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

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

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

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

New Predictor of In-Hospital Mortality of The Surgically Treated Haemorrhagic Stroke: Subanalysis

At present there are no specific limits on the level of inflammatory markers which can be used as a boundary between excessive or non-inflammatory responses. We investigate the leukocytes count at hospital admission of spontaneous intracerebral haemorrhage patients to be proposed as a boundary between excessive inflammation and not excessive. This is a subanalysis from the study of the neuroprotective effect of tigecycline on brain injury due to spontaneous intracerebral haemorrhage supratentorial who underwent evacuation of the hematoma. Leukocytosis defined as a leukocyte count ≥ 11.000 cells/mL. The primary outcome was inhospital mortality and the secondary outcome was length of hospital stay (LOS). Statistical analysis conducted by chi-square or Fisher’s exact test and logistic regression. Seventy patients were included. Approximately 79% of the patients had leucocytosis. Leucocytosis was not associated with inhospital mortality or LOS of 15 days or longer. However, a leucocyte count of 20,000 mm3 or higher was associated with in-hospital mortality (odds ratio, 9.09; 95% confidence interval, 1.97 to 42.06; P = 0.005). A leucocyte count of 20,000/mm3 or higher can be proposed as a boundary of the excessive inflammation on spontaneous intracerebral haemorrhage. Prediktor Baru Kematian di Rumah Sakit untuk Pasien Stroke Hemoragik yang Dilakukan Operasi: Hasil Subanalisis Saat ini belum ada penanda khusus untuk menilai suatu respons inflamasi yang berlebihan atau tidak. Penelitian ini bermaksud mengungkap jumlah leukosit tertentu sebagai penanda inflamasi yang berlebihan pada pasien perdarahan otak spontan yang dilakukan operasi evakuasi hematoma intracranial. Penelitian Ini adalah subanalisis dari studi efek neuroprotektif tigecycline pada cedera otak akibat perdarahan intraserebral spontan yang menjalani evakuasi hematoma. Leukositosis didefinisikan sebagai jumlah leukosit ≥ 11.000 sel / mL. Luaran utamanya adalah kematian di rumah sakit dan luaran sekundernya adalah lama perawatan di rumah sakit (LOS= length of stay). Analisis statistik dilakukan dengan chi-square atau uji eksak Fisher dan regresi logistik. Hasil: 70 pasien dilibatkan. Sekitar 79% dari pasien memiliki leukositosis. Leucocytosis tidak berhubungan dengan kematian di rumah sakit atau LOS 15 hari atau lebih. Namun, jumlah leukosit 20.000 mm3 atau lebih tinggi berhubungan dengan kematian di rumah sakit (rasio odds, 9,09; interval kepercayaan 95%, 1,97 hingga 42,06; P = 0,005). Jumlah leukosit 20.000 / mm3 atau lebih tinggi dapat diusulkan sebagai batas peradangan berlebihan pada perdarahan intraserebral spontan.&nbsp