Vol 6, No 1 (2019) > Mini Review Article >

Kajian Narrative terhadap Profil Farmakokinetik Antibiotik pada Pasien Kritis: Implikasi terhadap Ketercapaian Target Farmakokinetik-Farmakodinamik

Eko Setiawan , Widyati Widyati , Ferdy Royland Marpaung , Edy Sukandar , Susaniwati Susaniwati , Dwi Lily Lukas , Heru Wijono , Taufin Warindra , Roni Kurniawan , Tjipto Wibowo , Wahyu Hendradi , Menino Osbert Costa , Mohd-Hafiz Abdul-Aziz , Jason Roberts

 

Abstract:

ABSTRACT

The severity of diseases, the complexity of treatment, and the use of medical devices in the intensive care unit (ICU) may change the pharmacokinetics (PK) profile of antibiotics among critically ill patients.This narrative review aims to explain the PK profile of critically ill patients compared to other group of patients and to describe the pharmacokinetic-pharmacidynamic (PK-PD) target attainment among this group of patients. Only articles published less than 10 years ago were included in this narrative review. Evidences have indicated that critically ill patients have relatively larger volume distribution (Vd) of hydrophilic antibiotics compared to patients with stable conditions. The fluid shifting to interstitial space, hypoalbuminemia, and aggressive fluid treatment may contribute to the increase value of Vd in critically ill patients. The clearance (CL) of hydrophilic antibiotics in critically ill patients is highly determined by dynamic changing of renal function compared to patients in other wards. The phenomenon of augmented renal clearance and the use of high intensity of renal replacement therapy can increase the CL of hydrophilic antibiotics. The different PK profile of antibiotics may lead to the failure of attaining the PK-PD target if the dose of antibiotics is not adjusted according to such differences.


ABSTRAK

Tingkat keparahan penyakit yang relatif tinggi dibandingkan pasien di bangsal rawat lain dan penggunaan terapi serta alat medis yang relatif lebih kompleks di ruang intensive care unit (ICU) dapat berdampak pada perubahan profil farmakokinetik (PK) antibiotik pada pasien kritis. Tujuan utama kajian naratif ini adalah untuk memaparkan profil PK dan ketercapaian target farmakokinetik-farmakodinamik (PK-PD) pasien kritis di ICU. Hanya artikel yang diterbitkan dalam kurun waktu 10 tahun terakhir yang digunakan dalam kajian naratif ini. Bukti penelitian menunjukkan bahwa volume distribusi (Vd) antibiotik hidrofilik pada pasien kritis lebih besar dibandingkan dengan pasien yang relatif lebih stabil atau subyek sehat. Perpindahan cairan intravaskuler ke daerah interstitial, hipoalbuminemia, dan terapi cairan khususnya yang diberikan secara agresif merupakan faktor yang berkontribusi terhadap peningkatan Vd pada pasien kritis. Clearance (CL) antibiotik hidrofilik pada pasien kritis ditentukan oleh perubahan fungsi ginjal yang relatif lebih dinamis dibandingkan dengan pasien di ruang rawat inap lain. Fenomena augmented renal clearance yang umum dijumpai pada pasien kritis dan penggunaan renal replacement therapy dengan intensitas yang tinggi dapat meningkatkan CL antibiotik hidrofilik. Perbedaan profil PK tersebut berpotensi menyebabkan kegagalan untuk mencapai target PK-PD apabila tidak dilakukan penyesuaian dosis antibiotik pada pasien kritis. Identifikasi profil PK perlu diupayakan sebagai langkah awal untuk mengoptimalkan pemberian antibiotik pada kelompok pasien kritis.


Keywords: antibiotik; farmakokinetik-farmakodinamik; pasien kritis; ruang rawat intensif; antibiotics; critically ill patients; pharmacokinetics-pharmacodynamics; intensive care unit

Published at: Vol 6, No 1 (2019) pages: 1-12

DOI: 10.7454/psr.v6i1.4274


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