Ethical approval
The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Shangrao Fifth People's Hospital (No.2016‑12‑01). The informed consent was obtained from all patients prior to their enrollment in this study.
General information
This prospective observational study was carried out at the Integrated Intensive Care Unit of the Fifth People's Hospital of Shangrao City (Shangrao, China) from December 2016 to July 2017. A total of 48 patients with mechanical ventilated after cardiac surgery were enrolled in the study, and the attending physician decided whether to perform a fluid challenge. This decision was based on at least one clinical sign of inadequate tissue perfusion and no contraindications for infusion. Clinical signs of inadequate tissue perfusion were defined as follows: clinical signs of acute circulatory failure (Mean arterial pressure [MAP] decreased by 30% from baseline value, or need vasopressor drugs maintaining normal systolic blood pressure; heart rate increased by 10% from baseline after excluding arrhythmia; urine output of < 0.5 ml·kg-1·h-1 for at least 1 h; mottled skin, oliguria (diuresis below 0.5 ml·kg-1·h-1), arterial blood lactic acid increases 1.5-fold from base value, acute kidney failure, and/or clinical and laboratory signs of extracellular dehydration[4,12]. Exclusion criteria included clinical signs of hemorrhage, failure to postpone fluid challenge for several minutes, arrhythmia, PLR contraindication, left ventricular ejection fraction less than 0.30, pulmonary artery systolic pressure greater than 40mmHg, or known allergic reaction to albumin.
Echocardiography and Hemodynamic Data collection
Before operation, a 4-5.5fr central venous catheter was inserted into the right internal jugular vein or the right/left subclavian vein to monitor CVP, while a 7cm 3fr arterial catheter was inserted into the right or left femoral artery to monitor blood pressure dynamically. The standard transthoracic probe (3SP-D) of GE VIVIVIXE9 Doppler echocardiography was used to measure SV. On the five chambers apical view, the aortic blood flow was recorded using pulsed Doppler, with the sample volume placed on the annulus aorta. A velocity-time integral of the aortic blood flow was also measured. The aortic valve area was calculated from the diameter of the aortic orifice, measured at the insertion of the aortic cusps, as aortic area = (aortic diameter/2)2. SV and CO were measured with the equations SV = velocity-time integral (VTI) × aortic area, and CO = SV × heart rate. The aortic area was considered stable during the trial and was measured only once in the beginning. Every VTI measurement was taken based on approximately two to three measurements during one breathing cycle. All of the measurements were conducted by a cardiologist.
Study Design
The patient was in a supine position, with the upper body parts being 45° higher (Base 1) and four hemodynamic parameters (heart rate, blood pressure, SV, and CVP) were measured: The upper parts of the body were then lowered to achieve a horizontal position with the lower extremities being raised 45° using a specially formed angled board, and within 30 seconds to 1 minutes, the four hemodynamic parameters were measured again (Base 2). The patient was then placed back in the initial position (the upper parts being 45° higher) for 10 mins and the hemodynamic parameters were remeasured (Base 3). Subsequently, a bolus of the intravenous fluid challenge was given to the patient using 10 ml/kg of 5% albumin in 15 mins and the four hemodynamic parameters were measured immediately following the challenge. The patients showing an increase in SV >10% in response to volume expansion (VE) were considered responders, and the rest were defined as nonresponders. During the above-mentioned procedure, patients were kept fully sedated, and the parameters of vasoactive drugs, sedatives and mechanical ventilation remained unchanged.
Statistical methods
Continuous variables were presented as the mean ± standard deviation if normally distributed or median (range) if the distribution was not normal. Student’s unpaired t-test or the Mann–Whitney U-test was used to evaluate group differences. To assess the correlation between ΔSV-VE and PLR related ΔSV, ΔMAP, ΔHR, ΔCVP, and ΔCO, linear regression analysis was performed. Linear correlations were tested using the Pearson test and linear regression method. To determine the ability of all variables to predict fluid responsiveness, receiver operating characteristic (ROC) curves were generated, and the area under the ROC curve was calculated. The ROC curves were compared using the Hanley–McNeil test [13]. Youden’s index which was calculated as follows: Youden’s index = sensitivity + specificity – 1[14]. Cut-off values for ΔSV, ΔCO, ΔCVP, ΔMAP, and ΔHR were chosen to correspond to the best respective. Threshold indicator values such as sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were calculated for each hemodynamic indicator testing. A value of P < 0.05 was taken to indicate statistical significance. All statistical analysis was performed with IBM SPSS 23.0 for Windows (SPSS, Inc, Armonk, NY).