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Association of Dose of Intracranial Hypertension with Outcome in Subarachnoid Hemorrhage

The Original Article was published on 02 March 2021



In patients with aneurysmal subarachnoid hemorrhage (aSAH) the burden of intracranial pressure (ICP) and its contribution to outcomes remains unclear. In this multicenter study, the independent association between intensity and duration, or “dose,” of episodes of intracranial hypertension and 12-month neurological outcomes was investigated.


This was a retrospective analysis of multicenter prospectively collected data of 98 adult patients with aSAH amendable to treatment. Patients were admitted to the intensive care unit of two European centers (Medical University of Innsbruck [Austria] and San Gerardo University Hospital of Monza [Italy]) from 2009 to 2013. The dose of intracranial hypertension was visualized. The obtained visualizations allowed us to investigate the association between intensity and duration of episodes of intracranial hypertension and the 12-month neurological outcomes of the patients, assessed with the Glasgow Outcome Score. The independent association between the cumulative dose of intracranial hypertension and outcome for each patient was investigated by using multivariable logistic regression models corrected for age, occurrence of delayed cerebral ischemia, and the Glasgow Coma Scale score at admission.


The combination of duration and intensity defined the tolerance to intracranial hypertension for the two cohorts of patients. A semiexponential transition divided ICP doses that were associated with better outcomes (in blue) with ICP doses associated with worse outcomes (in red). In addition, in both cohorts, an independent association was found between the cumulative time that the patient experienced ICP doses in the red area and long-term neurological outcomes. The ICP pressure–time burden was a stronger predictor of outcomes than the cumulative time spent by the patients with an ICP greater than 20 mmHg.


In two cohorts of patients with aSAH, an association between duration and intensity of episodes of elevated ICP and 12-month neurological outcomes could be demonstrated and was visualized in a color-coded plot.

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  1. Etminan N, Chang H-S, Hackenberg K, de Rooij NK, Vergouwen MDI, Rinkel GJE, et al. Worldwide incidence of aneurysmal subarachnoid hemorrhage according to region, time period, blood pressure, and smoking prevalence in the population: a systematic review and meta-analysis. JAMA Neurol. 2019;76(5):588–97.

    Article  Google Scholar 

  2. Suarez JI, Tarr RW, Selman WR. Aneurysmal subarachnoid hemorrhage. N Engl J Med. 2006;354(4):387–96.

    CAS  Article  Google Scholar 

  3. Macdonald RL, Diringer MN, Citerio G. Understanding the disease: aneurysmal subarachnoid hemorrhage. Intensive Care Med. 2014;40(12):1940–3.

    Article  Google Scholar 

  4. Zoerle T, Lombardo A, Colombo A, Longhi L, Zanier ER, Rampini P, et al. Intracranial pressure after subarachnoid hemorrhage. Crit Care Med. 2015;43(1):168–76.

    CAS  Article  Google Scholar 

  5. Magni F, Pozzi M, Rota M, Vargiolu A, Citerio G. High-resolution intracranial pressure burden and outcome in subarachnoid hemorrhage. Stroke. 2015;46(9):2464–9.

    Article  Google Scholar 

  6. Brain Trauma Foundation, American Association of Neurological Surgeons (AANS), Congress of Neurological Surgeons (CNS), AANS/CNS Joint Section on Neurotrauma and Critical Care. Guidelines for the management of severe traumatic brain injury. VI. Indications for intracranial pressure monitoring. J Neurotrauma. 2007;24(Suppl 1):S37–S44.

    Google Scholar 

  7. Carney N, Totten AM, O’Reilly C, Ullman JS, Hawryluk GW, Bell MJ, et al. Guidelines for the management of severe traumatic brain injury, fourth edition. Neurosurgery. 2017;80(1):6–15.

    Article  Google Scholar 

  8. Vik A, Nag T, Fredriksli OA, Skandsen T, Moen KG, Schirmer-Mikalsen K, et al. Relationship of “dose” of intracranial hypertension to outcome in severe traumatic brain injury. J Neurosurg. 2008;109(4):678–84.

    Article  Google Scholar 

  9. Sheth KN, Stein DM, Aarabi B, Hu P, Kufera JA, Scalea TM, et al. Intracranial pressure dose and outcome in traumatic brain injury. Neurocrit Care. 2013;18(1):26–32.

    Article  Google Scholar 

  10. Güiza F, Depreitere B, Piper I, Citerio G, Chambers I, Jones PA, et al. Visualizing the pressure and time burden of intracranial hypertension in adult and paediatric traumatic brain injury. Intensive Care Med. 2015;41(6):1067–76.

    Article  Google Scholar 

  11. Bederson JB, Connolly ES Jr, Batjer HH, Dacey RG, Dion JE, Diringer MN, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke. 2009;40(3):994–1025.

    Article  Google Scholar 

  12. Helbok R, Olson DM, Le Roux PD, Vespa P, Participants in the International Multidisciplinary Consensus Conference on Multimodality Monitoring. Intracranial pressure and cerebral perfusion pressure monitoring in non-TBI patients: special considerations. Neurocrit Care. 2014;21(Suppl 2):S85–94.

    Article  Google Scholar 

  13. Frontera JA, Claassen J, Schmidt JM, Wartenberg KE, Temes R, Connolly ES Jr, et al. Prediction of symptomatic vasospasm after subarachnoid hemorrhage: the modified Fisher scale. Neurosurgery. 2006;59(1):21–7.

    Article  Google Scholar 

  14. Hunt WE, Hess RM. Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg. 1968;28(1):14–20.

    CAS  Article  Google Scholar 

  15. Report of World Federation of Neurological Surgeons Committee on a universal subarachnoid hemorrhage grading scale. J Neurosurg. 1988;68(6):985–6.

  16. Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet. 1974;2(7872):81–4.

    CAS  Article  Google Scholar 

  17. Jennett B, Bond M. Assessment of outcome after severe brain damage. Lancet. 1975;1(7905):480–4.

    CAS  Article  Google Scholar 

  18. Diringer MN, Bleck TP, Claude Hemphill JIII, Menon D, Shutter L, Vespa P, et al. Critical care management of patients following aneurysmal subarachnoid hemorrhage: recommendations from the Neurocritical Care Society’s Multidisciplinary Consensus Conference. Neurocrit Care. 2011;15(2):211–40.

    Article  Google Scholar 

  19. Vargha A, Delaney HD. A critique and improvement of the CL common language effect size statistics of McGraw and Wong. J Educ Behav Stat. 2000;25(2):101–32.

    Google Scholar 

  20. Cossu G, Messerer M, Stocchetti N, Levivier M, Daniel RT, Oddo M. Intracranial pressure and outcome in critically ill patients with aneurysmal subarachnoid hemorrhage: a systematic review. Minerva Anestesiol. 2016;82(6):684–96.

    PubMed  Google Scholar 

  21. Heuer GG, Smith MJ, Elliott JP, Winn HR, Leroux PD. Relationship between intracranial pressure and other clinical variables in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg. 2004;101(3):408–16.

    Article  Google Scholar 

  22. Budohoski KP, Czosnyka M, Kirkpatrick PJ, Smielewski P, Steiner LA, Pickard JD. Clinical relevance of cerebral autoregulation following subarachnoid haemorrhage. Nat Rev Neurol. 2013;9(3):152–63.

    CAS  Article  Google Scholar 

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We acknowledge valuable help in the collection of the data by Federico Magni, MD, and Alessia Vargiolu, PhD.


GM is supported by the Research Foundation, Flanders (FWO) as senior clinical investigator (1843118N). GM and FG receive project funding from Katholieke Universiteit Leuven (C2 project C24/17/072: A neuromonitor for the twenty-first century). GCa receives funding from the FWO as a PhD fellow (fellowship number: 1S28120N). MF received funding from the FWO as a PhD fellow (fellowship number: 11Y1118N). LH receives funding form the Austrian Scientific Fund. RH reports Grants and other funding from Bard Medical, other funding from Zoll Medical, Grants from Fresenius Kabi, and other funding from Integra Life Sciences, outside the submitted work. BD reports Grants from Medtronic and Johnson & Johnson, outside the submitted work.

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GCa contribute to the design of the study, analysis and interpretation of data, important intellectual content contribution, draft of the manuscript, revision of the manuscipt and final approval of the version to be published. FE, BI, LH and VR contributed to the data acquisition, revision of the manuscipt and final approval of the version to be published. MF contributed to interpretation of data, revision of the manuscipt and final approval of the version to be published. BD contributed to the study design,interpretation of data, revision of the manuscipt and final approval of the version to be published. FG, GM, GCi and RH contributed to the study design,interpretation of data and important intellectual content contribution, revision of the manuscipt and final approval of the version to be published.

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Correspondence to Geert Meyfroidt.

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Carra, G., Elli, F., Ianosi, B. et al. Association of Dose of Intracranial Hypertension with Outcome in Subarachnoid Hemorrhage. Neurocrit Care 34, 722–730 (2021).

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  • Subarachnoid hemorrhage
  • Intracranial hypertension
  • Critical care
  • Outcome assessment
  • Decision-making