Tigecycline reduced tumor necrosis factor alpha level and inhospital mortality in spontaneous supratentorial intracerebral hemorrhage

  • Mohamad Saekhu Department of Neurosurgery, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta
  • Hilman Mahyuddin Department of Neurosurgery, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta
  • Tegus A.S. Ronokusumo Department of Neurology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta
  • Sudigdo Sastroasmoro Department of Pediatric, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta
Keywords: inhospital mortality, SSIH, tigecycline, TNF-α
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Abstract

Background: The outcome of patients with spontaneous supratentorial intracerebral hemorrhage (SSICH) is unsatisfactory. Inflammatory response secondary to brain injury as well as those resulted from surgical procedure were considered responsible of this outcome. This study was intended to elucidate the anti-inflammatory activity of tigecycline by measuring TNF-α level and its neuroprotective effect as represented by inhospital mortality rate.

Methods: Patients with SSICH who were prepared for hematoma evacuation were randomized to receive either tigecycline (n=35) or fosfomycine (n=37) as prophylactic antibiotic. TNF-α level was measured in all subjects before surgery and postoperatively on day-1 and day-7. A repeated brain CT Scan was performed on postoperative day-7. The Glasgow outcome scale (GOS) and length of stay (LOS) were recorded at the time of hospital discharge. Data were analyzed using Mann-Whitney and Chi square test. Relative clinical effectiveness was measured by calculating the number needed to treat (NNT).

Results: There was a significant difference regarding the proportion of subject who had  reduced TNF-α level on postoperative day-7 between the groups receiving tigecycline and fosfomycine (62% vs 29%, p=0.022). Decrease brain edema on CT control (86% vs 80%, p=0.580). Tigecycline administration showed a tendency of better clinical effectiveness in lowering inhospital mortality (17% vs 35%; p=0.083; OR=0.49; NNT=5) and worse clinical outcome / GOS ≤ 2 (20% vs 38% ; p=0.096; OR=0.41; NNT=6). LOS ≥ 15 hari ( 40% vs 27%; p=0.243; OR=1.81; NNT=8).

Conclusion: Tigecycline showed anti-inflammatory and neuroprotective activities. These activities were associated with improved clinical outcome in patients with SSICH after hematoma evacuation.

Author Biography

Mohamad Saekhu, Department of Neurosurgery, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta
Neurosurgery Department, Faculty of Medicine, Universitas Indonesia

References

  1. Sacco S, Marini C, Toni D, Oliveri L, Carolei A. Incidence and 10-year survival of intracerebral hemorrhage in a population-based registry. Stroke. 2009;40(2):394–9. http://dx.doi.org/10.1161/STROKEAHA.108.523209

  2. Christensen MC, Mayer S, Ferran JM. Quality of life after intracerebral hemorrhage: result of the factor seven for acute hemorrhagic stroke (FAST) trial. Stroke. 2009;40(5):1677–82. http://dx.doi.org/10.1161/STROKEAHA.108.538967

  3. Patil CG, Alexander AL, Gephart Gephart MG, Lad SP, Arrigo RT, Boakye M. A population-based study of inpatient outcomes after operative managemant of nontraumatic intracerebral hemorrhage in the United States. World Neurosurg. 2012;78(6):640–5. http://dx.doi.org/10.1016/j.wneu.2011.10.042

  4. Belur PK, Chang JJ, He S, Emanuel BA, Mack WJ. Emerging experimental therapies for intracerebral hemorrhage: targeting mechanisms of secondary brain injury. Neurosurg Focus. 2013;34(5):E9. http://dx.doi.org/10.3171/2013.2.FOCUS1317

  5. Hyong A, Jadhav V, Lee S, Tong W, Rowe J, Zhang JH, Tang J. Rosiglitazone, a PPAR gamma agonist, attenuates inflammation after surgical brain injury in rodents. Brain Res. 2008;1215:218–24. http://dx.doi.org/10.1016/j.brainres.2008.04.025

  6. Minematsu K. Evacuation of intracerebral hematoma is likely to be beneficial. Stroke. 2003;34(6):1567–8. http://dx.doi.org/10.1161/01.STR.0000074549.37517.54

  7. Anik I, Secer HI, Anik Y, Duz B, Gonul E. Meta-analyses of intracerebral hematoma treatment. Turk Neurosurg. 2010;21(1):6–14. http://dx.doi.org/10.5137/1019-5149.jtn.3432-10.1

  8. Wang J, Dore S. Inflammation after intrcerebral hemorrhage. J Cereb Blood Flow Metab. 2007;27(5):894–908. DOI: 10.1038/sj.jcbfm.9600403

  9. Feigin VL, Anderson NE, Rinkel GJE, Algra A, Gijn JV, Bennett DA, et al. Corticosteroids in patients with hemorrhagic stroke. Stroke. 2006;37:1344–5. http://dx.doi.org/10.1161/01.STR.0000217375.18081.38

  10. Yrjänheikki J, Tikka T, Keinänen R, Goldsteins G, Chan PH, Koistinaho J. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc Natl Acad USA. 1999;96(23):13496–500. http://dx.doi.org/10.1073/pnas.96.23.13496

  11. Tikka T, Fiebich BL, Goldsteins G, Keinanen R, Koistinaho J. Minocycline, a tetracycline derivative, is neuroprotective againts excitotoxicity by inhibiting activation and proliferation of microglia. J Neurosci. 2001;21(8):2580–8.

  12. Brunswick AS, Hwang BY, Appelboom G, Hwang RY, Piazza MA, Connolly Jr ES. Serum biomarkers of spontaneous intracerebral hemorrhage induced secondary brain injury. J Neurol Sci. 2012;321(2012):1–10. http://dx.doi.org/10.1016/j.jns.2012.06.008

  13. Castillo J, Dávalos A, Alvarez-Sabin J, Pumar JM, Leira R, Silva Y, et al. Molecular signatures of brain injury after intracerebral hemorrhage. Neurology. 2002;58(4):624–9. http://dx.doi.org/10.1212/WNL.58.4.624

  14. Mayne M, Ni W, Yan HJ, Xue M, Johnston JB, Del Bigio MR, et al. Antisense oligodeoxynucleotide inhibition of tumor necrosis factor-alpha expression is neuroprotective after intracerebral hemorrhage. Stroke. 2001;32(1):240–8. http://dx.doi.org/10.1161/01.STR.32.1.240

  15. Salvatore CM, Techasaensiri C, Tagliabue C, Katz K, Leos N, Gomes AM, et al. Tigecycline therapy significantly reduces the concentrations of inflamatory pulmonary cytokines and chemokines in a murine model of Mycoplasma pneumoniae pneumonia. Antimicrob Agents Chemother. 2009;53(4):1546–51. http://dx.doi.org/10.1128/AAC.00979-08

  16. Kothari RU, Brott T, Broderick JP, Barsan WG, Sauerbeck LR, Zuccarello M, et al. The ABCs of measuring intracerebral hemorrhage volumes. Stroke. 1996;27(8):1304–5. http://dx.doi.org/10.1161/01.STR.27.8.1304

  17. Madiyono B, Moeslichan S, Sastroasmoro S, Budiman I, Purwanto SH. Perkiraan besar sampel. In: Sastroasmoro S, Ismael S, editors. Dasar-dasar Metodologi Penelitian Klinis. 5th ed. Jakarta: CV Sagung Seto;2014. p. 352–95. Indonesian.

  18. Sanchez CE, Ogilvy CS, Carter BS. Outcomes studies in cerebrovascular neurosurgery. Neurosurg Focus. 2007;22(3):E11. http://dx.doi.org/10.3171/foc.2007.22.3.13

  19. Oliveira RA, Araújo S, Falcão AL, Soares SM, Kosour C, Dragosavac D, et al. Glasgow outcome scale at hospital discharge as a prognostic index in patients with severe traumatic brain injury. Arq Neuropsiquatr. 2012;70(8):604–8. http://dx.doi.org/10.1590/S0004-282X2012000800009

  20. Broderick JP, Brott TG, Duldner JE, Tomsick T, Huster G. Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality. Stroke. 1993;24(7):987–93. http://dx.doi.org/10.1161/01.STR.24.7.987

  21. Hemphill III JC 3rd, Greenberg SM, Anderson CS, Becker K, Bendok BR, Cushman M, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professional from the American Heart Association/American Stroke Association. Stroke. 2015;46(7):2031–60. DOI: 10.1161/STR.0b013e3181ec611b

  22. Andres RH, Guzman R, Ducray AD, Mordasini P, Gera A, Barth A, et al. Cell replacement therapy for intracerebral hemorrhage. Neurosurg Focus. 2008;24(3–4):E16. http://dx.doi.org/10.3171/FOC/2008/24/3-4/E15

  23. Hwang BY, Appelboom G, Ayer A, Kellner CP, Kotchetkov IS, Gigante PR, et al. Advances in neuroprotective strategies: potential therapies for intracerebral hemorrhage. Cerebrovasc Dis. 2011;31(3):211–22. http://dx.doi.org/10.1159/000321870

  24. Katsuki H. Exploring neuroprotective drug therapies for intracerebral hemorrhage. J Pharmacol Sci. 2010;114(4):366–78. http://dx.doi.org/10.1254/jphs.10R05CR

  25. Xue M, Mikliaeva EI, Casha S, Zygun D, Demchuk A, Yong VW. Improving outcomes of neuroprotection by minocycline: guides from cell culture and intracerebral hemorrhage in mice. Am J Pathol. 2010;176(3):1193–202. http://dx.doi.org/10.2353/ajpath.2010.090361

  26. Shaikh PZ. Cytokines & their physiologic and pharmacologic functions in inflammation: a review. Int J of Pharm Life Sci. 2011;2(11):1247–63.

  27. Lei B, Dawson HN, Roulhac-Wilson B, Wang H, Laskowitz DT, James ML. Tumor necrosis factor a antagonism improves neurological recovery in murine intracerebral hemorrhage. J Neuroinflammation. 2013;10:103. http://dx.doi.org/10.1186/1742-2094-10-103

  28. Patil CG, Alexander AL, Hayden Gephart MG, Lad SP, Arrigo RT, Boakye M. A population-based study of inpatient outcomes after operative managemant of nontraumatic intracerebral hemorrhage in the United States. World Neurosurg. 2012;78(6):640–5. http://dx.doi.org/10.1016/j.wneu.2011.10.042

  29. Nag C, Das K, Ghosh M, Khandakar MR. Prediction of clinical outcome in acute hemorrhagic stroke from a single CT scan on admission. N Am J Med Sci. 2012;4(10):463–7. http://dx.doi.org/10.4103/1947-2714.101986

  30. Daverat P, Castel JP, Dartigues JF, Orgogozo JM. Death and functional outcome after spontaneous intracerebral hemorrhage. A prospective study of 166 cases using multivariate analysis. Stroke. 1991;22(1):1–6. http://dx.doi.org/10.1161/01.STR.22.1.1

  31. Ganti L, Jain A, Yerragondu N, Jain M, Bellolio MF, Gilmore RM, et al. Female gender remains an independent risk factor for poor outcome after acute nontraumatic intracerebral hemorrhage. Neurol Res Intl. 2013;2013:219097. http://dx.doi.org/10.1155/2013/219097

  32. Togha M, Bakhtavar K. Factor associated with in-hospital mortality following intracerebral hemorrhage: a three year study in Tehran, Iran. BMC Neurol. 2004;4:9. http://dx.doi.org/10.1186/1471-2377-4-9

  33. Yousuf RM, Fauzi ARM, Jamalludin AR, How SH, Amran M, Shahrin TCA, et al. Predictor of in-hospital mortality in primary intracerebral haemorrhage in East coast of Peninsular Malaysia. Neurology Asia. 2012;17(2):93–9.

Published
2016-07-26
How to Cite
1.
Saekhu M, Mahyuddin H, Ronokusumo TA, Sastroasmoro S. Tigecycline reduced tumor necrosis factor alpha level and inhospital mortality in spontaneous supratentorial intracerebral hemorrhage. Med J Indones [Internet]. 2016Jul.26 [cited 2019Nov.19];25(2):69-5. Available from: http://mji.ui.ac.id/journal/index.php/mji/article/view/1351
Section
Clinical Research

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