Effects of Intraoperative Fluid Therapy on Acute Kidney Injury After Thoracoscopic Lobectomy

Participants: Patients aged more than 18 years old who are scheduled to undergo thoracoscopic lobectomy well be enrolled in this trial. Participants will be randomly allocated to one of the two groups: (1) GDFT group and (2) restrictive fluid therapy group. Participants will be allocated in a 1:1 ratio using random numbers generated by Microsoft Excel.

Interventions: All participants will start lung function exercise, quit smoking, reinforce nutrition after hospitalization. Participants will fast for 6 hours and prohibit of drinking water for 2 hours before operation. Antibiotic will be used 1 hour before operation. No premedication will be administered to the patients. The electrocardiography (ECG), pulse oximetry, invasive arterial blood pressure, nasopharyngeal temperature, and bispectral index monitoring will be instituted. Urinary catheter will be inserted after anesthesia and removed immediately after operation. Patients will undergo thoracoscopic lobectomy under general anesthesia combined with paravertebral block. General anesthesia will be inducted with sufentanil, propofol, and rocuronium, and maintained with continuous infusion of propofol and remifentanil, intermittent injection of rocuronium. Lung-protective ventilation strategy will be used during mechanical ventilation. Recovery from general anesthesia as quickly as possible. Paravertebral block will be performed under the guidance of ultrasound after general anesthesia induction. Paravertebral block, patient controlled analgesia and oral analgesics will be used for postoperative analgesia. Recovering of oral rehydration, eating and getting out of bed as early as possible.

In GDFT group, the arterial catheter will be connected with FloTrac/Vigileo sensor (Edwards lifesciences, Irvine, CA, USA), The stroke volume variation (SVV) and cardiac index (CI) will be monitored. Fluid maintenance with 2 ml/kg/h of Ringer's solution of sodium acetate, when SVV＞13%, 4 mL/kg bolus of hydroxyethyl starch will be infused within 5 min. If SVV falls below 13%, the bolus will be suspended. If SVV is still more than 13%, 100 μg of phenylephrine will be administered when CI is more than 2.5 L/min/m2, 1 mg of dopamine will be administered when CI is less than 2.5 L/min/m2. When SVV＜13%, but mean arterial pressure (MAP)＜65 mmHg, 8 μg of norepinephrine will be administered. The hemodynamic status will be repeatedly measured every 10 min.

In restrictive fluid therapy group, fluid maintenance with 2 ml/kg/h of Ringer's solution of sodium acetate, hydroxyethyl starch will be infused to supply blood loss, the ratio of hydroxyethyl starch to blood loss is 1:1. 0.01-0.1 μg/kg/min of norepinephrine will be administered to maintain MAP＞65 mmHg.

Measurements: The primary outcome is the incidence of AKI after operation. The secondary outcomes include: (1) Incidence of renal replacement therapy, (2) Length of ICU stay after operation, (3) Length of hospital stay after operation, (4) Incidence of other complications including: infection, ALI, pneumonia, arrhythmia, heart failure, MINS, cardiac infarction.

Sample size: The primary outcome of this trial is the incidence of AKI after operation. Another study showed that the incidence of AKI was 4% and 2.9% in liberal infusion and GDFT respectively, the efficacy of intervention was 27.5%. Investigators hypothesis that restrictive fluid therapy combined with ERAS protocol has the same therapeutic effect as GDFT. The sample size for this study was calculated to achieve a statistical power of 0.8 and alpha error of 0.05 using a two-sided test. Considering a dropout rate of 10%, 138 patients are required in each group.

Statistical analysis: Normally distributed data will be presented as the mean±standard deviation. Categorical data will be presented as the number and the percentage of patients. The primary outcome (the incidence of AKI after operation) will be compared between the two groups with Pearson's chi-square test. The secondary outcomes will be compared between the two groups with independent-samples Student's t-tests for normally distributed continuous data and Pearson's chi-square test for categorical data. All statistical test are two-sided, and a P-value <0.05 will be considered statistically significant.