SKRIPSI

SULLY NUR AISYAH

STUDI PENGGUNAAN LAKTULOSA PADA

PASIEN SIROSIS HATI DENGAN HEPATIK
ENSEFALOPATI DI RSUD SIDOARJO

PROGRAM STUDI FARMASI

FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG
2020
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 KATA PENGANTAR

Assalamu’alaikum Warahmatullahi Wabarakatuh

Alhamdulillahirabbil’alamiin, segala puji bagi Allah SWT yang telah
melimpahkan rahmat, hidayah, dan inayah-Nya. Rabb yang telah memberikan nikmat
sehat, waktu, kemudahan, dan kesabaran sehingga penulis dapat menyelesaikan
skripsi yang berjudul STUDI PENGGUNAAN LAKTULOSA PADA PASIEN
SIROSIS HATI DENGAN HEPATIK ENSEFALOPATI DI RSUD SIDOARJO
untuk mencapai gelar sarjana farmasi pada Program Studi Farmasi Fakultas Ilmu
Kesehatan Universitas Muhammadiyah Malang. Dalam penyusunan skripsi ini, tidak
terlepas dari peranan pembimbing dan bantuan dari seluruh pihak. Oleh karena itu,
dengan segala kerendahan hati, penulis ingin mengucapkan banyak terima kasih
kepada:
1. Bapak Faqih Ruhyanudin, M.Kep., Sp. Kep. MB. selaku Dekan Fakultas Ilmu
Kesehatan Universitas Muhammadiyah Malang
2. Ibu apt.Dian Ermawati, M.Farm. selaku Ketua Progam Studi Farmasi Universitas
Muhammadiyah Malang
3. Direktur dan staf Rumah Sakit Umum Daerah Sidoarjo yang telah membantu
kelancaran penelitian, terutama staf rekamedis Ibu Alia Chaerunisa, A.Md.Kes
dan Muhammad Wahyu Setiawan A.Md. Kes.
4. Ibu Dr.apt.Hidajah Rachmawati, S.Si.,Sp.FRS. dan Bapak Drs.apt.Didik
Hasmono, MS. selaku pembimbing I dan II yang selalu meluangkan waktu untuk
membimbing, memberikan ilmu, arahan, nasehat, serta dorongan, selama
menempuh pendidikan hingga terselesaikannya tugas akhir ini
5. Ibu Dr.apt.Lilik Yusetyani, Sp.FRS. dan Ibu apt.Aghnia Fuadatul Inayah,
M.Farm.Klin. selaku penguji I dan II yang telah memberikan masukan dan saran
untuk penyempurnaan tugas akhir ini
6. Ibu apt.Ika Ratna Hidayati, S.Farm., M.Sc. selaku dosen wali yang telah
memberikan nasehat dan bimbingan sejak awal semester

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7. Seluruh jajaran prodi, dosen dan staf tata usaha Farmasi yang telah memberikan
dedikasi yang besar kepada penulis
8. Kedua orang tua, Ibu Ciplis Sruhartati dan Ayah Gatot Sumijarlan tercinta yang
selalu mendoakan dan memberikan yang terbaik untuk anak-anaknya.
Terimakasih atas motivasi, kerja keras dan jerih pasyah ibu dan ayah selama ini
sehingga penulis bisa menyelesaikan tugas akhir ini
9. Seluruh teman-teman Farmasi 2016, khususnya Farmasi C terimakasih atas
kebersamaan dan kenangan indah selama ini. Tanpa kalian penulis tidak dapat
menikmati hari-hari perkuliahan dengan sukacita
10. Semua pihak yang tidak dapat disebutkan satu persatu, penulis mengucapkan
mohon maaf dan terimakasih yang sebesar-besarnya
Semoga Allah SWT membalas segala kebaikan dan bantuan yang telah diberikan.
Kritik dan saran dari semua pihak sangat penulis harapkan agar dapat menjadi
intropeksi diri serta penyempurnaan karya penyusun selanjutnya. Semoga skripsi ini
dapat bermanfaat bagi siapapun yang membutukannya
Wassalamu’alaikum Warahmatullahi Wabarakatuh

Malang, 27 Juni 2020

Penulis

Sully Nur Aisyah

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 DAFTAR ISI

HALAMAN JUDUL .................................................................................................... i

Lembar Pengesahan .................................................................................................... ii
Lembar Pengujian ...................................................................................................... iii
KATA PENGANTAR ................................................................................................ iv
RINGKASAN ............................................................................................................. vi
ABSTRAK ................................................................................................................ viii
ABSTRACT ................................................................................................................ ix
DAFTAR ISI.........................................................................................................................x
DAFTAR TABEL ..................................................................................................... xiii
DAFTAR GAMBAR ................................................................................................ xiv
DAFTAR LAMPIRAN ............................................................................................. xv
DAFTAR SINGKATAN .......................................................................................... xvi
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 TINJAUAN PUSTAKA ................................................................................. 6
2.1 Hati ...................................................................................................................... 6
2.1.1 Anatomi Hati ................................................................................................ 6
2.1.2 Fisiologi Hati ................................................................................................ 7
2.1.3 Fungsi Hati ................................................................................................... 8
2.2 Tinjauan Sirosis Hati ......................................................................................... 10
2.2.1 Definisi Sirosis Hati .................................................................................... 10
2.2.2 Epidemiologi Sirosis Hati ........................................................................... 11
2.2.3 Etiologi Sirosis Hati .................................................................................... 11
2.2.4 Patofisiologi Sirosis Hati ............................................................................ 12
2.2.5 Klasifikasi Sirosis Hati ............................................................................... 13
2.2.6 Komplikasi Sirosis Hati .............................................................................. 14

2.2.7 Penatalaksanaan Sirosis Hati ...................................................................... 16

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 2.3 Tinjauan Hepatik Ensefalopati .......................................................................... 18
2.3.1 Definisi Hepatik Ensefalopati ..................................................................... 18
2.3.2 Epidemiologi Hepatik Ensefalopati ............................................................ 19
2.3.3 Etiologi Hepatik Ensefalopati ..................................................................... 19
2.3.4 Patofisiologi Hepatik Ensefalopati ............................................................. 20
2.3.5 Klasifikasi Hepatik Ensefalopati ................................................................ 22
2.3.6 Penatalaksanaan Hepatik Ensefalopati ....................................................... 23
2.4 Penggunaan Laktulosa pada Hepatik Ensefalopati ........................................... 26
2.4.1 Indikasi........................................................................................................ 26
2.4.2 Mekanisme Kerja ........................................................................................ 27
2.4.3 Farmakokinetika ......................................................................................... 27
2.4.4 Dosis dan Rute Pemberian .......................................................................... 28
2.4.5 Sediaan yang Beredar di Indonesia ............................................................. 28
BAB III KERANGKA KONSEPTUAL DAN OPERASIONAL .......................... 30
3.1 Kerangka Konseptual ........................................................................................ 30
3.2 Kerangka Operasional ....................................................................................... 32
BAB IV METODE PENELITIAN .......................................................................... 33
4.1 Rancangan Penelitian ........................................................................................ 33
4.2 Populasi dan Sampel ......................................................................................... 33
4.2.1 Populasi....................................................................................................... 33
4.2.2 Sampel ........................................................................................................ 33
4.2.3 Kriteria Data Inklusi ................................................................................... 33
4.2.4 Kriteria Data Eksklusi................................................................................. 33
4.3 Instrumen Penelitian .......................................................................................... 33
4.4 Tempat dan Waktu Penelitian ........................................................................... 34
4.5 Definisi Operasional .......................................................................................... 34
4.6 Metode Pengumpulan Data ............................................................................... 35
4.7 Analisis Data ..................................................................................................... 35
BAB V HASIL PENELITIAN ................................................................................. 36
5.1 Data Demografi Pasien...................................................................................... 36

5.1.1 Distribusi Berdasarkan Jenis Kelamin ........................................................ 36

5.1.2 Distribusi Berdasarkan Usia ....................................................................... 37
5.1.3 Distribusi Berdasarkan Status Pasien.......................................................... 37

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 5.2 Pola Penggunaan Laktulosa pada Pasien Sirosis Hati dengan Hepatik
Ensefalopati (HE) .................................................................................................... 37
5.2.1 Pola Penggunaan Terapi Laktulosa pada Pasien Hepatik Ensefalopati ...... 37
5.2.2 Pola Penggunaan Laktulosa Tunggal .......................................................... 38
5.2.3 Pola Penggunaan Laktulosa Kombinasi...................................................... 38
5.2.4 Pola Penggunaan Switch Kombinasi Dua ................................................... 39
5.2.5 Lama Penggunaan Terapi Laktulosa ........................................................... 39
5.3 Diagnosis Penyerta ............................................................................................ 39
5.4 Profil Terapi Lainnya ............................................................................................... 40
5.5 Lama Rawat Inap Pasien Sirosis Hati dengan Hepatik Ensefalopati ................. 41
5.6 Kondisi Keluar Rumah Sakit (KRS) Pasien Sirosis Hati dengan Hepatik
Ensefalopati ............................................................................................................. 42
BAB VI PEMBAHASAN .......................................................................................... 43
BAB VII KESIMPULAN DAN SARAN ................................................................. 52
DAFTAR PUSTAKA ................................................................................................ 53
LAMPIRAN ............................................................................................................... 60

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 DAFTAR TABEL

Tabel II.1 Stadium Hepatik Ensefalopati Kriteria West Haven ................................... 23

Tabel II.2 Sediaan Laktulosa di Indonesia .................................................................. 28
Tabel V.1 Distribusi Berdasarkan Jenis Kelamin........................................................ 36
Tabel V.2 Distribusi Berdasarkan Usia ....................................................................... 37
Tabel V.3 Distribusi Berdasrkan Status Pasien ........................................................... 37
Tabel V.4 Pola Penggunaan Terapi Laktulosa pada Pasien Hepatik Ensefalopati ...... 38
Tabel V.5 Pola Penggunaan Terapi Laktulosa Tunggal pada Pasien Hepatik
Ensefalopati ..................................................................................................... 38
Tabel V.6 Pola Penggunaan Laktulosa Kombinasi pada Pasien Hepatik Ensefalopati
..................................................................................................................................... 38
Tabel V.7 Penggunaan Switch Kombinasi Dua ........................................................... 39
Tabel V.8 Lama Penggunaan Terapi Laktulosa pada Pasien Hepatik Ensefalopati .... 39
Tabel V.9 Diagnosis Penyerta pada Pasien Sirosis Hati dengan Hepatik Ensefalopati
..................................................................................................................................... 40
Tabel V.10 Terapi Lainnya selain Laktulosa pada Pasien Sirosis Hati dengan Hepatik
Ensefalopati ..................................................................................................... 40
Tabel V.11 Lama Perawatan pada Pasien Hepatik Ensefalopati ................................. 41
Tabel V.12 Kondisi KRS Pasien Hepatik Ensefalopati ............................................... 42

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 DAFTAR GAMBAR
Gambar 2.1 Anatomi Hati ............................................................................................. 6
Gambar 2.2 Struktur Dasar Hati .................................................................................... 7
Gambar 2.3 Sirosis Mikronoduler dan Makronoduler ................................................ 10
Gambar 2.4 Patogenesis Komplikasi Sirosis............................................................... 12
Gambar 2.5 Komplikasi Sirosis Hati ........................................................................... 13
Gambar 2.6 Patofisiologi Hepatik Ensefalopati .......................................................... 21
Gambar 2.7 Mekanisme Kerja Laktulosa .................................................................... 27
Gambar 3.1 Skema Kerangka Konseptual .................................................................. 30
Gambar 3.2 Skema Kerangka Operasional ................................................................. 32
Gambar 5.1 Skema sampel yang memenuhi kriteria inklusi penelitian pada pasien
sirosis hati dengan hepatik ensefalopati di RSUD Sidoarjo ........................................ 36

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 DAFTAR LAMPIRAN
Lampiran 1. Daftar Riwayat Hidup ............................................................................. 60
Lampiran 2. Surat Pernyataan...................................................................................... 61
Lampiran 3. Surat Laik Etik ........................................................................................ 62
Lampiran 4. Lembar Pengumpul Data......................................................................... 63
Lampiran 5. Tabel Data Induk ................................................................................... 120

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 DAFTAR SINGKATAN
AAT : Aspartate Aminotransferase
ASDR : Age Spesific Death Rate
BBB : Blood Brain Barrier
BCAA : Branched Chain Amino Acids
BUN : Blood Urea Nitrogen
CSDR : Cause Spesific Death Rate
EASL : European Association for the Liver Dissease
EBL : Endoscopic Band Ligand
ECM : Extracelullar Matrix
FDA : Food and Drug Association
GABA : Γ-aminobutyric acid
GI : Gastrointestinal
HB : Hemoglobin
HCT : Hematocrit
HE : Hepatik Ensefalopati
ISO : Informasi Spesialite Obat
LED : Laju Endap Darah
LOLA : L-ornithine L-aspartate
MELD : Model for End-Stage Liver Disease
NAD : Non-absorbable Disaccharides
NIDDK: National Institute of Diabetes and Digestive and Kidney Disease
NSBB : Non-Selective β-blocker
OAT : Ornithine Aminotrasnferase
PLT : Platelet
RAAS : Renin Angiotensin Aldosterone System

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RBC : Red Blood Cell
RSUD : Rumah Sakit Umum Daerah
SBP : Spontaneous Bacterial Peritonitis
SGOT : Serum Glutamic Oxaloacetic Transaminase
SGPT : Serum Glutamic Pyruvic Transaminase
SSP : Sistem Syaraf Pusat
TIPS : Transjugular Intrahepatic Portosystemic
VEH : Variceal Esophageal Hemorrhage
WHO : World Health Organization
WBC : White Blood Cell

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