This single-center, prospective, observational interventional study was approved by the Ethics Committee of Tokyo Medical University Hospital (T2018-0065). The study protocol adhered to the principles of the Declaration of Helsinki; written informed consent was obtained from all patients. This registered clinical trial (UMIN000036376) included consecutive patients undergoing the RARP procedure at the Tokyo Medical University Hospital from April to August in 2019.
We enrolled male patients with the American Society of Anesthesiologists (ASA) Physical Status Classification score of 1 or 2 points, scheduled for RARP using a robotic operating system (da Vinci™ Surgical System, Intuitive Surgical, Inc., Sunnyvale, CA, USA). Patients with a history of chronic obstructive pulmonary disease, renal or heart failure, esophageal diseases, or body mass index (BMI) of ≥35 kg m−2 were excluded from this study.
No premedication was administered. Upon arriving in the operating theater, patients were monitored by electrocardiography; non-invasive automated blood pressure measurement and pulse oximetry were performed. SedLine® Brain Function Monitoring for patient state index (PSi) and O3® Regional Oximetry sensors for bilateral forebrain oxygenation (rSO2) monitoring were attached to the forehead and connected to Root Monitor® (Masimo, Irvine, CA, USA). A pulse oximetry probe was placed on the forefinger; body temperature was measured, using a 3M™ BearHugger™ deep temperature monitoring system. The patients were breathing a fraction of inspired oxygen (FIO2) of 1.0 for 3 min before the induction of general anesthesia with intravenous remifentanil at a rate of 0.3 μg kg−1 min−1 and propofol via target-controlled infusion to a plasma concentration of 4–4.5 μg mL−1. The lungs were ventilated manually, using a Jackson Rees breathing system via a face mask with an FIO2 of 1.0. Muscle relaxation was achieved with rocuronium of 1 mg kg−1 to facilitate orotracheal intubation. The patients were intubated with a cuffed reinforced tracheal tube with an internal diameter of 7.5 mm, using a McGrath MAC® video laryngoscope (Medtronic Co., USA). After confirming tracheal intubation, the lungs were ventilated using a mechanical ventilator (AVEA™ Ventilator Systems; CareFusion Inc., San Diego, CA, USA) with volume-controlled ventilation. The inspiratory-to-expiratory time ratio was 1:2.5 with an end-inspiratory pause of 20% and tidal volume (VT) of 6 mL kg−1 of the predicted body weight. The predicted body weight was calculated as 49.9 + 0.91 × (height [cm] − 152.4).
The respiratory rate was initially set at 12 breaths/min and changed to maintain normocapnia (end-tidal carbon dioxide partial pressure [EtCO2] of 35–45 mmHg). Patients were ventilated using oxygen and air, with an FIO2 of 0.5. After the recruitment maneuver (35 cmH2O CPAP for 30 s), 3 cmH2O PEEP was added. A 22-G arterial cannula was inserted percutaneously into the radial artery after the induction of anesthesia for continuous monitoring of arterial pressure and blood gas sampling; it was also connected to a Flo Trach™ sensor with a Vigileo monitor system (Edwards Lifesciences, Irvine, CA, USA) for continuous monitoring of arterial pressure wave form, based on cardiac index (CI) and stroke volume variation (SVV). Arterial blood gas analysis was performed within 1 min of sampling, using a blood gas analyzer (The epoc® Blood Analysis System, Co. Siemens Healthineers, PA, USA). To measure esophageal pressure and gastric suctioning, a 16-Fr SmartCath™ adult nasogastric tube with an esophageal balloon (Vyaire Medical Inc., Mettawa, IL, USA) was inserted transorally and advanced into the stomach. By pulling back the tube, the positioning of the balloon was confirmed in the presence of a cardiac oscillation reflective of cardiac activity and esophageal pressure wave fluctuation during a ventilation cycle. Furthermore, the balloon location was confirmed using an occlusion technique; the airway was occluded at end-expiration and esophageal pressure and airway pressure were simultaneously compared for similarity. The position of the catheter was also checked on routine postoperative chest radiography.
After the induction of anesthesia, patients were placed in a horizontal lithotomy position. Anesthesia was maintained with a continuous infusion of propofol, remifentanil, and rocuronium throughout the surgery. The infusion rate of propofol was adjusted to maintain the PSi in the range of 25–50, with the administration of remifentanil at the rate of 0.3 μg kg−1 min−1. The neuromuscular block was maintained by continuous intravenous administration of rocuronium at the rate of 0.3 mg kg−1 h−1. Hemodynamic stability (arterial systolic pressure and heart rate of 80–100% of the preanesthetic value) was maintained by fluid management or vasopressors. Specifically, standardized fluid management was performed using acetated Ringer’s solution. In cases of intraoperative hypotension (mean arterial pressure of <65 mmHg or a decrease in mean arterial pressure by >20% from baseline), 6% hydroxyethyl starch in 0.9% sodium chloride solution was given, provided the SVV was >13%; otherwise, it was managed with phenylephrine or ephedrine, as required.
Study protocol
The patient was placed in the 30° Trendelenburg lithotomy position with a positive-pressure capnoperitoneum and CO2 insufflation, when the respiratory rate increased to 15 breaths/min. Capnoperitoneum was kept at the pressure of 12 mmHg; however, pressure levels were occasionally changed at the surgeon’s discretion. PEEP level was initially maintained at 0 cmH2O for 30 min; thereafter, while the intraabdominal pressure was kept at 12 mmHg, blood gas levels and hemodynamic and ventilatory parameters were recorded. Esophageal and airway pressure values were simultaneously read on a monitor screen at end-inspiration and end-expiration. Ptp estimates for both phases were calculated, as the difference between airway and esophageal pressure values. The respiratory rate was changed, such that the ETCO2 levels were between 40 and 50 mmHg during surgery.
PEEP levels were increased by 5 cmH2O in a stepwise manner at 30-min intervals; measurements were performed before each increase. Recruitment maneuver was performed before each PEEP trial. Once the PEEP levels reached 15 cmH2O and the measurements were completed, PEEP levels were changed, such that the Ptp was 0 cmH2O (PtpEEP0).
Data collection
Patient characteristics of interest included height, weight, body mass index, ASA physical status, and respiratory function test findings. The values of the following parameters of respiratory mechanics were recorded: inspiratory peak pressure, inspiratory plateau pressure (Pplat), end-inspiratory esophageal pressure (PesoEIP), end-expiratory esophageal pressure (PesoEEP), and ETCO2.
Hemodynamic parameters of interest included heart rate, mean arterial pressure, arterial pressure wave form base CI, and SVV values. The following arterial blood gases were examined: pH, PO2, PCO2, and SaO2. Cerebral oxygenation was measured as bilateral rSO2 levels.
The following parameters were calculated as follows: respiratory system driving pressure (DP) = Pplat − PEEP; end-inspiratory transpulmonary pressure (PtpEIP) = Pplat − PesoEIP; end-expiratory transpulmonary pressure (PtpEEP) = PEEP − PesoEEP; transpulmonary driving pressure (PtpDP) = PtpEIP − PtpEEP; respiratory system compliance = VT/(Pplat − PEEP); chest wall compliance = VT/(PesoEIP − PesoEEP); and pulmonary compliance = VT/ PtpDP.
Data were collected (1) after the induction of anesthesia (baseline), (2) 30 min after capnoperitoneum and Trendelenburg position (PEEP0 cmH2O: PEEP0) were achieved, (3) 30 min after PEEP of 5 cmH2O (PEEP5) was achieved, (4) 30 min after PEEP of 10 cmH2O was achieved (PEEP10), (5) 30 min after PEEP15 cmH2O (PEEP15) was achieved, (6) 30 min after PEEP level corresponding to PtpEEP of 0 (PtpEEP0) was achieved, and (7) at the end of surgery. After the RALP procedure was completed, the patients were returned to the supine position and PEEP levels were set at 5 cmH2O.
Statistical analysis
The present study aimed to determine the PEEP levels, where the PtpEEP values exceeded 0 cmH2O during the RALP surgery, and to observe whether such PEEP levels were beneficial for oxygenation or respiratory mechanics parameters. A formal power analysis was not performed because this was an observational study; however, sample size calculation was performed based on the preliminary findings obtained from the first seven patients in the first 2 months. Since PtpDP from PEEP 0 to PtpEEP0 values were 9.3±5.8 cmH2O and 6.0±2.8 cmH2O, we calculated that 11 patients were required to test the null hypothesis at a significance level of 0.05 and power of 0.90. Accounting for possible study dropouts, we aimed to include 16 participants. Categorical variables were reported as counts and percentages. Continuous data were examined for normal distribution, using the Shapiro–Wilk test, and were presented as mean±standard deviation or median and interquartile range, as appropriate. The Friedman non-parametric test with Scheffe’s multiple comparison procedure was used to test for differences between each PEEP level. All analyses were performed using the statistical software package BellCurve for Excel for Windows® (Social Survey Research Information C., Ltd. Tokyo, Japan). P-values of <0.05 were considered statistically significant.