Neurocritical Care

, Volume 23, Issue 3, pp 330–338 | Cite as

The Association Between Spontaneous Hyperventilation, Delayed Cerebral Ischemia, and Poor Neurological Outcome in Patients with Subarachnoid Hemorrhage

  • Craig A. WilliamsonEmail author
  • Kyle M. Sheehan
  • Renuka Tipirneni
  • Christopher D. Roark
  • Aditya S. Pandey
  • B. Gregory Thompson
  • Venkatakrishna Rajajee
Original Article



The frequency and associations of spontaneous hyperventilation in subarachnoid hemorrhage (SAH) are unknown. Because hyperventilation decreases cerebral blood flow, it may exacerbate delayed cerebral ischemia (DCI) and worsen neurological outcome.


This is a retrospective analysis of data from a prospectively collected cohort of SAH patients at an academic medical center. Spontaneous hyperventilation was defined by PaCO2 <35 mmHg and pH >7.45 and subdivided into moderate and severe groups. Clinical and demographic characteristics of patients with and without spontaneous hyperventilation were compared using χ 2 or t tests. Bivariate and multivariable logistic regression analyses were conducted to examine the association of moderate and severe hyperventilation with DCI and discharge neurological outcome.


Of 207 patients, 113 (55 %) had spontaneous hyperventilation. Spontaneously hyperventilating patients had greater illness severity as measured by the Hunt–Hess, World Federation of Neurosurgical Societies (WFNS), and SAH sum scores. They were also more likely to develop the following complications: pneumonia, neurogenic myocardial injury, systemic inflammatory response syndrome (SIRS), radiographic vasospasm, DCI, and poor neurological outcome. In a multivariable logistic regression model including age, gender, WFNS, SAH sum score, pneumonia, neurogenic myocardial injury, etiology, and SIRS, only moderate [odds ratio (OR) 2.49, 95 % confidence interval (CI) 1.10–5.62] and severe (OR 3.12, 95 % CI 1.30–7.49) spontaneous hyperventilation were associated with DCI. Severe spontaneous hyperventilation (OR 4.52, 95 % CI 1.37–14.89) was also significantly associated with poor discharge outcome in multivariable logistic regression analysis.


Spontaneous hyperventilation is common in SAH and is associated with DCI and poor neurological outcome.


Stroke Subarachnoid hemorrhage Cerebral vasospasm Hyperventilation Respiratory alkalosis Hypocapnia Brain ischemia 


Conflict of interest

The authors declare that they have no conflict of interest.

Funding support


Supplementary material

12028_2015_138_MOESM1_ESM.docx (14 kb)
Supplementary material 1 (DOCX 13 kb)


  1. 1.
    Muizellar JP, Marmarou A, Ward JD, et al. Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial. J Neurosurg. 1991;75:731–9.CrossRefGoogle Scholar
  2. 2.
    Curley G, Kavanagh BP, Laffey JG. Hypocapnia and the injured brain: more harm than benefit. Crit Care Med. 2010;38:1348–59.PubMedGoogle Scholar
  3. 3.
    Huang CT, Cook AW, Lyons HA. Severe craniocerebral trauma and respiratory abnormalities. Arch Neurol. 1963;9:545–54.CrossRefPubMedGoogle Scholar
  4. 4.
    Lee MC, Klassen AC, Resch JA. Respiratory pattern disturbances in ischemic cerebral vascular disease. Stroke. 1971;5:612–6.CrossRefGoogle Scholar
  5. 5.
    Rout MW, Lane DJ, Wollner L. Prognosis in acute cerebrovascular accidents in relation to respiratory pattern and blood gas tensions. BMJ. 1971;3:7–9.PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Vapalahti M, Troupp H. Prognosis for patients with severe brain injuries. BMJ. 1971;3:404–7.PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    North BJ, Jennet S. Abnormal breathing patterns associated with acute brain damage. Arch Neurol. 1974;31:338–44.CrossRefPubMedGoogle Scholar
  8. 8.
    Raichle ME, Plum F. Hyperventilation and cerebral blood flow. Stroke. 1972;3:566–75.CrossRefPubMedGoogle Scholar
  9. 9.
    Coles JP, Minhas PS, Fryer TD, et al. Effect of hyperventilation on cerebral blood flow in traumatic head injury: clinical relevance and monitoring correlates. Crit Care Med. 2002;30:1950–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Coles JP, Fryer TD, Coleman MR, et al. Hyperventilation following head injury: effect on ischemic burden and cerebral oxidative metabolism. Crit Care Med. 2007;35:568–78.CrossRefPubMedGoogle Scholar
  11. 11.
    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;81:793–7.CrossRefPubMedGoogle Scholar
  12. 12.
    Suarez JI, Tarr RW, Selman WR. Aneurysmal subarachnoid hemorrhage. N Engl J Med. 2006;354:387–96.CrossRefPubMedGoogle Scholar
  13. 13.
    Van Gijn J, Kerr RS, Rinkel GJ. Subarachnoid hemorrhage. Lancet. 2007;369:306–18.CrossRefPubMedGoogle Scholar
  14. 14.
    Diringer MN, Bleck TP, Hemphill JC, et al. Critical care management of patient’s following aneurysmal subarachnoid hemorrhage: recommendations from the Neurocritical Care Society’s Multidisciplinary Consensus Conference. Neurocrit Care. 2011;15:211–40.CrossRefPubMedGoogle Scholar
  15. 15.
    Connolly ES, Rabinstein AA, Carhuapoma 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. 2012;43:1711–37.CrossRefPubMedGoogle Scholar
  16. 16.
    Hunt WE, Hess RM. Surgical risk as related to the time of intervention in the repair of cerebral aneurysms. J Neurosurg. 1968;28:14–20.CrossRefPubMedGoogle Scholar
  17. 17.
    Drake CG. Report of World Federation of Neurosurgeons committee on a universal subarachnoid hemorrhage grading system. J Neurosurg. 1988;68:985–6.Google Scholar
  18. 18.
    Hjidra A, van Gijn J, Nagelkerke NJD, Vermeulen M, van Cevel H. Prediction of delayed cerebral ischemia, rebleeding, and outcome after aneurysmal subarachnoid hemorrhage. Stroke. 1988;19:1250–6.CrossRefGoogle Scholar
  19. 19.
    Frontera JA, Claassen J, Schmidt JM, et al. Prediction of symptomatic vasospasm after subarachnoid hemorrhage: the modified Fisher scale. Neurosurgery. 2007;59:21–7.CrossRefGoogle Scholar
  20. 20.
    Mayer SA, Lin J, Homma S, et al. Myocardial injury and left ventricular performance after subarachnoid hemorrhage. Stroke. 1999;30:780–6.CrossRefPubMedGoogle Scholar
  21. 21.
    Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 1992;101:1644–55.CrossRefPubMedGoogle Scholar
  22. 22.
    Frontera JA, Fernandez A, Schmidt JM. Defining vasospasm after subarachnoid hemorrhage. What is the most clinically relevant definition? Stroke. 2009;40:1963–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Sulter G, Steen C, De Keyser J. Use of the Barthel index and modified Rankin scale in acute stroke trials. Stroke. 1999;30:1538–41.CrossRefPubMedGoogle Scholar
  24. 24.
    Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42:377–81.PubMedCentralCrossRefPubMedGoogle Scholar
  25. 25.
    Dhar R, Diringer MN. The burden of the systemic inflammatory response syndrome predicts vasospasm and outcome after subarachnoid hemorrhage. Neurocrit Care. 2008;8:404–12.PubMedCentralCrossRefPubMedGoogle Scholar
  26. 26.
    Tam AKH, Ilodigwe D, Mocco J, et al. Impact of systemic inflammatory response syndrome on vasospasm, cerebral infarction, and outcome after subarachnoid hemorrhage: exploratory analysis of CONSCIOUS-1 data. Neurocrit Care. 2013;13:182–9.CrossRefGoogle Scholar
  27. 27.
    Plum F, Swanson AG. Central neurogenic hyperventilation in man. AMA Arch Neurol Psychiatry. 1959;81:535–49.CrossRefPubMedGoogle Scholar
  28. 28.
    Tarulli AW, Lim C, Bui JD, et al. Central neurogenic hyperventilation: a case report and discussion of pathophysiology. Arch Neurol. 2005;62:1632–4.CrossRefPubMedGoogle Scholar
  29. 29.
    Ledet D, Delos NM, Khan R, et al. Central neurogenic hyperventilation and renal tubular acidosis in children with pontine gliomas. Neurology. 2014;82:1099–100.PubMedCentralCrossRefPubMedGoogle Scholar
  30. 30.
    Johnston SC, Singh V, Ralston HJ, Gold WM. Chronic dyspnea and hyperventilation in an awake patient with small subcortical infarcts. Neurology. 2001;47:2131–3.CrossRefGoogle Scholar
  31. 31.
    Nystad D, Salvesen R, Nielsen EW. Brainstem encephalitis with central neurogenic hyperventilation. J Neurol Neurosurg Psychiatry. 2007;78:107–8.PubMedCentralCrossRefPubMedGoogle Scholar
  32. 32.
    Takahashi M, Tsunemi T, Miyayosi T, Mizusawa H. Reversible central neurogenic hyperventilation in an awake patient with multiple sclerosis. J Neurol. 2007;254:1763–4.CrossRefPubMedGoogle Scholar
  33. 33.
    Plum F. Neurological integration of behavioral and metabolic control of breathing. In: Porter R, editor. Breathing: Hering–Breur Centenary Symposium: CIBA Foundation. London: Churchill; 1970. p. 159–75.CrossRefGoogle Scholar
  34. 34.
    Leitch AG, McLennan JE, Balkenhol RG, et al. Mechanisms of hyperventilation in head injury: case report and review. Neurosurgery. 1979;5:701–7.CrossRefPubMedGoogle Scholar
  35. 35.
    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;121:1056–62.CrossRefPubMedGoogle Scholar
  36. 36.
    Thompson BG, Pluta RM, Girton ME, Oldfield EH. Nitric oxide mediation of chemoregulation but not autoregulation of cerebral blood flow in primates. J Neurosurg. 1994;84:71–8.CrossRefGoogle Scholar
  37. 37.
    Fathi AR, Bakhtian KD, Pluta RM. The role of nitric oxide donors in treating cerebral vasospasm after subarachnoid hemorrhage. In: Feng H, et al., editors. Early brain injury or cerebral vasospasm, vol. 110., Acta Neurochirugica SupplementVienna: Springer; 2011. p. 93–7.CrossRefGoogle Scholar
  38. 38.
    Jaeckle KA, Digre KB, Jones CR, Bailey PL, McMahill PC. Central neurogenic hyperventilation: pharmacologic intervention with morphine sulfate and correlative analysis of respiratory, sleep, and oculomotor dysfunction. Neurology. 1990;40:1715–20.CrossRefPubMedGoogle Scholar
  39. 39.
    Adashi YU, Sano H, Doi M, Santo S. Central neurogenic hyperventilation treated with intravenous fentanyl followed by transdermal application. J Anes. 2007;21:417–9.CrossRefGoogle Scholar
  40. 40.
    Greenberg SB, Vender J. The use of neuromuscular blocking agents in the ICU: where are we now? Crit Care Med. 2014;41:1332–44.CrossRefGoogle Scholar
  41. 41.
    Sanfilippo F, Santonocito C, Veenith T, Astuto M, Maybauer MO. The role of neuromuscular blockade in patients with traumatic brain injury: a systematic review. Neurocrit Care. 2014;. doi: 10.1007/s12028-014-0061-1.Google Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Craig A. Williamson
    • 1
    • 2
    Email author
  • Kyle M. Sheehan
    • 1
    • 2
  • Renuka Tipirneni
    • 3
    • 4
  • Christopher D. Roark
    • 1
  • Aditya S. Pandey
    • 1
  • B. Gregory Thompson
    • 1
  • Venkatakrishna Rajajee
    • 1
    • 2
  1. 1.Department of NeurosurgeryUniversity of MichiganAnn ArborUSA
  2. 2.Department of NeurologyUniversity of MichiganAnn ArborUSA
  3. 3.Robert Wood Johnson Foundation Clinical Scholars ProgramUniversity of MichiganAnn ArborUSA
  4. 4.Division of General Medicine, Department of Internal MedicineUniversity of MichiganAnn ArborUSA

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