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

Latar belakang: Luaran perdarahan intraserebral spontan supratentorial (PISS) masih buruk. Respons inflamasi sekunder akibat cedera otak dan prosedur bedah diyakini sebagai penyebabnya. Penelitian ini bertujuan untuk mengetahui aktivitas antiinflamasi tigesiklin dengan menghitung kadar TNF-α, dan efek neuroproteksi yang dicerminkan oleh angka kematian di rumah sakit. Metode: 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). Hasil: 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). Kesimpulan: Tigesiklin memiliki kemampuan antiinflamasi dan neuroproteksi, serta memperbaiki luaran klinis pada PISS yang dilakukan evakuasi hematoma. 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.