2.1 Patients population
The study protocol was approved by the Ethics Committee for Clinical Trials of The Second Affiliated Hospital of Anhui Medical University, Hefei, China (approval NO.: PJ-YX2018-008(F1). Written informed consent was obtained from each patient. This trial was registered with the Chinese Clinical Trial Registry (ChiCTR1800017302). This manuscript adheres to the applicable Consolidated Standards of Reporting Trials (CONSORT) guidelines. We selected 102 ESRF patients with SHPT who were scheduled for parathyroidectomy in our hospital from August to December 2018. All patients were receiving hemodialysis thrice weekly or daily peritoneal dialysis. The patients had American Society of Anesthesiologists physical status II or III. Patients were randomized into two equal groups by a computerized random-number generator; a control group, managed with a restricted-fluid regimen Group C), and a PPV group (Group P) that was given normal saline infusion and monitored for change in PPV (Figure 1). Patients with primary hyperparathyroidism, severe pulmonary hypertension, arrhythmia, arteriosclerosis, aortic stenosis, or chronic cardiac dysfunction were excluded from the study. Patients with upper limb edema or malformation, or with blood pressure difference >10 mm Hg between the arms, also were excluded. In total, three patients were excluded from this study. The same operative team performed all operations.
2.2 Anesthesia and mechanical ventilation
No sedative or analgesic drugs were administered before the induction of anesthesia. Dialytic therapy was performed on the day before surgery. After their arrival in the operating room, patients received routine monitoring, including pulse oximetry (SPO2), electrocardiogram, bispectral index, and end-tidal CO2. CNAP was established and calibrated to measure blood pressure and other hemodynamic variables.
General anaesthesia was induced in all patients with bolus infusion of propofol (Fresenius Kabi AB, Macclesfeld, UK), with a goal of plasma concentration of 3.0–3.5 μg/mL; bolus remifentanil 1.5 μg/kg (Yichang Humanwell Pharmaceutical Co., Ltd., Yichang, China); and cisatracurium besylate 0.15 mg/kg (Jiangsu Hengrui Medicine Co., Ltd., Jiangsu, China). After tracheal intubation, ventilation was established with 6–8 mL/kg tidal volume, and respiratory rate was adjusted to target end-tidal CO2 of 35–45 mm Hg. Anesthesia was maintained with IV remifentanil (0.2–0.3 μg/kg/min), target-controlled infusion propofol, and cisatracurium besylate (0.1 mg/kg/min). During the operation, bispectral index values were maintained within 45 ± 5 by regulating the infusion rate of propofol. Thirty minutes before the end of the surgery, cisatracurium besylate infusion was stopped. Propofol and remifentanil were turned off in both groups after wound closure.
The endotracheal tube was removed when patients were able to follow verbal commands to open their eyes and the T4/T1 ratio was 90%. Patients were kept in the post-anesthesia care unit for one hour.2.3 Fluid management
In Group C, only vasoactive agents were administered, without fluid infusion. Bradycardia (HR < 40 beats/min) was treated with 0.5 mg intravenous atropine. Hypotension was defined as a decrease of >20% of the baseline systolic blood pressure. If hypotension occurred, ephedrine was given at increments of 6 mg. Infusion of dopamine was considered if the total ephedrine dose exceeded 40 mg. Hypertension (systolic blood pressure [SBP] >20% of the baseline SBP) was treated by infusion of 10 mg urapidil.
In Group P, intravenous fluid therapy and the use of vasoactive agents was determined according to the change of PPV and other hemodynamic variables (Figure 2). If PPV was >13%, 250 mL normal saline was administered over 1 min. Ephedrine was given at increments of 6 mg to keep mean arterial pressure > 65 mm Hg. Use of phenylephrine was avoided because of its propensity to induce intense vasoconstriction. Cardiac index (CI) was maintained above 2.5 L/min/m by pumping 3–5 μg/kg/min dobutamine intravenously, if needed. Fluid challenge status was evaluated every 15 minutes. Additional details of intraoperative fluid management are illustrated Figure 2.
2.4 Study parameters
In both patient groups, demographic data, dialysis history, preoperative complications, duration of operation, total volume of anesthetics (propofol, remifentanil and cisatracurium besylate) used, and intraoperative fluid and vasoactive agents infused were recorded. Postoperative complications, including hypotension, hypertension, pulmonary edema, infection, incision disunion and arteriovenous fistula occlusion, also were recorded.
Vital signs and weight were recorded before and after the last dialysis and before the administration of anesthesia. Values were considered “maximum,” “minimum,” or “baseline.” Hemodynamic variables were continually recorded at the beginning of mechanical ventilation (T1); before incision (T2); 30 min, 60 min, and 90 min during the operation (T3, T4, T5); and 120 min during the operation or at the end of the operation if the operative time was > 120 min (T6).
Blood samples were taken from the femoral artery before and 30 min after the operation and analyzed for brain naturietic peptide, blood gases, hemoglobin/hematocrit, lactate and electrolytes.
The primary endpoints of this study were the total volume of fluid administered, the doses of vasopressors used, and the incidence of postoperative complications. The secondary endpoints were abnormalities in blood gas values and electrolyte concentrations.
2.5 Data and statistical analysis
The sample size was determined based on our institutional records. A sample of 43 patients in each group was required to detect a 30% reduction in hypotension during and after operation at a significance level of 0.05. Considering a possible 20% dropout rate, a sample with a minimum of 51 per group was calculated.
Statistical analyses were performed with SPSS version 21.0 (SPSS Inc., Chicago, IL, USA). The data were tested for normal distribution with Kolmogorov-Sminov and for homogeneity of variances with Levene [6]. Normally distributed continuous data were presented as mean ± standard deviation, and abnormal distributions were expressed as median (25–75th percentile). Categorical variables were expressed as number (%). Independent-samples t-test was used to compare continuous variables between the two groups, and repeated-measures one-way ANOVA was used for in-group comparisons. All enumeration data were compared via chi-squared test. Comparisons between ranked data were made with the Kruskal-Wallis test or the Wilcoxon test. Binary logistic regression was used to determine the influence of age, gender, body mass index, and baseline hematocrit on the average PPV in the control group. P < .05 was considered statistically significant.