The current study was approved by the Khon Kaen University Ethics Committee in Human Research (HE611321) and registered at www.ClinicalTrials.gov (NCT04292951) on 03/03/2020. The study was conducted in accordance with Declaration of Helsinki and the ICH GCP.
Written informed consent was obtained from all subjects.
This study was reported according to the CONSORT (Consolidated Standards of Reporting Trials) guidelines.
Our study was a multi-center, prospective randomized double-blind (patient- and assessor-blinded) controlled trial. The sample size calculation was based on ICU LOS (4.9 ± 1.8 d) after cardiac surgery in a previous study . We determined that we needed a sample size of 42 per group to detect a 25% decrease in ICU LOS with an α-value of 0.05, a power (1-ß) of 0.80, and a 20% dropout. Block-of-4 randomization with 1:1 allocation ratio was performed using a computer-generated list kept in sealed opaque envelopes. We included patients of either sex who: 1) were 18 or older who underwent elective CABG with CPB under general anesthesia at Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand or Phramongkutklao Hospital, Bangkok, Thailand; and, 2) had an American Society of Anesthesiologists (ASA) classification between II and IV. We excluded patients needing redo surgery, having a contra-indication to central venous cannulation, requiring intra-aortic balloon pump, having ventricular arrhythmias, or having any inability to cooperate. All surgeons and anesthesiologists in the study were qualified personnel for cardiac surgery and anesthesia with > 5 years’ experience.
The patients were randomized to the EV1000 or Control group. All patients received standard cardiac anesthesia care as per our institution’s protocol. The monitors in the operation theater included electrocardiogram, pulse oximeter, non-invasive blood pressure, temperature, capnography, anesthetic gas analyzer, and urine output. The radial artery was cannulated and connected to a pressure transducer in the Control group to measure invasive blood pressure (IBP) or a FloTrac transducer in the EV1000 group to measure IBP as well as SVV, SVI, and CI. The internal jugular vein was cannulated and connected to another pressure transducer in the Control group to measure central venous pressure (CVP) or a pressure transducer connected to the FloTrac transducer in the EV1000 group to measure SVRI. All patients receive fentanyl 2–3 µg·kg− 1 and midazolam 1 mg as a premedication. Propofol 2–3 mg·kg− 1 or etomidate 0.3 mg·kg− 1 was used as an induction agent. Endotracheal intubation was facilitated using cis-atracurium 0.2 mg·kg− 1. Anesthesia was maintained with 50% oxygen in air and 1–2 % sevoflurane or 3–6 % desflurane adjusted to achieve 1 minimum alveolar concentration (MAC) on the monitor to maintain the depth of anesthesia. CPB was initiated after heparin 3–4 mg·kg− 1 was administered via the CVP catheter with an activated clotting time (ACT) > 480 s, with supplemental doses of 1–2 mg·kg− 1 to maintain ACT > 400–480 s. Mild hypothermia (32ºC) was maintained during CPB. Cardioplegia solution was infused via an aortic root catheter after aortic cross-clamping. Supplemental cardioplegia was administered at the discretion of the cardiac surgeon. During CPB, mean arterial pressure (MAP) was maintained in the range of 45–75 mmHg. After terminating the CPB, protamine 1 mg per 1 mg of pre-CPB heparin dose was slowly injected to reverse the effect of heparin. All patients were transferred to the ICU and mechanically ventilated. All patients received standard ICU care. The criteria for ventilator weaning and extubation were: good consciousness and motor power, stable cardiovascular status, a PaO2/FiO2 ratio ≥ 250 mmHg, and a respiratory rate of 10–25 times·min− 1. The criteria for ICU discharge were: good consciousness and neurological signs, stable cardiovascular status with no need for inotropic or vasopressor drugs and ICU monitoring, and stable respiratory status with oxygen requirement not more than 60%. Hospital discharge criteria were: stable cardiovascular and respiratory status, no drain or catheter retained, normal ambulation, no infection or serious complications, wound-stitch removed, and normal diet.
During the intraoperative period, both before and after CPB, the Control group received fluid, inotropic, or vasoactive drugs at the discretion of the attending anesthesiologists to achieve the following goals: MAP 65–90 mmHg; CVP 8–12 mmHg; urine output ≥ 0.5 mL·kg− 1·h− 1; SpO2 > 95%; and hematocrit 26–30%. Arterial blood gas (ABG) and electrolytes were monitored and corrected hourly. In the EV1000 group, the patients were managed to achieve the similar goals by receiving fluid, inotropic, or vasoactive drugs via the EGDT protocol using information from the FloTrac/EV1000 to achieve the following targets: SVV < 13%; SVI 33–65 mL·beat− 1·m− 2; CI 2.2-4.0 L·min− 1·m− 2; and SVRI 1600‑2500 dynes s− 1·cm− 5·m− 2. ABG and electrolytes were monitored and corrected in the same manner.
The volume of fluid, amount of inotropic, and vasoactive drugs used during pre-CPB, post-CPB, transfer to the ICU, and in the ICU were recorded. Also recorded were time of mechanical ventilation in the ICU, ICU and hospital LOS, and all complications.
Continuous data were tested for Gaussian distribution using the Shapiro-Wilk test. Data with a normal distribution were presented as a mean ± standard deviation (SD) and compared using the unpaired Student’s t-test. Data with non-Gaussian distribution were presented as a median (inter-quartile range) and compared using the Mann-Whitney U test. Categorical data were presented as a number (%) and compared using the χ2 test. The primary outcome was presented as a mean difference with a 95% confidence interval (CI). P < 0.05 was considered statistically significant. All data were analyzed using SPSS 16.0 (SPSS Inc., Chicago, IL, USA).