Skip to main content

Advertisement

SpringerLink
Log in

Early Celecoxib Use in Spontaneous Intracerebral Hemorrhage is Associated with Reduced Mortality

  • Original work
  • Published:
Neurocritical Care Aims and scope Submit manuscript

Abstract

Background

Hemorrhagic strokes constitute 10–15% of all strokes and have the worst mortality and morbidity of all subtypes. Mortality and morbidity of spontaneous intracerebral hemorrhage (sICH) are often secondary to the effects of inflammation, brain edema, and swelling. Studies have shown that celecoxib, a selective cyclooxygenase 2 (COX-2) inhibitor, reduces perihematomal edema formation and inflammation. This study aimed to examine the impact of celecoxib on sICH outcomes.

Methods

TriNetX, a multi-institutional research database, was retrospectively queried to identify patients with sICH. Outcomes in patients who received celecoxib within 5 days (cohort 1) were analyzed and compared to those in patients who did not receive celecoxib (cohort 2). The primary end point was mortality within 1 year of sICH. Secondary end points included ventilator dependence, tracheostomy, percutaneous endoscopic gastrostomy tube placement, craniotomy, deep venous thrombosis, pulmonary embolism, ischemic stroke, transient ischemia attack, myocardial infarction, and seizures. Further analysis was performed to assess these outcomes for patients treated with ibuprofen, a nonselective COX inhibitor.

Results

After propensity score matching, 833 patients were identified in each cohort based on celecoxib use. Mortality at 1 year was significantly reduced in patients with sICH receiving celecoxib compared to those who did not (13.33% vs. 17.77%; p = 0.0124). Risks of ventilator dependence, tracheostomy, percutaneous endoscopic gastrostomy tube placement, craniotomy, deep venous thrombosis, pulmonary embolism, ischemic stroke, transient ischemia attack, myocardial infarction, and seizures were not significantly increased in patients who received celecoxib within 5 days of sICH compared to those who did not receive celecoxib. There was no significant difference in mortality between patients based on ibuprofen administration.

Conclusions

There exists a growing interest in using COX-2 as a potential target strategy for neuroprotection in patients with sICH, with some evidence of a mortality benefit in small cohort studies. This study shows that early celecoxib use is associated with decreased mortality in patients with sICH.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Fernando SM, Qureshi D, Talarico R, Tanuseputro P, Dowlatshahi D, Sood MM, et al. Intracerebral hemorrhage incidence, mortality, and association with oral anticoagulation use: a population study. Stroke. 2021;52(5):1673–81.

    Article  PubMed  Google Scholar 

  2. Jaillard A, Cornu C, Durieux A, Moulin T, Boutitie F, Lees KR, MAST-E Group, et al. Hemorrhagic transformation in acute ischemic stroke. The MAST-E study. Stroke. 1999;30(7):1326–32.

    Article  CAS  PubMed  Google Scholar 

  3. McGuire AJ, Raikou M, Whittle I, Christensen MC. Long-term mortality, morbidity and hospital care following intracerebral hemorrhage: an 11-year cohort study. Cerebrovasc Dis. 2007;23(2–3):221–8.

    Article  PubMed  Google Scholar 

  4. Brott T, Broderick J, Kothari R, Barsan W, Tomsick T, Sauerbeck L, et al. Early hemorrhage growth in patients with intracerebral hemorrhage. Stroke. 1997;28(1):1–5.

    Article  CAS  PubMed  Google Scholar 

  5. Xi G, Keep RF, Hoff JT. Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol. 2006;5(1):53–63.

    Article  PubMed  Google Scholar 

  6. Tschoe C, Bushnell CD, Duncan PW, Alexander-Miller MA, Wolfe SQ. Neuroinflammation after intracerebral hemorrhage and potential therapeutic targets. J Stroke. 2020;22(1):29–46.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Lord AS, Gilmore E, Choi HA, Mayer SA, VISTA-ICH Collaboration. Time course and predictors of neurological deterioration after intracerebral hemorrhage. Stroke. 2015;46(3):647–52.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Gebel JM Jr, Jauch EC, Brott TG, Khoury J, Sauerbeck L, Salisbury S, et al. Natural history of perihematomal edema in patients with hyperacute spontaneous intracerebral hemorrhage. Stroke. 2002;33(11):2631–5.

    Article  PubMed  Google Scholar 

  9. Venkatasubramanian C, Mlynash M, Finley-Caulfield A, Eyngorn I, Kalimuthu R, Snider RW, et al. Natural history of perihematomal edema after intracerebral hemorrhage measured by serial magnetic resonance imaging. Stroke. 2011;42(1):73–80.

    Article  PubMed  Google Scholar 

  10. Kashiwazaki D, Tomita T, Shibata T, Yamamoto S, Hori E, Akioka N, et al. Impact of perihematomal edema on infectious complications after spontaneous intracerebral hemorrhage. J Stroke Cerebrovasc Dis. 2021;30(7):105827.

    Article  PubMed  Google Scholar 

  11. Huttner HB, Kohrmann M, Berger C, Georgiadis D, Schwab S. Predictive factors for tracheostomy in neurocritical care patients with spontaneous supratentorial hemorrhage. Cerebrovasc Dis. 2006;21(3):159–65.

    Article  PubMed  Google Scholar 

  12. Hemphill JC 3rd, Greenberg SM, Anderson CS, Becker K, Bendok BR, Cushman M, American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2015;46(7):2032–60.

    Article  PubMed  Google Scholar 

  13. Goldstein JN, Marrero M, Masrur S, Pervez M, Barrocas AM, Abdullah A, et al. Management of thrombolysis-associated symptomatic intracerebral hemorrhage. Arch Neurol. 2010;67(8):965–9.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Rodriguez-Luna D, Rodriguez-Villatoro N, Juega JM, Boned S, Muchada M, Sanjuan E, et al. Prehospital systolic blood pressure is related to intracerebral hemorrhage volume on admission. Stroke. 2018;49(1):204–6.

    Article  PubMed  Google Scholar 

  15. Zahuranec DB, Lisabeth LD, Sánchez BN, Smith MA, Brown DL, Garcia NM, et al. Intracerebral hemorrhage mortality is not changing despite declining incidence. Neurology. 2014;82(24):2180–6.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Park HK, Lee SH, Chu K, Roh JK. Effects of celecoxib on volumes of hematoma and edema in patients with primary intracerebral hemorrhage. J Neurol Sci. 2009;279(1–2):43–6.

    Article  CAS  PubMed  Google Scholar 

  17. Lee SH, Park HK, Ryu WS, Lee JS, Bae HJ, Han MK, et al. Effects of celecoxib on hematoma and edema volumes in primary intracerebral hemorrhage: a multicenter randomized controlled trial. Eur J Neurol. 2013;20(8):1161–9.

    Article  PubMed  Google Scholar 

  18. Chu K, Jeong SW, Jung KH, Han SY, Lee ST, Kim M, et al. Celecoxib induces functional recovery after intracerebral hemorrhage with reduction of brain edema and perihematomal cell death. J Cereb Blood Flow Metab. 2004;24(8):926–33.

    Article  CAS  PubMed  Google Scholar 

  19. Doré S, Otsuka T, Mito T, Sugo N, Hand T, Wu L, et al. Neuronal overexpression of cyclooxygenase-2 increases cerebral infarction. Ann Neurol. 2003;54(2):155–62.

    Article  PubMed  Google Scholar 

  20. Nogawa S, Zhang F, Ross ME, Iadecola C. Cyclo-oxygenase-2 gene expression in neurons contributes to ischemic brain damage. J Neurosci. 1997;17(8):2746–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Nagayama M, Niwa K, Nagayama T, Ross ME, Iadecola C. The cyclooxygenase-2 inhibitor NS-398 ameliorates ischemic brain injury in wild-type mice but not in mice with deletion of the inducible nitric oxide synthase gene. J Cereb Blood Flow Metab. 1999;19(11):1213–9.

    Article  CAS  PubMed  Google Scholar 

  22. Ironside N, Chen CJ, Dreyer V, Ding D, Buell TJ, Connolly ES. History of nonsteroidal anti-inflammatory drug use and functional outcomes after spontaneous intracerebral hemorrhage. Neurocrit Care. 2021;34(2):566–80.

    Article  CAS  PubMed  Google Scholar 

  23. Taquet M, Geddes JR, Husain M, Luciano S, Harrison PJ. 6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records. Lancet Psychiatry. 2021;8(5):416–27.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Taquet M, Husain M, Geddes JR, Luciano S, Harrison PJ. Cerebral venous thrombosis and portal vein thrombosis: a retrospective cohort study of 537,913 COVID-19 cases. EClinicalMedicine. 2021;39:101061.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Raiker R, DeYoung C, Pakhchanian H, Ahmed S, Kavadichanda C, Gupta L, et al. Outcomes of COVID-19 in patients with rheumatoid arthritis: a multicenter research network study in the United States. Semin Arthritis Rheum. 2021;51(5):1057–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Topaloglu U, Palchuk MB. Using a federated network of real-world data to optimize clinical trials operations. JCO Clin Cancer Inform. 2018;2(2):1–10.

    Article  PubMed  Google Scholar 

  27. Bhanja D, Hallan DR, Staub J, Rizk E, Zacko JC. Early celecoxib use in patients with traumatic brain injury. Neurocrit Care. 2023. https://doi.org/10.1007/s12028-023-01827-w.

    Article  PubMed  Google Scholar 

  28. Poon MT, Fonville AF, Al-Shahi SR. Long-term prognosis after intracerebral haemorrhage: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2014;85(6):660–7.

    Article  PubMed  Google Scholar 

  29. Aronowski J, Zhao X. Molecular pathophysiology of cerebral hemorrhage: secondary brain injury. Stroke. 2011;42(6):1781–6.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Strauss KI, Marini AM. Cyclooxygenase-2 inhibition protects cultured cerebellar granule neurons from glutamate-mediated cell death. J Neurotrauma. 2002;19(5):627–38.

    Article  PubMed  Google Scholar 

  31. Pelliccia F, Pasceri V, Granatelli A, Pristipino C, Speciale G, Roncella A, et al. Safety and efficacy of short-term celecoxib before elective percutaneous coronary intervention for stable angina pectoris. Am J Cardiol. 2006;98(11):1461–3.

    Article  CAS  PubMed  Google Scholar 

  32. Solomon SD, McMurray JJ, Pfeffer MA, Wittes J, Fowler R, Finn P, Adenoma Prevention with Celecoxib (APC) Study Investigators, et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 2005;352(11):1071–80.

    Article  CAS  PubMed  Google Scholar 

  33. Sinn DI, Lee ST, Chu K, Jung KH, Song EC, Kim JM, et al. Combined neuroprotective effects of celecoxib and memantine in experimental intracerebral hemorrhage. Neurosci Lett. 2007;411(3):238–42.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

The project described was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through grant UL1 TR002014. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA

    Bao Y. Sciscent, David R. Hallan, Debarati Bhanja, Jacob Staub, Derek Crossman, Elias B. Rizk, J. Christopher Zacko, Haejoe Park & Sprague W. Hazard

  2. Department of Anesthesia, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA

    Sprague W. Hazard

Authors
  1. Bao Y. Sciscent
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David R. Hallan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Debarati Bhanja
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jacob Staub
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Derek Crossman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Elias B. Rizk
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J. Christopher Zacko
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Haejoe Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Sprague W. Hazard
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization: DRH, EBR, JCZ, HP, SWH; methodology: DRH; software: DRH, BYS, DB, JS; formal analysis: DRH, BYS, DB; investigation: DRH, BYS, DB; resources: DRH, BYS, DB; data curation: DRH; original draft preparation: DRH, BYS, DB, JS, DC; review and editing: DRH, EBR, JCZ, HP, SWH; visualization: DRH, BYS, DB, JS, DC; supervision: EBR, JCZ, HP, SWH.

Corresponding author

Correspondence to David R. Hallan.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

This study used a deidentified database that does not require prior institutional review board approval.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sciscent, B.Y., Hallan, D.R., Bhanja, D. et al. Early Celecoxib Use in Spontaneous Intracerebral Hemorrhage is Associated with Reduced Mortality. Neurocrit Care (2024). https://doi.org/10.1007/s12028-024-01996-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12028-024-01996-2

Keywords

Search

Navigation