DERAJAT HIPOALBUMIN SEDANG SEBAGAI PREDIKTOR LUARAN BURUK PADA PENDERITA STROKE ISKEMIK AKUT.
TESIS
DERAJAT HIPOALBUMIN SEDANG SEBAGAI
PREDIKTOR LUARAN BURUK PADA PENDERITA
STROKE ISKEMIK AKUT
I KETUT CATUR WIPRADNYANA
PROGRAM PASCASARJANA
UNIVERSITAS UDAYANA
DENPASAR
2016
TESIS
DERAJAT HIPOALBUMIN SEDANG SEBAGAI
PREDIKTOR LUARAN BURUK PADA PENDERITA
STROKE ISKEMIK AKUT
I KETUT CATUR WIPRADNYANA
NIM: 1014068202
PROGRAM MAGISTER
PROGRAM STUDI ILMU BIOMEDIK
PROGRAM PASCASARJANA
UNIVERSITAS UDAYANA
DENPASAR
2016
i
DERAJAT HIPOALBUMIN SEDANG SEBAGAI
PREDIKTOR LUARAN BURUK PADA PENDERITA
STROKE ISKEMIK AKUT
Tesis untuk Memperoleh Gelar Magister
Pada Program Magister, Program Studi Biomedik,
Program Pascasarjana Universitas Udayana
I KETUT CATUR WIPRADNYANA
NIM: 1014068202
PROGRAM MAGISTER
PROGRAM STUDI ILMU BIOMEDIK
PROGRAM PASCASARJANA
UNIVERSITAS UDAYANA
DENPASAR
2016
ii
iii
Lembar Pengesahan
TESIS INI TELAH DISETUJUI
PADA TANGGAL 13 OKTOBER 2016
Pembimbing I,
Pembimbing II,
dr. Anak Agung Bagus Ngurah Nuartha, Sp.S(K)
Sp.S(K) FAAN
NIP. 19540114 198012 1 001
Dr. dr. Thomas Eko Purwata,
NIP. 19540420 198211 1 001
Mengetahui,
Ketua Program Studi Ilmu Biomedik
Program Pascasarjana
Universitas Udayana
Direktur
Program Pascasarjana
Universitas Udayana
Dr.dr.Gde Ngurah Indraguna Pinatih,M.Sc,Sp.GK
Sp. S (K)
NIP : 19580521 198503 1 002
Prof. Dr. dr.Anak Agung Raka Sudewi,
iii
NIP : 19590215 198510 2 001
Tesis ini Telah Diuji pada
Tanggal 13 Oktober 2016
Panitia Penguji Tesis Berdasarkan SK Rektor
Universitas Udayana, No: 5016/UN14.4/HK/2016 tanggal 10 Oktober 2016
Ketua
Sekretaris
Anggota
: dr. Anak Agung Bagus Ngurah Nuartha, Sp.S(K)
: Dr. dr. Thomas Eko Purwata, Sp.S(K) FAAN
:
1. Dr. dr. D.P.G. Purwa Samatra, Sp.S(K)
2. dr. Made Oka Adnyana , Sp.S(K)
3. dr. IGN Purna Putra, Sp.S(K)
iv
SURAT PERNYATAAN BEBAS PLAGIAT
Nama
: dr. I Ketut Catur Wipradnyana
NIM
: 1014068202
Program Studi
: Magister Ilmu Biomedik (Combine - Degree)
Judul
: Derajat Hipoalbumin Sedang Sebagai Prediktor Luaran
Buruk pada Penderita Stroke Iskemik Akut
Dengan ini menyatakan bahwa karya ilmiah tesis ini bebas plagiat.
Apabila di kemudian hari terbukti terdapat plagiat dalam karya ilmiah ini, maka
saya bersedia menerima sanksi sesuai peraturan Mendiknas RI No.17 tahun 2010
dan Peraturan Perundang-undangan yang berlaku.
Denpasar, .......................
Yang membuat pernyataan,
(dr. I Ketut Catur W.)
v
DAFTAR ISI
DAFTAR ISI ....................................................................................................
i
DAFTAR GAMBAR .......................................................................................
ii
DAFTAR SINGKATAN .................................................................................
iii
BAB I PENDAHULUAN ................................................................................
1
1.1 Latar Belakang .....................................................................................
1
1.2 Rumusan Masalah ................................................................................
4
1.3 Tujuan Penelitian .................................................................................
4
1.4 Manfaat Penelitian ...............................................................................
4
BAB II KAJIAN PUSTAKA ...........................................................................
6
2.1 Difinisi Stroke ......................................................................................
6
2.2 Epidemiologi Stroke ............................................................................
7
2.3 Klasifikasi Stroke .................................................................................
8
2.4 Patofisiologi Stroke Iskemik ................................................................
10
2.5 Iskemik dan Inflamasi ..........................................................................
14
2.6 Albumin Serum ....................................................................................
15
2.7 Albumin Serum dan Stroke Iskemik ....................................................
22
BAB III KERANGKA BERPIKIR, KONSEP DAN HIPOTESIS
PENELITIAN ..................................................................................................
26
3.1 Kerangka berpikir ................................................................................
26
3.2 Kerangka Konsep .................................................................................
28
3.3 Hipotesis penelitian ..............................................................................
29
BAB IV METODE PENELITIAN ..................................................................
30
4.1 Rancangan Penelitian ...........................................................................
30
4.2 Lokasi dan Waktu Penelitian ...............................................................
31
4.3 Ruang Lingkup penelitian ....................................................................
31
4.4 Penentuan Sumber Data .......................................................................
31
4.4.1 Populasi Target ...........................................................................
31
4.4.2 Populasi Terjangkau....................................................................
31
4.4.3 Sampling Frame ..........................................................................
31
xiii
4.4.4 Kriteria Subyek ...........................................................................
32
4.4.5 Besar Sampel ..............................................................................
33
4.4.6 Teknik Pengambilan Sampel ......................................................
35
4.5 Variabel Penelitian ...............................................................................
31
4.5.1 Klasifikasi Variabel.....................................................................
35
4.5.2 Definisi Operasional ...................................................................
35
4.6 Bahan Penelitian ..................................................................................
41
4.7 Instrumen Penelitian ............................................................................
41
4.8 Prosedur Penelitian ..............................................................................
41
4.9 Analisis Data ........................................................................................
44
BAB V HASIL PENELITIAN.........................................................................
45
5.1 Karakteristik Subyek Penelitian...........................................................
45
5.2 Analisis Bivariat Kadar Albumin dengan Luaran Klinis Neurologis Stroke
Iskhemik Akut....................................................................................... 47
5.3 Analisis Bivariat Usia, Jenis kelamin, Lokasi Infark, dan GCS dengan
Luaran Klinis Stroke Iskemik Akut................................................. .... 48
BAB VI PEMBAHASAN .................................................................................
51
6.1 Karakteristik Subjek Penelitian.............................................................
51
6.1.1 Usia..............................................................................................
51
6.1.2 Jenis Kelamin.............................................................................. .
53
6.1.3 Pendidikan....................................................................................
6.1.4 Pekerjaan..................................................................................... .
54
55
6.2 Analisis Bivariat....................................................................................
56
6.2.1Hubungan Kadar Albumin dengan Luaran Klinis Neurologis Stroke
Iskhemik Akut............................................................................ .. 56
6.2.2 Hubungan Usia dengan Luaran Klinis Stroke Iskemik Akut..... ..
59
6.2.3Hubungan Jenis Kelamin dengan Luaran Klinis Stroke Iskemik
Akut............................................................................................ . 60
6.2.4. Hubungan Letak Lesi dengan Luaran Stroke Iskemik.............. ..
62
6.2.5 Hubungan GCS dengan Luaran Stroke Iskemik........................ ..
63
6.3 Kekuatan dan Kelemahan Penelitian................................................... .
64
BAB VII SIMPULAN DAN SARAN........................................................... ...
65
7.1 Simpulan.............................................................................................. .
65
xiv
7.2 Saran.................................................................................................... .
65
DAFTAR PUSTAKA..................................................................................... .
66
LAMPIRAN..................................................................................................... .
70
xv
DAFTAR TABEL
5.1 Karakteristik Dasar Subjek Penelitian .....................................................
46
5.2 Analisis Bivariat Kadar Albumin sebagai Prediktor
Perburukan Klinis Penderita Stroke Iskemik............................................ 48
5.3 Analisis Bivariat Usia, Jenis Kelamin, Letak Lesi,GCS Awal Masuk dengan
Perburukan Klinis Penderita Stroke Iskemik........................................... 49
xvi
DAFTAR GAMBAR
Gambar 2.1 Daerah penumbra iskemik dan infarct core ................................
12
Gambar 2.2 Perkembangan luas lesi ischaemic penumbra dan infarct core
berdasarkan waktu.......................................................................
12
Gambar 2.3 Mekanisme seluler pada iskemik akut dan injury pada sistem
saraf pusat ...................................................................................
13
Gambar 2.4 Reaksi acute phase protein .........................................................
16
Gambar 2.5 Teori Aktivasi Respon Stres........................................................
25
Gambar 3.1 Kerangka Teori Penelitian........................................................... 27
Gambar 3.2 Kerangka Konsep Penelitian...................................................... .
xvii
28
DAFTAR SINGKATAN
ADO = Aliran Darah Otak
ALIAS = Albumin in acute stroke
AMPA = 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid
ATP = Adenosin Tripospat
DNA = Deoxyribonucleic Acid
EEG = Elektroencephalograpy
ICAM-1= intracellular adhesion molecule-1
IL-1β = Interleukin-1β
IL-6 = Interleukin-6
IL-10 = Interleukin-10
LACI = Lacunar Infarct
MRI = Magnetic Resonance Imaging
NIHSS = National Institutes of Health Stroke Scale
NMDA = N-Methyl-D-aspartate
NO = Nitrit Oxide
nNOS = Neuronal Nitrit-OxideSynthase
PACI = Partial Anterior Circulation Infact
PMS = Pure Motor Stroke
POCI = Posterior Circulation Infarct
PSS= Pure Sensory Stroke
ROS = Reactive Oxygen Species
TACI = Total Anterior Circulation Infarct
TGF- β = transforming growth factor β
TIA = Transient Ischemic Attack
TNF-α = Tumor Necrotic Factor-α
WHO = World Health Organization
WHO Monica = World Health Organization Multinational Monitoring of Trends
and Determinants in Cardiovascular Disease Project
xviii
DAFTAR LAMPIRAN
Lampiran 1 Keterangan Kelaikan Etik............................................................. 70
Lampiran 2 Surat Ijin Penelitian dari RSUP Sanglah ...................................... 71
Lampiran 3 Lembar Pengumpulan Data ........................................................... 72
Lampiran 4 Skala NIHSS.................................................................................. 74
Lampiran 5 Informed consent ........................................................................... 77
Lampiran 6 Formulir Persetujuan ..................................................................... 78
Lampiran 7 Data Subyek Penelitian.................................................................. 79
Lampiran 8 Analisis SPSS
xix
DERAJAT HIPOALBUMIN SEDANG SEBAGAI
PREDIKTOR LUARAN BURUK PADA PENDERITA
STROKE ISKEMIK AKUT
I KETUT CATUR WIPRADNYANA
PROGRAM PASCASARJANA
UNIVERSITAS UDAYANA
DENPASAR
2016
TESIS
DERAJAT HIPOALBUMIN SEDANG SEBAGAI
PREDIKTOR LUARAN BURUK PADA PENDERITA
STROKE ISKEMIK AKUT
I KETUT CATUR WIPRADNYANA
NIM: 1014068202
PROGRAM MAGISTER
PROGRAM STUDI ILMU BIOMEDIK
PROGRAM PASCASARJANA
UNIVERSITAS UDAYANA
DENPASAR
2016
i
DERAJAT HIPOALBUMIN SEDANG SEBAGAI
PREDIKTOR LUARAN BURUK PADA PENDERITA
STROKE ISKEMIK AKUT
Tesis untuk Memperoleh Gelar Magister
Pada Program Magister, Program Studi Biomedik,
Program Pascasarjana Universitas Udayana
I KETUT CATUR WIPRADNYANA
NIM: 1014068202
PROGRAM MAGISTER
PROGRAM STUDI ILMU BIOMEDIK
PROGRAM PASCASARJANA
UNIVERSITAS UDAYANA
DENPASAR
2016
ii
iii
Lembar Pengesahan
TESIS INI TELAH DISETUJUI
PADA TANGGAL 13 OKTOBER 2016
Pembimbing I,
Pembimbing II,
dr. Anak Agung Bagus Ngurah Nuartha, Sp.S(K)
Sp.S(K) FAAN
NIP. 19540114 198012 1 001
Dr. dr. Thomas Eko Purwata,
NIP. 19540420 198211 1 001
Mengetahui,
Ketua Program Studi Ilmu Biomedik
Program Pascasarjana
Universitas Udayana
Direktur
Program Pascasarjana
Universitas Udayana
Dr.dr.Gde Ngurah Indraguna Pinatih,M.Sc,Sp.GK
Sp. S (K)
NIP : 19580521 198503 1 002
Prof. Dr. dr.Anak Agung Raka Sudewi,
iii
NIP : 19590215 198510 2 001
Tesis ini Telah Diuji pada
Tanggal 13 Oktober 2016
Panitia Penguji Tesis Berdasarkan SK Rektor
Universitas Udayana, No: 5016/UN14.4/HK/2016 tanggal 10 Oktober 2016
Ketua
Sekretaris
Anggota
: dr. Anak Agung Bagus Ngurah Nuartha, Sp.S(K)
: Dr. dr. Thomas Eko Purwata, Sp.S(K) FAAN
:
1. Dr. dr. D.P.G. Purwa Samatra, Sp.S(K)
2. dr. Made Oka Adnyana , Sp.S(K)
3. dr. IGN Purna Putra, Sp.S(K)
iv
SURAT PERNYATAAN BEBAS PLAGIAT
Nama
: dr. I Ketut Catur Wipradnyana
NIM
: 1014068202
Program Studi
: Magister Ilmu Biomedik (Combine - Degree)
Judul
: Derajat Hipoalbumin Sedang Sebagai Prediktor Luaran
Buruk pada Penderita Stroke Iskemik Akut
Dengan ini menyatakan bahwa karya ilmiah tesis ini bebas plagiat.
Apabila di kemudian hari terbukti terdapat plagiat dalam karya ilmiah ini, maka
saya bersedia menerima sanksi sesuai peraturan Mendiknas RI No.17 tahun 2010
dan Peraturan Perundang-undangan yang berlaku.
Denpasar, .......................
Yang membuat pernyataan,
(dr. I Ketut Catur W.)
v
DAFTAR ISI
DAFTAR ISI ....................................................................................................
i
DAFTAR GAMBAR .......................................................................................
ii
DAFTAR SINGKATAN .................................................................................
iii
BAB I PENDAHULUAN ................................................................................
1
1.1 Latar Belakang .....................................................................................
1
1.2 Rumusan Masalah ................................................................................
4
1.3 Tujuan Penelitian .................................................................................
4
1.4 Manfaat Penelitian ...............................................................................
4
BAB II KAJIAN PUSTAKA ...........................................................................
6
2.1 Difinisi Stroke ......................................................................................
6
2.2 Epidemiologi Stroke ............................................................................
7
2.3 Klasifikasi Stroke .................................................................................
8
2.4 Patofisiologi Stroke Iskemik ................................................................
10
2.5 Iskemik dan Inflamasi ..........................................................................
14
2.6 Albumin Serum ....................................................................................
15
2.7 Albumin Serum dan Stroke Iskemik ....................................................
22
BAB III KERANGKA BERPIKIR, KONSEP DAN HIPOTESIS
PENELITIAN ..................................................................................................
26
3.1 Kerangka berpikir ................................................................................
26
3.2 Kerangka Konsep .................................................................................
28
3.3 Hipotesis penelitian ..............................................................................
29
BAB IV METODE PENELITIAN ..................................................................
30
4.1 Rancangan Penelitian ...........................................................................
30
4.2 Lokasi dan Waktu Penelitian ...............................................................
31
4.3 Ruang Lingkup penelitian ....................................................................
31
4.4 Penentuan Sumber Data .......................................................................
31
4.4.1 Populasi Target ...........................................................................
31
4.4.2 Populasi Terjangkau....................................................................
31
4.4.3 Sampling Frame ..........................................................................
31
xiii
4.4.4 Kriteria Subyek ...........................................................................
32
4.4.5 Besar Sampel ..............................................................................
33
4.4.6 Teknik Pengambilan Sampel ......................................................
35
4.5 Variabel Penelitian ...............................................................................
31
4.5.1 Klasifikasi Variabel.....................................................................
35
4.5.2 Definisi Operasional ...................................................................
35
4.6 Bahan Penelitian ..................................................................................
41
4.7 Instrumen Penelitian ............................................................................
41
4.8 Prosedur Penelitian ..............................................................................
41
4.9 Analisis Data ........................................................................................
44
BAB V HASIL PENELITIAN.........................................................................
45
5.1 Karakteristik Subyek Penelitian...........................................................
45
5.2 Analisis Bivariat Kadar Albumin dengan Luaran Klinis Neurologis Stroke
Iskhemik Akut....................................................................................... 47
5.3 Analisis Bivariat Usia, Jenis kelamin, Lokasi Infark, dan GCS dengan
Luaran Klinis Stroke Iskemik Akut................................................. .... 48
BAB VI PEMBAHASAN .................................................................................
51
6.1 Karakteristik Subjek Penelitian.............................................................
51
6.1.1 Usia..............................................................................................
51
6.1.2 Jenis Kelamin.............................................................................. .
53
6.1.3 Pendidikan....................................................................................
6.1.4 Pekerjaan..................................................................................... .
54
55
6.2 Analisis Bivariat....................................................................................
56
6.2.1Hubungan Kadar Albumin dengan Luaran Klinis Neurologis Stroke
Iskhemik Akut............................................................................ .. 56
6.2.2 Hubungan Usia dengan Luaran Klinis Stroke Iskemik Akut..... ..
59
6.2.3Hubungan Jenis Kelamin dengan Luaran Klinis Stroke Iskemik
Akut............................................................................................ . 60
6.2.4. Hubungan Letak Lesi dengan Luaran Stroke Iskemik.............. ..
62
6.2.5 Hubungan GCS dengan Luaran Stroke Iskemik........................ ..
63
6.3 Kekuatan dan Kelemahan Penelitian................................................... .
64
BAB VII SIMPULAN DAN SARAN........................................................... ...
65
7.1 Simpulan.............................................................................................. .
65
xiv
7.2 Saran.................................................................................................... .
65
DAFTAR PUSTAKA..................................................................................... .
66
LAMPIRAN..................................................................................................... .
70
xv
DAFTAR TABEL
5.1 Karakteristik Dasar Subjek Penelitian .....................................................
46
5.2 Analisis Bivariat Kadar Albumin sebagai Prediktor
Perburukan Klinis Penderita Stroke Iskemik............................................ 48
5.3 Analisis Bivariat Usia, Jenis Kelamin, Letak Lesi,GCS Awal Masuk dengan
Perburukan Klinis Penderita Stroke Iskemik........................................... 49
xvi
DAFTAR GAMBAR
Gambar 2.1 Daerah penumbra iskemik dan infarct core ................................
12
Gambar 2.2 Perkembangan luas lesi ischaemic penumbra dan infarct core
berdasarkan waktu.......................................................................
12
Gambar 2.3 Mekanisme seluler pada iskemik akut dan injury pada sistem
saraf pusat ...................................................................................
13
Gambar 2.4 Reaksi acute phase protein .........................................................
16
Gambar 2.5 Teori Aktivasi Respon Stres........................................................
25
Gambar 3.1 Kerangka Teori Penelitian........................................................... 27
Gambar 3.2 Kerangka Konsep Penelitian...................................................... .
xvii
28
DAFTAR SINGKATAN
ADO = Aliran Darah Otak
ALIAS = Albumin in acute stroke
AMPA = 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid
ATP = Adenosin Tripospat
DNA = Deoxyribonucleic Acid
EEG = Elektroencephalograpy
ICAM-1= intracellular adhesion molecule-1
IL-1β = Interleukin-1β
IL-6 = Interleukin-6
IL-10 = Interleukin-10
LACI = Lacunar Infarct
MRI = Magnetic Resonance Imaging
NIHSS = National Institutes of Health Stroke Scale
NMDA = N-Methyl-D-aspartate
NO = Nitrit Oxide
nNOS = Neuronal Nitrit-OxideSynthase
PACI = Partial Anterior Circulation Infact
PMS = Pure Motor Stroke
POCI = Posterior Circulation Infarct
PSS= Pure Sensory Stroke
ROS = Reactive Oxygen Species
TACI = Total Anterior Circulation Infarct
TGF- β = transforming growth factor β
TIA = Transient Ischemic Attack
TNF-α = Tumor Necrotic Factor-α
WHO = World Health Organization
WHO Monica = World Health Organization Multinational Monitoring of Trends
and Determinants in Cardiovascular Disease Project
xviii
DAFTAR LAMPIRAN
Lampiran 1 Keterangan Kelaikan Etik............................................................. 70
Lampiran 2 Surat Ijin Penelitian dari RSUP Sanglah ...................................... 71
Lampiran 3 Lembar Pengumpulan Data ........................................................... 72
Lampiran 4 Skala NIHSS.................................................................................. 74
Lampiran 5 Informed consent ........................................................................... 77
Lampiran 6 Formulir Persetujuan ..................................................................... 78
Lampiran 7 Data Subyek Penelitian.................................................................. 79
Lampiran 8 Analisis SPSS
xix