The Khon Kaen University Ethics Committee in Human Research approved the study (HE611321) on 11 September 2019. The study was registered at www.ClinicalTrials.gov (NCT04292951) on 3 March 2020. The first case of the study was recruited on 1 January 2020, the other were recruited after 3 March 2020. We failed to register before participant recruitment due to miscommunication in the team. All methods were performed in accordance with the Declaration of Helsinki and the ICH GCP, and all participants gave written informed consent before being recruited. Study reporting followed the Consolidated Standards of Reporting Trials (CONSORT) guidelines.
This study was a prospective, randomized, double-blind (patient- and assessor-blinded) controlled trial. The sample size calculation was based on an ICU LOS after OPCAB of 4.20 ± 0.82 d, as reported in a previous study . Twenty patients per group were needed to detect a 35% 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 a 1:1 allocation ratio was performed using a computer-generated list kept in sealed opaque envelopes. The included patients were 1) male or female; 2) 18 or over; 3) undergoing OPCAB under general anesthesia at Srinagarind Hospital or Queen Sirikit Heart Center of the Northeast, Khon Kaen University, Khon Kaen, Thailand; and, 4) between II and IV on the American Society of Anesthesiologists (ASA) classification. Patients were excluded if 1) urgent or repeat surgery was required; 2) a contraindication existed vis-à-vis central venous cannulation; 3) an intra-aortic balloon pump was needed; 4) ventricular arrhythmia was present; or, 5) they were unable or unwilling to cooperate. The surgeons and anesthesiologists had at least five years of experience in OPCAB surgery.
Patients were randomized to the EV1000 or Control group. Patients received standard cardiac anesthesia care as per standard protocol. Operative monitoring included electrocardiogram, pulse oximeter, non-invasive blood pressure, temperature, capnography, anesthetic gas analyzer, and urine output. In the Control group, the radial artery was cannulated and connected to a pressure transducer to measure invasive blood pressure. In the EV1000 group, the radial artery was cannulated and connected to a FloTrac transducer (Edwards Lifesciences, Irvine, CA, USA) connected to an EV1000 monitor (Edwards Lifesciences, Irvine, CA, USA) to measure invasive blood pressure, SVV, CI, and SVI. In the Control group, the internal jugular vein was cannulated and connected to another pressure transducer to measure CVP. In the EV1000 group, the internal jugular vein was cannulated and connected to a pressure transducer which was connected to the EV1000 monitor to measure SVRI.
Irrespective of group, induction was achieved by a premedication of fentanyl 2–3 µg·kg− 1 and midazolam 1 mg, propofol 2–3 µg·kg− 1 or etomidate 0.3 mg·kg− 1. Cis-atracurium 0.2 mg·kg− 1 was used to facilitate endotracheal intubation. Anesthesia was maintained with 50% oxygen in the air and 1–2% sevoflurane or 3–6% desflurane—adjusted to 1 minimum alveolar concentration (MAC) on the monitor to maintain the depth of anesthesia. Heparin 1.5-2 mg·kg− 1 was administered via the CVP catheter for an activated clotting time (ACT) of 300–350 s with additional doses to maintain ACT of 250–300 s. After the operation, protamine 0.3–0.5 mg per 1 mg of the initial dose of heparin was given stepwise to reverse the effect of heparin. Patients were moved to ICU, where they were mechanically ventilated and given standard care.
Ventilator weaning and extubation were performed according to 1) good consciousness and motor power; 2) stabilized cardiovascular status; 3) PaO2/FiO2 ratio ≥ 250 mmHg; and, 4) respiratory rate 10–25 times·min− 1. The ICU discharge criteria included 1) satisfactory consciousness and neurological signs; 2) steady cardiovascular status without any need for inotropic or vasopressor drugs or ICU monitoring; and, 3) a satisfactory respiratory status not requiring greater than 60% oxygen supplementation. The benchmarks for hospital discharge included 1) stable cardiovascular and respiratory status; 2) no drain or catheter needed; 3) normal ambulation; 4) no infection or serious complications; 5) no wound stitches; and, 6) normal diet.
Each patient's heart kept beating throughout the surgery. The patients were put in the Trendelenburg position during coronary anastomosis.
In the intraoperative period, the Control group received fluid, inotropic, or vasoactive drugs as per the attending anesthesiologist. The goals were: mean arterial pressure (MAP) 65–90 mmHg; CVP 8–12 mmHg; urine output ≥ 0.5 mL·kg− 1·h− 1; SpO2 > 95%; and hematocrit ≥ 30%. Arterial blood gas (ABG) and electrolytes were monitored hourly and corrected as required. The goals for patients in the EV1000 group were the same—i.e., MAP 65–90 mmHg; urine output ≥ 0.5 mL·kg− 1·h− 1; SpO2 > 95%; and hematocrit ≥ 30%—but achieved using the EGDT protocol with data from the FloTrac/EV1000. Patients first received fluid to maintain SVV < 13%, followed by inotropic drugs to maintain an SVI of 33–65 mL·beat− 1·m− 2 and a CI of 2.2-4.0 L·min− 1·m− 2, followed by vasoactive drugs to maintain an SVRI of 1,500‑2,500 dynes s− 1·cm− 5·m− 2. ABG and electrolytes were likewise monitored and corrected.
The recorded parameters included: volume of fluid, amount of inotropic and vasoactive drugs used during the intraoperative period, transfer to ICU, and in ICU. Also recorded were the duration of mechanical ventilation in the ICU, LOS in ICU and hospital, and complications.
The Shapiro-Wilk test was used to determine whether the continuous data were normally distributed. Data with a normal distribution were presented as means ± standard deviations (SD), while non-normal distributed data were presented as medians with interquartile ranges. Categorical data were presented as numbers (%). As appropriate, the differences between both groups were analyzed using the unpaired Student’s t-test, Mann-Whitney U test, χ2 test, or Fisher exact test. P < 0.05 was considered statistically significant. Statistical analyses were performed using SPSS 16.0 for Windows (SPSS, Chicago, IL, USA).