Optimal Positive End-Expiratory Pressure Obtained with Titration of Fraction of Inspiratory Oxygen: A Randomized Controlled Clinical Trial

Optimal Positive End-Expiratory Pressure Obtained with Titration of Fraction of Inspiratory Oxygen: A Randomized Controlled Clinical Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Optimal Positive End-Expiratory Pressure Obtained with Titration of Fraction of Inspiratory Oxygen: A Randomized Controlled Clinical Trial Lingling Gao, Li Yang, Lili Pan, Yun Cui, Yandong Jiang, Jun Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1078756/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Optimal intraoperative positive end expiratory pressure (PEEP) improves patient outcomes. The pulse-oximetry has been used to determine the lung opening and closing pressures. Therefore, we hypothesized that intraoperative optimal PEEP obtained by titrating inspiratory oxygen fraction (FiO 2 ) guided with pulse-oximetry could improve perioperative oxygenation. Methods Forty-six males undergoing elective robotic assisted laparoscopic prostatectomy were randomly assigned to either optimal PEEP (Group O, n=23) or control with fixed PEEP of 5 cmH 2 O (Group C, n=23). Optimal PEEP, defined as the PEEP with lowest FiO 2 or 0.21 to maintain SpO 2 ≥ 95%, was obtained in both groups after placing the patients in Trendelenburg position and peritoneal insufflation. Patients in Group O maintained the optimal PEEP and in Group C maintained PEEP of 5cmH 2 O intraoperatively. Both groups were extubated in a sitting position once the extubation criteria met. The primary outcome was the partial arterial oxygen pressure (PaO 2 )/inspiratory oxygen fraction (FiO 2 ) prior to extubation. Secondary outcome was the incidence of postoperative hypoxemia (SpO 2 ༜92% on room-air after extubation) in post-operative care unit. Results The median optimal PEEP was 16 cm H 2 O [inter-quartile range, 12-18]. The PaO 2 /FiO 2 prior to extubation was significantly higher in Group O than that in Group C (77.0±4.9kPa vs.60.6±5.9kPa, p=0.04); PaO 2 /FiO 2 was also significantly higher in Group O 30minutes after extubation (57.6±1.9 vs. 46.6±1.8kPa, p=0.01). The incidence of hypoxemia on room air in the post-operative care unit was significantly lower in the Group O than in the Group C (1/23, or 4.3% vs. 7/23 or 30.4%, p =0.02). Conclusions Intraoperative optimal PEEP can be achieved by titration of FiO 2 guided with SpO 2 . Maintaining intraoperative optimal PEEP improves intraoperative oxygenation and reduces the incidence of post-operative hypoxemia. Trial registration : Chinese Clinical Trial Registry identifier: ChiCTR2100051010. Prospectively registered on 10 September, 2021 Anesthesiology & Pain Medicine Positive end-expiratory pressure pulse oximetry fraction of inspiratory oxygenation oxygenation index robot-assisted laparoscopic prostatectomy Figures Figure 1 Figure 2 Figure 3 Background Optimal intraoperative positive end expiratory pressure (PEEP) has been demonstrated to improve patient outcomes[ 1 , 2 ]. However, the optimal PEEP is not only very different among individuals, but individual’s optimal PEEP is affected by positioning, muscle paralysis, and several other factors[ 3 , 4 ]. The common application of a fixed PEEP often leads to either lung overinflation or atelectasis. Therefore, optimal PEEP should be individualized and adjusted dynamically according to patients’ needs[ 5 ]. Several techniques have been used to determine the optimal PEEP[ 6 – 10 ]. For example, electrical impedance tomography (EIT) can be performed at the bedside[ 5 , 11 , 12 ]. However, the application of this technique requires special training, increases the workload of the care team, and the cost-efficiency of this procedure remains to be determined. Chest CT is the gold standard technique for the assessment of lung inflation [ 13 ]. However, it is not feasible for use at the bedside, it exposes patients to X-rays, and its cost-effectiveness is not favorable. Transpulmonary pressure is another alternative that can be used at the bedside and is potentially cost-effective[ 14 ]. However, it requires special training and additional equipment in order to measure transpulmonary pressure. Lung opening or closing pressure can be used to assess and calculate intrapulmonary shunts[ 15 ]. Normally, the physiologic shunt is set at approximately 5%; if arterial blood oxygen saturation is >97% on room air, the intrapulmonary shunt is estimated to be <7%[ 16 ]. Therefore, this method can be used to assess the fraction of intrapulmonary shunts and to subsequently estimate the optimal PEEP[ 17 , 18 ]. Recently, Ferrando et al. reported that optimal PEEP can be obtained via titration of PEEP by administering a minimal fraction of inspiratory oxygen (FiO 2 ) with the guidance of pulse oximetry (SpO 2 ) and measurements of transpulmonary pressure in anesthetized patients[ 19 ]. The authors found that the optimal PEEP values obtained using the two methods were comparable. Another study demonstrated that SpO 2 could be used to determine the individualized lung opening and closing pressures in patients undergoing anaesthesia and mechanical ventilation[ 20 ]. We hypothesized that optimal PEEP could be obtained by titration of intraoperative PEEP levels and FiO 2 with SpO 2 guidance. Our secondary hypothesis was that maintenance of intraoperative optimal PEEP derived via this method improves intraoperative oxygenation and reduces the incidence of postoperative hypoxemia. We tested our hypothesis in patients undergoing robotic-assisted laparoscopic prostatectomy (RALP). Methods Ethics This single-centre, two-arm, parallel, randomized controlled study was approved on 19 October 2020 by the Ethics Committee of the Fudan University Shanghai Cancer Center, No.270 DongAn road, Xuhui District, Shanghai, China under the number IRB2010225-11(Chairperson, Prof Jiong Wu) and registered in the Chinese Clinical Trial Registry on 10 September 2021 (ChiCTR 2100051010; Principal Investigator: JZ). The study was conducted from 6 May 2021 until 10 October 2021. All patients were approached by the principal investigator and after presentation of the study purposes, written informed consent was obtained before inclusion. All methods were carried out in accordance with Declaration of Helsinki. Inclusion and exclusion criteria Between 6 May 2021 and 10 October 2021, adult patients aged 18 years or older who were scheduled for elective robotic-assisted laparoscopic prostatectomy under general anaesthesia and who presented with ASA physical status of I-III were recruited for this study. Patients with acute or chronic respiratory disorders, including chronic obstructive pulmonary disease (COPD), asthma, pulmonary hypertension, neuromuscular disease, and/or preoperative SpO 2 <95% on room air were excluded. The patient enrollment process is illustrated in Fig.1. Anaesthesia management Patient’s general demographic and medical characteristics were abstracted from medical records; the characteristics investigated herein included sex, age, body mass index (BMI), predicted body weight (PBW), ASA classification, medical history, and preoperative SpO 2 on room air. Intravenous access was established upon arrival at the operating room. Routine monitoring for general anaesthesia was performed, including ECG, noninvasive blood pressure, SpO 2 , capnography, and temperature. A radial arterial line was established in order to continuously measure arterial blood pressure and an intermittent blood draw was conducted for blood gas analysis. Patients were pre-oxygenated as usual at an O 2 flow rate of 8 l min -1 until their expiratory oxygen concentration reached 80% or higher. Anaesthetic induction was conducted with intravenous targeted control infusion (TCI) 4 μg mL -1 of propofol (Marsh mode), 0.3 μg kg -1 of sufentanil, and 0.6 mg kg -1 of rocuronium[21]. A 7.0 size tracheal tube was inserted, and correct placement was confirmed with auscultation and the presence of bilateral equal breath sounds. General anaesthesia was maintained with continuous TCI infusion of 3-4 μg mL -1 propofol and 1-2 ng mL -1 remifentanil (Minto mode) as well as intermittent administration of rocuronium in order to maintain adequate muscle paralysis. Study protocol The study protocol is summarized in Fig.2. After tracheal intubation, mechanical ventilation was conducted with pressure-regulated volume-controlled ventilation using an operating room ventilator (Flow-I, Maquet Inc., Heidelberg, Germany). The ventilation was set at a tidal volume 6 mL kg -1 , was initiated with an FiO 2 of 1.0 to 0.21, a PEEP of 18 cmH 2 O, and a respiratory rate of 12-15 beats min -1 in order to keep the end-tidal CO 2 partial pressure between 35-45 mmHg. After placement in the Trendelenburg position and peritoneal insufflation, all patients received the first recruitment maneuver (RM1) of 40 cmH 2 O for 15 seconds followed by PEEP at 18 cmH 2 O, similar to a previous study demonstrating that the maximal optimal PEEP was not greater than 18 cmH 2 O 3 . If the peak inspiratory pressure was >40 cmH 2 O at a PEEP of 18 cmH 2 O, the participant’s study would be terminated. The target SpO 2 was 95-96%. The PEEP titration process is shown in Supplementary Fig.1. If the SpO 2 was at 95-96% with a FiO 2 of 0.21 and a PEEP of 18 cmH 2 O, the optimal PEEP was 18 cmH 2 O; this was kept constant throughout the procedure until extubation. If the SpO 2 was greater than 96%, the PEEP was reduced by 2 cmH 2 O step-wise, with each step lasting for 5 min until SpO 2 dropped below 95%. Then, PEEP was increased up to 18 cmH 2 O in reverse order in the same stepwise manner until the intended SpO 2 was reached and remained at a steady saturation of 95-96%. At a PEEP of 18 cmH 2 O, if the SpO 2 was lower than 95%, the FiO 2 was incrementally increased by 0.05 per step; each step lasted for 5 minutes in order to achieve an SpO 2 of 95-96%. If PEEP was increased to 18 cmH 2 O and FiO 2 was measured at 1.0 (while the SpO 2 remained lower than 95%), the study was terminated. The PEEP level at the minimal FiO 2 necessary to maintain a SpO 2 of 95-96% was considered the optimal PEEP. Once the optimal PEEP was achieved, patients randomized to Group C received a PEEP of 5 cmH 2 O intraoperatively or were maintained within Group O, thus maintaining optimal PEEP until extubation. Patients in both groups were extubated in the post anaesthesia care unit (PACU) in the sitting position once they met the criteria for extubation according to the judgment of their medical care team. For both groups, intraoperative pulmonary dynamic compliance (Cdyn), PEEP, FiO 2 (i.e., real-time FiO 2 obtained from the gas analyzer within the anaesthesia machine), driving pressure, and plateau pressure were recorded continuously. Intermittent blood gas analysis was performed in order to verify the accuracy of the SpO 2 readings and to calculate the alveolar-arterial gradient [P(A-a)O 2 ], while the respiratory rate was adjusted in order to maintain the PaCO 2 in the range of 35–45 mmHg. In the PACU, vital signs and arterial blood gas analysis were recorded at 5, 10, and 30 minutes after extubation, and supplementary O 2 was provided to the patients via nasal cannula if the SpO 2 was below 92%. Statistical analysis Intraoperative PaO 2 /FiO 2 was reported as 55.7±10.9 kPa before extubation in patients undergoing RALP[4]; we assumed that there were 10 kPa differences between the two groups, with a variance of 10.9 kPa, a statistical power of 80%, and a two-sided α significance level of 0.05. A sample size of 18 patients in each arm was required to test our hypothesis. Considering a dropout rate of 30%, a total of 24 patients for each group (for a total of 48 patients) were enrolled; randomization was performed using a minimization randomization method as previously described[22]. Patients were stratified by age (<65 vs. ≥65yrs) and BMI (<24 vs. ≥24 kg m -2 ) in order to test differences in age and BMI distribution. The randomization was performed via MinimPy2 software (version2.0, OSDN, Columbus, OH, USA). Randomization was performed the day before surgery by a research team member who was blinded to the trial condition. The data were managed and analyzed by an independent researcher (PL). Continuous variables were presented as means ± SD or medians with IQR according to whether the distribution was normal, while categorical variables were presented as counts and percentages. The χ 2 -test was used to compare differences in patient characteristics between the two groups. The unpaired t tests were used to compare differences in oxygen indices, driving pressure, and Cdyn at different time points. Repeated-measures analysis of variance (ANOVA) was used to compare differences in P aO 2 /FiO 2 , driving pressure, and Cdyn under mechanical ventilation prior to extubation. Differences in vital parameters, vasoactive medication dosage, and incidence of complications were tested via unpaired t tests, and the Wilcoxon Man-Whitney test was used when the data were not normally distributed. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS)software (version 24, IBM, Armonk, NY, USA) and GraphPad Prism 8.0 software (GraphPad Inc., San Diego, CA, USA). Statistical significance was set at P < 0.05. Results Clinical characteristics A total of 48 patients were initially enrolled in this study, though two patients were excluded from the study due to operation cancelation. Therefore, a total of 46 patients completed the study and underwent a final analysis (Fig. 1 ). There were no statistically significant differences between the two groups in terms of clinical characteristics (Table 1 ) or perioperative data (Table 2 ). Optimal PEEP level For all patients (i.e., including those in both groups) the median optimal PEEP was 16 cm H 2 O (interquartile range, 12-18). The FiO 2 needed to obtain the optimal PEEP was 0.21±0.03. The details of the titration process are presented in Supplementary Table 1 . The time allotted to complete the titration of the optimal PEEP was half an hour or less. Primary outcome The P aO 2 /FiO 2 was statistically significantly higher in Group O than in Group C prior to extubation (77.0±4.9 kPa vs. 60.6±5.9 kPa, P =0.04) (Figure 3a). Secondary outcomes The respiratory mechanics corresponding to FiO 2 are shown in Fig.3b. There was no statistically significant difference in the driving pressure between the two groups (Fig.3c). The Cdyn was higher in Group O than in Group C (43.4±2.7 ml cm H 2 O -1 vs. 36.5±3.4 ml cm H 2 O -1 , P =0.032) prior to extubation (Fig.3d). Intraoperative respiratory parameters and P aO 2 /FiO 2 during PEEP intervention are shown in Supplementary Table 2. Postoperative hypoxemia was defined as postoperative hypoxemia if SpO 2 <92% was detected in room air within 30 min after extubation in the PACU. The incidence of hypoxemia was statistically significantly lower in Group O as compared to Group C (1/23 or 4.3% vs. 7/23 or 30.4%, P =0.02) (Table 2). The P(A-a) O 2 in Group C (9.0±2.0 kPa) was statistically significantly higher than that in Group O (3.62±0.9 kPa, P =0.01). P aO 2 /FiO 2 ratios at three time points in the PACU after extubation are shown in Supplementary Figure 2. Discussion The main findings of this study are as follows: (1) intraoperative optimal PEEP can be achieved by titration of PEEP and FiO 2 guided by the SpO 2 readout in patients likely requiring high PEEP; (2) maintaining optimal PEEP improves intraoperative oxygenation and reduces FiO 2 to maintain normoxemia; and (3) the benefit of intraoperative optimal PEEP remains postoperatively in terms of reductions in the incidence of postoperative hypoxemia. Our results confirmed the observations from a previous study[ 4 ] demonstrating that using equipment for routine anaesthesia care can obtain optimal PEEP. This technique has the substantial advantage of being simple to use. In this study, titration of PEEP and FiO 2 were started simultaneously as the surgery progressed. Therefore, clinicians were able to obtain individualized optimal PEEP levels without interrupting or prolonging the surgery. This technique does not require additional training or equipment such as an intra-esophageal balloon to calculate transpulmonary pressure[ 23 ] or electric impedance tomography to measure lung aeration[ 9 , 24 ]. All the equipment needed to obtain and maintain the optimal PEEP is readily available in any modern operating room or anaesthesia site. In addition, PEEP can be constantly reassessed and adjusted intraoperatively in order to maintain the optimal PEEP when respiratory mechanics change due to changes in the patient’s position or intra-abdominal insufflation pressure. A new algorithm may be developed using a closed-loop system to assess PEEP and automatically implicate the individual’s optimal PEEP using this technique. We tested our hypothesis in patients who underwent RALP because this population is more likely to require high PEEP to minimize intraoperative atelectasis[ 25 ]. The surgery was performed within the pneumoperitoneum with an intra-abdominal pressure of approximately15 mmHg, and the patient was placed in a steep Trendelenburg position (approximately 30 degrees) intraoperatively for over 3-4 hours[ 26 , 27 ]. Therefore, patients are more prone to perioperative atelectasis formation if the PEEP is not high enough to counteract the reduction in functional residual capacity[ 28 ]. However, in our institute, a PEEP of 5 cmH 2 O for patients undergoing robotic-assisted laparoscopic prostatectomy is a common practice. There are a few recommendations stating that the PEEP should be higher than 5 cmH 2 O if the patient is in the Trendelenburg position and/or if there is pneumoperitoneum[ 29 ]. A PEEP of 5 cmH 2 O seems to be lower than that reported in the literature. However, guidelines for selecting PEEP for this patient population are unavailable due to insufficient literature informing these criteria. Any fixed PEEP would render some patients either below and above the optimal PEEP as the variation in optimal PEEP is large[ 4 ], and optimal PEEP is likely not a constant but rather varies depending on the patient’s physiology and positioning as well as the specific surgical intervention[ 30 ].The range of optimal PEEP observed in this study ranged between 2 and 18 cmH 2 O. We encountered a patient who was able to maintain a SpO 2 >95% with a FiO 2 of 0.21, even when the PEEP was set at 2 cmH 2 O. We also performed arterial blood gas analysis and confirmed that the SpO 2 and arterial hemoglobin oxygen saturation readouts were comparable. This indicates that, even with pneumoperitoneum and in the steep Trendelenburg position, this patient had an intrapulmonary shunt of less than 10% with a PEEP of 2 cmH 2 O [ 16 ]. A question remains as to whether the optimal PEEP we obtained was truly the optimal PEEP, since we did not have access to validation via a chest CT scan or electric impedance tomography. However, though this is a scientifically important question, but it may not be clinically important. Specifically, the approach employed in this study may not achieve a true PEEP (with no over- or under-PEEP). However, the oxygenation index improved by 27% (77.0/60.6 kPa) in Group O vs. Group C prior to extubation. Further studies are needed to determine the efficacy of this technique for achieving true optimal PEEP versus that obtained with EIT. Nevertheless, using this technique, we could achieve clinically relevant improvements in intraoperative oxygenation as compared with routine care. The mean FiO 2 used to achieve optimal PEEP was 0.21, the SpO 2 was 95%-96% prior to extubation, and the intrapulmonary shunt was estimated to be <10% (as compared with that of the control group). Because we chose to titrate the optimal PEEP stepwise and bidirectionally, we were unlikely to inflate the lung at the optimal PEEP level. Therefore, even though the optimal PEEP in the present study may not be a true optimal PEEP, it is likely very close to the true optimal PEEP and the difference between the two may not have clinical implications. Further studies are needed to assess the agreement of optimal PEEP obtained with the method used in this study as well as other well-established techniques, such as CT scans or EIT. It is important to note that we found that the benefit of intraoperative optimal PEEP is sustained postoperatively. This is consistent with previous observations suggesting that intraoperatively individualized PEEP can reduce postoperative atelectasis[ 2 ]. However, a recent study[ 31 ] showed that intraoperative PEEP only improves intraoperative, but not postoperative, oxygenation. This discrepancy among studies, including our current study, maybe due to the different extubation approaches employed in the investigations. It is well known that a patient's functional residual capacity (FRC) depends on sedation level, muscle tone, and position[ 32 ]. In our institution, it is routine practice for patients to be extubated in a sitting position. We observed the benefit of intraoperative PEEP on postoperative oxygenation when all patients were extubated in the sitting position. Therefore, patients likely maintain a larger FRC (i.e., closer to the normal value) than that of patients extubated in the supine position. This notion requires further validation. However, in a report by Simon et al., the position of the patients during extubation was not stated[ 31 ]. In our study, because there were no statistically significant differences between the two groups in terms of the consumption of intraoperative and postoperative narcotic and residual sedation levels in the PACU, the reduction in the incidence of postoperative hypoxemia in room air in Group O was likely due to a reduction in postoperative atelectasis. Since the sample size was relatively small, we could not determine the effect of intraoperative PEEP on other outcomes, such as the incidence of reintubation and postoperative pneumonia. Nevertheless, the intrapulmonary shunt in these patients was an important factor. This is because we chose an SpO 2 of 92% or lower as the cutoff for the diagnosis of hypoxemia on room air; if we assume that the hypoxemia was due to the intrapulmonary shunt only and that no hypoxic vasoconstriction was involved, at an SpO 2 of 92%, the intrapulmonary shunt was estimated to be approximately 24% using the equation described previously[ 16 ]. Further studies should be conducted to assess the effect of intraoperative optimal PEEP on outcomes. In addition to the substantial strengths of this investigation, this study had several limitations. First, we did not validate our observation that the optimal PEEP achieved with this technique is indeed the true optimal PEEP. Validation using EIT or transpulmonary pressure will be important for assessing the sensitivity and specificity of this method. Second, the inaccuracy of pulse oximetry for reporting hemoglobin oxygen saturation was recently determined by the FDA. However, in this study, we validated SpO 2 readings using arterial blood gas analysis. In addition, we used the same brand of oximetry in both groups of patients. Therefore, this potential inaccuracy does not affect our conclusions. Third, it is possible that the PEEP obtained in our study is above the true optimal PEEP. However, we allowed for the descending and ascending stepwise titration of FiO 2 and PEEP. Therefore, over- and under-PEEP at the level that would affect outcomes are possible, but unlikely. Though we may not achieve a perfectly individualized optimal PEEP, but in practical terms, the PEEP value achieved in our study is likely close to the true value when the intrapulmonary shunt is less than 10%. Conclusion In conclusion, individualized optimal PEEP can be achieved with equipment available for anaesthesia by titration of PEEP and FiO 2 guided by SpO 2 . Maintaining intraoperative optimal PEEP improves intraoperative oxygenation and reduces the incidence of postoperative hypoxemia in patients likely to require high intraoperative PEEP. Since the method we used in this study to obtain optimal PEEP, this approach is practical and hopefully clinicians are willing to adopt it and improve the quality of care. List Of Abbreviations PEEP: positive end expiratory pressure; FiO2: inspiratory oxygen fraction; PaO 2 : partial arterial oxygen pressure; EIT: electrical impedance tomography; SPO 2 : pulse oximetry; RALP: robotic-assisted laparoscopic prostatectomy; COPD: chronic obstructive pulmonary disease; BMI: body mass index; PBW: predicted body weight; TCI: targeted control infusion; RM: recruitment maneuver; PACU: post anaesthesia care unit; Cdyn: dynamic compliance; FRC: functional residual capacity Declarations Ethics approval and consent to participate This study was approved by the Ethics Committee of the Fudan University Shanghai Cancer Center, with the ethics number IRB2010225-11. The patients provided written consent. All methods were carried out in accordance with Declaration of Helsinki. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interest: Dr. Yandong Jiang is a consultant of Vyaire, which was not involved in the design, conduct or publication of this work. The other authors declare no conflicts of interest. Funding This work was funded by a grant from the Shanghai Science and Technology Committee (No.20Y11906200). The funder was not involved in the design, conduct, or publication of this work. Authors’ contributions LLG conducted data analysis and manuscript preparation, drafted and finalized the manuscript; LY participated in study design, data analysis and manuscript preparation. LLP participated in protocol optimization, data retrieval and data analysis. YC participated in protocol optimization and manuscript preparation. YDJ participated in study design, data analysis, drafted and edited the manuscript. 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Stat Med 2009; 28:3329–3346. Keller SP,Fessler HE Monitoring of oesophageal pressure. Curr Opin Crit Care 2014; 20:340–346. Franchineau G, Brechot N, Lebreton G, Hekimian G, Nieszkowska A, Trouillet JL,et al. Bedside Contribution of Electrical Impedance Tomography to Setting Positive End-Expiratory Pressure for Extracorporeal Membrane Oxygenation-treated Patients with Severe Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med 2017; 196:447–457. Kalmar AF, Foubert L, Hendrickx JF, Mottrie A, Absalom A, Mortier EP,et al. Influence of steep Trendelenburg position and CO(2) pneumoperitoneum on cardiovascular, cerebrovascular, and respiratory homeostasis during robotic prostatectomy. Br J Anaesth 2010; 104:433–439. Gainsburg DM Anesthetic concerns for robotic-assisted laparoscopic radical prostatectomy. Minerva Anestesiol 2012; 78:596–604. Awad H, Walker CM, Shaikh M, Dimitrova GT, Abaza R,O'Hara J Anesthetic considerations for robotic prostatectomy: a review of the literature. J Clin Anesth 2012; 24:494–504. Yurtdas G,Akdevelioglu Y A New Approach to Polycystic Ovary Syndrome: The Gut Microbiota. J Am Coll Nutr 2019:1–12. Shono A, Katayama N, Fujihara T, Bohm SH, Waldmann AD, Ugata K,et al. Positive End-expiratory Pressure and Distribution of Ventilation in Pneumoperitoneum Combined with Steep Trendelenburg Position. Anesthesiology 2020; 132:476–490. Sahetya S, Goligher E,Slutsky A Searching for the Optimal PEEP in Patients Without ARDS: High, Low, or in Between? JAMA 2020; 324:2490–2492. Simon P, Girrbach F, Petroff D, Schliewe N, Hempel G, Lange M,et al. Individualized versus Fixed Positive End-expiratory Pressure for Intraoperative Mechanical Ventilation in Obese Patients: A Secondary Analysis. Anesthesiology 2021; 134:887–900. Wahba RW Perioperative functional residual capacity. Can J Anaesth 1991; 38:384–400. Yamamoto N, Miyashita T, Takaki S,Goto T Effects of Breathing Pattern on Oxygen Delivery Via a Nasal or Pharyngeal Cannula. Respir Care 2015; 60:1804–1809. Tables Table 1. Patient clinical characteristics Characteristic Group C (n=23) Group O (n=23) p value Age(years) ＜65 ≥65 10(43.5) 13(56.5) 8(34.8) 15(65.2) 0.55 BMI (kg/m 2 ) 0.77 ＜24 12(52.2) 13(56.5) ≥24 ASA physical status 11(47.8) 10(43.5) I II Smoking status Never Ever Current Comorbidity Hypertension Diabetes 2(8.7) 21(91.3) 15(65.3) 3(13.0) 5(21.7) 8 (34.8) 3(13.0) 3(13.0) 20(87.0) 14(60.9) 4(17.4) 5(21.7) 6 (26.1) 4(17.4) 1.00 0.13 0.75 1.00 Note: Data are presented as numbers (%). Group C, control group with fixed PEEP of 5cmH 2 O; Group O, optimized PEEP group with individualized PEEP at which SpO 2 is maintained at 95-96% with minimal FiO 2 ; BMI, body mass index; ASA, American Society of Anesthesiologists. Table 2. Intraoperative data Group C (n=23) Group O (n=23) p value Anesthesia duration (min) 227.3±7.8 218.7±5.6 0.38 Surgery duration(min) 169.1±6.4 174.1±4.2 0.47 Total amount of fluid infusion (ml) 2070±56.7 1904±68.4 0.07 Blood loss(ml) 118.7±10.0 97.8±5.9 0.08 Urinary output (ml) 347.8±37.7 358.7±51.7 0.87 Vasoactive injections Received medication, n (%) 21(91.3) 22(95.7) 0.55 Ephedrine (mg) 6.8±1.0 7.2±1.2 0.80 Phenylephrine (μg) 194.8±44.9 183.0±52.0 0.87 P(A-a) O 2 pre-extubation(kPa) 9.0±2.0 3.62±0.9 0.01 SpO 2 ＜92% at PACU on room air, n(%) 7(30.4) 1(4.3) 0.02 Note: Data are presented as mean ± SD or numbers (%); P(A-a)O 2 : alveolar-arterial gradient; PACU: post-anesthesia care unit ;pre-extubation: before extubation. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1078756","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":65267174,"identity":"219fcbd0-d732-4bae-99a4-42cc1f65e439","order_by":0,"name":"Lingling Gao","email":"","orcid":"","institution":"Fudan University Shanghai Cancer Center, Fudan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Lingling","middleName":"","lastName":"Gao","suffix":""},{"id":65267175,"identity":"287e6817-849c-4a7e-8002-32bec890266c","order_by":1,"name":"Li Yang","email":"","orcid":"","institution":"Fudan University Shanghai Cancer Center, Fudan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Yang","suffix":""},{"id":65267176,"identity":"de052dd0-17fa-4e68-a501-3485b7492a3d","order_by":2,"name":"Lili Pan","email":"","orcid":"","institution":"Fudan University Shanghai Cancer Center, Fudan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Lili","middleName":"","lastName":"Pan","suffix":""},{"id":65267177,"identity":"1bd781ab-87bf-4a80-933d-b1e87eb146d1","order_by":3,"name":"Yun Cui","email":"","orcid":"","institution":"UESTC Chengdu Women’s \u0026 Children’s Central Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yun","middleName":"","lastName":"Cui","suffix":""},{"id":65267178,"identity":"2467225e-8b24-433a-a198-071366d37a55","order_by":4,"name":"Yandong Jiang","email":"","orcid":"","institution":"University of Texas, Houston Health Science Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yandong","middleName":"","lastName":"Jiang","suffix":""},{"id":65267179,"identity":"95c8b3e1-4f3f-41bd-806c-edcd5642a5ea","order_by":5,"name":"Jun Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA20lEQVRIiWNgGAWjYLACxgYgwd7AeCCBNC08BxhI1SKRwHCAKNXys5ufPfy5wy5PPvLxgwMP2w7nMbAfProBnxaDO8fMDSTPJBcb3k4zOJDYdriYgSct7QZeLRIJZhKGbcyJG2cngLUkNkjwmOHVIj8j/ZtEYlt94saZxz8Qp4XhRo6ZxEGgyvkSPETaYnAjp9ywse144gaenIIDCefSE9sI+QXosG0Pf7ZVJ85vP77x4Y8y68R+9sPH8DuMgYENYt0BIMHIBuMSo0W+AUT+IUL9KBgFo2AUjDgAALzGVfF/dXNaAAAAAElFTkSuQmCC","orcid":"","institution":"Fudan University Shanghai Cancer Center, Fudan University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Jun","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2021-11-14 10:29:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1078756/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1078756/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":16021144,"identity":"25ca3823-b6f7-4fd0-85a4-21ee88e78ca6","added_by":"auto","created_at":"2021-11-30 15:42:09","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":70337,"visible":true,"origin":"","legend":"Flowchart of patient enrollment. PEEP, positive end expiratory pressure.","description":"","filename":"fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1078756/v1/5986149ea128cc4f6adcc3a4.jpg"},{"id":16021806,"identity":"70afefa5-f743-487f-89cc-e15835c4d4df","added_by":"auto","created_at":"2021-11-30 15:45:09","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":136046,"visible":true,"origin":"","legend":"Experimental protocol for PEEP titration. TV, tidal volume; ETCO2, end expiratory carbon dioxide partial pressure; SpO2, pulse oxygen saturation; RM, recruitment maneuver; PACU, postanaesthesia care unit. PEEP, positive end expiratory pressure; PaO2, oxygen partial pressure in arterial blood; FiO2, fraction of inspired oxygen. ","description":"","filename":"fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1078756/v1/28bd53217b4c25af8dac5411.jpg"},{"id":16021145,"identity":"67f4c477-8712-4d64-839b-293296893e88","added_by":"auto","created_at":"2021-11-30 15:42:09","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":62336,"visible":true,"origin":"","legend":"Time course of respiratory mechanics. (a) PaO2/FiO2; (b) Time course of FiO2; (c) Driving pressure; (d) Cdyn; *P＜0.05，**P＜0.01. PEEP, positive end expiratory pressure; PaO2, partial pressure of oxygen in arterial blood; FiO2, fraction of inspired oxygen; Cdyn, dynamic compliance.","description":"","filename":"fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1078756/v1/dab39d5ed106531e3ea36a59.jpg"},{"id":18356773,"identity":"e1508452-e79f-4600-85eb-782069ad63ea","added_by":"auto","created_at":"2022-02-18 09:59:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":587220,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1078756/v1/2edc85c3-85e8-4219-948f-de31b33488ef.pdf"},{"id":16021146,"identity":"f535c448-f3f1-4358-94a7-06c78b62f723","added_by":"auto","created_at":"2021-11-30 15:42:09","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":1491581,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTablesandFigures.docx","url":"https://assets-eu.researchsquare.com/files/rs-1078756/v1/fc64bfab19e4dff8e79021cd.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eOptimal Positive End-Expiratory Pressure Obtained with Titration of Fraction of Inspiratory Oxygen: A Randomized Controlled Clinical Trial\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eOptimal intraoperative positive end expiratory pressure (PEEP) has been demonstrated to improve patient outcomes[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, the optimal PEEP is not only very different among individuals, but individual\u0026rsquo;s optimal PEEP is affected by positioning, muscle paralysis, and several other factors[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The common application of a fixed PEEP often leads to either lung overinflation or atelectasis. Therefore, optimal PEEP should be individualized and adjusted dynamically according to patients\u0026rsquo; needs[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Several techniques have been used to determine the optimal PEEP[\u003cspan additionalcitationids=\"CR7 CR8 CR9\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. For example, electrical impedance tomography (EIT) can be performed at the bedside[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, the application of this technique requires special training, increases the workload of the care team, and the cost-efficiency of this procedure remains to be determined. Chest CT is the gold standard technique for the assessment of lung inflation [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. However, it is not feasible for use at the bedside, it exposes patients to X-rays, and its cost-effectiveness is not favorable. Transpulmonary pressure is another alternative that can be used at the bedside and is potentially cost-effective[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. However, it requires special training and additional equipment in order to measure transpulmonary pressure. Lung opening or closing pressure can be used to assess and calculate intrapulmonary shunts[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Normally, the physiologic shunt is set at approximately 5%; if arterial blood oxygen saturation is \u0026gt;97% on room air, the intrapulmonary shunt is estimated to be \u0026lt;7%[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Therefore, this method can be used to assess the fraction of intrapulmonary shunts and to subsequently estimate the optimal PEEP[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRecently, Ferrando et al. reported that optimal PEEP can be obtained via titration of PEEP by administering a minimal fraction of inspiratory oxygen (FiO\u003csub\u003e2\u003c/sub\u003e) with the guidance of pulse oximetry (SpO\u003csub\u003e2\u003c/sub\u003e) and measurements of transpulmonary pressure in anesthetized patients[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The authors found that the optimal PEEP values obtained using the two methods were comparable. Another study demonstrated that SpO\u003csub\u003e2\u003c/sub\u003e could be used to determine the individualized lung opening and closing pressures in patients undergoing anaesthesia and mechanical ventilation[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. We hypothesized that optimal PEEP could be obtained by titration of intraoperative PEEP levels and FiO\u003csub\u003e2\u003c/sub\u003e with SpO\u003csub\u003e2\u003c/sub\u003e guidance. Our secondary hypothesis was that maintenance of intraoperative optimal PEEP derived via this method improves intraoperative oxygenation and reduces the incidence of postoperative hypoxemia. We tested our hypothesis in patients undergoing robotic-assisted laparoscopic prostatectomy (RALP).\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eEthics\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis single-centre, two-arm, parallel, randomized controlled study was approved on 19 October 2020 by the Ethics Committee of\u0026nbsp;the Fudan\u0026nbsp;University Shanghai Cancer Center, No.270 DongAn road, Xuhui District, Shanghai, China under the number IRB2010225-11(Chairperson, Prof Jiong Wu)\u0026nbsp;and registered in the Chinese Clinical Trial Registry on 10 September 2021 (ChiCTR 2100051010; Principal Investigator: JZ). The study was conducted\u0026nbsp;from 6 May 2021 until 10 October 2021.\u0026nbsp;All patients were approached by the principal investigator and after presentation of the study purposes, written informed consent was obtained before inclusion. All methods were carried out in accordance with Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInclusion and exclusion criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBetween 6 May 2021 and 10 October 2021, adult patients aged 18 years or older who were scheduled for elective robotic-assisted laparoscopic prostatectomy under general anaesthesia and who presented with ASA physical status of I-III were recruited for this study. Patients with acute or chronic respiratory disorders, including\u0026nbsp;chronic obstructive pulmonary disease (COPD), asthma, pulmonary hypertension, neuromuscular disease,\u0026nbsp;and/or\u0026nbsp;preoperative SpO\u003csub\u003e2\u003c/sub\u003e\u0026lt;95% on room air were excluded. The patient enrollment process is illustrated in Fig.1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnaesthesia management\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatient\u0026rsquo;s\u0026nbsp;general demographic and medical characteristics\u0026nbsp;were abstracted from medical records; the characteristics investigated herein included\u0026nbsp;sex, age, body mass index (BMI), predicted body weight (PBW), ASA classification, medical history, and preoperative SpO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003eon room air. Intravenous access was established upon arrival at the operating room. Routine monitoring for general anaesthesia was performed, including ECG, noninvasive blood pressure, SpO\u003csub\u003e2\u003c/sub\u003e, capnography, and temperature.\u0026nbsp;A radial arterial line was established in order to continuously measure arterial blood pressure and an intermittent blood draw was conducted for blood gas analysis. Patients were pre-oxygenated as usual at an O\u003csub\u003e2\u003c/sub\u003e flow rate of 8 l min\u003csup\u003e-1\u003c/sup\u003e until their expiratory oxygen concentration reached 80% or higher. Anaesthetic induction was conducted with intravenous targeted control infusion (TCI) 4 \u0026mu;g mL\u003csup\u003e-1\u003c/sup\u003e of propofol (Marsh mode), 0.3 \u0026mu;g kg\u003csup\u003e-1\u003c/sup\u003e of sufentanil, and 0.6 mg kg\u003csup\u003e-1\u003c/sup\u003e of rocuronium[21]. A 7.0 size tracheal tube was inserted, and correct placement was confirmed with auscultation and the presence of bilateral equal breath sounds. General anaesthesia was maintained with continuous TCI infusion of 3-4 \u0026mu;g mL\u003csup\u003e-1\u003c/sup\u003e propofol and 1-2 ng mL\u003csup\u003e-1\u003c/sup\u003e remifentanil (Minto mode) as well as intermittent administration of rocuronium in order to maintain adequate muscle paralysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy protocol\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol is summarized in Fig.2. After tracheal intubation, mechanical ventilation was conducted with pressure-regulated volume-controlled ventilation using an operating room ventilator (Flow-I, Maquet Inc., Heidelberg, Germany). The ventilation was set at a tidal volume 6 mL kg\u003csup\u003e-1\u003c/sup\u003e, was initiated with an FiO\u003csub\u003e2\u003c/sub\u003e of 1.0 to 0.21, a PEEP of 18 cmH\u003csub\u003e2\u003c/sub\u003eO, and a respiratory rate of 12-15\u0026nbsp;beats min\u003csup\u003e-1\u003c/sup\u003e in order to keep the end-tidal CO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003epartial pressure between 35-45 mmHg. After placement in\u0026nbsp;the\u0026nbsp;Trendelenburg position and peritoneal insufflation, all patients received the first recruitment maneuver (RM1) of 40 cmH\u003csub\u003e2\u003c/sub\u003eO for 15 seconds followed by PEEP at 18 cmH\u003csub\u003e2\u003c/sub\u003eO, similar\u0026nbsp;to a previous study\u0026nbsp;demonstrating\u0026nbsp;that the maximal optimal PEEP was not greater than\u0026nbsp;18 cmH\u003csub\u003e2\u003c/sub\u003eO\u003csup\u003e3\u003c/sup\u003e. If\u0026nbsp;the peak inspiratory\u0026nbsp;pressure was \u0026gt;40 cmH\u003csub\u003e2\u003c/sub\u003eO at\u0026nbsp;a PEEP of\u0026nbsp;18 cmH\u003csub\u003e2\u003c/sub\u003eO, the participant\u0026rsquo;s study would be terminated. The target SpO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003ewas 95-96%.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe PEEP titration process is shown in Supplementary Fig.1. If the SpO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003ewas at 95-96% with a FiO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003eof 0.21 and a PEEP of 18 cmH\u003csub\u003e2\u003c/sub\u003eO, the optimal PEEP was 18 cmH\u003csub\u003e2\u003c/sub\u003eO; this was kept constant throughout the procedure until extubation. If the SpO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003ewas greater than 96%, the PEEP was reduced by 2 cmH\u003csub\u003e2\u003c/sub\u003eO step-wise,\u0026nbsp;with each step lasting for 5\u0026nbsp;min until SpO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003edropped below 95%. Then,\u0026nbsp;PEEP was increased up to 18 cmH\u003csub\u003e2\u003c/sub\u003eO in reverse order in the same stepwise manner until the intended SpO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003ewas reached and remained at a steady saturation of 95-96%. At\u0026nbsp;a PEEP of 18 cmH\u003csub\u003e2\u003c/sub\u003eO, if the SpO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003ewas lower than 95%, the FiO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003ewas incrementally increased by 0.05 per step; each step\u0026nbsp;lasted for 5\u0026nbsp;minutes in order to achieve an SpO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003eof 95-96%. If PEEP was increased to 18 cmH\u003csub\u003e2\u003c/sub\u003eO and FiO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003ewas measured at 1.0 (while the SpO\u003csub\u003e2\u003c/sub\u003e remained lower than 95%), the study was terminated. The PEEP level at the minimal FiO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003enecessary to maintain a SpO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003eof 95-96% was considered\u0026nbsp;the optimal PEEP.\u0026nbsp;Once the optimal PEEP was achieved, patients randomized to Group C received a PEEP of 5 cmH\u003csub\u003e2\u003c/sub\u003eO intraoperatively or were maintained within Group O, thus maintaining optimal PEEP until extubation. Patients in both groups were extubated in the post anaesthesia care unit (PACU) in the sitting position once they met the criteria for extubation according to the judgment of their medical care team.\u003c/p\u003e\n\u003cp\u003eFor both groups, intraoperative pulmonary dynamic compliance (Cdyn), PEEP, FiO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003e(i.e., real-time FiO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003eobtained from the gas analyzer within the anaesthesia machine), driving pressure,\u0026nbsp;and plateau pressure\u0026nbsp;were recorded continuously. Intermittent blood gas analysis was performed in order to verify the accuracy of the SpO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003ereadings and to calculate the \u003ca href=\"https://respiratorycram.com/understanding-oxygenation-the-alveolar-arterial-gradient/\" target=\"_blank\"\u003ealveolar-arterial gradient\u003c/a\u003e [P(A-a)O\u003csub\u003e2\u003c/sub\u003e], while\u0026nbsp;the\u0026nbsp;respiratory rate was adjusted in order to maintain the PaCO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003ein the range of 35\u0026ndash;45 mmHg. In\u0026nbsp;the PACU,\u0026nbsp;vital signs and arterial blood gas analysis were recorded at 5, 10, and 30 minutes after extubation, and supplementary O\u003csub\u003e2\u0026nbsp;\u003c/sub\u003ewas provided to the patients via nasal cannula if the SpO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003ewas below 92%.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIntraoperative PaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003ewas reported as 55.7\u0026plusmn;10.9 kPa before extubation in patients undergoing RALP[4]; we assumed that there were 10 kPa differences between\u0026nbsp;the two groups,\u0026nbsp;with a variance of 10.9 kPa, a statistical power of 80%, and a two-sided \u0026alpha; significance level of 0.05. A sample size of 18 patients in each arm was required to test our hypothesis. Considering a dropout rate of 30%, a total of 24 patients for each group (for a total of 48 patients) were enrolled; randomization was performed using a minimization randomization method as previously described[22]. Patients were stratified by age (\u0026lt;65 vs. \u0026ge;65yrs) and BMI (\u0026lt;24 vs. \u0026ge;24 kg m\u003csup\u003e-2\u003c/sup\u003e) in order to test differences in age and BMI distribution. The randomization was performed via MinimPy2 software (version2.0, OSDN, Columbus, OH, USA). Randomization was performed the day before surgery by a research team member who was blinded to the trial condition. The data were managed and analyzed by an independent researcher (PL).\u003c/p\u003e\n\u003cp\u003eContinuous variables were presented as means \u0026plusmn; SD or medians with IQR according to whether the distribution was normal, while categorical variables were presented as counts and percentages. The \u003cem\u003e\u0026chi;\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e-test was used to compare differences in patient characteristics between the two groups. The unpaired \u003cem\u003et\u003c/em\u003e tests were used to compare differences in oxygen indices, driving pressure, and Cdyn at different time points. Repeated-measures analysis of variance (ANOVA) was used to compare differences in \u003cem\u003eP\u003c/em\u003eaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e, driving pressure, and Cdyn under mechanical ventilation prior to extubation. Differences in vital parameters, vasoactive medication dosage, and incidence of complications were tested via unpaired \u003cem\u003et\u003c/em\u003e tests, and the Wilcoxon Man-Whitney test was used when the data were not normally distributed. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS)software (version 24, IBM, Armonk, NY, USA) and GraphPad Prism 8.0 software (GraphPad Inc., San Diego, CA, USA). Statistical significance was set at \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eClinical characteristics\u003c/h2\u003e \u003cp\u003eA total of 48 patients were initially enrolled in this study, though two patients were excluded from the study due to operation cancelation. Therefore, a total of 46 patients completed the study and underwent a final analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). There were no statistically significant differences between the two groups in terms of clinical characteristics (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) or perioperative data (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOptimal PEEP level\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor all patients\u0026nbsp;(i.e., including those in both groups) the median optimal PEEP was 16 cm H\u003csub\u003e2\u003c/sub\u003eO (interquartile range, 12-18). The FiO\u003csub\u003e2\u003c/sub\u003e needed to obtain the optimal PEEP was 0.21\u0026plusmn;0.03. The details of the titration process are presented in Supplementary Table 1\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003eThe time allotted to complete the titration of\u0026nbsp;the\u0026nbsp;optimal PEEP was half an hour or less.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrimary outcome\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe \u003cem\u003eP\u003c/em\u003eaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e\u003csub\u003e\u0026nbsp;\u003c/sub\u003ewas statistically significantly higher in Group O than in Group C prior to extubation (77.0\u0026plusmn;4.9 kPa vs. 60.6\u0026plusmn;5.9 kPa, \u003cem\u003eP\u003c/em\u003e=0.04) (Figure 3a).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSecondary outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe\u0026nbsp;respiratory mechanics corresponding\u0026nbsp;to FiO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003eare shown in Fig.3b.\u0026nbsp;There was no statistically significant difference in\u0026nbsp;the driving pressure between\u0026nbsp;the two groups (Fig.3c). The Cdyn was higher in Group O than in Group C (43.4\u0026plusmn;2.7 ml cm H\u003csub\u003e2\u003c/sub\u003eO\u003csup\u003e-1\u003c/sup\u003e vs. 36.5\u0026plusmn;3.4 ml cm H\u003csub\u003e2\u003c/sub\u003eO\u003csup\u003e-1\u003c/sup\u003e, \u003cem\u003eP\u003c/em\u003e=0.032) prior to extubation (Fig.3d). Intraoperative respiratory parameters and \u003cem\u003eP\u003c/em\u003eaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e during PEEP intervention are shown in Supplementary Table 2.\u003c/p\u003e\n\u003cp\u003ePostoperative hypoxemia was defined\u0026nbsp;as postoperative hypoxemia\u0026nbsp;if SpO\u003csub\u003e2\u003c/sub\u003e\u0026lt;92% was detected in room air within 30 min after extubation in the PACU. The incidence of hypoxemia was statistically significantly lower in Group O as compared to Group C (1/23 or 4.3% vs. 7/23 or 30.4%, \u003cem\u003eP\u003c/em\u003e=0.02) (Table 2). The P(A-a) O\u003csub\u003e2\u003c/sub\u003e in Group C (9.0\u0026plusmn;2.0 kPa) was statistically significantly higher than that in Group O (3.62\u0026plusmn;0.9 kPa, \u003cem\u003eP\u003c/em\u003e=0.01). \u003cem\u003eP\u003c/em\u003eaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003eratios at three time points in the PACU after extubation are shown in Supplementary Figure 2.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe main findings of this study are as follows: (1) intraoperative optimal PEEP can be achieved by titration of PEEP and FiO\u003csub\u003e2\u003c/sub\u003e guided by the SpO\u003csub\u003e2\u003c/sub\u003e readout in patients likely requiring high PEEP; (2) maintaining optimal PEEP improves intraoperative oxygenation and reduces FiO\u003csub\u003e2\u003c/sub\u003e to maintain normoxemia; and (3) the benefit of intraoperative optimal PEEP remains postoperatively in terms of reductions in the incidence of postoperative hypoxemia.\u003c/p\u003e \u003cp\u003eOur results confirmed the observations from a previous study[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] demonstrating that using equipment for routine anaesthesia care can obtain optimal PEEP. This technique has the substantial advantage of being simple to use. In this study, titration of PEEP and FiO\u003csub\u003e2\u003c/sub\u003e were started simultaneously as the surgery progressed. Therefore, clinicians were able to obtain individualized optimal PEEP levels without interrupting or prolonging the surgery. This technique does not require additional training or equipment such as an intra-esophageal balloon to calculate transpulmonary pressure[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] or electric impedance tomography to measure lung aeration[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. All the equipment needed to obtain and maintain the optimal PEEP is readily available in any modern operating room or anaesthesia site. In addition, PEEP can be constantly reassessed and adjusted intraoperatively in order to maintain the optimal PEEP when respiratory mechanics change due to changes in the patient\u0026rsquo;s position or intra-abdominal insufflation pressure. A new algorithm may be developed using a closed-loop system to assess PEEP and automatically implicate the individual\u0026rsquo;s optimal PEEP using this technique.\u003c/p\u003e \u003cp\u003eWe tested our hypothesis in patients who underwent RALP because this population is more likely to require high PEEP to minimize intraoperative atelectasis[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. The surgery was performed within the pneumoperitoneum with an intra-abdominal pressure of approximately15 mmHg, and the patient was placed in a steep Trendelenburg position (approximately 30 degrees) intraoperatively for over 3-4 hours[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Therefore, patients are more prone to perioperative atelectasis formation if the PEEP is not high enough to counteract the reduction in functional residual capacity[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. However, in our institute, a PEEP of 5 cmH\u003csub\u003e2\u003c/sub\u003eO for patients undergoing robotic-assisted laparoscopic prostatectomy is a common practice. There are a few recommendations stating that the PEEP should be higher than 5 cmH\u003csub\u003e2\u003c/sub\u003eO if the patient is in the Trendelenburg position and/or if there is pneumoperitoneum[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. A PEEP of 5 cmH\u003csub\u003e2\u003c/sub\u003eO seems to be lower than that reported in the literature. However, guidelines for selecting PEEP for this patient population are unavailable due to insufficient literature informing these criteria. Any fixed PEEP would render some patients either below and above the optimal PEEP as the variation in optimal PEEP is large[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], and optimal PEEP is likely not a constant but rather varies depending on the patient\u0026rsquo;s physiology and positioning as well as the specific surgical intervention[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].The range of optimal PEEP observed in this study ranged between 2 and 18 cmH\u003csub\u003e2\u003c/sub\u003eO. We encountered a patient who was able to maintain a SpO\u003csub\u003e2\u003c/sub\u003e\u0026gt;95% with a FiO\u003csub\u003e2\u003c/sub\u003e of 0.21, even when the PEEP was set at 2 cmH\u003csub\u003e2\u003c/sub\u003eO. We also performed arterial blood gas analysis and confirmed that the SpO\u003csub\u003e2\u003c/sub\u003e and arterial hemoglobin oxygen saturation readouts were comparable. This indicates that, even with pneumoperitoneum and in the steep Trendelenburg position, this patient had an intrapulmonary shunt of less than 10% with a PEEP of 2 cmH\u003csub\u003e2\u003c/sub\u003eO [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA question remains as to whether the optimal PEEP we obtained was truly the optimal PEEP, since we did not have access to validation via a chest CT scan or electric impedance tomography. However, though this is a scientifically important question, but it may not be clinically important. Specifically, the approach employed in this study may not achieve a true PEEP (with no over- or under-PEEP). However, the oxygenation index improved by 27% (77.0/60.6 kPa) in Group O vs. Group C prior to extubation. Further studies are needed to determine the efficacy of this technique for achieving true optimal PEEP versus that obtained with EIT. Nevertheless, using this technique, we could achieve clinically relevant improvements in intraoperative oxygenation as compared with routine care. The mean FiO\u003csub\u003e2\u003c/sub\u003e used to achieve optimal PEEP was 0.21, the SpO\u003csub\u003e2\u003c/sub\u003e was 95%-96% prior to extubation, and the intrapulmonary shunt was estimated to be \u0026lt;10% (as compared with that of the control group). Because we chose to titrate the optimal PEEP stepwise and bidirectionally, we were unlikely to inflate the lung at the optimal PEEP level. Therefore, even though the optimal PEEP in the present study may not be a true optimal PEEP, it is likely very close to the true optimal PEEP and the difference between the two may not have clinical implications. Further studies are needed to assess the agreement of optimal PEEP obtained with the method used in this study as well as other well-established techniques, such as CT scans or EIT.\u003c/p\u003e \u003cp\u003eIt is important to note that we found that the benefit of intraoperative optimal PEEP is sustained postoperatively. This is consistent with previous observations suggesting that intraoperatively individualized PEEP can reduce postoperative atelectasis[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, a recent study[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] showed that intraoperative PEEP only improves intraoperative, but not postoperative, oxygenation. This discrepancy among studies, including our current study, maybe due to the different extubation approaches employed in the investigations. It is well known that a patient's functional residual capacity (FRC) depends on sedation level, muscle tone, and position[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. In our institution, it is routine practice for patients to be extubated in a sitting position. We observed the benefit of intraoperative PEEP on postoperative oxygenation when all patients were extubated in the sitting position. Therefore, patients likely maintain a larger FRC (i.e., closer to the normal value) than that of patients extubated in the supine position. This notion requires further validation. However, in a report by Simon et al., the position of the patients during extubation was not stated[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. In our study, because there were no statistically significant differences between the two groups in terms of the consumption of intraoperative and postoperative narcotic and residual sedation levels in the PACU, the reduction in the incidence of postoperative hypoxemia in room air in Group O was likely due to a reduction in postoperative atelectasis. Since the sample size was relatively small, we could not determine the effect of intraoperative PEEP on other outcomes, such as the incidence of reintubation and postoperative pneumonia. Nevertheless, the intrapulmonary shunt in these patients was an important factor. This is because we chose an SpO\u003csub\u003e2\u003c/sub\u003e of 92% or lower as the cutoff for the diagnosis of hypoxemia on room air; if we assume that the hypoxemia was due to the intrapulmonary shunt only and that no hypoxic vasoconstriction was involved, at an SpO\u003csub\u003e2\u003c/sub\u003e of 92%, the intrapulmonary shunt was estimated to be approximately 24% using the equation described previously[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Further studies should be conducted to assess the effect of intraoperative optimal PEEP on outcomes.\u003c/p\u003e \u003cp\u003eIn addition to the substantial strengths of this investigation, this study had several limitations. First, we did not validate our observation that the optimal PEEP achieved with this technique is indeed the true optimal PEEP. Validation using EIT or transpulmonary pressure will be important for assessing the sensitivity and specificity of this method. Second, the inaccuracy of pulse oximetry for reporting hemoglobin oxygen saturation was recently determined by the FDA. However, in this study, we validated SpO\u003csub\u003e2\u003c/sub\u003e readings using arterial blood gas analysis. In addition, we used the same brand of oximetry in both groups of patients. Therefore, this potential inaccuracy does not affect our conclusions. Third, it is possible that the PEEP obtained in our study is above the true optimal PEEP. However, we allowed for the descending and ascending stepwise titration of FiO\u003csub\u003e2\u003c/sub\u003e and PEEP. Therefore, over- and under-PEEP at the level that would affect outcomes are possible, but unlikely. Though we may not achieve a perfectly individualized optimal PEEP, but in practical terms, the PEEP value achieved in our study is likely close to the true value when the intrapulmonary shunt is less than 10%.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, individualized optimal PEEP can be achieved with equipment available for anaesthesia by titration of PEEP and FiO\u003csub\u003e2\u003c/sub\u003e guided by SpO\u003csub\u003e2\u003c/sub\u003e. Maintaining intraoperative optimal PEEP improves intraoperative oxygenation and reduces the incidence of postoperative hypoxemia in patients likely to require high intraoperative PEEP. Since the method we used in this study to obtain optimal PEEP, this approach is practical and hopefully clinicians are willing to adopt it and improve the quality of care.\u003c/p\u003e"},{"header":"List Of Abbreviations","content":"\u003cp\u003ePEEP: positive end expiratory pressure;\u0026nbsp;FiO2: inspiratory oxygen fraction;\u0026nbsp;PaO\u003csub\u003e2\u003c/sub\u003e: partial arterial oxygen pressure; EIT: electrical impedance tomography;\u0026nbsp;SPO\u003csub\u003e2\u003c/sub\u003e: pulse oximetry; RALP: robotic-assisted laparoscopic prostatectomy; COPD: chronic obstructive pulmonary disease; BMI: body mass index; PBW: predicted body weight; TCI: targeted control infusion; RM: recruitment maneuver; PACU: post anaesthesia care unit; Cdyn: dynamic compliance; FRC: functional residual capacity\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of\u0026nbsp;the Fudan\u0026nbsp;University Shanghai Cancer Center, with the ethics number IRB2010225-11. The patients provided written consent. All methods were carried out in accordance with Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interest:\u003c/strong\u003e Dr. Yandong Jiang is a consultant of Vyaire, which was not involved in the design, conduct or publication of this work.\u0026nbsp;The other authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was funded by a grant from the Shanghai Science and Technology Committee (No.20Y11906200). The funder was not involved in the design, conduct, or publication of this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLLG conducted data analysis and manuscript preparation, drafted and finalized the manuscript; LY participated in study design, data analysis and manuscript preparation. LLP participated in protocol optimization, data retrieval and data analysis. YC participated in protocol optimization and manuscript preparation. YDJ participated in study design, data analysis, drafted and edited the manuscript. JZ participated study design, data collection\u0026nbsp;and analysis, manuscript preparation and finalization.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAssistance with the study: The authors thank the Local Ethics Committee of the Fudan University Shanghai Cancer Center for their review and revision for important intellectual content. The authors would also like to thank the urologists at the Fudan University Shanghai Cancer Center for their help and support on this project.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMeininger D, Byhahn C, Mierdl S, Westphal K,Zwissler B Positive end-expiratory pressure improves arterial oxygenation during prolonged pneumoperitoneum. Acta Anaesthesiol Scand 2005; 49:778\u0026ndash;783.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePereira SM, Tucci MR, Morais CCA, Simoes CM, Tonelotto BFF, Pompeo MS,et al. 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Individualized positive end-expiratory pressure in obese patients during general anaesthesia: a randomized controlled clinical trial using electrical impedance tomography. British journal of anaesthesia 2017; 119:1194\u0026ndash;1205.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSuter P, Fairley B,Isenberg M Optimum end-expiratory airway pressure in patients with acute pulmonary failure. The New England journal of medicine 1975; 292:284\u0026ndash;289.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChiumello D, Cressoni M, Chierichetti M, Tallarini F, Botticelli M, Berto V,et al. Nitrogen washout/washin, helium dilution and computed tomography in the assessment of end expiratory lung volume. Critical care (London, England) 2008; 12:R150.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaisch S, Reissmann H, Fuellekrug B, Weismann D, Rutkowski T, Tusman G,et al. Compliance and dead space fraction indicate an optimal level of positive end-expiratory pressure after recruitment in anesthetized patients. Anesth Analg 2008; 106:175\u0026ndash;181, table of contents.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBlankman P, Shono A, Hermans BJ, Wesselius T, Hasan D,Gommers D Detection of optimal PEEP for equal distribution of tidal volume by volumetric capnography and electrical impedance tomography during decreasing levels of PEEP in post cardiac-surgery patients. Br J Anaesth 2016; 116:862\u0026ndash;869.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBian W, Chen W, Chao Y, Wang L, Li L, Guan J,et al. Application of dead space fraction to titrate optimal positive end-expiratory pressure in an ARDS swine model. Exp Ther Med 2017; 13:1572\u0026ndash;1577.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMuders T, Luepschen H, Zinserling J, Greschus S, Fimmers R, Guenther U,et al. 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Effect of Titrating Positive End-Expiratory Pressure (PEEP) With an Esophageal Pressure-Guided Strategy vs an Empirical High PEEP-Fio2 Strategy on Death and Days Free From Mechanical Ventilation Among Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA 2019; 321:846\u0026ndash;857.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSpadaro S, Karbing DS, Mauri T, Marangoni E, Mojoli F, Valpiani G,et al. Effect of positive end-expiratory pressure on pulmonary shunt and dynamic compliance during abdominal surgery. Br J Anaesth 2016; 116:855\u0026ndash;861.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoe P,Jones J Analysis of factors which affect the relationship between inspired oxygen partial pressure and arterial oxygen saturation. British journal of anaesthesia 1993; 71:488\u0026ndash;494.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMietto C, Malbrain ML,Chiumello D Transpulmonary pressure monitoring during mechanical ventilation: a bench-to-bedside review. Anaesthesiol Intensive Ther 2015; 47 Spec No:s27\u0026ndash;37.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLundin S, Grivans C,Stenqvist O Transpulmonary pressure and lung elastance can be estimated by a PEEP-step manoeuvre. Acta anaesthesiologica Scandinavica 2015; 59:185\u0026ndash;196.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFerrando C, Tusman G, Suarez-Sipmann F, Leon I, Pozo N, Carbonell J,et al. Individualized lung recruitment maneuver guided by pulse-oximetry in anesthetized patients undergoing laparoscopy: a feasibility study. Acta Anaesthesiol Scand 2018; 62:608\u0026ndash;619.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTusman G, Groisman I, Fiolo FE, Scandurra A, Arca JM, Krumrick G,et al. Noninvasive monitoring of lung recruitment maneuvers in morbidly obese patients: the role of pulse oximetry and volumetric capnography. Anesth Analg 2014; 118:137\u0026ndash;144.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThomson A, Morrison G, Thomson E, Beattie C, Nimmo A,Glen J Induction of general anaesthesia by effect-site target-controlled infusion of propofol: influence of pharmacokinetic model and ke0 value. Anaesthesia 2014; 69:429\u0026ndash;435.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHan B, Enas NH,McEntegart D Randomization by minimization for unbalanced treatment allocation. Stat Med 2009; 28:3329\u0026ndash;3346.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKeller SP,Fessler HE Monitoring of oesophageal pressure. Curr Opin Crit Care 2014; 20:340\u0026ndash;346.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFranchineau G, Brechot N, Lebreton G, Hekimian G, Nieszkowska A, Trouillet JL,et al. Bedside Contribution of Electrical Impedance Tomography to Setting Positive End-Expiratory Pressure for Extracorporeal Membrane Oxygenation-treated Patients with Severe Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med 2017; 196:447\u0026ndash;457.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKalmar AF, Foubert L, Hendrickx JF, Mottrie A, Absalom A, Mortier EP,et al. Influence of steep Trendelenburg position and CO(2) pneumoperitoneum on cardiovascular, cerebrovascular, and respiratory homeostasis during robotic prostatectomy. Br J Anaesth 2010; 104:433\u0026ndash;439.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGainsburg DM Anesthetic concerns for robotic-assisted laparoscopic radical prostatectomy. Minerva Anestesiol 2012; 78:596\u0026ndash;604.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAwad H, Walker CM, Shaikh M, Dimitrova GT, Abaza R,O'Hara J Anesthetic considerations for robotic prostatectomy: a review of the literature. J Clin Anesth 2012; 24:494\u0026ndash;504.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYurtdas G,Akdevelioglu Y A New Approach to Polycystic Ovary Syndrome: The Gut Microbiota. J Am Coll Nutr 2019:1\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShono A, Katayama N, Fujihara T, Bohm SH, Waldmann AD, Ugata K,et al. Positive End-expiratory Pressure and Distribution of Ventilation in Pneumoperitoneum Combined with Steep Trendelenburg Position. Anesthesiology 2020; 132:476\u0026ndash;490.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSahetya S, Goligher E,Slutsky A Searching for the Optimal PEEP in Patients Without ARDS: High, Low, or in Between? JAMA 2020; 324:2490\u0026ndash;2492.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSimon P, Girrbach F, Petroff D, Schliewe N, Hempel G, Lange M,et al. Individualized versus Fixed Positive End-expiratory Pressure for Intraoperative Mechanical Ventilation in Obese Patients: A Secondary Analysis. Anesthesiology 2021; 134:887\u0026ndash;900.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWahba RW Perioperative functional residual capacity. Can J Anaesth 1991; 38:384\u0026ndash;400.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamamoto N, Miyashita T, Takaki S,Goto T Effects of Breathing Pattern on Oxygen Delivery Via a Nasal or Pharyngeal Cannula. Respir Care 2015; 60:1804\u0026ndash;1809.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Patient clinical characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" id=\"isPasted\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"32.6278659611993%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"4.409171075837743%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"23.80952380952381%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup C\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=23)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"22.39858906525573%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup O\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=23)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"16.75485008818342%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" width=\"37.03703703703704%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge(years)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e＜65\u003c/p\u003e\n \u003cp\u003e\u0026ge;65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"23.80952380952381%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10(43.5)\u003c/p\u003e\n \u003cp\u003e13(56.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"22.39858906525573%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8(34.8)\u003c/p\u003e\n \u003cp\u003e15(65.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"16.75485008818342%\"\u003e\n \u003cp\u003e0.55\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.513227513227513%\"\u003e\n \u003cp\u003e\u003cstrong\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" width=\"11.11111111111111%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"23.80952380952381%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"22.39858906525573%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.167548500881834%\"\u003e\n \u003cp\u003e0.77\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.56183745583039%\"\u003e\n \u003cp\u003e＜24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"9.363957597173146%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"23.851590106007066%\"\u003e\n \u003cp\u003e12(52.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"22.43816254416961%\"\u003e\n \u003cp\u003e13(56.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"16.784452296819786%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.56183745583039%\"\u003e\n \u003cp\u003e\u0026ge;24\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eASA physical status\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"9.363957597173146%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"23.851590106007066%\"\u003e\n \u003cp\u003e11(47.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"22.43816254416961%\"\u003e\n \u003cp\u003e10(43.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"16.784452296819786%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" width=\"37.03703703703704%\"\u003e\n \u003cp\u003eI\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eSmoking status\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNever\u003c/p\u003e\n \u003cp\u003eEver\u003c/p\u003e\n \u003cp\u003eCurrent\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eComorbidity\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003cp\u003eDiabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"23.80952380952381%\"\u003e\n \u003cp\u003e2(8.7)\u003c/p\u003e\n \u003cp\u003e21(91.3)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15(65.3)\u003c/p\u003e\n \u003cp\u003e3(13.0)\u003c/p\u003e\n \u003cp\u003e5(21.7)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8 (34.8)\u003c/p\u003e\n \u003cp\u003e3(13.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"22.39858906525573%\"\u003e\n \u003cp\u003e3(13.0)\u003c/p\u003e\n \u003cp\u003e20(87.0)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14(60.9)\u003c/p\u003e\n \u003cp\u003e4(17.4)\u003c/p\u003e\n \u003cp\u003e5(21.7)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (26.1)\u003c/p\u003e\n \u003cp\u003e4(17.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"16.75485008818342%\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eNote:\u0026nbsp;\u003c/strong\u003eData are presented as\u0026nbsp;numbers (%). Group C, control group with fixed PEEP of 5cmH\u003csub\u003e2\u003c/sub\u003eO; Group O, optimized PEEP group with individualized PEEP at which SpO\u003csub\u003e2\u003c/sub\u003e is maintained at 95-96% with minimal FiO\u003csub\u003e2\u003c/sub\u003e; BMI, body mass index; ASA, American Society of Anesthesiologists.\u003c/p\u003e\n\u003cp\u003e\u003cstrong id=\"isPasted\"\u003eTable 2. Intraoperative data\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"48.4641638225256%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.283276450511945%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup C\u003c/strong\u003e(n=23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.43003412969283%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eO\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e(n=23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.822525597269625%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"48.4641638225256%\"\u003e\n \u003cp\u003eAnesthesia duration\u0026nbsp;(min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.283276450511945%\"\u003e\n \u003cp\u003e227.3\u0026plusmn;7.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.43003412969283%\"\u003e\n \u003cp\u003e218.7\u0026plusmn;5.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.822525597269625%\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"48.4641638225256%\"\u003e\n \u003cp\u003eSurgery duration(min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.283276450511945%\"\u003e\n \u003cp\u003e169.1\u0026plusmn;6.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.43003412969283%\"\u003e\n \u003cp\u003e174.1\u0026plusmn;4.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.822525597269625%\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"48.4641638225256%\"\u003e\n \u003cp\u003eTotal amount of fluid infusion\u0026nbsp;(ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.283276450511945%\"\u003e\n \u003cp\u003e2070\u0026plusmn;56.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.43003412969283%\"\u003e\n \u003cp\u003e1904\u0026plusmn;68.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.822525597269625%\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"48.4641638225256%\"\u003e\n \u003cp\u003eBlood loss(ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.283276450511945%\"\u003e\n \u003cp\u003e118.7\u0026plusmn;10.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.43003412969283%\"\u003e\n \u003cp\u003e97.8\u0026plusmn;5.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.822525597269625%\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"48.4641638225256%\"\u003e\n \u003cp\u003eUrinary output\u0026nbsp;(ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.283276450511945%\"\u003e\n \u003cp\u003e347.8\u0026plusmn;37.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.43003412969283%\"\u003e\n \u003cp\u003e358.7\u0026plusmn;51.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.822525597269625%\"\u003e\n \u003cp\u003e0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"48.4641638225256%\"\u003e\n \u003cp\u003eVasoactive injections\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.283276450511945%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.43003412969283%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.822525597269625%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"48.4641638225256%\"\u003e\n \u003cp\u003eReceived medication, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.283276450511945%\"\u003e\n \u003cp\u003e21(91.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.43003412969283%\"\u003e\n \u003cp\u003e22(95.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.822525597269625%\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"48.4641638225256%\"\u003e\n \u003cp\u003eEphedrine (mg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.283276450511945%\"\u003e\n \u003cp\u003e6.8\u0026plusmn;1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.43003412969283%\"\u003e\n \u003cp\u003e7.2\u0026plusmn;1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.822525597269625%\"\u003e\n \u003cp\u003e0.80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"48.4641638225256%\"\u003e\n \u003cp\u003ePhenylephrine (\u0026mu;g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.283276450511945%\"\u003e\n \u003cp\u003e194.8\u0026plusmn;44.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.43003412969283%\"\u003e\n \u003cp\u003e183.0\u0026plusmn;52.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.822525597269625%\"\u003e\n \u003cp\u003e0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"48.4641638225256%\"\u003e\n \u003cp\u003eP(A-a) O\u003csub\u003e2\u003c/sub\u003epre-extubation(kPa)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.283276450511945%\"\u003e\n \u003cp\u003e9.0\u0026plusmn;2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.43003412969283%\"\u003e\n \u003cp\u003e3.62\u0026plusmn;0.9\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.822525597269625%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"48.4641638225256%\"\u003e\n \u003cp\u003eSpO\u003csub\u003e2\u003c/sub\u003e＜92%\u0026nbsp;at PACU on room air, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.283276450511945%\"\u003e\n \u003cp\u003e7(30.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.43003412969283%\"\u003e\n \u003cp\u003e1(4.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.822525597269625%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.02\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNote:\u0026nbsp;\u003c/strong\u003eData are presented as\u0026nbsp;mean \u0026plusmn; SD or numbers (%);\u0026nbsp;P(A-a)O\u003csub\u003e2\u003c/sub\u003e: alveolar-arterial gradient; PACU: post-anesthesia care unit ;pre-extubation: before extubation.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Positive end-expiratory pressure, pulse oximetry, fraction of inspiratory oxygenation, oxygenation index, robot-assisted laparoscopic prostatectomy","lastPublishedDoi":"10.21203/rs.3.rs-1078756/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1078756/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eOptimal intraoperative positive end expiratory pressure (PEEP) improves patient outcomes. The pulse-oximetry has been used to determine the lung opening and closing pressures. Therefore, we hypothesized that intraoperative optimal PEEP obtained by titrating inspiratory oxygen fraction (FiO\u003csub\u003e2\u003c/sub\u003e) guided with pulse-oximetry could improve perioperative oxygenation.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eForty-six males undergoing elective robotic assisted laparoscopic prostatectomy were randomly assigned to either optimal PEEP (Group O, n=23) or control with fixed PEEP of 5 cmH\u003csub\u003e2\u003c/sub\u003eO (Group C, n=23). Optimal PEEP, defined as the PEEP with lowest FiO\u003csub\u003e2\u003c/sub\u003e or 0.21 to maintain SpO\u003csub\u003e2\u003c/sub\u003e\u0026ge; 95%, was obtained in both groups after placing the patients in Trendelenburg position and peritoneal insufflation. Patients in Group O maintained the optimal PEEP and in Group C maintained PEEP of 5cmH\u003csub\u003e2\u003c/sub\u003eO intraoperatively. Both groups were extubated in a sitting position once the extubation criteria met. The primary outcome was the partial arterial oxygen pressure (PaO\u003csub\u003e2\u003c/sub\u003e)/inspiratory oxygen fraction (FiO\u003csub\u003e2\u003c/sub\u003e) prior to extubation. Secondary outcome was the incidence of postoperative hypoxemia (SpO\u003csub\u003e2\u003c/sub\u003e༜92% on room-air after extubation) in post-operative care unit.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe median optimal PEEP was 16 cm H\u003csub\u003e2\u003c/sub\u003eO [inter-quartile range, 12-18]. The PaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003eprior to extubation was significantly higher in Group O than that in Group C (77.0\u0026plusmn;4.9kPa vs.60.6\u0026plusmn;5.9kPa, p=0.04); PaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e was also significantly higher in Group O 30minutes after extubation (57.6\u0026plusmn;1.9 vs. 46.6\u0026plusmn;1.8kPa, p=0.01). The incidence of hypoxemia on room air in the post-operative care unit was significantly lower in the Group O than in the Group C (1/23, or 4.3% vs. 7/23 or 30.4%, \u003cem\u003ep\u003c/em\u003e =0.02).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIntraoperative optimal PEEP can be achieved by titration of FiO\u003csub\u003e2\u003c/sub\u003e guided with SpO\u003csub\u003e2\u003c/sub\u003e. Maintaining intraoperative optimal PEEP improves intraoperative oxygenation and reduces the incidence of post-operative hypoxemia.\u003c/p\u003e\u003ch2\u003eTrial registration\u003c/h2\u003e \u003cp\u003e: Chinese Clinical Trial Registry identifier: ChiCTR2100051010. Prospectively registered on 10 September, 2021\u003c/p\u003e","manuscriptTitle":"Optimal Positive End-Expiratory Pressure Obtained with Titration of Fraction of Inspiratory Oxygen: A Randomized Controlled Clinical Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-11-30 15:42:07","doi":"10.21203/rs.3.rs-1078756/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b4301dac-214b-433b-96ea-9eefeebb5df3","owner":[],"postedDate":"November 30th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":8717285,"name":"Anesthesiology \u0026 Pain Medicine"}],"tags":[],"updatedAt":"2022-02-18T09:59:15+00:00","versionOfRecord":[],"versionCreatedAt":"2021-11-30 15:42:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1078756","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1078756","identity":"rs-1078756","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}