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Mahyuddin, Hilman
Department of Neurosurgery, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta
Medicine & Pharmacology

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MMP-9, brain edema, and length of hospital stay of patients with spontaneous supratentorial intracerebral hemorrhage after hematoma evacuation along with the administration of tigecycline Saekhu, Mohamad; Ibrahim, Nurhadi; Timan, Ina S.; Madjid, Amir S.; Muttaqin, Zainal; Ronokusumo, Teguh A.S.; Sastroasmoro, Sudigdo; Mahyuddin, Hilman
Medical Journal of Indonesia Vol 25, No 4 (2016): December
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (434.882 KB) | DOI: 10.13181/mji.v25i4.1520

Abstract

Background: The high plasma level of matrix metalloproteinses–9 (MMP-9) is believed to disrupt the blood-brain barrier (BBB) and cause brain edema, as well as increase patient’s length of hospital stay (LOS). Tigecycline showed ability to reduce the MMP-9 level on study in animals. This study aimed to evaluate whether tigecycline can reduce the plasma levels of MMP-9; brain edema; and LOS of patients with supratentorial spontaneous intracerebral hemorrhage (SSICH).Methods: A randomized clinical trial (RCT) was conducted on 72 SSICH patients who underwent hematoma evacuation in eleven hospitals in Jakarta; 100 mg tigecycline (n=35) or 2 g fosfomycine (n=37) administered intravenously before skin incision as an prophylactic antibiotics to avoid post-operative infections. Plasma levels of MMP-9 were measured in all subjects before and on the first and seventh day after the surgery. Reduction of brain edema was assessed by comparing the extent of brain edema on computed tomography scan (CT scan) before and CT scan after surgery. The length of stay (LOS) was recorded at the time of hospital discharge either survive or death. Data were analyzed using Mann-Whitney and Chi-Square test.Results: There were non-significant statistical differences between two groups in the proportion of subjects with reduced MMP-9 levels on the first day (48% vs 50%; p=0.902; OR=1.1) and seventh day after the surgery (33% vs 48%; p=0.296; OR=1.9); proportion of the subjects with brain edema reduction (86% vs 80%, p=0.58); LOS (median 12 days vs 13 days, p=0.256; LOS ≥15 days 40% vs 27%; p=0.243; OR=1.81; NNT=8).Conclusion: On SSICH patients who underwent hematoma evacuation, tigecycline did not either reduce MMP-9 levels and brain edema or shorthen LOS.
Tigecycline reduced tumor necrosis factor alpha level and inhospital mortality in spontaneous supratentorial intracerebral hemorrhage Saekhu, Mohamad; Mahyuddin, Hilman; Ronokusumo, Tegus A.S.; Sastroasmoro, Sudigdo
Medical Journal of Indonesia Vol 25, No 2 (2016): June
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (428.806 KB) | DOI: 10.13181/mji.v25i2.1351

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.
Co-Authors A.A. Ketut Agung Cahyawan W Amir S. Madjid, Amir S. Ina S. Timan, Ina S. Mohamad Saekhu Nurhadi Ibrahim Ronokusumo, Teguh A.S. Ronokusumo, Tegus A.S. Sudigdo Sastroasmoro