Study design
This was an observational prospective cohort pilot study, which was approved by our Institutional Review Board and was registered by the Clinical Research Information Service (Clinical Trial.gov ID: NCT03372135).
Subjects
The study was conducted between December 2017 and May 2018. Patients (with the age of more than 55 years old, ASA I-III) who underwent RARC and open abdominal surgery in horizontal position were included. All recipients were free of intracranial surgery and intracranial pathology (e.g., cerebral infarction). We also excluded patients who suffered from alcoholism or took psychotropic medication. Illiteracy, visual and hearing impairment and those who affected by low preoperative mini-mental state examination (MMSE) scores (less than 24) were eliminated as well.
Preoperative and postoperative tests
Regarding preoperative cognitive dysfunction scales, C-reactive protein (CRP) and S-100β were tested. Laboratory variables of S-100β (brain injury biomarker) and CRP (an acute-phase protein in response to inflammation) were measured 48 h after surgery as well. Cognitive dysfunction scales were used to evaluate patients in the period of 1 week and 3 months [17] after surgery to compare with preoperative results. The test battery [18] included MMSE, a test of examination of functions including registration, attention and calculation, recall, language, ability to follow simple commands, and orientation; Brief Visuospatial Memory Test–Revised (BVMT-R), an assessment of non-verbal learning and memory; Symbol Digit Modalities Test, a test of psychomotor speed and attentional control; Trail Making Test (TMT), to assess visual scanning, psychomotor speed, attention, and executive function; Digit Span Test (DST), measuring attention and short-term verbal memory; and Stroop Color and Word Test (SCWT), a test for word-naming and resistance to interference. These tests were administered by experienced research personnel, who trained and supervised by a senior neuropsychologist.
Position and insufflation during RARC
CO2 pneumoperitoneum with a stable abdominal pressure of 1.2 kPa and flow of 1.5 kPa, accompanied with 40 to 45° Trendelenburg positioning were performed in all patients in RARC group after anesthesia induction. When bladder isolation, ureters blocking, and lymph node dissection finished, patients were returned to the horizontal position and deflation.
General anesthesia and monitoring
After a recipient was placed supine in the operating room, routine monitoring was performed using electrocardiography, pulse oximetry, non-invasive blood pressure, and end-tidal CO2 (etCO2). In accordance with our protocol, anesthesia was induced with propofol and sufentanil, with tracheal intubation facilitated with Rocuronium bromide. Anesthesia was maintained with sevoflurane in a 60% oxygen-air mixture accompanied by continuous infusions of remifentanil and cisatracurium. Then, the direct arterial pressure was monitored by femoral arterial catheterization. To monitor central venous pressure, a central venous catheter inserted into the internal jugular vein was connected to a sensor.
Measurements of cerebral rSO2 and intraoperative variables
NIRS can be used to detect changes in oxygenated and deoxygenated hemoglobin associated with brain tissue hypoxia and estimate changes in cerebral blood volume and flow. For cerebral oximetry, sensors were placed on the patient’s forehead bilaterally. Cerebral rSO2 values were obtained from an INVOS 5100C Cerebral/Somatic Oximeter System, which generates 2 wavelengths of infrared light (730 and 805 nm) and penetrates into the skull and cerebral tissues. The cerebral oximetry sensor is consisted of a light-emitting diode and 2 detectors located at distances of 30 and 40 mm from the light-emitting diode to avoid light attenuation or extracranial contamination. Cerebral rSO2 values were automatically recorded every 5–6 s from the digital output port of the monitor to the personal computer.
Measurements of heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), etCO2 and cerebral oxygen were simultaneously performed after entering the operating room (T0; baseline), anesthesia induction (T1), Trendelenburg positioning (T2), 1 h, 2 h, and 3 h after Trendelenburg positioning (T3, T4, T5 respectively), and after desufflation in a horizontal position (T6). We obtained arterial blood gas and vein blood gas for measurements of hemoglobin (Hb), serum glucose, sodium, potassium, base excess, lactic acid, PaCO2, PaO2, PvCO2, and PvO2 before the operation, and 10 min after desufflation.
Neuropsychological assessment
We used Z score to analyze and comprehensively evaluate POCD [19]. Six cognitive scores (MMSE, BVMT-R, Symbol Digit Modalities Test, TMT, DST, and SCWT) [20] were combined into a composite cognitive score by averaging the Z scores of each test from the patients’ preoperative assessments. Thus, by definition, the mean preoperative score is 0 and the standard deviation is 1. When there were significant findings (≥ 1.96) in postoperative neurocognitive tests or the total Z score ≥ 1.96, then the patients were defined as POCD [15]. In this calculation, timed test scores were inverted to be consistent with non-timed tests, such that higher values represent superior performance for all tests.
Statistical analysis
Data are presented as mean ± standard deviation (SD). With Comparing the incidence rate of POCD, the concentration of CRP and s100β between RARC group and control group was compared using the one-tailed Fisher’s exact test and independent sample t-test. Nonparametric test (Kruskal-Wallis test) was used for the cerebral oxygen saturation value and vital signs of RARC group during different time points. P-value of less than 0.05 was statistically considered significant. Statistical analysis was performed using the GraphPad Prism 5.01 software (GraphPad Inc., CA, USA).