Disertasi

Pengaruh Variabilitas Glukosa Darah Perioperatif terhadap Fungsi Organ Pasien Pasca-Bedah Pintas Arteri Koroner: Kajian pada Fungsi Perfusi dan Oksigenasi Mikrosirkulasi = The Influence of Perioperative Blood Glucose Variability on Organ Function in Patients Following Coronary Artery Bypass Surgery: A Study on Microcirculation Perfusion and Oxygenation.

Variabilitas glukosa darah perioperatif memiliki pengaruh dalam kejadian morbiditas dan mortalitas pasien pasca bedah pintas arteri koroner (BPAK). Namun, belum diketahui hubungan variabilitas glukosa darah perioperatif dengan komposit disfungsi organ melalui mekanisme perubahan mikrosirkulasi perioperatif bedah jantung. Penelitian ini bertujuan untuk menganalisis pengaruh variabilitas glukosa darah perioperatif terhadap komposit organ dan mikrosirkulasi pasien pasca-BPAK. Penelitian menggunakan kohort prospektif yang dilakukan secara multisenter pada dua rumah sakit di Jakarta pada periode bulan April–Agustus 2023. Subjek penelitian ini adalah pasien dewasa dengan penyakit jantung koroner yang menjalani BPAK elektif dan menggunakan mesin pintas jantung paru. Data karakteristik demografis dan klinis dikumpulkan sebelum operasi. Variabel glukosa darah diambil secara intermiten sebanyak tiga periode waktu yaitu saat operasi tiap 30–90 menit serta hari pertama dan kedua perawatan intensif tiap 2–4 jam melalui akses vena sentral (CVC). Variabilitas glukosa darah yang dinilai antara lain standard deviation (SD), coefficient of variation (CV), mean absolute glucose (MAG), dan mean amplitude glucose excursion (MAGE). Komposit disfungsi organ dinilai menggunakan cardiac surgery score (CASUS) pada hari pertama dan kedua perawatan intensif. Parameter mikrosirkulasi dibagi dua jenis yaitu perfusi dan oksigenasi. Perfusi mikrosirkulasi, terdiri dari proportion of perfused vessel (PPV), perfused vessel density (PVD), microvascular flow index (MFI), dan flow heterogeneity index (FHI), direkam menggunakan pencitraan sidestream dark-field (SDF) dan dianalisis dengan program automated visual analytics (AVA) 4.1. Oksigenasi mikrosirkulasi, terdiri dari laktat dan rasio ekstraksi oksigen (O2ER), dinilai dari sampel darah. Penilaian komposit fungsi organ dilakukan menggunakan cardiac surgery score (CASUS) yang dilakukan pada hari pertama dan kedua perawatan intensif dengan skor > 6,5 sebagai disfungsi organ. Sebanyak 51 subjek memenuhi kriteria pemilihan diikutkan dalam penelitian dengan rerata usia 60,9 ± 6,7 tahun dan mayoritas laki-laki (80,4%). SD, CV, dan MAGE glukosa darah perioperatif dan pascaoperasi memiliki hubungan dalam kejadian disfungsi organ hari kedua ICU. Nilai SD perioperasi memiliki kemampuan diskriminasi yang sangat baik dengan AUC 0,923 dan titik potong 55,32 sebagai batas terjadi disfungsi organ (sensitivitas 100% dan spesifisitas 83%). PPV hari kedua ICU berkorelasi CV perioperatif (r = -0,299) dan pascaoperasi (r = -0,321). PVD hari kedua ICU berkorelasi dengan SD intraoperasi (r = -0,323), CV perioperatif (r = -0,341) dan intraoperasi (r = -0,384), serta MAGE perioperatif (r = -0,334) dan intraoperasi (r = -0,379). Laktat hari pertama ICU berkorelasi dengan SD intraoperasi (r = 0,290) dan pascaoperasi (r = 0,366) serta CV pascaoperasi (r = 0,419). PPV, PVD, dan laktat memiliki hubungan dengan kejadian disfungsi organ, dengan kemampuan diskriminasi terbesar adalah PPV hari pertama dan kedua ICU (AUC 0,963 dan 1,000). Variabilitas glukosa darah (SD, CV, MAGE) perioperatif memiliki pengaruh terhadap kejadian disfungsi organ (nilai CASUS ≥ 6,5) melalui mekanisme perubahan perfusi dan oksigenasi mikrosirkulasi pada pasien yang menjalani bedah pintas arteri koroner elektif.
Kata Kunci: variabilitas glukosa darah, bedah pintas arteri koroner, disfungsi organ


Perioperative blood glucose variability has an impact on the incidence of morbidity and mortality in patients after coronary artery bypass grafting (CABG). However, the relationship between perioperative blood glucose variability and composite organ dysfunction through the mechanism of perioperative microcirculation changes in cardiac surgery is not yet known. This study aims to analyze the effect of perioperative blood glucose variability on organ composite and microcirculation in post-CABG patients. This is a prospective cohort study that will take place between April and August 2023 in two hospitals in Jakarta. This study involved adult patients with coronary artery disease who had elective coronary artery bypass grafting (CABG) using a cardiopulmonary bypass machine. Demographic and clinical characteristic data were collected before the operation. Blood glucose variables were taken intermittently at three time periods: during the operation every 30 to 90 minutes and on the first and second days of intensive care every 2 to 4 hours by central venous access (CVC). The assessed glucose variability included standard deviation (SD), coefficient of variation (CV), mean absolute glucose (MAG), and mean amplitude glucose excursion (MAGE). Composite organ dysfunction was assessed using the cardiac surgery score (CASUS) on the first and second days of intensive care. Microcirculation parameters are divided into two types: perfusion and oxygenation. Microcirculatory perfusion, consisting of the proportion of perfused vessels (PPV), perfused vessel density (PVD), microvascular flow index (MFI), and flow heterogeneity index (FHI), is recorded using sidestream dark-field (SDF) imaging and analyzed with the automated visual analytics (AVA) 4.1 program. Microcirculatory oxygenation, consisting of lactate and oxygen extraction ratio (O2ER), is assessed from blood samples. The composite assessment of organ function is conducted using the cardiac surgery score (CASUS) performed on the first and second days of intensive care, with a score ≥ 6.5 indicating organ dysfunction. A total of 51 subjects met the selection criteria and were included in the study, with an average age of 60.9 ± 6.7 years and the majority being male (80.4%). SD, CV, and MAGE of perioperative and postoperative blood glucose have a relationship with the incidence of organ dysfunction on the second day in the ICU. The perioperative SD value has an excellent discrimination ability with an AUC of 0.923 and a cutoff point of 55.32 as the threshold for organ dysfunction (sensitivity 100% and specificity 83%). The second-day ICU PPV correlates with perioperative CV (r = -0.299) and postoperative CV (r = -0.321). The second-day ICU PVD correlates with intraoperative SD (r = -0.323), perioperative CV (r = -0.341), and intraoperative CV (r = -0.384), as well as perioperative MAGE (r = - 0.334) and intraoperative MAGE (r = -0.379). The first-day ICU lactate correlates with intraoperative SD (r = 0.290) and postoperative SD (r = 0.366) as well as postoperative CV (r = 0.419). PPV, PVD, and lactate are associated with the occurrence of organ dysfunction, with the greatest discrimination ability being the first- and second-day ICU PPV (AUC 0.963 and 1.000). Perioperative blood glucose variability (SD, CV, MAGE) affects the incidence of organ dysfunction (CASUS value ≥ 6.5) via processes including altered perfusion and oxygenation in patients undergoing elective coronary artery bypass surgery.
Kata Kunci: blood glucose variability, coronary artery bypass graft, organ dysfunction