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No exacerbation of perihematomal edema with intraclot urokinase in patients with spontaneous intracerebral hemorrhage

  • Clinical Article - Vascular
  • Published:
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Abstract

Background

Perihematomal edema (PHE) can worsen patient outcomes after spontaneous intracerebral hemorrhage (ICH). Minimally invasive surgery (MIS) in combination with thrombolytic removal of hematoma has been proven to be a promising treatment strategy. However, preclinical studies have suggested that intraclot thrombolysis may exacerbate PHE after ICH. Herein, we investigated the effects of MIS and urokinase on PHE.

Methods

ICH patients were retrospectively identified from our institutional ICH database. Computerized volumetric analysis was applied to assess changes in both ICH and PHE volumes using computed tomographic (CT) scans of T1 (pre-MIS) and T2 (post-MIS) time points. Relative PHE (rPHE) was calculated as a ratio of PHE and T1 ICH volume.

Results

Data from 60 MIS plus urokinase (MIS + U), 20 MIS aspiration only (MO), and 30 control patients were analyzed. The ICH volume, PHE volume and rPHE on T2 CT in both MIS + U and MO groups significantly decreased as compared with the control group (ICH volume, 13.7 ± 5.7 ml, 17.0 ± 10.5 ml vs. 30.5 ± 10.3 ml, P < 0.01; PHE volume, 36.5 ± 18.9 ml, 32.2 ± 17.5 ml vs. 45.4 ± 16.0 ml, P < 0.01; rPHE, 0.9 ± 0.4, 0.8 ± 0.4 vs.1.4 ± 0.5, P < 0.01). Between the MIS + U and MO groups, the ICH volume, PHE volume and rPHE at T2 trended towards similarity, but was not significant (P = 0.09, P = 0.40, P = 0.43). Furthermore, we found a significant correlation between the percent of ICH removal and PHE reduction (r = 0.59, P < 0.01). There was no correlation between the cumulative dose of urokinase and either T2 PHE volume (r = 0.19; P = 0.16) or T2 rPHE (r = -0.12; P = 0.37).

Conclusions

Hematoma evacuation using MIS leads to a significant reduction in PHE. Furthermore, the use of urokinase does not exacerbate PHE, making its hypothesized proedematous effects unlikely when the thrombolytic is administered directly into the clot.

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Abbreviations

ICH:

Intracerebral hemorrhage

CT:

Computed tomography

PHE:

Perihematomal edema

rPHE:

Relative perihematomal edema

MIS:

Minimally invasive surgery

IVH:

Intraventricular hemorrhage

MO:

Minimally invasive surgery aspiration only

MIS + U:

Minimally invasive surgery aspiration plus urokinase

GCS:

Glasgow coma scale

mRS:

Modified Rankin scale

rt-PA:

Recombinant tissue-type plasminogen activator

NICU:

Neurological intensive care unit

CNS:

Central nervous system

References

  1. Appelboom G, Bruce SS, Hickman ZL, Zacharia BE, Carpenter AM, Vaughan KA, Duren A, Hwang RY, Piazza M, Lee K, Claassen J, Mayer S, Badjatia N, Connolly ES Jr (2013) Volume-dependent effect of perihaematomal oedema on outcome for spontaneous intracerebral haemorrhages. J Neurol Neurosurg Psychiatry 84:488–493

    Article  PubMed  Google Scholar 

  2. Arima H, Wang JG, Huang Y, Heeley E, Skulina C, Parsons MW, Peng B, Li Q, Su S, Tao QL, Li YC, Jiang JD, Tai LW, Zhang JL, Xu E, Cheng Y, Morgenstern LB, Chalmers J, Anderson CS, INTERACT Investigators (2009) Significance of perihematomal edema in acute intracerebral hemorrhage: the INTERACT trial. Neurology 73:1963–1968

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Broderick JP, Brott TG, Duldner JE, Tomsick T, Huster G (1993) Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality. Stroke 24:987–993

    Article  CAS  PubMed  Google Scholar 

  4. Carhuapoma JR, Barrett RJ, Keyl PM, Hanley DF, Johnson RR (2008) Stereotactic aspiration-thrombolysis of intracerebral hemorrhage and its impact on perihematoma brain edema. Neurocrit Care 8:322–329

    Article  PubMed Central  PubMed  Google Scholar 

  5. Ducruet AF, Hickman ZL, Zacharia BE, Grobelny BT, Narula R, Guo KH, Claassen J, Lee K, Badjatia N, Mayer SA, Connolly ES Jr (2010) Exacerbation of perihematomal edema and sterile meningitis with intraventricular administration of tissue plasminogen activator in patients with intracerebral hemorrhage. Neurosurgery 66:648–655

    Article  PubMed  Google Scholar 

  6. Figueroa BE, Keep RF, Betz AL, Hoff JT (1998) Plasminogen activators potentiate thrombin-induced brain injury. Stroke 29:1202–1207

    Article  CAS  PubMed  Google Scholar 

  7. Keep RF, Hua Y, Xi G (2012) Intracerebral haemorrhage: mechanisms of injury and therapeutic targets. Lancet Neurol 11:720–731

    Article  CAS  PubMed  Google Scholar 

  8. Lian LF, Xu F, Tang ZP, Xue Z, Liang QM, Hu Q, Zhu WH, Kang HC, Liu XY, Wang FR, Zhu SQ (2014) Intraclot recombinant tissue-type plasminogen activator reduces perihematomal edema and mortality in patients with spontaneous intracerebral hemorrhage. J Huazhong Univ Sci Technolog Med Sci 34:165–171

    CAS  PubMed  Google Scholar 

  9. Mendelow AD, Gregson BA, Fernandes HM, Murray GD, Teasdale GM, Hope DT, Karimi A, Shaw MD, Barer DH, STICH investigators (2005) Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet 365:387–397

    Article  PubMed  Google Scholar 

  10. Mendelow AD, Gregson BA, Rowan EN, Murray GD, Gholkar A, Mitchell PM, STICH II Investigators (2013) Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial. Lancet 382:397–408

    Article  PubMed Central  PubMed  Google Scholar 

  11. Montes JM, Wong JH, Fayad PB, Awad IA (2000) Stereotactic computed tomographic-guided aspiration and thrombolysis of intracerebral hematoma: protocol and preliminary experience. Stroke 31:834–840

    Article  CAS  PubMed  Google Scholar 

  12. Morgenstern LB, Hemphill JC 3rd, Anderson C, Becker K, Broderick JP, Connolly ES Jr, Greenberg SM, Huang JN, MacDonald RL, Messé SR, Mitchell PH, Selim M, Tamargo RJ, American Heart Association Stroke Council and Council on Cardiovascular Nursing (2010) Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 41:2108–2129

    Article  PubMed  Google Scholar 

  13. Mould WA, Carhuapoma JR, Muschelli J, Lane K, Morgan TC, McBee NA, Bistran-Hall AJ, Ullman NL, Vespa P, Martin NA, Awad I, Zuccarello M, Hanley DF, MISTIE Investigators (2013) Minimally invasive surgery plus recombinant tissue-type plasminogen activator for intracerebral hemorrhage evacuation decreases perihematomal edema. Stroke 44:627–634

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Okuda M, Suzuki R, Moriya M, Fujimoto M, Chang CW, Fujimoto T (2006) The effect of hematoma removal for reducing the development of brain edema in cases of putaminal hemorrhage. Acta Neurochir Suppl 96:74–77

    Article  CAS  PubMed  Google Scholar 

  15. Rohde V, Rohde I, Thiex R, Ince A, Jung A, Dückers G, Gröschel K, Röttger C, Küker W, Müller HD, Gilsbach JM (2002) Fibrinolysis therapy achieved with tissue plasminogen activator and aspiration of the liquefied clot after experimental intracerebral hemorrhage: rapid reduction in hematoma volume but intensification of delayed edema formation. J Neurosurg 97:954–962

    Article  CAS  PubMed  Google Scholar 

  16. Ropper AH (1986) Lateral displacement of the brain and level of consciousness in patients with an acute hemispheral mass. N Engl J Med 314:953–958

    Article  CAS  PubMed  Google Scholar 

  17. Ruiz-Sandoval JL, Chiquete E, Romero-Vargas S, Padilla-Martinez JJ, Gonzalez-Cornejo S (2007) Grading scale for prediction of outcome in primary intracerebral hemorrhages. Stroke 38:1641–1644

    Article  PubMed  Google Scholar 

  18. Staykov D, Wagner I, Volbers B, Hauer EM, Doerfler A, Schwab S, Bardutzky J (2011) Natural course of perihemorrhagic edema after intracerebral hemorrhage. Stroke 42:2625–2629

    Article  PubMed  Google Scholar 

  19. Tang ZP, Shi YH, Yin XP, Xu JZ, Zhang SM, Wang W (2012) Modifying the details of aspiration operation may contribute to the improvement of prognosis of patients with ICH. Turk Neurosurg 22:13–20

    PubMed  Google Scholar 

  20. Teernstra OP, Evers SM, Lodder J, Leffers P, Franke CL, Blaauw G, Multicenter randomized controlled trial (SICHPA) (2003) Stereotactic treatment of intracerebral hematoma by means of a plasminogen activator: a multicenter randomized controlled trial (SICHPA). Stroke 34:968–974

    Article  CAS  PubMed  Google Scholar 

  21. van Asch CJ, Luitse MJ, Rinkel GJ, van der Tweel I, Algra A, Klijn CJ (2010) Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol 9:167–176

    Article  PubMed  Google Scholar 

  22. Venkatasubramanian C, Mlynash M, Finley-Caulfield A, Eyngorn I, Kalimuthu R, Snider RW, Wijman CA (2011) Natural history of perihematomal edema after intracerebral hemorrhage measured by serial magnetic resonance imaging. Stroke 42:73–80

    Article  PubMed Central  PubMed  Google Scholar 

  23. Volbers B, Staykov D, Wagner I, Dörfler A, Saake M, Schwab S, Bardutzky J (2011) Semi-automatic volumetric assessment of perihemorrhagic edema with computed tomography. Eur J Neurol 18:1323–1328

    Article  PubMed  Google Scholar 

  24. Volbers B, Wagner I, Willfarth W, Doerfler A, Schwab S, Staykov D (2013) Intraventricular fibrinolysis does not increase perihemorrhagic edema after intracerebral hemorrhage. Stroke 44:362–366

    Article  CAS  PubMed  Google Scholar 

  25. Wang WZ, Jiang B, Liu HM, Li D, Lu CZ, Zhao YD, Sander JW (2009) Minimally invasive craniopuncture therapy vs. conservative treatment for spontaneous intracerebral hemorrhage: results from a randomized clinical trial in China. Int J Stroke 4:11–16

    Article  PubMed  Google Scholar 

  26. Xu F, Tang Z, Luo X, Kang H, Hu Q, Wang W, Zhu S (2010) No evidence of preoperative hematoma growth representing an increased postoperative rebleeding risk for minimally invasive aspiration and thrombolysis of ICH. Br J Neurosurg 24:268–274

    PubMed  Google Scholar 

  27. Zazulia AR, Diringer MN, Derdeyn CP, Powers WJ (1999) Progression of mass effect after intracerebral hemorrhage. Stroke 30:1167–1173

    Article  CAS  PubMed  Google Scholar 

  28. Zhou H, Zhang Y, Liu L, Huang Y, Tang Y, Su J, Hua W, Han X, Xue J, Dong Q (2011) Minimally invasive stereotactic puncture and thrombolysis therapy improves long-term outcome after acute intracerebral hemorrhage. J Neurol 258:661–669

    Article  PubMed Central  PubMed  Google Scholar 

  29. Zhou X, Chen J, Li Q, Ren G, Yao G, Liu M, Dong Q, Guo J, Li L, Guo J, Xie P (2012) Minimally invasive surgery for spontaneous supratentorial intracerebral hemorrhage: a meta-analysis of randomized controlled trials. Stroke 43:2923–2930

    Article  PubMed  Google Scholar 

  30. Ziai W, Moullaali T, Nekoovaght-Tak S, Ullman N, Brooks JS, Morgan TC, Hanley DF (2013) No exacerbation of perihematomal edema with intraventricular tissue plasminogen activator in patients with spontaneous intraventricular hemorrhage. Neurocrit Care 18:354–361

    Article  PubMed  Google Scholar 

  31. Zimmerman RD, Maldjian JA, Brun NC, Horvath B, Skolnick BE (2006) Radiologic estimation of hematoma volume in intracerebral hemorrhage trial by CT scan. AJNR Am J Neuroradiol 27:666–670

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Research was supported by grants from the National Natural Science Foundation of China (No.81171089 and No. 30770751). Research was also supported by grants from the Key Clinical Program of the Ministry of Health of China (2010) and the Future Program of New Technology and New Business in Tongji Hospital (2012).

The authors would like to thank Dr. Austin Cape and Dr. Laura Darnieder for their careful reading and feedback in the preparation and revision of this manuscript.

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China

    Lifei Lian, Feng Xu, Qi Hu, Qiming Liang, Wenhao Zhu, Huicong Kang, Xiaoyan Liu, Zhouping Tang & Suiqiang Zhu

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  1. Lifei Lian
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Correspondence to Suiqiang Zhu.

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Lian, L., Xu, F., Hu, Q. et al. No exacerbation of perihematomal edema with intraclot urokinase in patients with spontaneous intracerebral hemorrhage. Acta Neurochir 156, 1735–1744 (2014). https://doi.org/10.1007/s00701-014-2130-9

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  • DOI: https://doi.org/10.1007/s00701-014-2130-9

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