Neurocritical Care

, Volume 18, Issue 1, pp 45–53 | Cite as

Relationship Between Temperature, Hematoma Growth, and Functional Outcome After Intracerebral Hemorrhage

  • Fred RinconEmail author
  • Patrick Lyden
  • Stephan A. Mayer
Original Article



Fever and hematoma growth are known to be independent predictors of poor outcome after intracerebral hemorrhage (ICH). We sought to assess the distribution of temperature at different stages in relation to hematoma growth and functional outcome at 90 days in a cohort of ICH patients.


Data of patients registered in the Virtual International Stroke Trials Archive—ICH were analyzed. Temperatures at baseline, 24, 48, 72, and 168 h were assessed in relation to the hematoma growth and functional outcome at 90 days. We calculated the daily linear variation of each subject’s temperature by subtracting 37 °C from the maximal daily recorded temperature (delta-temperature). We used logistic regression and mixed-effects models to identify factors associated with hematoma growth, poor outcome, and temperature elevation after ICH.


303 patients were included in the analysis. The average age was 66 ± 12 years, 200 (66 %) were males, median admission NIHSS was 13 [Interquartile range (IQR), 9–18), median GCS was 15 (IQR, 14–15). Hematoma growth occurred in 22 % and poor functional outcome at 90-days occurred in 41 % of the patients. Cumulative delta-temperature at 72 h was associated with hematoma growth; age, ICH score, hematoma growth, and cumulative delta-temperature at 168 h were associated with poor outcome at 90 days. Factors associated with fever in mixed-models were day after onset of ICH, hypertension, base hematoma volume, intraventricular-hemorrhage, pneumonia, and hematoma growth.


There is a temporal and independent association between fever and hematoma growth. Fever after ICH is associated with poor outcome at 90 days. Future research is needed to study the mechanisms of this phenomenon and if early protocols of temperature modulation would be associated with improved outcomes after ICH.


Fever Stroke VISTA 



Dr. Rincon has received salary support from the American Heart Association (AHA 12CRP12050342).

Conflict of interest



  1. 1.
    Brott T, Broderick J, Kothari R, et al. Early hemorrhage growth in patients with intracerebral hemorrhage. Stroke. 1997;28:1–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Gebel JM Jr, Jauch EC, Brott TG, et al. Relative edema volume is a predictor of outcome in patients with hyperacute spontaneous intracerebral hemorrhage. Stroke. 2002;33:2636–41.PubMedCrossRefGoogle Scholar
  3. 3.
    Fujii Y, Takeuchi S, Sasaki O, Minakawa T, Tanaka R. Multivariate analysis of predictors of hematoma enlargement in spontaneous intracerebral hemorrhage. Stroke. 1998;29:1160–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Fujii Y, Tanaka R, Takeuchi S, Koike T, Minakawa T, Sasaki O. Hematoma enlargement in spontaneous intracerebral hemorrhage. J Neurosurg. 1994;80:51–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Kazui S, Naritomi H, Yamamoto H, Sawada T, Yamaguchi T. Enlargement of spontaneous intracerebral hemorrhage. Incidence and time course. Stroke. 1996;27:1783–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Wada R, Aviv RI, Fox AJ, et al. CT angiography “spot sign” predicts hematoma expansion in acute intracerebral hemorrhage. Stroke. 2007;38:1257–62.PubMedCrossRefGoogle Scholar
  7. 7.
    Mayer SA. Ultra-early hemostatic therapy for intracerebral hemorrhage. Stroke. 2003;34:224–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Mayer SA, Lignelli A, Fink ME, et al. Perilesional blood flow and edema formation in acute intracerebral hemorrhage: a SPECT study. Stroke. 1998;29:1791–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Becker KJ, Baxter AB, Bybee HM, Tirschwell DL, Abouelsaad T, Cohen WA. Extravasation of radiographic contrast is an independent predictor of death in primary intracerebral hemorrhage. Stroke. 1999;30:2025–32.PubMedCrossRefGoogle Scholar
  10. 10.
    Qureshi AI, Ali Z, Suri MF, et al. Extracellular glutamate and other amino acids in experimental intracerebral hemorrhage: an in vivo microdialysis study. Crit Care Med. 2003;31:1482–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Gordon CR, Merchant RS, Marmarou A, Rice CD, Marsh JT, Young HF. Effect of murine recombinant interleukin-1 on brain oedema in the rat. Acta Neurochir Suppl (Wien). 1990;51:268–70.Google Scholar
  12. 12.
    Megyeri P, Abraham CS, Temesvari P, Kovacs J, Vas T, Speer CP. Recombinant human tumor necrosis factor alpha constricts pial arterioles and increases blood–brain barrier permeability in newborn piglets. Neurosci Lett. 1992;148:137–40.PubMedCrossRefGoogle Scholar
  13. 13.
    Marti-Fabregas J, Borrell M, Silva Y, et al. Hemostatic proteins and their association with hematoma growth in patients with acute intracerebral hemorrhage. Stroke. 2010;41:2976–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Takahashi H, Urano T, Nagai N, Takada Y, Takada A. Progressive expansion of hypertensive intracerebral hemorrhage by coagulopathy. Am J Hematol. 1998;59:110–4.PubMedCrossRefGoogle Scholar
  15. 15.
    Olivot JM, Mlynash M, Kleinman JT, et al. MRI profile of the perihematomal region in acute intracerebral hemorrhage. Stroke. 2010;41:2681–3.PubMedCrossRefGoogle Scholar
  16. 16.
    Power C, Henry S, Del Bigio MR, et al. Intracerebral hemorrhage induces macrophage activation and matrix metalloproteinases. Ann Neurol. 2003;53:731–42.PubMedCrossRefGoogle Scholar
  17. 17.
    Felberg RA, Grotta JC, Shirzadi AL, et al. Cell death in experimental intracerebral hemorrhage: the “black hole” model of hemorrhagic damage. Ann Neurol. 2002;51:517–24.PubMedCrossRefGoogle Scholar
  18. 18.
    Greer DM, Funk SE, Reaven NL, Ouzounelli M, Uman GC. Impact of fever on outcome in patients with stroke and neurologic injury: a comprehensive meta-analysis. Stroke. 2008;39:3029–35.PubMedCrossRefGoogle Scholar
  19. 19.
    Rincon F, Patel U, Schorr C, Dellinger RP, Parrillo J, Zanotti-Cavazoni S. Effect of Early hyperthermia on hospital mortality in critically-ill neurological patients: a matched cohort study (NCS abstracts). Neurocrit Care. 2011;15(Suppl 1):181.Google Scholar
  20. 20.
    Sacho RH, Vail A, Rainey T, King AT, Childs C. The effect of spontaneous alterations in brain temperature on outcome: a prospective observational cohort study in patients with severe traumatic brain injury. J Neurotrauma. 2010;27:2157–64.PubMedCrossRefGoogle Scholar
  21. 21.
    Childs C, Wieloch T, Lecky F, Machin G, Harris B, Stocchetti N. Report of a consensus meeting on human brain temperature after severe traumatic brain injury: its measurement and management during pyrexia. Front Neurol. 2010;1:146.PubMedGoogle Scholar
  22. 22.
    O’Grady NP, Barie PS, Bartlett JG, et al. Guidelines for evaluation of new fever in critically ill adult patients: 2008 update from the American College of Critical Care Medicine and the Infectious Diseases Society of America. Crit Care Med. 2008;36:1330–49.PubMedCrossRefGoogle Scholar
  23. 23.
    Badjatia N. Hyperthermia and fever control in brain injury. Crit Care Med. 2009;37:S250–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Dietrich WD. The importance of brain temperature in cerebral injury. J Neurotrauma. 1992;9(Suppl 2):S475–85.PubMedGoogle Scholar
  25. 25.
    Zhao H, Steinberg GK, Sapolsky RM. General versus specific actions of mild-moderate hypothermia in attenuating cerebral ischemic damage. J Cereb Blood Flow Metab. 2007;27:1879–94.PubMedCrossRefGoogle Scholar
  26. 26.
    Ali M, Bath PM, Curram J, et al. The virtual international stroke trials archive. Stroke. 2007;38:1905–10.PubMedCrossRefGoogle Scholar
  27. 27.
    Dowlatshahi D, Demchuk AM, Flaherty ML, Ali M, Lyden PL, Smith EE. Defining hematoma expansion in intracerebral hemorrhage: relationship with patient outcomes. Neurology. 2011;76:1238–44.PubMedCrossRefGoogle Scholar
  28. 28.
    Lyden P, Brott T, Tilley B, et al. Improved reliability of the NIH Stroke Scale using video training. NINDS TPA Stroke Study Group. Stroke. 1994;25:2220–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet. 1974;2:81–4.PubMedCrossRefGoogle Scholar
  30. 30.
    Hemphill JC 3rd, Bonovich DC, Besmertis L, Manley GT, Johnston SC. The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke. 2001;32:891–7.PubMedCrossRefGoogle Scholar
  31. 31.
    van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1988;19:604–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Lyden PD, Shuaib A, Lees KR, et al. Safety and tolerability of NXY-059 for acute intracerebral hemorrhage: the CHANT Trial. Stroke. 2007;38:2262–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Schwarz S, Hafner K, Aschoff A, Schwab S. Incidence and prognostic significance of fever following intracerebral hemorrhage. Neurology. 2000;54:354–61.PubMedCrossRefGoogle Scholar
  34. 34.
    Fernandez A, Schmidt JM, Claassen J, et al. Fever after subarachnoid hemorrhage: risk factors and impact on outcome. Neurology. 2007;68:1013–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Naidech AM, Bendok BR, Bernstein RA, et al. Fever burden and functional recovery after subarachnoid hemorrhage. Neurosurgery 2008;63:212–7; discussion 7–8.Google Scholar
  36. 36.
    Saini M, Saqqur M, Kamruzzaman A, Lees KR, Shuaib A. Effect of hyperthermia on prognosis after acute ischemic stroke. Stroke. 2009;40:3051–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Fang SB, Chang YT, Chuo YH, Tsai ST, Tseng CL. Hyperthermia as an early sign of intracranial hemorrhage in full-term neonates. Pediatr Neonatol. 2008;49:71–6.PubMedCrossRefGoogle Scholar
  38. 38.
    MacLellan CL, Girgis J, Colbourne F. Delayed onset of prolonged hypothermia improves outcome after intracerebral hemorrhage in rats. J Cereb Blood Flow Metab. 2004;24:432–40.PubMedCrossRefGoogle Scholar
  39. 39.
    MacLellan CL, Silasi G, Poon CC, et al. Intracerebral hemorrhage models in rat: comparing collagenase to blood infusion. J Cereb Blood Flow Metab. 2008;28:516–25.PubMedCrossRefGoogle Scholar
  40. 40.
    Kollmar R, Staykov D, Dorfler A, Schellinger PD, Schwab S, Bardutzky J. Hypothermia reduces perihemorrhagic edema after intracerebral hemorrhage. Stroke. 2010;41:1684–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Broderick J, Connolly S, Feldmann E, et al. Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Stroke. 2007;38:2001–23.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  1. 1.Departments of Neurology and Neurosurgery, Division of Critical Care and NeurotraumaThomas Jefferson UniversityPhiladelphiaUSA
  2. 2.Department of NeurologyCedar’s-Sinai Medical CenterLos AngelesUSA
  3. 3.Departments of Neurology and Neurosurgery, Division of Neurocritical CareColumbia UniversityNew YorkUSA

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