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"Peran Atorvastatin Sebagai Protektor Otak Pada Pasien Cedera Otak Traumatik Sedang Ditinjau Dari Kadar Tissue Plasminogen Activator, Tumor Necrosis Factor Alpha Dan Laju Perbaikan Skor Gcs"

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Cedera otak traumatik (COT) masih menjadi masalah morbiditas dan
mortalitas utama di dunia. Pasca COT, pasien yang selamat sering mengalami
dengan gangguan kognitif dan intelektual, perubahan mood , tingkah laku dan
Sindrom Distress Pascatrauma (SDPT). Prioritas penanganan adalah mencegah
berkembangnya cedera otak sekunder yang dapat memperburuk outcome dengan
cara melakukan proteksi otak. Salah satu teknik proteksi otak yaitu dengan
menggunakan obat yang memiliki efek proteksi otak. Statin memiliki efek
pleiotropik yang bersifat kolesterol-independen dengan efek yang potensial dalam
tata laksana gangguan neurologis diantaranya mengurangi efek trombosis dan
kaskade koagulasi dan antiinflamasi.Tujuan penelitian ini adalah untuk melihat
pengaruh pemberian atorvastatin 40 mg per oral terhadap kadar tPA dan TNF-α,
serta laju perbaikan skor GCS pasien COT sedang. Metode: desain penelitian ini
adalah uji klinis acak buta tunggal menggunakan atorvastatin 40 mg per oral via
sonde selama 7 hari. Sebanyak 37 pasien COT sedang yang menjalani
pembedahan dan sesuai kriteria inklusi diikutkan dalam penelitian dan dilakukan
randomisasi, Tiga pasien dikeluarkan dari penelitian, karena gagal dalam proses
pengambilan darah. Pengambilan sampel darah dilakukan sebanyak 3 kali: 0 jam,
24 jam dan 72 jam pasca pemberian obat untuk diperiksa kadar tPA antigen, tPA
activity dan TNF-α. Untuk menilai laju perbaikan skor GCS dilakukan observasi
GCS selama 7 hari. Hasil penelitian ini dianalisa dengan uji two way repeated
measure ANOVA: kadar tPA antigen awal tidak berbeda bermakna antara kedua
kelompok (16,45 (4,32) ng/mL vs. 20,95 (4,32) ng/mL, p=0,467), begitu pula
pada pengukuran 24 jam (16,97 (4,79) vs. 21,40 (4,79), p=0,519). Pada
pengukuran 72 jam juga tidak berbeda bermakna (20,21 (4,60) vs. 15,78 ((4,60),
p=0,501). Kadar tPA activity awal tidak berbeda bermakna antara kedua
kelompok (0,74 (0,20; 9,87) ng/mL vs. 1,22 (0,20; 23,51) ng/mL, p=0,371). Kadar
24 jam dan 72 jam juga tidak berbeda bermakna (0,84 (0,20; 27,030) ng/mL vs.
0,79 (0,20; 31,62) ng/mL, p=0,929) dan (1,01 (0,20; 11,20) ng/mL vs. 0,57 (0,20;
26,49) ng/mL, p=0,261). Pengukuran awal kadar TNF-α kedua kelompok tidak
berbeda bermakna (7,01 (0,77) pg/mL vs. 5,55 (0,77) pg/mL, p=0,188). Demikian
juga pada pengukuran 24 jam dan 72 jam (6,37 (0,72) pg/mL vs 5,47 (0,72)
pg/mL, p=0,380) dan (6,49 (0,89) pg/mL vs. 6,17 (0,84) pg/mL, p=0,792). Pada
Kurva Kaplan-Meier terlihat median survival kelompok atorvastatin mencapai
skor GCS 15 pada 1 hari pasca pemberian obat dan pada hari ke 5 semua subyek
sudah mencapai GCS 15, sementara pada kelompok plasebo median survival
dicapai pada hari ke 3 dan tidak semua subyek mencapai skor GCS 15 hingga 7
hari pengamatan. Hal ini bermakna secara statistik dengan nilai p = 0,001.
Simpulan dari penelitian ini, atorvastatin tidak meningkatkan kadar tPA,
atorvastatin tidak menurunkan kadar TNF-α. Atorvastatin terbukti mempercepat
laju perbaikan skor GCS pasien COT sedang.

Kata Kunci: atorvastatin, COT, laju perbaikan skor GCS, TNF-α, tPA,

ABSTRACT
Traumatic brain injury (TBI) still stands as a major morbidity and
mortality problem in the world. After TBI, surviving patients will expressed
cognitive and intellectual disturbances, mood and behaviour changes and Post
Traumatic Distress Syndrome (PTDS). Priority of management is to prevent
secondary brain injury after trauma which can make worst the outcome. Brain
protection is a method to prevent secondary brain injury and neurofarmacologic
is one technique to do brain protection Statin had a cholesterol-independent
pleiotropic effect with potential effects in the management of neurological
disorders such as reducing the effects of thrombosis, coagulation and antiinflammatory
cascade. The aim of this study was to examine the effect of oral
atorvastatin 40 mg toward levels of tPA, TNF-α, and the rate of improvement of
GCS score of patients with moderate TBI. Method: design of this study was a
single blind randomized clinical trial using atorvastatin 40 mg orally with NGT
for 7 days. A total of 37 patients who met the eligibility criteria underwent
surgery were included in the study. Three patients were excluded from the study
due to failure in the blood-taking process. Blood sampling was performed 3 times:
0, 24 and 72 hours post-drug administration to check antigen tPA levels, tPA
activity and TNF-α. To assess the rate of improvement of GCS score, GCS
observation was performed for 7 days. The results of this study were: baseline
tPA antigen level between two groups were no significant difference (16.45 (4.32)
ng mL vs. 20.95 (3.32) ng/mL, p=0.467). At 24 and 72 hours measurement were
not significantly different (16.97 (4.79) ng/mL vs. 21.40 (4.79) ng/mL, p=0.519)
and (20.21 (4.60) ng/mL vs. 15.78 (4.60) ng/mL, p=0.501). There were no
significant different of tPA activity between two groups (0.74 (0.20; 9.87) ng/mL
vs 1.22 (0.20; 23.51) ng/mL, p=0.371); (0.84 (0.20; 7.03) ng/mL vs 0.79 (0.20;
31.62) ng/mL, p=0.929) and (1.01 (0.20; 11.20) ng/mL vs 0.57 (0.20; 26.49)
ng/mL, p=0.261) respectively. There were no significant different of TNF-α level
betweet two groups (7.01 (0.77) pg/mL vs. 5.55 (0.77) pg/mL, p=0.188); (6.37
(0.72) pg/mL vs. 5.47 (0.72) pg/mL, p=0.380) and (6.49 (0.84) pg/mL vs. 6.17
(0.84) pg/mL, p=0.792) respectively. Kaplan-Meier curve survival analysis
showed that in the atorvastatin group median survival reached GCS score 15 on
first day after atorvasvatin administration and on fifth day all subjects had
achieved GCS 15, while in the placebo group median survival GCS score 15 was
achieved on third day and not all subjects achieved a GCS score of 15 after 7
days of observation (p=0.001). Conclusions of this study, atorvastatin 40 mg
orally did not increased tPA levels, and atorvastatin did not decreased TNF-α
levels. Adjunctive therapy of 40 mg atorvastatin proved to accelerate the
improvement rate of GCS score in patients with moderate TBI.

Keywords: atorvastatin, GCS score improvement rate, TBI, TNF-α, tPA.

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D4598

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Bandung : ., 2017

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Indonesia

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NONE

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