Association between Intraoperative End-Tidal Carbon Dioxide and Postoperative Nausea and Vomiting in Gynecologic Laparoscopic Surgery

Association between Intraoperative End-Tidal Carbon Dioxide and Postoperative Nausea and Vomiting in Gynecologic Laparoscopic Surgery | 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 Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Association between Intraoperative End-Tidal Carbon Dioxide and Postoperative Nausea and Vomiting in Gynecologic Laparoscopic Surgery Li Dong, Chikashi Takeda, Hajime Yamazaki, Miho Hamada, Akiko Hirotsu, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1313239/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract PURPOSE Gynecologic laparoscopic surgery has a high incidence of postoperative nausea and vomiting (PONV). Studies suggest that low intraoperative end-tidal carbon dioxide (EtCO 2 ) is associated with an increased incidence of PONV, but the results have not been consistent among studies. This study investigated the association between intraoperative EtCO 2 and PONV in patients undergoing gynecologic laparoscopic surgeries under general anesthesia. METHODS This retrospective cohort study involved patients who underwent gynecologic laparoscopic surgeries under general anesthesia at Kyoto University Hospital. We defined hypocapnia as a mean EtCO 2 of <35 mmHg. Multivariable modified Poisson regression analysis examined the association between low EtCO 2 and PONV two days after surgery and the postoperative length of hospital stay (PLOS). RESULTS Of the 739 patients, 120 (16%) had low EtCO 2 , and 430 (58%) developed PONV two days after surgery. There was no substantial association between low EtCO 2 and increased incidence of PONV (adjusted risk ratio: 0.96; 95% confidence interval [CI]: 0.80–1.14; p = 0.658). Furthermore, there was no substantial association between low EtCO 2 and prolonged PLOS (adjusted difference in PLOS: 0.13; 95% CI, −1.00 to 1.28; p = 0.816). CONCLUSION Intraoperative low EtCO 2 was not substantially associated with either increased incidence of PONV or prolonged PLOS. EtCO2 gynecologic laparoscopy postoperative nausea and vomiting laparoscopy postoperative length of hospital stay Figures Figure 1 Introduction The incidence of postoperative nausea and vomiting (PONV) remains high despite considerable improvements in treatment over the past few decades. PONV is nausea or vomiting in the first 24 to 48 h after surgery 1 . Well-established risk factors for PONV include female gender, history of PONV or motion sickness, nonsmoking, and postoperative opioid use 2 . The risk of PONV is up to 80% in high-risk patients with all four risk factors 3 . The incidence of PONV is particularly high among patients undergoing gynecologic laparoscopic surgery 4 . PONV is associated with decreased patient satisfaction 5 , increased postoperative complications 6 , and longer postoperative length of hospital stay (PLOS) 7 . Hypocapnia may be associated with decreased systemic vasodilation 8 and may cause tissue ischemia 9 , intestinal ischemia 10 , and cerebral ischemia 11 , 12 . Animal studies have reported that serotonin levels in the brain, a highly emetogenic substance, increase with intestinal 13 , 14 and cerebral ischemia 15 . Based on the hypothesis associating hypocapnia with increased serotonin levels due to intestinal and cerebral ischemia, studies associate intraoperative hypocapnia with increased incidence of PONV 16 , 17 . However, the relationship between hypocapnia and PONV remains unclear because some studies had conflicting results 18 , 19 . Therefore, we examined the association between intraoperative end-tidal carbon dioxide (EtCO 2 ) and the incidence of PONV in patients undergoing gynecologic laparoscopic surgery. We adjusted for important confounding factors and assessed the effects of the duration and severity of low EtCO 2 exposure. Methods Ethics The Certified Review Board of Kyoto University, Kyoto, Japan (Chairperson Prof. Shinji Kosugi) approved the protocol for this study (approval no.: R1272-3, January 23, 2020). Additionally, the informed consent requirement was waived due to this study’s retrospective nature. Study design, setting, and population In this single-center retrospective cohort study, we used data from the Kyoto University Hospital IMProve Anaesthesia Care and ouTcomes (Kyoto-IMPACT) database. The Kyoto-IMPACT database aims to clarify the relationship between intraoperative respiratory and cardiovascular parameters and postoperative outcomes. We consecutively selected patients who underwent surgery under the care of anesthesiologists at Kyoto University Hospital (1,121 beds). We have published several studies using the Kyoto-IMPACT database 20 , 21 . We included adult female patients aged 18 years or older who underwent gynecologic laparoscopic surgery (i.e., adnexal surgery and/or hysterectomy) at Kyoto University Hospital between January 2012 and December 2017. The gynecologic laparoscopic surgery population was selected because the predicted incidence rate of PONV in this population is 30%–40%, assumed to be a medium risk of PONV 4 . The exclusion criteria were as follows: 1) patients with postoperative intensive care unit admission; 2) those who underwent multiple surgeries within one week during the study period; 3) those who received epidural anesthesia; 4) those with missing smoking data, and 5) those with missing intraoperative EtCO 2 data. Data collection We collected data from the anesthesia information management and electronic medical record systems and constructed the Kyoto-IMPACT database. EtCO 2 was continuously measured using a sidestream gas analyzer (GF-220R Multigas/Flow Unit, Nihon Kohden®, Japan) that was automatically uploaded to the anesthesia information management system every 60 s. Intraoperative EtCO 2 was the mean EtCO 2 level from skin incision to skin closure. We removed EtCO 2 levels lower than 20 mmHg as artifacts (EtCO 2 during aspiration or position change). The definitions of variables, including the minimum and maximum EtCO 2 levels, can be found in Supplementary Data Table S1. We collected data on PONV by reviewing all clinical data contained in the electronic medical records. Ward nurses assessed the presence of nausea and vomiting at least twice daily. We defined PONV as one or more episodes of nausea or vomiting during the first two days after surgery and vomiting as one or more episodes of vomiting during the same period. Exposure To determine how EtCO 2 affects PONV, we defined exposure by calculating the dose, time, and cumulative effects of EtCO 2 . First, we evaluated the dose effects of EtCO 2 using the mean EtCO 2 . Next, we divided the patients into two groups based on the cutoff EtCO 2 level of 35 mmHg proposed by Way and Hill 22 . We defined low EtCO 2 as a mean EtCO 2 lower than 35 mmHg and normal EtCO 2 as a mean EtCO 2 greater than or equal to 35 mmHg. We classified the patients in either of these groups and used them as the primary exposure for further analysis. Additionally, we categorized the mean EtCO 2 levels into quartiles (i.e., <35, 35–37, 37–40, and ≥40 mmHg) because the relationship between EtCO 2 and PONV might not be linear. To assess the effects of the duration and severity of low EtCO 2 exposure, we determined the time effect based on the minutes when the EtCO 2 level was below 35 mmHg and measured the cumulative effect as the area with EtCO 2 levels below the threshold of 35 mmHg for each patient. Furthermore, we categorized the minutes and area under the threshold of an EtCO 2 level of 35 mmHg into quartiles; the lowest quartile was the reference category. Outcomes The primary outcome in this study was PONV, defined as PONV for two days postoperatively. The secondary outcomes were nausea for two days postoperatively, vomiting for two days postoperatively, PONV for 3–7 days postoperatively, and PLOS. We defined PLOS as the duration of hospital stay after surgery for patients who survived until discharge. Statistical analysis We analyzed the relationship between intraoperative EtCO 2 and PONV before data collection. We used the Mann–Whitney test for group comparisons, and continuous variables were expressed as the median and interquartile range (IQR), and categorical variables were expressed as counts and percentages (%). First, we performed modified Poisson regression analysis with robust variance to calculate the risk ratio for low EtCO 2 (mean EtCO 2 of less than 35 mmHg) and PONV, with the reference category of normal EtCO 2 (mean EtCO 2 ≥ 35 mmHg) 23 . Additionally, we calculated the risk ratios of the mean EtCO 2 level in the first quartile (mean EtCO 2 of less than 35 mmHg), third quartile (mean EtCO 2 of 37–40 mmHg), and fourth quartile (mean EtCO 2 of more than or equal to 40 mmHg). The second quartile (mean EtCO 2 of 35–37 mmHg) was the reference category because it was considered normocapnia. Furthermore, we examined the time and cumulative effects of EtCO 2 by evaluating how each quartile affected PONV, with the first quartile (with minutes under an EtCO 2 of 35 mmHg and the area below the threshold of 35 mmHg) being the reference category. We created a model using the covariates previously used to demonstrate the relationship between intraoperative EtCO 2 and PONV. The model included age, smoking history, surgery duration, body mass index (BMI), total intravenous anesthesia (TIVA), mean arterial pressure (MAP), intraoperative fentanyl use, postoperative fentanyl dose for intravenous patient-controlled analgesia (IVPCA), the use of prophylactic antiemetics, the addition of droperidol to postoperative IVPCA, American Society of Anesthesiologists Physical Status (ASAPS), malignancy, and emergency surgery. Additionally, a modified Poisson regression model investigated whether the dose, time, or cumulative effect of EtCO 2 affects postoperative nausea two days, vomiting two days, and PONV 3–7 days postoperatively, adjusting for the aforementioned models. To further evaluate the relationship between EtCO 2 and PLOS, we performed a linear regression analysis adjusting for the possible covariates in the aforementioned models. The relationship between intraoperative EtCO 2 and PONV may depend on patient and surgical characteristics. Therefore, we performed a subgroup analysis to assess this potential heterogeneity. We used the modified Poisson regression model for the following subgroups: (i) age (≥50/<50 years), (ii) malignancy (yes/no), (iii) smoking history (ever smoked/never smoked), (iv) duration of surgery (≥4/<4 hours), (v) TIVA (yes/no), and (vi) the use of intraoperative prophylactic antiemetics (yes/no). We calculated the crude risk ratio of PONV in each subgroup and examined the interaction between subgroups and intraoperative EtCO 2 . To maximize statistical power, all eligible patients enrolled in the Kyoto-IMPACT database since 2012, when postoperative nausea and vomiting began to be recorded in their current form, were included in the analysis. To determine the study power, we estimated that approximately 120 laparoscopic gynecologic surgeries were performed annually at Kyoto University Hospital, with 720 surgeries performed over six years. The risk ratio was 1.53, the incidence of PONV was 40% 4 , and the proportion of low EtCO 2 was 50% 24 , giving an estimated power of 80%. The rate of missing data was 0.04%, so we conducted a complete case analysis. All statistical tests were two-tailed. We used Stata/SE 15.1 (StataCorp LLC, College Station, Texas, USA) to conduct all statistical analyses. Results Baseline patient characteristics Of the 790 patients who underwent laparoscopic gynecologic surgery between 2008 and 2017, 774 met our inclusion criteria, and we included 739 in the complete case analysis (Figure 1). Low EtCO 2 (defined as the mean EtCO 2 level of less than 35 mmHg) occurred in 120 patients (16%), whereas PONV occurred in 430 patients (58%). Table 1 shows the overall baseline characteristics of the study participants. The median EtCO 2 values were 37 mmHg (IQR, 35–40 mmHg) overall, 33 mmHg (IQR, 32–34 mmHg) in patients with low EtCO 2 , and 38 mmHg (IQR, 36–40mmHg) in patients with normal EtCO 2 . Association between low EtCO 2 and PONV Table 2 shows the study’s main results. PONV occurred in 67 (55.83%) of the 120 patients in the low EtCO 2 group, whereas 363 (58.64%) of the 619 patients were in the normal EtCO 2 group. We could not find a substantial association between low EtCO 2 and PONV (crude risk ratio, 0.95; 95% confidence interval [CI], 0.80–1.13; p = 0.577) (adjusted risk ratio, 0.96; 95% CI, 0.80–1.14; p = 0.658). For further analysis, we divided EtCO 2 into quartiles. The second quartile (mean EtCO 2 35–37 mmHg) was the reference, and the definition of low EtCO 2 was the lowest quartile of mean EtCO 2 (mean EtCO 2 of less than 35 mmHg). The second (mean EtCO 2 of 35–37 mmHg), third (mean EtCO 2 37–40 mmHg), and fourth (mean EtCO 2 ≥ 40 mmHg) quartiles of mean EtCO 2 values were not substantially associated with increased incidence of PONV, with low EtCO 2 (first quartile [mean EtCO 2 of less than 35 mmHg]) as the reference category. For the time effects of EtCO 2 , compared with short-term exposure (first quartile of exposure time to EtCO 2 of less than 35 mmHg, 0–11 min), long-term exposure to EtCO 2 levels of less than 35 mmHg (fourth quartile of exposure time to EtCO 2 of less than 35 mmHg, 67–613 min) was not substantially associated with increased incidence of PONV (crude risk ratio, 1.09; 95% CI, 0.91–1.30; p = 0.323) (adjusted risk ratio, 1.03; 95% CI, 0.87–1.22; p = 0.700). Finally, for the cumulative effects of EtCO 2 , the fourth quartile of the area under the EtCO 2 threshold of 35 mmHg (108–2,213) was not substantially associated with increased incidence of PONV compared with the first quartile (0–7) (crude risk ratio, 1.08; 95% CI, 0.91–1.29; p = 0.346) (adjusted risk ratio, 1.03; 95% CI, 0.87–1.23; p = 0.654). Association between low EtCO 2 and nausea and vomiting 2 days postoperatively and PONV 3–7 day postoperatively The adjusted risk ratio for the low EtCO 2 group (mean EtCO 2 of less than 35 mmHg) did not indicate an association between low EtCO 2 and nausea and vomiting two days postoperatively or PONV 3–7 days postoperatively (Table 3), with normal EtCO 2 being the reference category. Association between low EtCO 2 and PLOS The median PLOS was six days (IQR, 5–8 days) (Table 4). The median PLOS in patients with low EtCO 2 was not different from that in patients with normal EtCO 2 (6 days [IQR, 5–8 days] vs. 6 days (IQR, 5–7 days); p = 0.782). Linear regression analysis showed that low EtCO 2 was not likely to be associated with PLOS (crude adjusted difference in PLOS , −0.15; 95% CI, −1.29 to 0.97; p = 0.783) (adjusted difference in PLOS, −0.13; 95% CI, −1.00 to 1.28; p = 0.816). Subgroup analysis Subgroup analyses included age (≥50/<50 years), malignancy, smoking history, duration of surgery (≥4 hours/<4 hours), TIVA, and the use of intraoperative prophylactic antiemetics. There was no interaction between these variables and PONV (Table 5). Discussion In this retrospective cohort study, intraoperative EtCO 2 was not substantially associated with increased incidence of PONV and prolonged PLOS in patients undergoing gynecologic laparoscopic surgery. Furthermore, we examined the effects of the duration and severity of low EtCO 2 exposure using the time and cumulative effects of EtCO 2 but found no clear association. Two small studies have studied whether there is an association between low EtCO 2 and PONV 17 , 18 , but the results have been inconsistent. A randomized controlled trial (RCT) involving 75 patients who underwent percutaneous nephrolithotripsy reported that the hypercapnia management group had less PONV 17 . However, a prospective observational study involving 90 pediatric patients who underwent inguinal surgery has reported that elevated levels of EtCO 2 were an independent predictor of PONV 18 . As the aforementioned studies have different types of surgery and patient backgrounds, their results might not be directly applicable to patients undergoing gynecologic laparoscopic surgery. Furthermore, three studies on patients who had undergone gynecologic surgery have shown inconsistent results. An RCT involving 387 patients who underwent gynecologic laparoscopic surgery reported mild hypercapnia management did not reduce PONV 19 . That study did not evaluate the effects of low EtCO 2 (mean EtCO 2 level of less than 35 mmHg). Alternatively, a retrospective cohort study involving 146 patients undergoing open gynecologic surgery has reported that the minimum EtCO 2 level of ≤31 mmHg lasting longer than 10 min was associated with an increased incidence of PONV 16 . Still, that study only evaluated the effects of extremely low EtCO2 levels (mean EtCO2 of ≤31 mmHg). It did not evaluate the dose and time effects of low EtCO2 below the commonly defined EtCO 2 level of 35 mmHg. Furthermore, an RCT involving 60 patients undergoing gynecologic laparoscopic surgery reported that low EtCO 2 management reduced the incidence of nausea, PONV score, and the use of rescue antiemetics 25 ; these results differed from the two aforementioned studies. Management to keep EtCO2 at a low level may avoid PONV by inhibiting cerebral vasodilation, preventing increased intracranial pressure caused by the pneumoperitoneum and Trendelenburg position, which would not affect the ischemia-sensitive vestibular system. However, this study may have an internal validity problem in which it was not blinded. Furthermore, it had a generalizability problem because it excluded patients with severe systemic diseases, ASAPS-III patients, those with a history of PONV motion sickness, and smokers. Considering that the results of previous studies are inconsistent, the evidence on the association between intraoperative low EtCO 2 and PONV remains limited. Therefore, we conducted this study, which involved the largest cohort from real-world data, which provided a sufficient sample size, resulting in a statistical power of 80% to detect a risk ratio of 1.53. Furthermore, adjusting for important confounders, such as blood pressure, age, and intraoperative fentanyl use, and assessing the dose-effect of low EtCO 2 (mean EtCO 2 of less than 35 mmHg) and the effects of the duration and severity of low EtCO 2 exposure, we could not demonstrate an association between low EtCO 2 and PONV. Even extremely low EtCO 2 , defined as EtCO 2 of less than 31 mmHg sustained for more than 10 minutes 16 , failed to show an association with PONV (Supplemental Data Table S2). This study has several strengths. First, it investigated the association between the effects of EtCO 2 and PONV and PLOS, the dose effects of EtCO 2 (mean level of less than 35 mmHg) and the effects of the duration (time effects, long-term exposure to EtCO 2 of less than 35 mmHg) and severity (cumulative effects, area under the threshold of EtCO 2 of less than 35 mmHg). Among the three previous studies that examined the association between intraoperative low EtCO 2 and PONV, which only evaluated the dose effects 19 , 17 , 18 , only one study evaluated the association between the time effects of low EtCO 2 and PONV 16 . Second, this study adjusted for potential confounding factors that were not adjusted in previous studies, such as blood pressure, age, and intraoperative fentanyl use, using a modified Poisson regression model. Third, this was a large study with sufficient sample size. All previous studies had small sample sizes, so the number of confounding factors that can be adjusted is limited. This study has several limitations. First, we extracted information on the presence of nausea and vomiting from the records of assessments performed by the ward nurses at least twice a day, so PONV occurring at other times may have been overlooked. However, we thought that moderate to severe PONV reported voluntarily by patients or required treatment was fully measured. Second, we did not consider the PaCO 2 –EtCO 2 gap to calibrate EtCO 2 levels using PaCO 2 levels. Thus, we underestimated the effects of low EtCO 2 and overestimated the effects of hypercapnia. However, since PaCO 2 is usually 2–5 mmHg higher than EtCO 2 in healthy populations, this was considered a limited effect. Last, there may be unknown and unmeasured confounding factors, such as potential reasons for anesthesiologists to target a specific EtCO 2 level, missing data on intraoperative ventilation parameters, and PONV risk factors among patient factors is, history of PONV and motion sickness. Conclusion Intraoperative low EtCO 2 (less than 35 mmHg) was not substantially associated with either increased incidence of PONV or prolonged PLOS in patients undergoing gynecologic laparoscopic surgery. Declarations Acknowledgments Assistance with the study We are grateful to Mr. Yoshihiro Kinoshita, Ms. Tomoko Hosoya, and Mr. Yohei Taniguchi (Medical Information Systems Section, Management Division, Kyoto University Hospital, Kyoto, Japan) for their assistance in data collection for this study. Financial support and sponsorship This work was supported in part by the Japan Society for the Promotion of Science KAKENHI program (grant number: 20K09242, principal investigator: Toshiyuki Mizota) and the 2019 Kyoto University ISHIZUE Research Development Program (principal investigator: Toshiyuki Mizota). Conflict of Interest The authors have no conflicts of interest. Ethics approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The Certified Review Board of Kyoto University, Kyoto, Japan (Chairperson Prof. Shinji Kosugi) approved the protocol for this study (approval no.: R1272-3, January 23, 2020). Additionally, the informed consent requirement was waived due to this study’s retrospective nature. Authorship clarified Conceptualization: Li Dong Methodology: Li Dong, Toshiyuki Mizota, Yosuke Yamamoto, Chikashi Takeda, Hajime Yamazaki, Miho Hamada, Akiko Hirotsu Formal analysis and investigation: Li Dong, Chikashi Takeda, Hajime Yamazaki, Miho Hamada, Akiko Hirotsu, Yosuke Yamamoto, Toshiyuki Mizota Writing - original draft preparation: Li Dong Writing - review and editing: Li Dong, Chikashi Takeda, Hajime Yamazaki, Miho Hamada, Akiko Hirotsu, Yosuke Yamamoto, Toshiyuki Mizota Editing and approval of the manuscript: Li Dong, Chikashi Takeda, Hajime Yamazaki, Miho Hamada, Akiko Hirotsu, Yosuke Yamamoto, Toshiyuki Mizota Funding acquisition: Toshiyuki Mizota Resources: Li Dong,Toshiyuki Mizota Supervision: Toshiyuki Mizota References Pierre, S. & Whelan, R. Nausea and vomiting after surgery. Continuing Education in Anaesthesia Critical Care & Pain 13 , 28-32, doi:10.1093/bjaceaccp/mks046 (2012). Gan, T. J. et al. 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Comparison of different end-tidal carbon dioxide levels in preventing postoperative nausea and vomiting in gynaecological patients undergoing laparoscopic surgery. Journal of Obstetrics and Gynaecology , 1-8, doi:10.1080/01443615.2020.1789961 (2020). Tables Table 1. Patient characteristics (n = 739 ) Characteristics All patients (n = 739) Low EtCO 2 (n = 120) Normal EtCO 2 (n = 619) Age, years 45 (36–56) 47 (34–58) 44 (36–55) ASA-PS I 402 (54.55%) 60 (50.42%) 342 (55.34%) II 322 (43.69%) 58 (48.74%) 264 (42.72%) III 13 (1.76%) 1 (0.84%) 12 (1.94%) BMI 21.28 (19.35–23.62) 21.73 (19.38–24.45) 21.16 (19.35–23.52) Malignant 205 (27.74%) 25 (20.83%) 180 (29.08%) Never smoker 567 (76.73%) 87 (72.50%) 480 (77.54) Emergency surgery 42 (5.70%) 6 (5.04%) 36 (5.83%) Duration of surgery, minute 186 (125–270) 156 (110–233) 195 (129–276) Blood loss, ml 10 (0–100) 0 (0–75) 17 (0–100) Transfusion volume, ml 0 (0) 0 (0) 0 (0) Infusion volume, ml 1400 (1000–2040) 1265 (920–1920) 1450 (1000–2060) TIVA 135 (18.27%) 25 (20.83%) 110 (17.77%) Mean MAP, mmHg 73 (68–80) 73 (68–81) 73 (68–80) Intraoperative antiemetics use 284 (38.43%) 37 (30.83%) 247 (39.90%) Addition of droperidol in IVPCA 321 (43.44%) 38 (31.67%) 283 (45.72%) Total intraoperative fentanyl dose (μg) 200 (150–250) 200 (100–250) 200 (150–250) Postoperative fentanyl dose in IVPCA (μg/h) 20 (0–25) 20 (0–25) 20 (0–25) Mean EtCO 2 37 (35–40) 33 (32–34) 38 (36–40) Minimum EtCO 2 31 (29–33) 28 (26–30) 32 (30–34) Maximum EtCO 2 42 (40–46) 37 (36–39) 43 (41–47) Values are given as median (interquartile range) or count (%). Abbreviations: ASAPS, American Society of Anesthesiologists Physical Status; BMI, body mass index; TIVA, total intravenous anesthesia; MAP, mean arterial pressure; IVPCA, intravenous patient-controlled analgesia; EtCO 2 , end-tidal carbon dioxide. Table 2 . Multivariable analysis of the relationship between EtCO 2 and POD2-PONV N POD2-PONV Crude Risk Ratio (95% CI) P - value Adjusted Risk Ratio (95% CI) P - value Mean EtCO 2 Normal EtCO 2 619 363 (58.64%) 1 - 1 - Low EtCO 2 120 67 (55.83%) 0.95 (0.80–1.13) 0.577 0.96 (0.80–1.14) 0.658 Mean EtCO 2 <35 mmHg 120 67 (55.83%) 1.01 (0.82–1.24) 0.906 1.04 (0.85–1.28) 0.650 35–37 mmHg 171 101 (59.06%) 1.07 (0.89–1.27) 0.451 1.09 (0.92–1.30) 0.284 37–40 mmHg 254 155 (61.02%) 1.10 (0.94–1.29) 0.217 1.15 (0.98–1.34) 0.079 ≥40 mmHg 194 107 (55.15%) 1 - 1 - Minutes below EtCO 2 35 mmHg Quartile value 1 (0–11 min) 185 102 (55.14%) 1 - 1 - Quartile value 2 (12–25 min) 187 106 (56.68%) 1.02 (0.85–1.23) 0.764 1.04 (0.87–1.24) 0.653 Quartile value 3 (26–66 min) 181 110 (60.77%) 1.10 (0.92–1.31) 0.276 1.10 (0.93–1.30) 0.222 Quartile value 4 (67–613 min) 186 112 (60.22%) 1.09 (0.91–1.30) 0.323 1.03 (0.87–1.22) 0.700 Area under the threshold of EtCO 2 35 mmHg Quartile value 1 (0–7) 183 98 (53.55%) 1 - 1 - Quartile value 2 (8–36) 182 104 (57.14%) 1.03 (0.86–1.23) 0.744 1.01 (0.85–1.21) 0.825 Quartile value 3 (37–107) 186 113 (60.75%) 1.08 (0.91–1.29) 0.358 1.10 (0.93–1.30) 0.232 Quartile value 4 (108–2213) 188 115 (61.17%) 1.08 (0.91–1.29) 0.346 1.03 (0.87–1.23) 0.654 Abbreviations: EtCO 2 , end-tidal carbon dioxide; POD 2, postoperative day 2; PONV, postoperative nausea and vomiting; CI, confidence interval; MAP, mean arterial pressure; IVPCA, intravenous patient-controlled analgesia; BMI, body mass index; ASAPS, American Society of Anesthesiologists Physical Status. Table 3 . Multivariable analysis of the relationship between EtCO 2 and secondary outcomes Number of Events (%) Crude Risk Ratio (95% CI) P -value Adjusted Risk Ratio (95% CI) P - value POD2 : Postoperative nausea Normal EtCO 2 346/619 (55.90%) 1 - 1 - Low EtCO 2 66/120 (55.00%) 0.98 (0.82–1.17) 0.857 0.99 (0.82–1.18) 0.916 POD2 : Postoperative vomiting Normal EtCO 2 184/619 (29.73%) 1 - 1 - Low EtCO 2 37/120 (30.83%) 1.03 (0.77–1.39) 0.807 1.17 (0.88–1.55) 0.264 POD 3 –7 : PONV Normal EtCO 2 383/619 (61.87%) 1 - 1 - Low EtCO 2 70/120 (58.33%) 0.94 (0.80–1.11) 0.480 0.95 (0.81–1.12) 0.583 Abbreviations: EtCO 2 , end-tidal carbon dioxide; POD 2, postoperative day 2; POD 3–7, postoperative days 3 to 7; PONV, postoperative nausea and vomiting; CI, confidence interval; MAP, mean arterial pressure; IVPCA, intravenous patient-controlled analgesia; BMI, body mass index; ASAPS, American Society of Anesthesiologists Physical Status. Table 4 . Multivariable analysis of the relationship between EtCO 2 and PLOS Median (IQR) P value Crude difference in PLOS (95% CI) P-value Adjusted difference in PLOS (95% CI) P - value Length of stay(day) Normal EtCO 2 6 (5–8) 0.782 1 - 1 - Low EtCO 2 6 (5–7) −0.15 (−1.29 to 0.97) 0.783 0.13 (−1.00 to 1.28) 0.816 Abbreviations: EtCO 2 , end-tidal carbon dioxide; PLOS, postoperative length of stay; IQR, interquartile range; CI, confidence interval; MAP, mean arterial pressure; IVPCA, intravenous patient-controlled analgesia; BMI, body mass index; ASAPS, American Society of Anesthesiologists Physical Status. Table 5. Subgroup analyses stratified by patient and operative variable N POD2-PONV Crude risk ratio (95% CI) of low EtCO 2 P - value P for interaction Overall 739 430 (58.19%) 0.95 (0.80–1.13) 0.577 Age(year) 0.837 <50 454 246 (54.19%) 0.96 (0.76–1.20) 0.725 ≥50 285 184 (64.56%) 0.91 (0.70–1.18) 0.486 Malignancy 0.594 Yes 205 135 (65.85%) 0.90 (0.64–1.26) 0.540 No 534 295 (55.24%) 0.98 (0.80–1.20) 0.913 Smoking history 0.640 Ever 172 92 (53.49%) 1.02 (0.72–1.45) 0.892 Never 567 338 (59.61%) 0.93 (0.76–1.14) 0.511 Duration of surgery (h) 0.491 ≥4 238 148 (62.18%) 0.87 (0.61–1.23) 0.442 <4 501 282 (56.29%) 0.99 (0.51–1.21) 0.959 TIVA 0.274 Yes 604 369 (61.09%) 0.91 (0.76–1.10) 0.376 No 135 61 (45.19%) 1.19 (0.77–1.83) 0.428 Intraoperative antiemetics 0.990 Yes 284 168 (59.15%) 0.95 (0.70–1.28) 0.757 No 455 262 (57.58%) 0.95 (0.77–1.17) 0.666 Abbreviations: POD 2, postoperative day 2; PONV, postoperative nausea and vomiting; CI, confidence interval; TIVA, total intravenous anesthesia. Additional Declarations No competing interests reported. Supplementary Files PONVSupplementaldata0131.pdf Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 28 Feb, 2022 Reviews received at journal 12 Feb, 2022 Reviewers agreed at journal 03 Feb, 2022 Reviewers invited by journal 03 Feb, 2022 Editor assigned by journal 03 Feb, 2022 Editor invited by journal 02 Feb, 2022 Submission checks completed at journal 02 Feb, 2022 First submitted to journal 30 Jan, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies 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-1313239","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":80925715,"identity":"2ba68f45-6c89-4f7a-a747-62814a907314","order_by":0,"name":"Li Dong","email":"","orcid":"","institution":"Kyoto University Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Dong","suffix":""},{"id":80925716,"identity":"abf5ad1d-c2d6-4024-9122-b69702e8dfb0","order_by":1,"name":"Chikashi Takeda","email":"","orcid":"","institution":"Kyoto University Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Chikashi","middleName":"","lastName":"Takeda","suffix":""},{"id":80925717,"identity":"e73eb474-5fd5-4110-9845-cd8f83ee4212","order_by":2,"name":"Hajime Yamazaki","email":"","orcid":"","institution":"Kyoto University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hajime","middleName":"","lastName":"Yamazaki","suffix":""},{"id":80925718,"identity":"9e42f83f-be39-4863-9dda-0d492e147d4a","order_by":3,"name":"Miho Hamada","email":"","orcid":"","institution":"Kyoto University Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Miho","middleName":"","lastName":"Hamada","suffix":""},{"id":80925719,"identity":"8b2152bb-2beb-4cdc-9e89-8c5e49fc48ff","order_by":4,"name":"Akiko Hirotsu","email":"","orcid":"","institution":"Kyoto University Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Akiko","middleName":"","lastName":"Hirotsu","suffix":""},{"id":80925720,"identity":"d0904a2e-be54-498b-8911-f68b9016f15c","order_by":5,"name":"Yosuke Yamamoto","email":"","orcid":"","institution":"Kyoto University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yosuke","middleName":"","lastName":"Yamamoto","suffix":""},{"id":80925721,"identity":"578a3ff0-5472-4c00-a6ff-70b5a03827f0","order_by":6,"name":"Toshiyuki Mizota","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAklEQVRIie3Qv0oDMRzA8V8IpMvJrTnwFYSfFE6E0GcpHNyk4iQOh2RKl9rZPsa9we84OCev68EJGlw7OImDiuUUWyipHQvNdwgJ4UP+APh8uxjvRoUgAZhe23ARgvSPyP8JdKRcJ86ORj378prN+tjeEpsadRNCgPCeQe/EQeISEqSqjfGxHrLcpDLSAbJxBfxUO0klSbQKmzNk1pQSn+YIBxo4koswI+mrXiG0OOVzI+FCFobijuS/hG8+RXB8mCT9qLkYFnd1Gk21uCwPK+l+y+zePl+/DY4nzXlhx1cqDIHndp6pxPVjKwVATPxMF1eSCW5DAD6Wy8EWxOfz+fajb8L1WckT2CWBAAAAAElFTkSuQmCC","orcid":"","institution":"Kyoto University Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Toshiyuki","middleName":"","lastName":"Mizota","suffix":""}],"badges":[],"createdAt":"2022-01-31 04:59:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1313239/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1313239/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":17920942,"identity":"7407845a-8a02-444f-9b98-36f007d88308","added_by":"auto","created_at":"2022-02-03 21:17:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":70623,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of this study\u003c/p\u003e\u003cp\u003eWe consecutively included patients aged 18 years or older who underwent laparoscopic gynecologic surgery under general anesthesia at Kyoto University Hospital from 2012 to 2017. Subsequently, cases that met the eligibility criteria were selected and analyzed as complete cases.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-1313239/v1/64acc3d3981403bcf0c86eb0.png"},{"id":17920944,"identity":"0a097363-48ac-44a2-b353-4cc7386070e3","added_by":"auto","created_at":"2022-02-03 21:17:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":568432,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1313239/v1/5f8cd8b0-b8b9-4be4-9964-8db5c4ad4363.pdf"},{"id":17920943,"identity":"3f711743-8b30-4569-8e2d-20fa3a1c912b","added_by":"auto","created_at":"2022-02-03 21:17:51","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":94045,"visible":true,"origin":"","legend":"","description":"","filename":"PONVSupplementaldata0131.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1313239/v1/53017c7857e7a82ebaa5ed1f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association between Intraoperative End-Tidal Carbon Dioxide and Postoperative Nausea and Vomiting in Gynecologic Laparoscopic Surgery","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe incidence of postoperative nausea and vomiting (PONV) remains high despite considerable improvements in treatment over the past few decades. PONV is nausea or vomiting in the first 24 to 48 h after surgery\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Well-established risk factors for PONV include female gender, history of PONV or motion sickness, nonsmoking, and postoperative opioid use\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. The risk of PONV is up to 80% in high-risk patients with all four risk factors\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. The incidence of PONV is particularly high among patients undergoing gynecologic laparoscopic surgery\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. PONV is associated with decreased patient satisfaction\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e, increased postoperative complications\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e, and longer postoperative length of hospital stay (PLOS)\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eHypocapnia may be associated with decreased systemic vasodilation\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e and may cause tissue ischemia\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e, intestinal ischemia\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e, and cerebral ischemia\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Animal studies have reported that serotonin levels in the brain, a highly emetogenic substance, increase with intestinal \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e and cerebral ischemia\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Based on the hypothesis associating hypocapnia with increased serotonin levels due to intestinal and cerebral ischemia, studies associate intraoperative hypocapnia with increased incidence of PONV\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. However, the relationship between hypocapnia and PONV remains unclear because some studies had conflicting results\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTherefore, we examined the association between intraoperative end-tidal carbon dioxide (EtCO\u003csub\u003e2\u003c/sub\u003e) and the incidence of PONV in patients undergoing gynecologic laparoscopic surgery. We adjusted for important confounding factors and assessed the effects of the duration and severity of low EtCO\u003csub\u003e2\u003c/sub\u003e exposure.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eEthics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe\u0026nbsp;Certified Review Board\u0026nbsp;of Kyoto University, Kyoto, Japan (Chairperson Prof.\u0026nbsp;Shinji Kosugi) approved the protocol for this study (approval no.: R1272-3, January 23, 2020).\u0026nbsp;Additionally, the informed consent\u0026nbsp;requirement\u0026nbsp;was waived\u0026nbsp;due to this study\u0026rsquo;s\u0026nbsp;retrospective nature.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy design, setting, and population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this single-center\u0026nbsp;retrospective cohort study, we used data from the Kyoto University Hospital IMProve Anaesthesia Care and ouTcomes (Kyoto-IMPACT) database. The Kyoto-IMPACT database aims to clarify the relationship between intraoperative respiratory and cardiovascular parameters and\u0026nbsp;postoperative\u0026nbsp;outcomes. We consecutively selected patients who\u0026nbsp;underwent\u0026nbsp;surgery under the care of\u0026nbsp;anesthesiologists\u0026nbsp;at Kyoto University Hospital (1,121\u0026nbsp;beds). We have published several\u0026nbsp;studies\u0026nbsp;using the Kyoto-IMPACT database\u003csup\u003e20\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e21\u003c/sup\u003e.\u0026nbsp;We included adult female patients aged 18 years or older who underwent\u0026nbsp;gynecologic\u0026nbsp;laparoscopic surgery (i.e.,\u0026nbsp;adnexal surgery and/or hysterectomy) at Kyoto University Hospital between January 2012 and December 2017. The\u0026nbsp;gynecologic\u0026nbsp;laparoscopic surgery population was\u0026nbsp;selected\u0026nbsp;because\u0026nbsp;the\u0026nbsp;predicted incidence rate of\u0026nbsp;PONV in this population is\u0026nbsp;30%\u0026ndash;40%,\u0026nbsp;assumed\u0026nbsp;to be a\u0026nbsp;medium risk of PONV\u003csup\u003e4\u003c/sup\u003e.\u0026nbsp;The exclusion\u0026nbsp;criteria were\u0026nbsp;as follows: 1)\u0026nbsp;patients with\u0026nbsp;postoperative\u0026nbsp;intensive care unit\u0026nbsp;admission; 2)\u0026nbsp;those who underwent\u0026nbsp;multiple surgeries within\u0026nbsp;one\u0026nbsp;week during the study period; 3)\u0026nbsp;those who received\u0026nbsp;epidural\u0026nbsp;anesthesia; 4)\u0026nbsp;those with\u0026nbsp;missing smoking data, and 5)\u0026nbsp;those with\u0026nbsp;missing intraoperative EtCO\u003csub\u003e2\u003c/sub\u003e data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ecollection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe collected data from the\u0026nbsp;anesthesia\u0026nbsp;information management and electronic medical record\u0026nbsp;systems\u0026nbsp;and constructed the Kyoto-IMPACT database. EtCO\u003csub\u003e2\u003c/sub\u003e was continuously measured using a sidestream gas\u0026nbsp;analyzer\u0026nbsp;(GF-220R Multigas/Flow Unit, Nihon Kohden\u0026reg;, Japan) that was automatically uploaded to the\u0026nbsp;anesthesia\u0026nbsp;information management system every 60\u0026nbsp;s. Intraoperative EtCO\u003csub\u003e2\u003c/sub\u003e was the mean EtCO\u003csub\u003e2\u003c/sub\u003e level from skin incision to skin closure. We removed EtCO\u003csub\u003e2\u003c/sub\u003e levels\u0026nbsp;lower\u0026nbsp;than 20 mmHg as artifacts (EtCO\u003csub\u003e2\u003c/sub\u003e during aspiration or position change).\u0026nbsp;The definitions\u0026nbsp;of variables, including\u0026nbsp;the\u0026nbsp;minimum and maximum EtCO\u003csub\u003e2\u003c/sub\u003e levels, can be found in Supplementary Data Table S1. We collected data\u0026nbsp;on\u0026nbsp;PONV by reviewing all clinical data contained in the electronic medical\u0026nbsp;records. Ward nurses assessed the\u0026nbsp;presence of nausea and vomiting at least twice daily. We defined PONV as one or more episodes of nausea or vomiting during the first two\u0026nbsp;days\u0026nbsp;after surgery and vomiting as one or more episodes of vomiting during the same period.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExposure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo determine how EtCO\u003csub\u003e2\u003c/sub\u003e affects PONV, we defined exposure by calculating the dose, time, and cumulative effects of EtCO\u003csub\u003e2\u003c/sub\u003e.\u0026nbsp;First, we\u0026nbsp;evaluated\u0026nbsp;the\u0026nbsp;dose effects\u0026nbsp;of EtCO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003eusing the mean EtCO\u003csub\u003e2\u003c/sub\u003e.\u0026nbsp;Next, we\u0026nbsp;divided\u0026nbsp;the\u0026nbsp;patients into two groups based on the\u0026nbsp;cutoff EtCO\u003csub\u003e2\u003c/sub\u003elevel of 35 mmHg proposed by Way and Hill\u003csup\u003e22\u003c/sup\u003e. We defined low EtCO\u003csub\u003e2\u003c/sub\u003e as a mean EtCO\u003csub\u003e2\u003c/sub\u003e lower than\u0026nbsp;35 mmHg and normal EtCO\u003csub\u003e2\u003c/sub\u003e as\u0026nbsp;a mean EtCO\u003csub\u003e2\u003c/sub\u003e greater than or equal to\u0026nbsp;35 mmHg. We classified\u0026nbsp;the\u0026nbsp;patients in either of these groups and used them as the primary exposure for further analysis.\u0026nbsp;Additionally, we categorized\u0026nbsp;the\u0026nbsp;mean EtCO\u003csub\u003e2\u003c/sub\u003e levels\u0026nbsp;into quartiles (i.e., \u0026lt;35, 35\u0026ndash;37, 37\u0026ndash;40, and \u0026ge;40 mmHg)\u0026nbsp;because the relationship between EtCO\u003csub\u003e2\u003c/sub\u003e and PONV\u0026nbsp;might\u0026nbsp;not be linear. To assess the\u0026nbsp;effects\u0026nbsp;of\u0026nbsp;the\u0026nbsp;duration and severity of low EtCO\u003csub\u003e2\u003c/sub\u003e exposure, we determined the time effect based on the minutes\u0026nbsp;when the\u0026nbsp;EtCO\u003csub\u003e2\u003c/sub\u003e level was below\u0026nbsp;35 mmHg and\u0026nbsp;measured\u0026nbsp;the cumulative effect\u0026nbsp;as\u0026nbsp;the area with EtCO\u003csub\u003e2\u003c/sub\u003e levels\u0026nbsp;below the threshold of 35 mmHg for each patient. Furthermore,\u0026nbsp;we categorized\u0026nbsp;the minutes and area under the threshold of an EtCO\u003csub\u003e2\u003c/sub\u003e level\u0026nbsp;of 35 mmHg into quartiles; the lowest quartile was\u0026nbsp;the reference category.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary\u0026nbsp;outcome\u0026nbsp;in this study\u0026nbsp;was PONV, defined as PONV for\u0026nbsp;two\u0026nbsp;days\u0026nbsp;postoperatively. The secondary\u0026nbsp;outcomes were nausea for\u0026nbsp;two\u0026nbsp;days\u0026nbsp;postoperatively, vomiting for\u0026nbsp;two\u0026nbsp;days\u0026nbsp;postoperatively, PONV for 3\u0026ndash;7 days\u0026nbsp;postoperatively, and PLOS. We defined PLOS as the duration of hospital\u0026nbsp;stay\u0026nbsp;after surgery for patients who survived\u0026nbsp;until\u0026nbsp;discharge.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe analyzed\u0026nbsp;the relationship between intraoperative EtCO\u003csub\u003e2\u003c/sub\u003e and PONV before data collection.\u0026nbsp;We used the\u0026nbsp;Mann\u0026ndash;Whitney test for group comparisons,\u0026nbsp;and\u0026nbsp;continuous variables\u0026nbsp;were expressed as the\u0026nbsp;median and interquartile range (IQR), and categorical variables were expressed as counts and percentages (%).\u003c/p\u003e\n\u003cp\u003eFirst,\u0026nbsp;we performed\u0026nbsp;modified\u0026nbsp;Poisson\u0026nbsp;regression analysis with robust variance to calculate the risk ratio for low EtCO\u003csub\u003e2\u003c/sub\u003e (mean EtCO\u003csub\u003e2\u003c/sub\u003e of less than\u0026nbsp;35 mmHg) and PONV, with the reference category of normal EtCO\u003csub\u003e2\u003c/sub\u003e (mean EtCO\u003csub\u003e2\u003c/sub\u003e \u0026ge; 35 mmHg)\u003csup\u003e23\u003c/sup\u003e.\u0026nbsp;Additionally, we calculated\u0026nbsp;the risk ratios of\u0026nbsp;the\u0026nbsp;mean EtCO\u003csub\u003e2\u003c/sub\u003e level\u0026nbsp;in the first quartile (mean EtCO\u003csub\u003e2\u003c/sub\u003e of less than\u0026nbsp;35 mmHg), third quartile (mean EtCO\u003csub\u003e2\u003c/sub\u003e of\u0026nbsp;37\u0026ndash;40\u0026nbsp;mmHg), and fourth quartile (mean EtCO\u003csub\u003e2\u003c/sub\u003e of more than or equal to\u0026nbsp;40 mmHg). The\u0026nbsp;second quartile (mean EtCO\u003csub\u003e2\u003c/sub\u003e of\u0026nbsp;35\u0026ndash;37 mmHg) was the reference category\u0026nbsp;because it\u0026nbsp;was\u0026nbsp;considered normocapnia. Furthermore, we examined the time and cumulative effects\u0026nbsp;of EtCO\u003csub\u003e2\u003c/sub\u003e by evaluating how each quartile affected PONV, with the first quartile\u0026nbsp;(with minutes under an EtCO\u003csub\u003e2\u003c/sub\u003e of 35 mmHg and the area below the threshold of 35 mmHg) being the reference category. We\u0026nbsp;created\u0026nbsp;a model\u0026nbsp;using the covariates previously used to demonstrate the relationship between intraoperative EtCO\u003csub\u003e2\u003c/sub\u003e and PONV. The model included age, smoking history,\u0026nbsp;surgery\u0026nbsp;duration, body mass index (BMI), total intravenous\u0026nbsp;anesthesia\u0026nbsp;(TIVA), mean arterial pressure (MAP), intraoperative fentanyl use,\u0026nbsp;postoperative\u0026nbsp;fentanyl dose for intravenous patient-controlled analgesia\u0026nbsp;(IVPCA),\u0026nbsp;the\u0026nbsp;use of prophylactic antiemetics, the addition of droperidol to\u0026nbsp;postoperative\u0026nbsp;IVPCA, American Society of\u0026nbsp;Anesthesiologists\u0026nbsp;Physical Status (ASAPS), malignancy, and emergency surgery.\u0026nbsp;Additionally, a modified\u0026nbsp;Poisson\u0026nbsp;regression model\u0026nbsp;investigated\u0026nbsp;whether the dose, time, or cumulative\u0026nbsp;effect\u0026nbsp;of EtCO\u003csub\u003e2\u003c/sub\u003e affects\u0026nbsp;postoperative\u0026nbsp;nausea\u0026nbsp;two\u0026nbsp;days, vomiting\u0026nbsp;two\u0026nbsp;days, and PONV 3\u0026ndash;7 days\u0026nbsp;postoperatively, adjusting for the\u0026nbsp;aforementioned\u0026nbsp;models. To further evaluate the relationship between EtCO\u003csub\u003e2\u003c/sub\u003e and PLOS, we performed a linear regression analysis adjusting for the possible covariates in the\u0026nbsp;aforementioned\u0026nbsp;models.\u003c/p\u003e\n\u003cp\u003eThe relationship between intraoperative EtCO\u003csub\u003e2\u003c/sub\u003e and PONV may\u0026nbsp;depend\u0026nbsp;on patient and surgical characteristics. Therefore,\u0026nbsp;we performed a\u0026nbsp;subgroup analysis to assess this potential heterogeneity.\u0026nbsp;We used\u0026nbsp;the modified\u0026nbsp;Poisson\u0026nbsp;regression model for the following subgroups: (i) age (\u0026ge;50/\u0026lt;50 years), (ii) malignancy (yes/no), (iii) smoking history (ever smoked/never smoked), (iv) duration of surgery (\u0026ge;4/\u0026lt;4 hours), (v) TIVA (yes/no), and (vi)\u0026nbsp;the\u0026nbsp;use of intraoperative prophylactic antiemetics\u0026nbsp;(yes/no).\u0026nbsp;We calculated the crude\u0026nbsp;risk ratio of PONV in each subgroup and\u0026nbsp;examined\u0026nbsp;the interaction between subgroups and intraoperative EtCO\u003csub\u003e2\u003c/sub\u003e.\u003c/p\u003e\n\u003cp\u003eTo maximize statistical power, all eligible patients enrolled in the Kyoto-IMPACT database since 2012, when\u0026nbsp;postoperative\u0026nbsp;nausea and vomiting began to be recorded in their current form, were included in the analysis. To determine the study power, we estimated that approximately 120 laparoscopic\u0026nbsp;gynecologic\u0026nbsp;surgeries were performed annually at Kyoto University Hospital, with 720 surgeries performed over\u0026nbsp;six\u0026nbsp;years. The risk ratio was 1.53, the incidence of PONV was 40%\u003csup\u003e4\u003c/sup\u003e, and the proportion of low EtCO\u003csub\u003e2\u003c/sub\u003e was 50%\u003csup\u003e24\u003c/sup\u003e, giving an estimated power of 80%. The rate of missing data was 0.04%, so we conducted a complete case analysis. All statistical tests were two-tailed. We used Stata/SE 15.1 (StataCorp LLC, College Station, Texas, USA) to conduct all statistical analyses.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eBaseline patient characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOf the 790 patients who underwent laparoscopic\u0026nbsp;gynecologic\u0026nbsp;surgery between 2008 and 2017, 774 met our inclusion criteria, and\u0026nbsp;we\u0026nbsp;included\u0026nbsp;739 in the\u0026nbsp;complete case analysis (Figure\u0026nbsp;1). Low EtCO\u003csub\u003e2\u003c/sub\u003e (defined as\u0026nbsp;the\u0026nbsp;mean EtCO\u003csub\u003e2\u003c/sub\u003e level of\u0026nbsp;less than 35 mmHg) occurred in 120 patients\u0026nbsp;(16%), whereas\u0026nbsp;PONV occurred in 430 patients\u0026nbsp;(58%).\u0026nbsp;Table 1 shows the overall baseline characteristics of the study participants. The median EtCO\u003csub\u003e2\u003c/sub\u003e values were 37 mmHg (IQR,\u0026nbsp;35\u0026ndash;40 mmHg) overall, 33 mmHg (IQR,\u0026nbsp;32\u0026ndash;34 mmHg) in patients with low EtCO\u003csub\u003e2\u003c/sub\u003e, and 38 mmHg (IQR,\u0026nbsp;36\u0026ndash;40mmHg) in patients with\u0026nbsp;normal\u0026nbsp;EtCO\u003csub\u003e2\u003c/sub\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssociation between\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003elow\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;EtCO\u003csub\u003e2\u003c/sub\u003e and PONV\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 2 shows the study\u0026rsquo;s\u0026nbsp;main results.\u0026nbsp;PONV occurred in\u0026nbsp;67 (55.83%)\u0026nbsp;of the\u0026nbsp;120 patients in the\u0026nbsp;low EtCO\u003csub\u003e2\u003c/sub\u003e group,\u0026nbsp;whereas 363 (58.64%)\u0026nbsp;of\u0026nbsp;the\u0026nbsp;619\u0026nbsp;patients were in\u0026nbsp;the normal EtCO\u003csub\u003e2\u003c/sub\u003e group. We could not find a substantial association between low EtCO\u003csub\u003e2\u003c/sub\u003e and PONV\u0026nbsp;(crude risk ratio,\u0026nbsp;0.95;\u0026nbsp;95% confidence interval\u0026nbsp;[CI],\u0026nbsp;0.80\u0026ndash;1.13; \u003cem\u003ep\u003c/em\u003e = 0.577) (adjusted risk ratio,\u0026nbsp;0.96;\u0026nbsp;95% CI, 0.80\u0026ndash;1.14; \u003cem\u003ep\u003c/em\u003e = 0.658).\u0026nbsp;For further analysis,\u0026nbsp;we\u0026nbsp;divided\u0026nbsp;EtCO\u003csub\u003e2\u003c/sub\u003e into quartiles. The\u0026nbsp;second quartile (mean EtCO\u003csub\u003e2\u003c/sub\u003e 35\u0026ndash;37 mmHg) was the reference,\u0026nbsp;and the\u0026nbsp;definition of\u0026nbsp;low EtCO\u003csub\u003e2\u003c/sub\u003e was\u0026nbsp;the lowest quartile of mean EtCO\u003csub\u003e2\u003c/sub\u003e (mean EtCO\u003csub\u003e2\u003c/sub\u003e of less than\u0026nbsp;35 mmHg). The second (mean EtCO\u003csub\u003e2\u003c/sub\u003e of\u0026nbsp;35\u0026ndash;37 mmHg), third (mean EtCO\u003csub\u003e2\u003c/sub\u003e 37\u0026ndash;40 mmHg), and fourth (mean EtCO\u003csub\u003e2\u003c/sub\u003e \u0026ge; 40 mmHg)\u0026nbsp;quartiles\u0026nbsp;of mean EtCO\u003csub\u003e2\u003c/sub\u003e values were not substantially associated with increased\u0026nbsp;incidence of\u0026nbsp;PONV, with low EtCO\u003csub\u003e2\u003c/sub\u003e (first quartile\u0026nbsp;[mean EtCO\u003csub\u003e2\u003c/sub\u003e of less than\u0026nbsp;35 mmHg])\u0026nbsp;as the reference category.\u003c/p\u003e\n\u003cp\u003eFor the time effects of EtCO\u003csub\u003e2\u003c/sub\u003e, compared with short-term exposure (first quartile of exposure time to EtCO\u003csub\u003e2\u003c/sub\u003e of less than\u0026nbsp;35 mmHg,\u0026nbsp;0\u0026ndash;11 min), long-term exposure to EtCO\u003csub\u003e2\u003c/sub\u003e levels\u0026nbsp;of less than\u0026nbsp;35 mmHg (fourth quartile of exposure time to EtCO\u003csub\u003e2\u003c/sub\u003e of less than\u0026nbsp;35 mmHg, 67\u0026ndash;613 min) was not substantially associated with increased\u0026nbsp;incidence of\u0026nbsp;PONV\u0026nbsp;(crude risk ratio,\u0026nbsp;1.09;\u0026nbsp;95% CI, 0.91\u0026ndash;1.30; \u003cem\u003ep\u003c/em\u003e = 0.323) (adjusted risk ratio,\u0026nbsp;1.03;\u0026nbsp;95% CI, 0.87\u0026ndash;1.22; \u003cem\u003ep\u003c/em\u003e = 0.700).\u003c/p\u003e\n\u003cp\u003eFinally, for the cumulative effects of EtCO\u003csub\u003e2\u003c/sub\u003e, the fourth quartile of\u0026nbsp;the\u0026nbsp;area under the EtCO\u003csub\u003e2\u003c/sub\u003e threshold of 35 mmHg (108\u0026ndash;2,213) was not substantially associated with increased\u0026nbsp;incidence of\u0026nbsp;PONV compared with the first quartile (0\u0026ndash;7)\u0026nbsp;(crude risk ratio,\u0026nbsp;1.08;\u0026nbsp;95% CI, 0.91\u0026ndash;1.29; \u003cem\u003ep\u003c/em\u003e = 0.346) (adjusted risk ratio,\u0026nbsp;1.03;\u0026nbsp;95% CI, 0.87\u0026ndash;1.23; \u003cem\u003ep\u003c/em\u003e = 0.654).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssociation between low EtCO\u003csub\u003e2\u003c/sub\u003e and nausea\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;and\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003evomiting\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;2 days postoperatively\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;and\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ePONV\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;3\u0026ndash;7 day\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003epostoperatively\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe adjusted risk ratio for the low EtCO\u003csub\u003e2\u003c/sub\u003e group (mean EtCO\u003csub\u003e2\u003c/sub\u003e of less than\u0026nbsp;35 mmHg)\u0026nbsp;did not\u0026nbsp;indicate\u0026nbsp;an association between low EtCO\u003csub\u003e2\u003c/sub\u003e and nausea\u0026nbsp;and\u0026nbsp;vomiting\u0026nbsp;two days postoperatively\u0026nbsp;or PONV\u0026nbsp;3\u0026ndash;7 days postoperatively\u0026nbsp;(Table 3), with\u0026nbsp;normal EtCO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003ebeing\u0026nbsp;the reference category.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssociation between low EtCO\u003csub\u003e2\u003c/sub\u003e and PLOS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe median PLOS was\u0026nbsp;six days\u0026nbsp;(IQR, 5\u0026ndash;8 days)\u0026nbsp;(Table 4). The median PLOS in patients with low EtCO\u003csub\u003e2\u003c/sub\u003e was not different from\u0026nbsp;that in patients with\u0026nbsp;normal EtCO\u003csub\u003e2\u003c/sub\u003e (6\u0026nbsp;days [IQR, 5\u0026ndash;8 days]\u0026nbsp;vs. 6\u0026nbsp;days\u0026nbsp;(IQR, 5\u0026ndash;7 days); \u003cem\u003ep\u003c/em\u003e = 0.782).\u0026nbsp;Linear regression analysis showed that low EtCO\u003csub\u003e2\u003c/sub\u003e was not likely to be associated with PLOS\u0026nbsp;(crude adjusted difference in PLOS\u0026nbsp;, \u0026minus;0.15;\u0026nbsp;95% CI,\u0026nbsp;\u0026minus;1.29\u0026nbsp;to\u0026nbsp;0.97; \u003cem\u003ep\u0026nbsp;\u003c/em\u003e=\u0026nbsp;0.783) (adjusted difference in PLOS, \u0026minus;0.13;\u0026nbsp;95% CI,\u0026nbsp;\u0026minus;1.00\u0026nbsp;to\u0026nbsp;1.28; \u003cem\u003ep\u0026nbsp;\u003c/em\u003e=\u0026nbsp;0.816).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSubgroup analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSubgroup analyses included age (\u0026ge;50/\u0026lt;50 years), malignancy, smoking history, duration of surgery (\u0026ge;4 hours/\u0026lt;4 hours), TIVA, and the use of intraoperative prophylactic antiemetics. There was no interaction between these variables and PONV (Table 5).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this retrospective cohort study, intraoperative EtCO\u003csub\u003e2\u003c/sub\u003e was not substantially associated with increased incidence of PONV and prolonged PLOS in patients undergoing gynecologic laparoscopic surgery. Furthermore, we examined the effects of the duration and severity of low EtCO\u003csub\u003e2\u003c/sub\u003e exposure using the time and cumulative effects of EtCO\u003csub\u003e2\u003c/sub\u003e but found no clear association.\u003c/p\u003e \u003cp\u003eTwo small studies have studied whether there is an association between low EtCO\u003csub\u003e2\u003c/sub\u003e and PONV\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e, but the results have been inconsistent. A randomized controlled trial (RCT) involving 75 patients who underwent percutaneous nephrolithotripsy reported that the hypercapnia management group had less PONV\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. However, a prospective observational study involving 90 pediatric patients who underwent inguinal surgery has reported that elevated levels of EtCO\u003csub\u003e2\u003c/sub\u003e were an independent predictor of PONV\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. As the aforementioned studies have different types of surgery and patient backgrounds, their results might not be directly applicable to patients undergoing gynecologic laparoscopic surgery.\u003c/p\u003e \u003cp\u003eFurthermore, three studies on patients who had undergone gynecologic surgery have shown inconsistent results. An RCT involving 387 patients who underwent gynecologic laparoscopic surgery reported mild hypercapnia management did not reduce PONV\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. That study did not evaluate the effects of low EtCO\u003csub\u003e2\u003c/sub\u003e (mean EtCO\u003csub\u003e2\u003c/sub\u003e level of less than 35 mmHg). Alternatively, a retrospective cohort study involving 146 patients undergoing open gynecologic surgery has reported that the minimum EtCO\u003csub\u003e2\u003c/sub\u003e level of \u0026le;31 mmHg lasting longer than 10 min was associated with an increased incidence of PONV\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Still, that study only evaluated the effects of extremely low EtCO2 levels (mean EtCO2 of \u0026le;31 mmHg). It did not evaluate the dose and time effects of low EtCO2 below the commonly defined EtCO\u003csub\u003e2\u003c/sub\u003e level of 35 mmHg. Furthermore, an RCT involving 60 patients undergoing gynecologic laparoscopic surgery reported that low EtCO\u003csub\u003e2\u003c/sub\u003e management reduced the incidence of nausea, PONV score, and the use of rescue antiemetics\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e; these results differed from the two aforementioned studies. Management to keep EtCO2 at a low level may avoid PONV by inhibiting cerebral vasodilation, preventing increased intracranial pressure caused by the pneumoperitoneum and Trendelenburg position, which would not affect the ischemia-sensitive vestibular system. However, this study may have an internal validity problem in which it was not blinded. Furthermore, it had a generalizability problem because it excluded patients with severe systemic diseases, ASAPS-III patients, those with a history of PONV motion sickness, and smokers.\u003c/p\u003e \u003cp\u003eConsidering that the results of previous studies are inconsistent, the evidence on the association between intraoperative low EtCO\u003csub\u003e2\u003c/sub\u003e and PONV remains limited. Therefore, we conducted this study, which involved the largest cohort from real-world data, which provided a sufficient sample size, resulting in a statistical power of 80% to detect a risk ratio of 1.53. Furthermore, adjusting for important confounders, such as blood pressure, age, and intraoperative fentanyl use, and assessing the dose-effect of low EtCO\u003csub\u003e2\u003c/sub\u003e (mean EtCO\u003csub\u003e2\u003c/sub\u003e of less than 35 mmHg) and the effects of the duration and severity of low EtCO\u003csub\u003e2\u003c/sub\u003e exposure, we could not demonstrate an association between low EtCO\u003csub\u003e2\u003c/sub\u003e and PONV. Even extremely low EtCO\u003csub\u003e2\u003c/sub\u003e, defined as EtCO\u003csub\u003e2\u003c/sub\u003e of less than 31 mmHg sustained for more than 10 minutes\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e, failed to show an association with PONV (Supplemental Data Table S2).\u003c/p\u003e \u003cp\u003eThis study has several strengths. First, it investigated the association between the effects of EtCO\u003csub\u003e2\u003c/sub\u003e and PONV and PLOS, the dose effects of EtCO\u003csub\u003e2\u003c/sub\u003e (mean level of less than 35 mmHg) and the effects of the duration (time effects, long-term exposure to EtCO\u003csub\u003e2\u003c/sub\u003e of less than 35 mmHg) and severity (cumulative effects, area under the threshold of EtCO\u003csub\u003e2\u003c/sub\u003e of less than 35 mmHg). Among the three previous studies that examined the association between intraoperative low EtCO\u003csub\u003e2\u003c/sub\u003e and PONV, which only evaluated the dose effects \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e, only one study evaluated the association between the time effects of low EtCO\u003csub\u003e2\u003c/sub\u003e and PONV\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Second, this study adjusted for potential confounding factors that were not adjusted in previous studies, such as blood pressure, age, and intraoperative fentanyl use, using a modified Poisson regression model. Third, this was a large study with sufficient sample size. All previous studies had small sample sizes, so the number of confounding factors that can be adjusted is limited.\u003c/p\u003e \u003cp\u003eThis study has several limitations. First, we extracted information on the presence of nausea and vomiting from the records of assessments performed by the ward nurses at least twice a day, so PONV occurring at other times may have been overlooked. However, we thought that moderate to severe PONV reported voluntarily by patients or required treatment was fully measured. Second, we did not consider the PaCO\u003csub\u003e2\u003c/sub\u003e\u0026ndash;EtCO\u003csub\u003e2\u003c/sub\u003e gap to calibrate EtCO\u003csub\u003e2\u003c/sub\u003e levels using PaCO\u003csub\u003e2\u003c/sub\u003e levels. Thus, we underestimated the effects of low EtCO\u003csub\u003e2\u003c/sub\u003e and overestimated the effects of hypercapnia. However, since PaCO\u003csub\u003e2\u003c/sub\u003e is usually 2\u0026ndash;5 mmHg higher than EtCO\u003csub\u003e2\u003c/sub\u003e in healthy populations, this was considered a limited effect. Last, there may be unknown and unmeasured confounding factors, such as potential reasons for anesthesiologists to target a specific EtCO\u003csub\u003e2\u003c/sub\u003e level, missing data on intraoperative ventilation parameters, and PONV risk factors among patient factors is, history of PONV and motion sickness.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIntraoperative low EtCO\u003csub\u003e2\u003c/sub\u003e (less than 35 mmHg) was not substantially associated with either increased incidence of PONV or prolonged PLOS in patients undergoing gynecologic laparoscopic surgery.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssistance with the study\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe are grateful to Mr. Yoshihiro Kinoshita, Ms. Tomoko Hosoya, and Mr. Yohei Taniguchi (Medical Information Systems Section, Management Division, Kyoto University Hospital, Kyoto, Japan) for their assistance in data collection for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinancial support and sponsorship\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported in part by the Japan Society for the Promotion of Science KAKENHI program (grant number: 20K09242, principal investigator: Toshiyuki Mizota) and the 2019 Kyoto University ISHIZUE Research Development Program (principal investigator: Toshiyuki Mizota).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no\u0026nbsp;conflicts\u0026nbsp;of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.\u0026nbsp;The\u0026nbsp;Certified Review Board\u0026nbsp;of Kyoto University, Kyoto, Japan (Chairperson Prof.\u0026nbsp;Shinji Kosugi) approved the protocol for this study (approval no.: R1272-3, January 23, 2020).\u0026nbsp;Additionally, the informed consent\u0026nbsp;requirement\u0026nbsp;was waived\u0026nbsp;due to this study\u0026rsquo;s\u0026nbsp;retrospective nature.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthorship clarified\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: Li Dong\u003c/p\u003e\n\u003cp\u003eMethodology: Li Dong, Toshiyuki Mizota, Yosuke Yamamoto, Chikashi Takeda, Hajime Yamazaki, Miho Hamada, Akiko Hirotsu\u003c/p\u003e\n\u003cp\u003eFormal analysis and investigation: Li Dong, Chikashi Takeda, Hajime Yamazaki, Miho Hamada, Akiko Hirotsu, Yosuke Yamamoto, Toshiyuki Mizota\u003c/p\u003e\n\u003cp\u003eWriting - original draft preparation: Li Dong\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWriting - review and editing: Li Dong, Chikashi Takeda, Hajime Yamazaki, Miho Hamada, Akiko Hirotsu, Yosuke Yamamoto, Toshiyuki Mizota\u003c/p\u003e\n\u003cp\u003eEditing and approval of the manuscript: Li Dong, Chikashi Takeda, Hajime Yamazaki, Miho Hamada, Akiko Hirotsu, Yosuke Yamamoto, Toshiyuki Mizota\u003c/p\u003e\n\u003cp\u003eFunding acquisition: Toshiyuki Mizota\u003c/p\u003e\n\u003cp\u003eResources: Li Dong,Toshiyuki Mizota\u003c/p\u003e\n\u003cp\u003eSupervision: Toshiyuki Mizota\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ePierre, S. \u0026amp; Whelan, R. 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Splanchnic hemodynamics and gut mucosal-arterial PCO(2) gradient during systemic hypocapnia. \u003cem\u003eJ Appl Physiol (1985)\u003c/em\u003e \u003cstrong\u003e87\u003c/strong\u003e, 1102-1106, doi:10.1152/jappl.1999.87.3.1102 (1999).\u003c/li\u003e\n\u003cli\u003eBurykh, E. A. Interaction of hypocapnia, hypoxia, brain blood flow, and brain electrical activity in voluntary hyperventilation in humans. \u003cem\u003eNeurosci Behav Physiol\u003c/em\u003e \u003cstrong\u003e38\u003c/strong\u003e, 647-659, doi:10.1007/s11055-008-9029-y (2008).\u003c/li\u003e\n\u003cli\u003eTakahashi, C. E.\u003cem\u003e et al.\u003c/em\u003e Association of intraprocedural blood pressure and end tidal carbon dioxide with outcome after acute stroke intervention. \u003cem\u003eNeurocrit Care\u003c/em\u003e \u003cstrong\u003e20\u003c/strong\u003e, 202-208, doi:10.1007/s12028-013-9921-3 (2014).\u003c/li\u003e\n\u003cli\u003eYuzo Teramoto, T. U., Nobuo Nagai, Yumiko Takada, Kazuyuki Ikeda, Akikazu Takada. 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The association of intraoperative end-tidal carbon dioxide with the risk of postoperative nausea and vomiting. \u003cem\u003eJ Anesth\u003c/em\u003e \u003cstrong\u003e34\u003c/strong\u003e, 195-201, doi:10.1007/s00540-019-02715-4 (2020).\u003c/li\u003e\n\u003cli\u003eSaghaei, M., Matin, G. \u0026amp; Golparvar, M. Effects of intra-operative end-tidal carbon dioxide levels on the rates of post-operative complications in adults undergoing general anesthesia for percutaneous nephrolithotomy: A clinical trial. \u003cem\u003eAdvanced biomedical research\u003c/em\u003e \u003cstrong\u003e3\u003c/strong\u003e, 84, doi:10.4103/2277-9175.127997 (2014).\u003c/li\u003e\n\u003cli\u003eAltay, N., Yal\u0026ccedil;ın, S., Aydoğan, H., K\u0026uuml;\u0026ccedil;\u0026uuml;k, A. \u0026amp; Y\u0026uuml;ce, H. H. 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Intraoperative end-tidal carbon dioxide concentrations: what is the target? \u003cem\u003eAnesthesiol Res Pract\u003c/em\u003e \u003cstrong\u003e2011\u003c/strong\u003e, 271539, doi:10.1155/2011/271539 (2011).\u003c/li\u003e\n\u003cli\u003eZou, G. A modified poisson regression approach to prospective studies with binary data. \u003cem\u003eAm J Epidemiol\u003c/em\u003e \u003cstrong\u003e159\u003c/strong\u003e, 702-706, doi:10.1093/aje/kwh090 (2004).\u003c/li\u003e\n\u003cli\u003eAkkermans, A.\u003cem\u003e et al.\u003c/em\u003e An observational study of end-tidal carbon dioxide trends in general anesthesia. \u003cem\u003eCanadian journal of anaesthesia = Journal canadien d\u0026apos;anesthesie\u003c/em\u003e \u003cstrong\u003e66\u003c/strong\u003e, 149-160, doi:10.1007/s12630-018-1249-1 (2019).\u003c/li\u003e\n\u003cli\u003eBesir, A. \u0026amp; Tugcugil, E. Comparison of different end-tidal carbon dioxide levels in preventing postoperative nausea and vomiting in gynaecological patients undergoing laparoscopic surgery. \u003cem\u003eJournal of Obstetrics and Gynaecology\u003c/em\u003e, 1-8, doi:10.1080/01443615.2020.1789961 (2020).\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003ePatient characteristics (n = 739\u003cstrong\u003e)\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"40.86538461538461%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAll patients\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 739)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e\u003cstrong\u003eLow EtCO\u003csub\u003e2\u003c/sub\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 120)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNormal EtCO\u003csub\u003e2\u003c/sub\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 619)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"40.86538461538461%\"\u003e\n \u003cp\u003eAge, years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e45 (36\u0026ndash;56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e47 (34\u0026ndash;58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e44 (36\u0026ndash;55)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"40.86538461538461%\"\u003e\n \u003cp\u003eASA-PS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"40.86538461538461%\"\u003e\n \u003cp\u003e\u0026nbsp;I\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e402 (54.55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e60 (50.42%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e342 (55.34%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"40.86538461538461%\"\u003e\n \u003cp\u003e\u0026nbsp;II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e322 (43.69%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e58 (48.74%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e264 (42.72%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"40.86538461538461%\"\u003e\n \u003cp\u003e\u0026nbsp;III\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e13 (1.76%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e1 (0.84%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e12 (1.94%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"40.86538461538461%\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e21.28 (19.35\u0026ndash;23.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e21.73 (19.38\u0026ndash;24.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e21.16 (19.35\u0026ndash;23.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"40.86538461538461%\"\u003e\n \u003cp\u003eMalignant\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e205 (27.74%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e25 (20.83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e180 (29.08%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"40.86538461538461%\"\u003e\n \u003cp\u003eNever smoker\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e567 (76.73%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e87 (72.50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e480 (77.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"40.86538461538461%\"\u003e\n \u003cp\u003eEmergency surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e42 (5.70%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e6 (5.04%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e36 (5.83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"40.86538461538461%\"\u003e\n \u003cp\u003eDuration of surgery, minute\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e186 (125\u0026ndash;270)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e156 (110\u0026ndash;233)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e195 (129\u0026ndash;276)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"40.86538461538461%\"\u003e\n \u003cp\u003eBlood loss, ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e10 (0\u0026ndash;100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e0 (0\u0026ndash;75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e17 (0\u0026ndash;100)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"40.86538461538461%\"\u003e\n \u003cp\u003eTransfusion volume, ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"40.86538461538461%\"\u003e\n \u003cp\u003eInfusion volume, ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e1400 (1000\u0026ndash;2040)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e1265 (920\u0026ndash;1920)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e1450 (1000\u0026ndash;2060)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"40.86538461538461%\"\u003e\n \u003cp\u003eTIVA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e135 (18.27%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e25 (20.83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e110 (17.77%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"40.86538461538461%\"\u003e\n \u003cp\u003eMean MAP, mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e73 (68\u0026ndash;80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e73 (68\u0026ndash;81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e73 (68\u0026ndash;80)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"40.86538461538461%\"\u003e\n \u003cp\u003eIntraoperative antiemetics use\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e284 (38.43%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e37 (30.83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e247 (39.90%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"40.86538461538461%\"\u003e\n \u003cp\u003eAddition of droperidol in IVPCA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e321 (43.44%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e38 (31.67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e283 (45.72%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"40.86538461538461%\"\u003e\n \u003cp\u003eTotal intraoperative fentanyl dose (\u0026mu;g)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e200 (150\u0026ndash;250)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e200 (100\u0026ndash;250)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e200 (150\u0026ndash;250)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"40.86538461538461%\"\u003e\n \u003cp\u003ePostoperative fentanyl dose in IVPCA (\u0026mu;g/h)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e20 (0\u0026ndash;25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e20 (0\u0026ndash;25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e20 (0\u0026ndash;25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"40.86538461538461%\"\u003e\n \u003cp\u003eMean EtCO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e37 (35\u0026ndash;40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e33 (32\u0026ndash;34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e38 (36\u0026ndash;40)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"40.86538461538461%\"\u003e\n \u003cp\u003eMinimum EtCO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e31 (29\u0026ndash;33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e28 (26\u0026ndash;30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e32 (30\u0026ndash;34)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"40.86538461538461%\"\u003e\n \u003cp\u003eMaximum EtCO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e42 (40\u0026ndash;46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e37 (36\u0026ndash;39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.71153846153846%\"\u003e\n \u003cp\u003e43 (41\u0026ndash;47)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eValues are given as median (interquartile range) or count (%).\u003c/p\u003e\n\u003cp\u003eAbbreviations: ASAPS, American Society of Anesthesiologists Physical Status; BMI, body mass index; TIVA,\u0026nbsp;total\u0026nbsp;intravenous anesthesia; MAP, mean arterial pressure; IVPCA, intravenous patient-controlled analgesia; EtCO\u003csub\u003e2\u003c/sub\u003e, end-tidal carbon dioxide.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003eMultivariable analysis of the relationship between EtCO\u003csub\u003e2\u003c/sub\u003e and POD2-PONV\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.766990291262136%\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePOD2-PONV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCrude\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRisk Ratio\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRisk Ratio\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean EtCO\u003csub\u003e2\u003c/sub\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.766990291262136%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003eNormal EtCO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.766990291262136%\"\u003e\n \u003cp\u003e619\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003e363 (58.64%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003eLow EtCO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.766990291262136%\"\u003e\n \u003cp\u003e120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003e67 (55.83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e0.95 (0.80\u0026ndash;1.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e0.577\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e0.96 (0.80\u0026ndash;1.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e0.658\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean EtCO\u003csub\u003e2\u003c/sub\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.766990291262136%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003e\u0026lt;35 mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.766990291262136%\"\u003e\n \u003cp\u003e120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003e67 (55.83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1.01 (0.82\u0026ndash;1.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e0.906\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1.04 (0.85\u0026ndash;1.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e0.650\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003e35\u0026ndash;37 mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.766990291262136%\"\u003e\n \u003cp\u003e171\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003e101 (59.06%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1.07 (0.89\u0026ndash;1.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e0.451\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1.09 (0.92\u0026ndash;1.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e0.284\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003e37\u0026ndash;40 mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.766990291262136%\"\u003e\n \u003cp\u003e254\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003e155 (61.02%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1.10 (0.94\u0026ndash;1.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e0.217\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1.15 (0.98\u0026ndash;1.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e0.079\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003e\u0026ge;40 mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.766990291262136%\"\u003e\n \u003cp\u003e194\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003e107 (55.15%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" valign=\"top\" width=\"100%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMinutes below EtCO\u003csub\u003e2\u003c/sub\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e35 mmHg\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003eQuartile\u0026nbsp;value 1 (0\u0026ndash;11 min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.766990291262136%\"\u003e\n \u003cp\u003e185\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003e102 (55.14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003eQuartile\u0026nbsp;value 2 (12\u0026ndash;25 min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.766990291262136%\"\u003e\n \u003cp\u003e187\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003e106 (56.68%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1.02 (0.85\u0026ndash;1.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e0.764\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1.04 (0.87\u0026ndash;1.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e0.653\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003eQuartile\u0026nbsp;value 3 (26\u0026ndash;66 min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.766990291262136%\"\u003e\n \u003cp\u003e181\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003e110 (60.77%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1.10 (0.92\u0026ndash;1.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e0.276\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1.10 (0.93\u0026ndash;1.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e0.222\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003eQuartile\u0026nbsp;value 4 (67\u0026ndash;613 min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.766990291262136%\"\u003e\n \u003cp\u003e186\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003e112 (60.22%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1.09 (0.91\u0026ndash;1.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e0.323\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1.03 (0.87\u0026ndash;1.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e0.700\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" valign=\"top\" width=\"100%\"\u003e\n \u003cp\u003e\u003cstrong\u003eArea under the threshold of EtCO\u003csub\u003e2\u003c/sub\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e35 mmHg\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003eQuartile\u0026nbsp;value 1 (0\u0026ndash;7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.766990291262136%\"\u003e\n \u003cp\u003e183\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003e98 (53.55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003eQuartile\u0026nbsp;value 2 (8\u0026ndash;36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.766990291262136%\"\u003e\n \u003cp\u003e182\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003e104 (57.14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1.03 (0.86\u0026ndash;1.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e0.744\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1.01 (0.85\u0026ndash;1.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e0.825\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003eQuartile\u0026nbsp;value 3 (37\u0026ndash;107)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.766990291262136%\"\u003e\n \u003cp\u003e186\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003e113 (60.75%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1.08 (0.91\u0026ndash;1.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e0.358\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1.10 (0.93\u0026ndash;1.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e0.232\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003eQuartile\u0026nbsp;value 4\u0026nbsp;(108\u0026ndash;2213)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.766990291262136%\"\u003e\n \u003cp\u003e188\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.34304207119741%\"\u003e\n \u003cp\u003e115 (61.17%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1.08 (0.91\u0026ndash;1.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e0.346\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.446601941747574%\"\u003e\n \u003cp\u003e1.03 (0.87\u0026ndash;1.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.326860841423947%\"\u003e\n \u003cp\u003e0.654\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: EtCO\u003csub\u003e2\u003c/sub\u003e, end-tidal carbon dioxide; POD 2,\u0026nbsp;postoperative\u0026nbsp;day\u0026nbsp;2; PONV,\u0026nbsp;postoperative\u0026nbsp;nausea and vomiting; CI, confidence interval; MAP, mean arterial pressure; IVPCA, intravenous patient-controlled analgesia; BMI, body mass index; ASAPS, American Society of Anesthesiologists Physical Status.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003eMultivariable analysis of the relationship between EtCO\u003csub\u003e2\u003c/sub\u003e and secondary outcomes\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"17.690875232774673%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.85661080074488%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of Events\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.366852886405958%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCrude\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRisk Ratio\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.614525139664805%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.905027932960895%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRisk Ratio\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.56610800744879%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" width=\"100%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePOD2\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ePostoperative nausea\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"17.690875232774673%\"\u003e\n \u003cp\u003eNormal EtCO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.85661080074488%\"\u003e\n \u003cp\u003e346/619 (55.90%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.366852886405958%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.614525139664805%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.905027932960895%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.56610800744879%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"17.690875232774673%\"\u003e\n \u003cp\u003eLow EtCO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.85661080074488%\"\u003e\n \u003cp\u003e66/120 (55.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.366852886405958%\"\u003e\n \u003cp\u003e0.98 (0.82\u0026ndash;1.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.614525139664805%\"\u003e\n \u003cp\u003e0.857\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.905027932960895%\"\u003e\n \u003cp\u003e0.99 (0.82\u0026ndash;1.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.56610800744879%\"\u003e\n \u003cp\u003e0.916\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" width=\"100%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePOD2\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ePostoperative vomiting\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"17.690875232774673%\"\u003e\n \u003cp\u003eNormal EtCO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.85661080074488%\"\u003e\n \u003cp\u003e184/619 (29.73%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.366852886405958%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.614525139664805%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.905027932960895%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.56610800744879%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"17.690875232774673%\"\u003e\n \u003cp\u003eLow EtCO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.85661080074488%\"\u003e\n \u003cp\u003e37/120 (30.83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.366852886405958%\"\u003e\n \u003cp\u003e1.03 (0.77\u0026ndash;1.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.614525139664805%\"\u003e\n \u003cp\u003e0.807\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.905027932960895%\"\u003e\n \u003cp\u003e1.17 (0.88\u0026ndash;1.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.56610800744879%\"\u003e\n \u003cp\u003e0.264\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" width=\"100%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePOD\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003cstrong\u003e\u0026ndash;7\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ePONV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"17.690875232774673%\"\u003e\n \u003cp\u003eNormal EtCO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.85661080074488%\"\u003e\n \u003cp\u003e383/619 (61.87%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.366852886405958%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.614525139664805%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.905027932960895%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.56610800744879%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"17.690875232774673%\"\u003e\n \u003cp\u003eLow EtCO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.85661080074488%\"\u003e\n \u003cp\u003e70/120 (58.33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.366852886405958%\"\u003e\n \u003cp\u003e0.94 (0.80\u0026ndash;1.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.614525139664805%\"\u003e\n \u003cp\u003e0.480\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.905027932960895%\"\u003e\n \u003cp\u003e0.95 (0.81\u0026ndash;1.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.56610800744879%\"\u003e\n \u003cp\u003e0.583\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: EtCO\u003csub\u003e2\u003c/sub\u003e, end-tidal carbon dioxide; POD 2,\u0026nbsp;postoperative\u0026nbsp;day\u0026nbsp;2; POD 3\u0026ndash;7,\u0026nbsp;postoperative days 3\u0026nbsp;to\u0026nbsp;7; PONV,\u0026nbsp;postoperative\u0026nbsp;nausea and vomiting; CI, confidence interval; MAP, mean arterial pressure; IVPCA, intravenous patient-controlled analgesia; BMI, body mass index; ASAPS, American Society of Anesthesiologists Physical Status.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4\u003c/strong\u003e\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003eMultivariable analysis of the relationship between EtCO\u003csub\u003e2\u003c/sub\u003e and PLOS\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.939597315436242%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.073825503355705%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(IQR)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.563758389261745%\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.14765100671141%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCrude\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003edifference in PLOS (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.563758389261745%\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.14765100671141%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003edifference in PLOS\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;(95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.563758389261745%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" valign=\"top\" width=\"100%\"\u003e\n \u003cp\u003e\u003cstrong\u003eLength of stay(day)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.939597315436242%\"\u003e\n \u003cp\u003eNormal EtCO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.073825503355705%\"\u003e\n \u003cp\u003e6 (5\u0026ndash;8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.563758389261745%\"\u003e\n \u003cp\u003e0.782\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.14765100671141%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.563758389261745%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.14765100671141%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.563758389261745%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.939597315436242%\"\u003e\n \u003cp\u003eLow EtCO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.073825503355705%\"\u003e\n \u003cp\u003e6 (5\u0026ndash;7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.563758389261745%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.14765100671141%\"\u003e\n \u003cp\u003e\u0026minus;0.15\u0026nbsp;(\u0026minus;1.29\u0026nbsp;to\u0026nbsp;0.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.563758389261745%\"\u003e\n \u003cp\u003e0.783\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.14765100671141%\"\u003e\n \u003cp\u003e0.13\u0026nbsp;(\u0026minus;1.00\u0026nbsp;to\u0026nbsp;1.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.563758389261745%\"\u003e\n \u003cp\u003e0.816\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: EtCO\u003csub\u003e2\u003c/sub\u003e, end-tidal carbon dioxide; PLOS,\u0026nbsp;postoperative\u0026nbsp;length of stay; IQR,\u0026nbsp;interquartile range; CI, confidence interval; MAP, mean\u0026nbsp;arterial pressure; IVPCA, intravenous\u0026nbsp;patient-controlled analgesia; BMI, body mass index; ASAPS, American Society of Anesthesiologists Physical Status.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5.\u0026nbsp;\u003c/strong\u003eSubgroup analyses stratified by patient and operative variable\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.516778523489933%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.382550335570469%\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.771812080536913%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePOD2-PONV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.013422818791945%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCrude risk ratio\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(95% CI) of\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003elow\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;EtCO\u003csub\u003e2\u003c/sub\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.395973154362416%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.919463087248323%\"\u003e\n \u003cp\u003e\u003cstrong\u003eP for\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003einteraction\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.516778523489933%\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.382550335570469%\"\u003e\n \u003cp\u003e739\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.771812080536913%\"\u003e\n \u003cp\u003e430 (58.19%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.013422818791945%\"\u003e\n \u003cp\u003e0.95 (0.80\u0026ndash;1.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.395973154362416%\"\u003e\n \u003cp\u003e0.577\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.919463087248323%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"34.899328859060404%\"\u003e\n \u003cp\u003eAge(year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.771812080536913%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.013422818791945%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.395973154362416%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.919463087248323%\"\u003e\n \u003cp\u003e0.837\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.516778523489933%\"\u003e\n \u003cp\u003e\u0026lt;50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.382550335570469%\"\u003e\n \u003cp\u003e454\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.771812080536913%\"\u003e\n \u003cp\u003e246 (54.19%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.013422818791945%\"\u003e\n \u003cp\u003e0.96 (0.76\u0026ndash;1.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.395973154362416%\"\u003e\n \u003cp\u003e0.725\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.919463087248323%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.516778523489933%\"\u003e\n \u003cp\u003e\u0026ge;50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.382550335570469%\"\u003e\n \u003cp\u003e285\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.771812080536913%\"\u003e\n \u003cp\u003e184 (64.56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.013422818791945%\"\u003e\n \u003cp\u003e0.91 (0.70\u0026ndash;1.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.395973154362416%\"\u003e\n \u003cp\u003e0.486\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.919463087248323%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"34.899328859060404%\"\u003e\n \u003cp\u003eMalignancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.771812080536913%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.013422818791945%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.395973154362416%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.919463087248323%\"\u003e\n \u003cp\u003e0.594\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.516778523489933%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.382550335570469%\"\u003e\n \u003cp\u003e205\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.771812080536913%\"\u003e\n \u003cp\u003e135 (65.85%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.013422818791945%\"\u003e\n \u003cp\u003e0.90 (0.64\u0026ndash;1.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.395973154362416%\"\u003e\n \u003cp\u003e0.540\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.919463087248323%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.516778523489933%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.382550335570469%\"\u003e\n \u003cp\u003e534\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.771812080536913%\"\u003e\n \u003cp\u003e295 (55.24%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.013422818791945%\"\u003e\n \u003cp\u003e0.98 (0.80\u0026ndash;1.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.395973154362416%\"\u003e\n \u003cp\u003e0.913\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.919463087248323%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" width=\"87.08053691275168%\"\u003e\n \u003cp\u003eSmoking history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.919463087248323%\"\u003e\n \u003cp\u003e0.640\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.516778523489933%\"\u003e\n \u003cp\u003eEver\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.382550335570469%\"\u003e\n \u003cp\u003e172\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.771812080536913%\"\u003e\n \u003cp\u003e92 (53.49%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.013422818791945%\"\u003e\n \u003cp\u003e1.02 (0.72\u0026ndash;1.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.395973154362416%\"\u003e\n \u003cp\u003e0.892\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.919463087248323%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.516778523489933%\"\u003e\n \u003cp\u003eNever\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.382550335570469%\"\u003e\n \u003cp\u003e567\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.771812080536913%\"\u003e\n \u003cp\u003e338 (59.61%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.013422818791945%\"\u003e\n \u003cp\u003e0.93 (0.76\u0026ndash;1.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.395973154362416%\"\u003e\n \u003cp\u003e0.511\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.919463087248323%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" width=\"87.08053691275168%\"\u003e\n \u003cp\u003eDuration of surgery (h)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.919463087248323%\"\u003e\n \u003cp\u003e0.491\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.516778523489933%\"\u003e\n \u003cp\u003e\u0026ge;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.382550335570469%\"\u003e\n \u003cp\u003e238\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.771812080536913%\"\u003e\n \u003cp\u003e148 (62.18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.013422818791945%\"\u003e\n \u003cp\u003e0.87 (0.61\u0026ndash;1.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.395973154362416%\"\u003e\n \u003cp\u003e0.442\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.919463087248323%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.516778523489933%\"\u003e\n \u003cp\u003e\u0026lt;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.382550335570469%\"\u003e\n \u003cp\u003e501\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.771812080536913%\"\u003e\n \u003cp\u003e282 (56.29%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.013422818791945%\"\u003e\n \u003cp\u003e0.99 (0.51\u0026ndash;1.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.395973154362416%\"\u003e\n \u003cp\u003e0.959\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.919463087248323%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" width=\"87.08053691275168%\"\u003e\n \u003cp\u003eTIVA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.919463087248323%\"\u003e\n \u003cp\u003e0.274\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.516778523489933%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.382550335570469%\"\u003e\n \u003cp\u003e604\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.771812080536913%\"\u003e\n \u003cp\u003e369 (61.09%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.013422818791945%\"\u003e\n \u003cp\u003e0.91 (0.76\u0026ndash;1.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.395973154362416%\"\u003e\n \u003cp\u003e0.376\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.919463087248323%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.516778523489933%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.382550335570469%\"\u003e\n \u003cp\u003e135\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.771812080536913%\"\u003e\n \u003cp\u003e61 (45.19%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.013422818791945%\"\u003e\n \u003cp\u003e1.19 (0.77\u0026ndash;1.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.395973154362416%\"\u003e\n \u003cp\u003e0.428\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.919463087248323%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.563025210084035%\"\u003e\n \u003cp\u003eIntraoperative antiemetics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" width=\"59.49579831932773%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.941176470588236%\"\u003e\n \u003cp\u003e0.990\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.516778523489933%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.382550335570469%\"\u003e\n \u003cp\u003e284\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.771812080536913%\"\u003e\n \u003cp\u003e168 (59.15%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.013422818791945%\"\u003e\n \u003cp\u003e0.95 (0.70\u0026ndash;1.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.395973154362416%\"\u003e\n \u003cp\u003e0.757\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.919463087248323%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.516778523489933%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.382550335570469%\"\u003e\n \u003cp\u003e455\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.771812080536913%\"\u003e\n \u003cp\u003e262 (57.58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.013422818791945%\"\u003e\n \u003cp\u003e0.95 (0.77\u0026ndash;1.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.395973154362416%\"\u003e\n \u003cp\u003e0.666\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.919463087248323%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: POD 2,\u0026nbsp;postoperative\u0026nbsp;day\u0026nbsp;2; PONV,\u0026nbsp;postoperative\u0026nbsp;nausea and vomiting; CI, confidence interval; TIVA,\u0026nbsp;total\u0026nbsp;intravenous anesthesia.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"EtCO2, gynecologic laparoscopy, postoperative nausea and vomiting, laparoscopy, postoperative length of hospital stay","lastPublishedDoi":"10.21203/rs.3.rs-1313239/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1313239/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePURPOSE\u003c/h2\u003e \u003cp\u003eGynecologic laparoscopic surgery has a high incidence of postoperative nausea and vomiting (PONV). Studies suggest that low intraoperative end-tidal carbon dioxide (EtCO\u003csub\u003e2\u003c/sub\u003e) is associated with an increased incidence of PONV, but the results have not been consistent among studies. This study investigated the association between intraoperative EtCO\u003csub\u003e2\u003c/sub\u003e and PONV in patients undergoing gynecologic laparoscopic surgeries under general anesthesia.\u003c/p\u003e\u003ch2\u003eMETHODS\u003c/h2\u003e \u003cp\u003eThis retrospective cohort study involved patients who underwent gynecologic laparoscopic surgeries under general anesthesia at Kyoto University Hospital. We defined hypocapnia as a mean EtCO\u003csub\u003e2\u003c/sub\u003e of \u0026lt;35 mmHg. Multivariable modified Poisson regression analysis examined the association between low EtCO\u003csub\u003e2\u003c/sub\u003e and PONV two days after surgery and the postoperative length of hospital stay (PLOS).\u003c/p\u003e\u003ch2\u003eRESULTS\u003c/h2\u003e \u003cp\u003eOf the 739 patients, 120 (16%) had low EtCO\u003csub\u003e2\u003c/sub\u003e, and 430 (58%) developed PONV two days after surgery. There was no substantial association between low EtCO\u003csub\u003e2\u003c/sub\u003e and increased incidence of PONV (adjusted risk ratio: 0.96; 95% confidence interval [CI]: 0.80\u0026ndash;1.14; \u003cem\u003ep\u003c/em\u003e = 0.658). Furthermore, there was no substantial association between low EtCO\u003csub\u003e2\u003c/sub\u003e and prolonged PLOS (adjusted difference in PLOS: 0.13; 95% CI, \u0026minus;1.00 to 1.28; \u003cem\u003ep\u003c/em\u003e = 0.816).\u003c/p\u003e\u003ch2\u003eCONCLUSION\u003c/h2\u003e \u003cp\u003eIntraoperative low EtCO\u003csub\u003e2\u003c/sub\u003e was not substantially associated with either increased incidence of PONV or prolonged PLOS.\u003c/p\u003e","manuscriptTitle":"Association between Intraoperative End-Tidal Carbon Dioxide and Postoperative Nausea and Vomiting in Gynecologic Laparoscopic Surgery","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-02-03 21:17:48","doi":"10.21203/rs.3.rs-1313239/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2022-02-28T08:28:08+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-02-12T21:13:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"13695680-ecd6-4900-ba52-969fac0177ab","date":"2022-02-03T07:41:31+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-02-03T06:48:16+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-02-03T06:46:27+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2022-02-02T19:57:10+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-02-02T09:28:32+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2022-01-31T04:57:57+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9529d5e6-dc6d-4111-8c70-9a807eebe91e","owner":[],"postedDate":"February 3rd, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2022-04-06T07:44:19+00:00","versionOfRecord":[],"versionCreatedAt":"2022-02-03 21:17:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1313239","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1313239","identity":"rs-1313239","version":["v1"]},"buildId":"eB-D7MK2yqyqIWuf3Ze0-","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}