This was a single-center, parallel-group RCT conducted at Peking Union Medical College Hospital, a class A tertiary comprehensive hospital. Ethical permission was obtained from the Ethical Committee of Peking Union Medical College Hospital (ZS-1290). All patients were instructed about benefits and risks of the study and each participant signed an informed consent form. The trial is registered at www.clinicaltrials.gov (NCT02470221).
Patients admitted to the Department of Orthopedics of Peking Union Medical College Hospital (PUMCH) with the confirmed diagnosis of degenerative spinal stenosis, and who had indication for decompressive surgery under general anesthesia, were enrolled from March 1, 2017 to September 30, 2017. Inclusion criteria were age > 60, American Society of Anesthesiologists score II-III, and expected duration of operation > 2 h. Patients with severe cardiac arrhythmia (which would affect the accuracy of stroke volume variation as an indicator of fluid responsiveness), vascular disease (which would prohibit radial artery cannulation), and mental disorder were excluded.
Patients were assigned to one of the two groups (control group and GDT group) using a computer-generated randomization scheme. Allocation concealment was obtained using number labeled opaque envelopes that were opened just before the surgery. Patients were excluded from analysis if any of the following events occurred: vascular access line could not be established; LiDCO cardiac output monitor (LiDCO Ltd, Cambridge, UK) failed to calibrate; or the plan of surgery or anesthesia was changed. Data were collected by persons unaware of treatment allocation.
Intraoperative Management and Monitoring
All patients who received surgical decompression for lumbar spinal stenosis under general anesthesia were managed according to our national guidelines. Thus, after induction, patients were placed in the prone position supported by 4 pads (2 pads under the shoulders and 2 under pelvic sites) to suspend the chest and abdomen from the operation bed. A LiDCO monitor, calibrated according to the manufacturer’s instructions, recorded stroke volume, cardiac output and systemic vascular resistance during anesthesia. All patients were monitored intra- and post-operatively according to currently recommended standards to maintain arterial oxygen saturation of hemoglobin (SaO2) >96%, hemoglobin (>80 g/L), core temperature (>36.5°C) and heart rate (50-100/min). Ringer’s lactate was administered at 3 ml/kg/h for maintenance of fluid balance. Additional fluid was administered at the discretion of the attending anesthesiologist, based on patients’ pulse, arterial pressure, urine output, core-peripheral temperature gradient, serum lactate, and base excess. A dose of 6 mg ephedrine or 50 μg phenylephrine was given when fluid boluses failed to keep the systolic arterial pressure >90 mm Hg or mean arterial pressure (MAP) >65 mmHg. If such episodes occurred, they were recorded as hypotensive events. Patients in both groups also received a dose of 4 mg ondansetron as a prophylactic antiemetic during induction. Postoperative analgesia was provided with intravenous morphine infusion.
Goal-directed Fluid Therapy
Patients in the GDT group received the fluid management depicted in Figure 1. This protocol was based on the Frank-Starling mechanism of the heart. Fluid maintenance was set at 3-5 ml/kg/h of normal saline. Optimal stroke volume (SV) was maintained with targeted crystalloid boluses given as indicated according to invasive continuous hemodynamics monitoring. If MAP dropped more than 30%, or stroke volume variation (SVV) was more than 13%, boluses of 3 ml/kg (Figure 1) were given and SV response recorded. If a response was recorded (SV increase >10%), another bolus was given. If no response was recorded (SV was not elevated by more than 10%), no further bolus was given unless the SV decreased by 10%. Vasopressor or inotrope was not administered unless the MAP dropped persistently.
Anesthesiologist-directed Fluid Therapy (control group)
Patients in the control group received conventional fluid therapy, decided by the attending anesthesiologists based on the patient’s hemodynamic condition and responses, to maintain MAP >65 mm Hg, heart rate 50-100 bpm, and urine output >0.5 ml/kg/h.
The primary outcome of interest was the postoperative complications from admission to the operating theatre to 30 days after the surgery, include nausea and vomiting, infectious complications, delayed wound healing, cardiac events and kidney disorders .
The secondary outcomes of interest was the change of lactic acid concentrations throughout the perioperative period and intraoperative fluid balance. Arterial blood gas (ABG) and lactic acid were measured at 7 predefined times: T0, 24 h before surgery; T1, beginning of the operation; T2, 1h after the operation began; T3, 2h after the operation began; T4, end of the operation surgery; T5, discharge from the post-anesthesia care unit; and T6, 24 h after surgery.
The primary endpoint of the study was the concentration of lactate acid in the perioperative period. In a previous report, the average lactate concentration during the operative period was 2.015± 0.986 mmol/l8. We expected that a difference of 0.50 mmol/l in lactate concentration would be clinically meaningful. Therefore, we estimated that a total of 66 patients (33 in each group) would be needed to detect a difference with a power of 90% (α=0.05). Considering missing data or loss of follow up, we enrolled 40 patients in each arm. Data were analyzed on an intention-to-treat basis. Changes of lactate over time were tested with repeated-measure analysis of variance (ANOVA). The primary outcome data were normally distributed after reciprocal transformation and analyzed with the t-test. Categorical data were tested with Chi-square test and Chi-square test for trend. Data are presented as mean ± standard deviation when normally distributed. A p value of 0.05 was considered significant. All data were analyzed with SPSS (IBM SPSS Statistics v24, IBM, Armonk, NY, USA).