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SKRIPSI
KHAIRUN NI’MAH
STUDI PENGGUNAAN CEFTRIAXONE PADA
PASIEN SIROSIS HATI DENGAN
SPONTANEOUS BACTERIAL PERITONITIS
(SBP) (Penelitian dilakukan di Rumah Sakit Umum Daerah Sidoarjo)
PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERITAS MUHAMMADIYAH MALANG
2019
iv
KATA PENGANTAR
Bismillahirrahmanirrahim
Assalamu’alaikum warahmatullah wabarakatuh
Puji syukur kehadirat Allah SWT. yang telah melimpahkan berkah dan
nikmat kepada hamba-Nya, karena dengan pertolongan-Nya skripsi yang berjudul
studi penggunaan ceftriaxone pada pasien sirosis hati dengan spontaneous bacterial
peritonitis (SBP) dapat diselesaikan dengan tepat waktu dan sebaik-baiknya.
Selanjutnya saya ingin mengucapkan terima kasih yang tidak terhingga kepada:
1. Bapak Drs. Didik Hasmono, M.S., Apt. selaku pembimbing I yang telah
meluangkan waktu untuk membimbing dan memberikan arahan serta ilmu,
selama menempuh pendidikan hingga terselesaikannya tugas akhir ini.
2. Ibu Dr. Dra. Lilik Yusetyani, Apt., Sp.FRS. selaku Pembimbing II yang selalu
meluangkan waktunya untuk membimbing dan memberikan arahan kepada
penulis sehingga tugas akhir ini dapat diselesaikan dengan baik.
3. Ibu Hidajah Rachmawati, S.Si., Apt., Sp. FRS. dan Ibu Dra. Uswatun
Chasanah, M.Kes., Apt. selaku penguji I dan II yang telah memberikan
masukan dan saran pada tugas akhir ini.
4. Bapak Faqih Ruhyanudin, M.Kep., Sp. Kep. MB. selaku Dekan Fakultas Ilmu
Kesehatan Universitas Muhammadiyah Malang.
5. Ibu Dian Ermawati, M.Farm., Apt. selaku Ketua Progam Studi Farmasi
Universitas Muhammadiyah Malang.
6. Direktur dan staf Rumah Sakit Umum Daerah Sidoarjo yang telah membantu
kelancaran penelitian, terutama ibu Alia.
7. Seluruh jajaran prodi, dosen dan staf tata usaha Farmasi yang telah
memberikan dedikasi yang besar kepada penulis.
8. Ketiga orang tua tercinta ayahanda Hartani, ibunda Salasiah, dan ibunda Siti
Rahma; kakakku Noor Jannah, Khairani; adikku Rusyadi, Fahdiya, Alfian
soleh. Terimakasih atas dukungan, kepercayaan, dan doa yang tidak pernah
putus dari keluarga sehingga membuat penulis bisa melangkah dalam
kehidupan sampai sejauh ini.
v
9. Sahabat-sahabatku dari MAN Model Palangka Raya, Mutia Khairun Nisa dan
Wahyu Anggun Ningtyas. Terimakasih atas nasihat-nasihat kalian sehingga
penulis tidak mudah putus asa.
10. Sahabatku dari farmasi UMM, Laura Mayang Lestari, yang selalu berbagi
suka dan duka dalam 4 tahun terakhir. Serta sahabat-sahabatku yang juga dari
farmasi UMM, terutama Rizki, Irene, Zunik, Iril, Wika, Diana, Ryan, Fauz,
dan Amat yang sudah saling dukung selama masa perkuliahan. Terimakasih
atas pemikiran-pemikiran kalian yang membuat kita akhirnya menemukan
titik temu dalam perbedaan. Semoga silaturahmi selalu terjalin diantara kita.
11. Teman-teman farmasi UMM angkatan 2015. Terimakasih atas kebersamaan
kita selama 4 tahun terakhir yang dengan suka hati selalu berbagi informasi
terkait perkuliahan.
Akhir kata, penulis memohon maaf atas kekurangan dan ketidaksempurnaan
dalam penulisan skripsi ini dan dengan senang hati menerima kritik dan saran yang
bersifat membangun. Semoga skripsi ini dapat bermanfaat bagi penulis maupun
pembaca dalam menambah wawasan dibidang farmasi klinis.
Wassalamu’alaikum warahmatullah wabarakatuh.
Malang, 24 Agustus 2019
Penyusun
Khairun Ni’mah
x
DAFTAR ISI
Halaman
Lembar Pengesahan .............................................................................................. ii
Lembar Pengujian ................................................................................................ iii
KATA PENGANTAR .......................................................................................... iv
RINGKASAN ....................................................................................................... vi
ABSTRAK .......................................................................................................... viii
ABSTRACT .......................................................................................................... ix
DAFTAR ISI .......................................................................................................... x
DAFTAR TABEL............................................................................................... xiv
DAFTAR GAMBAR ........................................................................................... xv
DAFTAR LAMPIRAN ...................................................................................... xvi
DAFTAR SINGKATAN ................................................................................... xvii
BAB I PENDAHULUAN ...................................................................................... 1
1.1 Latar Belakang.......................................................................................... 1
1.2 Rumusan Masalah .................................................................................... 4
1.3 Tujuan Penelitian ...................................................................................... 4
1.3.1 Tujuan Umum ................................................................................... 4
1.3.2 Tujuan Khusus .................................................................................. 4
1.4 Manfaat Penelitian .................................................................................... 4
BAB II TINJAUAN PUSTAKA .......................................................................... 5
2.1 Anatomi dan Fungsi Hati.......................................................................... 5
2.1.1 Anatomi Hati ..................................................................................... 5
2.1.2 Sirkulasi Hati ..................................................................................... 6
2.1.3 Metabolisme dan Fungsi Hati ........................................................... 6
2.1.3.1 Metabolisme............................................................................... 6
2.1.3.2 Metabolisme Obat ...................................................................... 7
2.1.3.3 Sintesis ....................................................................................... 7
2.1.3.4 Fungsi Imunologis ..................................................................... 8
2.1.3.5 Detoksifikasi .............................................................................. 8
2.2 Sirosis Hati ............................................................................................... 8
2.2.1 Definisi Sirosis Hati .......................................................................... 8
2.2.2 Epidemiologi Sirosis Hati ................................................................. 9
xi
2.2.3 Etiologi Sirosis Hati ........................................................................ 10
2.2.4 Klasifikasi Sirosis Hati .................................................................... 11
2.2.5 Patofisiologi Sirosis Hati................................................................. 11
2.2.6 Komplikasi Sirosis Hati .................................................................. 13
2.2.6.1 Hipertensi Portal ...................................................................... 13
2.2.6.2 Asites ....................................................................................... 14
2.2.6.3 Varises Esofagus ...................................................................... 15
2.2.6.4 Ensefalopati Hepatik ................................................................ 16
2.2.6.5 Sindrom Hepatorenal ............................................................... 17
2.2.6.6 SBP .......................................................................................... 18
2.2.7 Data Klinis dan Data Laboratorium Sirosis Hati ............................ 18
2.2.7.1 Data Klinis ............................................................................... 18
2.2.7.2 Data Laboratorium ................................................................... 19
2.2.8 Penatalaksanaan Sirosis Hati........................................................... 21
2.2.8.1 Penatalaksanaan Hipertensi Portal dan Varises Esofagus ....... 21
2.2.8.2 Penatalaksanaan Asites ............................................................ 24
2.2.8.3 Penatalaksanaan Enselopati Hepatik ....................................... 24
2.2.8.4 Penatalaksanaan Sindrom Hepatorenal .................................... 28
2.3 SBP (Spontaneous Bacterial Peritonitis) ............................................... 29
2.3.1 Definisi SBP .................................................................................... 29
2.3.2 Epidemiologi SBP ........................................................................... 29
2.3.3 Etiologi SBP .................................................................................... 30
2.3.4 Patofisiologi SBP ............................................................................ 30
2.3.5 Manifestasi Klinis SBP ................................................................... 31
2.4 Penatalaksanaan SBP (Spontaneous Bacterial Peritonitis) .................... 32
2.4.1 Albumin........................................................................................... 32
2.4.2 Terapi Antibiotik Empiris ............................................................... 33
2.4.3 Terapi Antibiotik Profilaksis ........................................................... 34
2.4.4 Antibiotik Penisilin ......................................................................... 35
2.4.5 Antibiotik Quinolon ........................................................................ 35
2.4.6 Antibiotik Sefalosporin ................................................................... 36
2.4.6.1 Klasifikasi Sefalosporin ........................................................... 36
2.4.6.2 Farmakokinetika Sefalosporin ................................................. 39
2.4.6.3 Resistensi Bakteri .................................................................... 39
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2.4.6.4 Efek Samping Sefalosporin ..................................................... 39
2.4.6.5 Sefalosporin untuk SBP ........................................................... 40
2.5 Tinjauan Seftriakson ............................................................................... 40
2.5.1 Mekanisme Kerja Seftriakson ......................................................... 41
2.5.2 Indikasi dan Dosis Seftriakson ........................................................ 41
2.5.3 Kontraindikasi Seftriakson .............................................................. 43
2.5.4 Sifat Farmakokinetika dan Farmakodinamik Seftriakson ............... 43
2.5.5 Interaksi Seftriakson........................................................................ 46
2.5.6 Efek Samping Seftriakson ............................................................... 46
2.5.7 Parameter dan Monitoring............................................................... 47
2.5.8 Penyimpanan dan Administrasi....................................................... 48
2.5.9 Nama Dagang Seftriakson............................................................... 48
2.6 Penggunaan Seftriakson pada SBP ......................................................... 49
BAB III KERANGKA KONSEPTUAL ............................................................ 51
BAB IV METODE PENELITIAN .................................................................... 53
4.1 Rancangan Penelitian ............................................................................. 53
4.2 Populasi dan Sampel............................................................................... 53
4.2.1 Populasi ........................................................................................... 53
4.2.2 Sampel ............................................................................................. 53
4.2.3 Kriteria Inklusi ................................................................................ 53
4.2.4 Kriteria Eksklusi.............................................................................. 53
4.2 Bahan Penelitian ..................................................................................... 53
4.3 Instrumen Penelitian ............................................................................... 53
4.4 Tempat dan Waktu Penelitian ................................................................ 54
4.5 Definisi Operasional ............................................................................... 54
4.6 Metode Pengumpulan Data .................................................................... 54
4.7 Analisis Data .......................................................................................... 55
BAB V HASIL PENELITIAN ........................................................................... 56
5.1 Data Demografi Pasien ........................................................................... 56
5.1.1 Jenis Kelamin .................................................................................. 56
5.1.2 Usia ................................................................................................. 57
5.1.3 Status Pasien.................................................................................... 57
5.2 Komplikasi Penyerta Pasien Sirosis Hati dengan SBP........................... 58
5.3 Pola Penggunaan Seftriakson pada Pasien Sirosis Hati dengan SBP ..... 58
xiii
5.3.1 Pola Penggunaan Terapi Seftriakson .............................................. 58
5.3.2 Pola Penggunaan Terapi Seftriakson Tunggal ................................ 58
5.3.3 Pola Penggunaan Terapi Antibiotik Kombinasi .............................. 59
5.3.4 Pola Penggunaan Switch Seftriakson .............................................. 59
5.3.5 Lama Penggunaan Terapi Seftriakson ............................................ 60
5.3.6 Terapi selain Seftriakson pada Pasien Sirosis Hati dengan SBP .... 60
5.4 Lama Rawat Inap Pasien Sirosis Hati dengan SBP ................................ 61
5.5 Kondisi Keluar Rumah Sakit Pasien Sirosis Hati dengan SBP .............. 61
BAB VI PEMBAHASAN .................................................................................... 62
BAB VII KESIMPULAN DAN SARAN ........................................................... 76
7.1 Kesimpulan ............................................................................................. 76
7.2 Saran ....................................................................................................... 76
DAFTAR PUSTAKA .......................................................................................... 77
xiv
DAFTAR TABEL
Tabel Halaman
II.1 Stadium ensefalopati hepatik .......................................................................... 17
II.2 Manifestasi klinis SBP (dalam %) .................................................................. 32
II.3 Klasifikasi sefalosporin .................................................................................. 38
II.4 Persentase efek samping seftriakson .............................................................. 47
II.5 Nama dagang seftriakson ............................................................................... 48
V.1 Distribusi jenis kelamin pasien sirosis hati dengan SBP................................ 57
V.2 Pengolompokkan usia pasien sirosis hati dengan SBP .................................. 57
V.3 Status pasien sirosis hati dengan SBP ............................................................ 57
V.4 Komplikasi penyerta pasien sirosis hati dengan SBP .................................... 58
V.5 Pola penggunaan terapi seftriakson pada pasien sirosis dengan SBP ............ 58
V.6 Pola penggunaan terapi seftriakson tunggal ................................................... 59
V.7 Pola penggunaan terapi antibiotik kombinasi ................................................ 59
V.8 Pola penggunaan switch terapi antibiotik....................................................... 59
V.9 Lama penggunaan terapi seftriakson .............................................................. 60
V.10 Terapi selain seftriakson pada pasien sirosis hati dengan SBP .................... 60
V.11 Lama rawat inap pasien sirosis hati dengan SBP ......................................... 61
V.12 Kondisi KRS pasien sirosis hati dengan SBP .............................................. 61
xv
DAFTAR GAMBAR
Gambar Halaman
2.1 Struktur hati anterior ......................................................................................... 5
2.2 Anatomi hati dengan sirosis mikronodular ....................................................... 9
2.3 Anatomi hati dengan sirosis makronodular....................................................... 9
2.4 Patofisiologi sirosis hati .................................................................................. 12
2.5 Sirkulasi Kolateral Portosistemik pada Sirosis Hati ....................................... 13
2.6 Anatomi sistem vena porta .............................................................................. 13
2.7 Pasien asites .................................................................................................... 14
2.8 Patofisiologi asites .......................................................................................... 15
2.9 Profilaksis primer pada sirosis dengan perdarahan varises ............................. 21
2.10 Patofisiologi SBP .......................................................................................... 30
2.11 Struktur kimia seftriakson ............................................................................. 40
2.12 Kurva konsentrasi-waktu seftriakson secara IV dan IM ............................... 44
2.13 Kurva konsentrasi-waktu seftriakson dosis 2x200 mg vs 1x400 mg ............ 45
3.1 Skema kerangka konseptual ............................................................................ 51
3.2 Skema kerangka operasional ........................................................................... 52
5.1 Skema kriteria inklusi dan eksklusi pada penelitian sirosis dengan SBP ....... 56
xvi
DAFTAR LAMPIRAN
Lampiran Halaman
1 Daftar Riwayat Hidup ........................................................................................ 91
2 Surat Pernyataan................................................................................................. 92
3 Surat Tugas Skripsi ............................................................................................ 93
4 Laik Etik ............................................................................................................. 94
5 Surat Ijin Penelitian ............................................................................................ 95
6 Data Nilai Normal .............................................................................................. 96
7 Tabel Data Induk ................................................................................................ 97
77
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