cerebral blood flow. J. Neurosurg. 53, 305–308 (1980).

    Article  CAS  PubMed  Google Scholar 

  83. Pickard, J. D. et al. in Stimulated Cerebral Blood Flow (eds Schmiedek, P. et al.) 220–225 (Springer-Verlag, Berlin, 1992).

    Book  Google Scholar 

  84. Voldby, B., Enevoldsen, E. M. & Jensen, F. T. Cerebrovascular reactivity in patients with ruptured intracranial aneurysms. J. Neurosurg. 62, 59–67 (1985).

    Article  CAS  PubMed  Google Scholar 

  85. Yundt, K. D., Grubb, R. L. Jr, Diringer, M. N. & Powers, W. J. Autoregulatory vasodilation of parenchymal vessels is impaired during cerebral vasospasm. J. Cereb. Blood Flow Metab. 18, 419–424 (1998).

    Article  CAS  PubMed  Google Scholar 

  86. Connolly, E. S. Jr et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 43, 1711–1737 (2012).

    Article  PubMed  Google Scholar 

  87. Powers, W. J. et al. Autoregulation of cerebral blood flow surrounding acute (6 to 22 hours) intracerebral hemorrhage. Neurology 57, 18–24 (2001).

    Article  CAS  PubMed  Google Scholar 

  88. Cossu, M. et al. Autoregulation of cortical blood flow during surgery for ruptured intracranial aneurysms. J. Neurosurg. Sci. 43, 99–105 (1999).

    CAS  PubMed  Google Scholar 

  89. Dernbach, P. D., Little, J. R., Jones, S. C. & Ebrahim, Z. Y. Altered cerebral autoregulation and CO2 reactivity after aneurysmal subarachnoid hemorrhage. Neurosurgery 22, 822–826 (1988).

    Article  CAS  PubMed  Google Scholar 

  90. Manno, E. M., Gress, D. R., Schwamm, L. H., Diringer, M. N. & Ogilvy, C. S. Effects of induced hypertension on transcranial Doppler ultrasound velocities in patients after subarachnoid hemorrhage. Stroke 29, 422–428 (1998).

    Article  CAS  PubMed  Google Scholar 

  91. Muench, E. et al. Effects of positive end-expiratory pressure on regional cerebral blood flow, intracranial pressure, and brain tissue oxygenation. Crit. Care Med. 33, 2367–2372 (2005).

    Article  PubMed  Google Scholar 

  92. Tenjin, H. et al. Dysautoregulation in patients with ruptured aneurysms: cerebral blood flow measurements obtained during surgery by a temperature-controlled thermoelectrical method. Neurosurgery 23, 705–709 (1988).

    Article  CAS  PubMed  Google Scholar 

  93. Bijlenga, P. et al. “Optimal cerebral perfusion pressure” in poor grade patients after subarachnoid hemorrhage. Neurocrit. Care 13, 17–23 (2010).

    Article  PubMed  Google Scholar 

  94. Christ, M. et al. Continuous cerebral autoregulation monitoring by improved cross-correlation analysis: comparison with the cuff deflation test. Intensive Care Med. 33, 246–254 (2007).

    Article  PubMed  Google Scholar 

  95. Lang, E. W., Diehl, R. R. & Mehdorn, H. M. Cerebral autoregulation testing after aneurysmal subarachnoid hemorrhage: the phase relationship between arterial blood pressure and cerebral blood flow velocity. Crit. Care Med. 29, 158–163 (2001).

    Article  CAS  PubMed  Google Scholar 

  96. Rasulo, F. A. et al. Are optimal cerebral perfusion pressure and cerebrovascular autoregulation related to long-term outcome in patients with aneurysmal subarachnoid hemorrhage? J. Neurosurg. Anesthesiol. 24, 3–8 (2012).

    Article  PubMed  Google Scholar 

  97. Soehle, M., Jaeger, M. & Meixensberger, J. Online assessment of brain tissue oxygen autoregulation in traumatic brain injury and subarachnoid hemorrhage. Neurol. Res. 25, 411–417 (2003).

    Article  PubMed  Google Scholar 

  98. Tseng, M. Y. et al. Enhancement of cerebral blood flow using systemic hypertonic saline therapy improves outcome in patients with poor-grade spontaneous subarachnoid hemorrhage. J. Neurosurg. 107, 274–282 (2007).

    Article  PubMed  Google Scholar 

  99. Ratsep, T. & Asser, T. Cerebral hemodynamic impairment after aneurysmal subarachnoid hemorrhage as evaluated using transcranial doppler ultrasonography: relationship to delayed cerebral ischemia and clinical outcome. J. Neurosurg. 95, 393–401 (2001).

    Article  CAS  PubMed  Google Scholar 

  100. Tseng, M. Y., Czosnyka, M., Richards, H., Pickard, J. D. & Kirkpatrick, P. J. Effects of acute treatment with pravastatin on cerebral vasospasm, autoregulation, and delayed ischemic deficits after aneurysmal subarachnoid hemorrhage: a phase II randomized placebo-controlled trial. Stroke 36, 1627–1632 (2005).

    Article  CAS  PubMed  Google Scholar 

  101. Tseng, M. Y., Czosnyka, M., Richards, H., Pickard, J. D. & Kirkpatrick, P. J. Effects of acute treatment with statins on cerebral autoregulation in patients after aneurysmal subarachnoid hemorrhage. Neurosurg. Focus 21, E10 (2006).

    Article  PubMed  Google Scholar 

  102. Tseng, M. Y. et al. Effects of acute pravastatin treatment on intensity of rescue therapy, length of inpatient stay, and 6-month outcome in patients after aneurysmal subarachnoid hemorrhage. Stroke 38, 1545–1550 (2007).

    Article  CAS  PubMed  Google Scholar 

  103. Tseng, M. Y. et al. Acute systemic erythropoietin therapy to reduce delayed ischemic deficits following aneurysmal subarachnoid hemorrhage: a Phase II randomized, double-blind, placebo-controlled trial. Clinical article. J. Neurosurg. 111, 171–180 (2009).

    Article  CAS  PubMed  Google Scholar 

  104. Jaeger, M., Soehle, M., Schuhmann, M. U. & Meixensberger, J. Clinical significance of impaired cerebrovascular autoregulation after severe aneurysmal subarachnoid hemorrhage. Stroke 43, 2097–2101 (2012).

    Article  PubMed  Google Scholar 

  105. Budohoski, K. P. et al. Impairment of cerebral autoregulation predicts delayed cerebral ischemia after subarachnoid hemorrhage: a prospective observational study. Stroke 43, 3230–3237 (2012).

    Article  PubMed  Google Scholar 

  106. Dankbaar, J. W. et al. Relationship between vasospasm, cerebral perfusion, and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Neuroradiology 51, 813–819 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  107. The STASH trial. SimvaSTatin in Aneurysmal Subarachnoid Haemorrhage [online], (2012).

  108. Aries, M. J. et al. Continuous determination of optimal cerebral perfusion pressure in traumatic brain injury. Crit. Care Med. 40, 2456–2463 (2012).

    Article  PubMed  Google Scholar 

  109. Steiner, L. A. et al. Continuous monitoring of cerebrovascular pressure reactivity allows determination of optimal cerebral perfusion pressure in patients with traumatic brain injury. Crit. Care Med. 30, 733–738 (2002).

    Article  PubMed  Google Scholar 

  110. Budohoski, K. P. et al. What comes first? The dynamics of cerebral oxygenation and blood flow in response to changes in arterial pressure and intracranial pressure after head injury. Br. J. Anaesth. 108, 89–99 (2012).

    Article  CAS  PubMed  Google Scholar 

  111. Radolovich, D. K. et al. Transient changes in brain tissue oxygen in response to modifications of cerebral perfusion pressure: an observational study. Anesth. Analg. 110, 165–173 (2010).

    Article  PubMed  Google Scholar 

  112. Barth, M. et al. Correlation of clinical outcome with pressure-, oxygen-, and flow-related indices of cerebrovascular reactivity in patients following aneurysmal SAH. Neurocrit. Care 12, 234–243 (2010).

    Article  PubMed  Google Scholar 

  113. Hecht, N. et al. Modified flow- and oxygen-related autoregulation indices for continuous monitoring of cerebral autoregulation. J. Neurosci. Methods 201, 399–403 (2011).

    Article  PubMed  Google Scholar 

  114. Vajkoczy, P. et al. Continuous monitoring of regional cerebral blood flow: experimental and clinical validation of a novel thermal diffusion microprobe. J. Neurosurg. 93, 265–274 (2000).

    Article  CAS  PubMed  Google Scholar 

  115. Ohmae, E. et al. Cerebral hemodynamics evaluation by near-infrared time-resolved spectroscopy: correlation with simultaneous positron emission tomography measurements. Neuroimage 29, 697–705 (2006).

    Article  PubMed  Google Scholar 

  116. Gupta, A. K. et al. Measurement of brain tissue oxygenation performed using positron emission tomography scanning to validate a novel monitoring method. J. Neurosurg. 96, 263–268 (2002).

    Article  PubMed  Google Scholar 

  117. Czosnyka, M., Brady, K., Reinhard, M., Smielewski, P. & Steiner, L. A. Monitoring of cerebrovascular autoregulation: facts, myths, and missing links. Neurocrit. Care 10, 373–386 (2009).

    Article  PubMed  Google Scholar 

  118. Tiecks, F. P., Lam, A. M., Aaslid, R. & Newell, D. W. Comparison of static and dynamic cerebral autoregulation measurements. Stroke 26, 1014–1019 (1995).

    Article  CAS  PubMed  Google Scholar 

  119. Smielewski, P. et al. Assessment of cerebral autoregulation using carotid artery compression. Stroke 27, 2197–2203 (1996).

    Article  CAS  PubMed  Google Scholar 

  120. Dawson, S. L., Blake, M. J., Panerai, R. B. & Potter, J. F. Dynamic but not static cerebral autoregulation is impaired in acute ischaemic stroke. Cerebrovasc. Dis. 10, 126–132 (2000).

    Article  CAS  PubMed  Google Scholar 

  121. Budohoski, K. P. et al. The relationship between cerebral blood flow autoregulation and cerebrovascular pressure reactivity after traumatic brain injury. Neurosurgery 71, 652–660 (2012).

    Article  PubMed  Google Scholar 

  122. Soehle, M., Czosnyka, M., Pickard, J. D. & Kirkpatrick, P. J. Continuous assessment of cerebral autoregulation in subarachnoid hemorrhage. Anesth. Analg. 98, 1133–1139 (2004).

    Article  PubMed  Google Scholar 

  123. CARNet. Cerebral Autoregulation Research Network [online], (2012).

  124. Johansson, B. B. Indomethacin and cerebrovascular permeability to albumin in acute hypertension and cerebral embolism in the rat. Exp. Brain Res. 42, 331–336 (1981).

    CAS  PubMed  Google Scholar 

  125. Hasegawa, Y., Suzuki, H., Sozen, T., Altay, O. & Zhang, J. H. Apoptotic mechanisms for neuronal cells in early brain injury after subarachnoid hemorrhage. Acta Neurochir. Suppl. 110, 43–48 (2010).

    Google Scholar 

  126. Nornes, H., Aaslid, R. & Lindegaard, K. F. Intracranial pulse pressure dynamics in patients with intracranial hypertension. Acta Neurochir. (Wien) 38, 177–186 (1977).

    Article  CAS  Google Scholar 

  127. Voldby, B. & Enevoldsen, E. M. Intracranial pressure changes following aneurysm rupture. Part 1: clinical and angiographic correlations. J. Neurosurg. 56, 186–196 (1982).

    Article  CAS  PubMed  Google Scholar 

  128. Connolly, E. S. Jr et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 43, 1711–1737 (2012).

    Article  PubMed  Google Scholar 

  129. Vergouwen, M. D. et al. Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group. Stroke 41, 2391–2395 (2010).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

J. D. Pickard and M. Czosnyka are supported by the National Institute of Health Research, Biomedical Research Centre (Neuroscience Theme). J. D. Pickard is also supported by the National Institute of Health Research Senior Investigator Award. K. P. Budohoski received a grant from St Catharine's College, University of Cambridge, UK.

Author information

Authors and Affiliations

  1. Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge, CB2 0QQ, UK

    Karol P. Budohoski, Marek Czosnyka, Peter J. Kirkpatrick, Peter Smielewski & John D. Pickard

  2. Department of Anaesthesia, Lausanne University Hospital, Rue du Bugnon 46, Lausanne, CH-1011, Switzerland

    Luzius A. Steiner

Authors
  1. Karol P. Budohoski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marek Czosnyka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter J. Kirkpatrick
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peter Smielewski
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Luzius A. Steiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. John D. Pickard
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

K. P. Budohoski researched data for the article. K. P. Budohoski and M. Czosnyka wrote the article. All authors contributed equally to discussion of content and to the review and/or editing of the manuscript before submission.

Corresponding author

Correspondence to Karol P. Budohoski.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

Cerebral autoregulation following SAH: direct blood-flow methods for measurement of static autoregulation (DOC 70 kb)

Supplementary Table 2

Cerebral autoregulation following SAH: indirect measurements (DOC 54 kb)

Supplementary Table 3

Cerebral autoregulation following SAH: indirect blood-flow methods for measurement of dynamic autoregulation (DOC 118 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Budohoski, K., Czosnyka, M., Kirkpatrick, P. et al. Clinical relevance of cerebral autoregulation following subarachnoid haemorrhage. Nat Rev Neurol 9, 152–163 (2013). https://doi.org/10.1038/nrneurol.2013.11

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneurol.2013.11

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing