Cerebral oxygenation in 45-degree trendelenburg position for robot-assisted radical prostatectomy: a single-center, open, controlled pilot study

We enrolled in our study a total of 58 consecutive male patients (study group) who underwent robot-assisted radical prostatectomy (RALP) for localized prostate cancer therapy and 22 consecutive male patients undergoing robot-assisted partial nephrectomy (RAPN) (control group) for suspected kidney-cell carcinoma at the Wels-Grieskirchen Medical Center. We chose the RAPN procedure for our control group since it is a routine, robotically-assisted procedure at our institution, and a horizontal position is maintained during the entire procedure. Preoperative oncological staging and the indication for the above-mentioned surgical intervention were determined according to the current guidelines of the European Association of Urology (EAU) on prostate cancer and renal cell carcinoma. General anesthesia was induced with 150–200 µg of fentanyl and 150–200 mg of propofol then 0.6 mg/kg of rocuronium was administered followed by orotracheal intubation. General anesthesia was maintained with sevoflurane (MAC 0.9–1.2) and continuous infusion of remifentanil (1–2.5 µg/kg/min). Pneumoperitoneum was induced by insufflating CO2 with gas pressure set to 8 mmHg during the whole operation. After pneumoperitoneum was achieved, study patients were positioned in 45° Trendelenburg by tilting the operating table. Control group patients were brought into flank position prior to inducing pneumoperitoneum with the operation table slightly flexed. Once the procedure started, this patient position was maintained during the entire procedure. All surgeries were performed by experienced urologists (> 100 robot-assisted procedures) using the da Vinci® Si Surgical System (Intuitive Surgical, Sunnyvale, CA, USA) with the surgeon performing the procedure at a control table located away from the operating table. Patients provided informed consent prior to inclusion in our study, which was approved by our local ethics committee (ethics committee of Upper Austria (Study Nr. O-18-13)); it was therefore conducted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Our sole exclusion criterion was involvement in any other clinical study, but this did not apply since no patients screened met this criterion. The study was designed and conducted in accordance with the consort criteria.

Patient demographics and ASA classification was recorded 24–6 h prior to surgery. In addition, mini-mental status test (MMS) was carried out, and a standard blood workup (hemoglobin, hematocrit, blood coagulation parameters) was obtained. Furthermore, we documented baseline blood pressure and heart frequency. Intraoperative heart frequency (HF), cerebral oxygenation (rSO2), and blood pressure (RR) were obtained and recorded prior to final positioning and consecutively at 10-min intervals throughout the procedure. Also the FiO2 was (= fraction of inspired oxygen) was monitored. To measure rSO2, bilateral cerebral oximetry sensors were placed on the patient’s forehead and rSO2 was continuously monitored using near infrared spectroscopy (NIRS) and the INVOS analytics tool for recording. We also recorded total operating time, time in Trendelenburg position and time of robotic actuation. Within 6–24 h after surgery, standard blood panel was repeated and all patients underwent a MMS Test. Complications were classified according to the Clavien Dindo classification and recorded over a 3 months follow up for all included patients.

This trial was designed to explore whether a 45 Degree Trendelenburg Position causes any differences in intraoperative clinical parameters, or changes in the MMS exam result in comparison with patients not in a head-down position. Patients were included in this exploratory study applying the intention-to-treat principle. All statistical calculations were performed by an experienced and licensed statistician (H.W.). Changes in the MMS exam outcome before and after surgery were subjected to the Wilcoxon rank-sum test. To analyze the evolvement of parameters during surgery, we made an exploratory comparison of the different variables at the same time point, followed by a longitudinal analysis of a variable’s evolvement, and investigated the change in a given variable compared to its initial value by linear mixed effects models. To analyze changes, the response variable’s pre-operation value centered at a reasonable value and that variable’s interaction with time were included in the model. All statistical computations were performed using the R statistics software (Version 3.5.2). All tests were two-sided with p < 0.05 considered to indicate statistical significance, but as this is not a confirmatory trial, significant results can be interpreted only as indicating a potential association.

All patients included in our study underwent a complete evaluation, and we observed no drop outs. Median age in our study group was 66, ranging from 48 to 79 years. Our control group’s median age was 56 years (45–84). ASA classification showed a median of 2 for both groups. Routine blood panel revealed a median hemoglobin value of 15.3 g/dl (13–17.1) for the RALP group and 14 g/dl (10.20–16.30) for the RAPN group. Median preoperative RR was 137.5 (94–210)/80 (60–110) for our study group and 146.5 (100–180)/80 (60–103) for the control group. The median HF measured 66 bpm (45–92) (RALP) and 70 bpm (60–100) (RAPN). No significant difference was detected in individual preoperative patient characteristics (Table 1) except for the RALP group’s higher hemoglobin value.

The preoperative MMS exam revealed a median point value of 30 (IQR = 1) for RALP and a point value of 30 (IQR = 0.75) for RAPN. There was no statistically significant difference here, either (p = 0.29).

Total median operation time was 180 min (IQR = 56.75; documentation for 2 procedures missing) for the RALP group and 140.5 min (IQR = 76.50) for the RAPN group, thus the study group’s surgery time was longer (p = 0.01). Also, the RALP group’s robotic-actuation time (= console time) was significantly longer than the RAPN group’s (p = 0.001). RR values exhibited no difference in systolic values, but the prostate group’s diastolic values were significantly higher, although that effect vanished after about 120 min’ operation time. However, since the RAPN group’s operation time was shorter, we had access to fewer measurements after 120 min, with only 1 measurement at 210 min. Our analysis of any statistical change in systolic RR compared to the initial value showed no group difference either. We noted a significant difference between the RALP and RAPN group in diastolic RR compared to the initial valued (p = 0.00), with the prostate group’s RR values significantly higher 120 min into the operation. Age also seemed to reveal an effect on the change in diastolic RR, with the patients over 60 showing significantly lower values (p = 0.00). HF during surgery did not differ significantly between groups in either the longitudinal analysis or analysis of change during the operation. We did, however, observe a tendency for older patients (> 60 years) to present a lower heart frequency. Intraoperative FiO2 measurements revealed very little variation, with no group difference in the intraoperative change versus the initial value. Although the former was also not associated with patient BMI, higher-BMI patients revealed a generally higher FiO2 (p = 0.01). The pCO2 (mean overall change: − 0.73 ± 0.18; p < 0.001) value and pO2 (mean overall change: 0.95 ± 0.09; p < 0.001) and rSO2 value (mean change: − 0.18 ± 0.08; p < 0.03) showed a significantly smaller change in patients with an initially higher value (see also Fig. 1). Patient characteristics demonstrated no significant influence in these values or any difference between study groups.

Patients were monitored for perioperative and postoperative complications until 3 months after surgery. A total of 22 complications were recorded within the RAPN group and classified according to the Clavien Dindo classification: 10 were classified as category 1, 4 as category 2, 3 as 3a, and 4 as 3b. There were no category 4 or 5 complications. All complications were closely analyzed to determine whether any had been specifically caused by or related to patient positioning, but none were detected.

Postoperative repetition of the MMS exam yielded no significant difference compared to the preoperative value in the RALP group (p = 0.16) and RAPN group (p = 0.19), suggesting no negative effect of the operation and intraoperative positioning on cognitive function (Fig. 2).