Tigecycline reduced tumor necrosis factor alpha level and inhospital mortality in spontaneous supratentorial intracerebral hemorrhage
DOI:
https://doi.org/10.13181/mji.v25i2.1351Keywords:
inhospital mortality, SSIH, tigecycline, TNF-αAbstract
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: Pasien dengan PISS yang akan dilakukan evakuasi hematoma, dirandomisasi untuk jenis antibiotik profilaksis tigesiklin (n=35) atau fosfomisin (n=37). Pada semua subjek diukur kadar TNF-α sebelum pembedahan serta hari ke-1 dan ke-7 pascabedah. Pada hari ke-7 dilakukan pemeriksaan CT Scan ulang. Skor Glasgow outcome scale (GOS) dan lama rawat dicatat pada saat keluar rumah sakit. Data dianalisis dengan uji Mann-Whitney atau uji kai kuadrat. Efektivitas klinis relatif dinilai dengan menghitung number needed to treat (NNT).
Results: Didapatkan perbedaan bermakna pada proporsi subjek yang mengalami penurunan kadar TNF-α pada kelompok tigesiklin dibanding fosfomisin pada hari ke-7 pascabedah (62% vs 29%, p=0,022). Pengurangan edema pacsa operasi berbeda tidak bermakna pada kedua kelompok (86% vs 80%, p=0,580). Tigesiklin menunjukkan efektivitas klinis mengurangi luaran buruk (GOS ≤ 2 (20% vs 38% ; p=0,096; OR=0,41; NNT=6) dan inhospital mortality (17% vs 35%; p=0,083; OR=0,49; NNT=5). 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.
Downloads
References
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
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
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
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
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
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
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
Wang J, Dore S. Inflammation after intrcerebral hemorrhage. J Cereb Blood Flow Metab. 2007;27(5):894-908. DOI: 10.1038/sj.jcbfm.9600403
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
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
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.
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
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
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
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
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
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.
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
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
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
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
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
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
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
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
Shaikh PZ. Cytokines & their physiologic and pharmacologic functions in inflammation: a review. Int J of Pharm Life Sci. 2011;2(11):1247-63.
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
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
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
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
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
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
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
How to Cite
Issue
Section
License
Authors who publish with Medical Journal of Indonesia agree to the following terms:
- Authors retain copyright and grant Medical Journal of Indonesia right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial License that allows others to remix, adapt, build upon the work non-commercially with an acknowledgment of the work’s authorship and initial publication in Medical Journal of Indonesia.
- Authors are permitted to copy and redistribute the journal's published version of the work non-commercially (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in Medical Journal of Indonesia.
