Effects of Intraoperative Fluid Balance During Pancreatoduodenectomy on Postoperative Pancreatic Fistula: An Observational Cohort Study

Effects of Intraoperative Fluid Balance During Pancreatoduodenectomy on Postoperative Pancreatic Fistula: An Observational Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effects of Intraoperative Fluid Balance During Pancreatoduodenectomy on Postoperative Pancreatic Fistula: An Observational Cohort Study Le Zhang, Yuelun Zhang, Le Shen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2465372/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 13 Apr, 2023 Read the published version in BMC Surgery → Version 1 posted 9 You are reading this latest preprint version Abstract Background: Perioperative fluid management during major abdominal surgery has been controversial. Postoperative pancreatic fistula (POPF) is a critical complication of pancreaticoduodenectomy (PD). We conducted a retrospective cohort study to analyze the impact of intraoperative fluid balance on the development of POPF Methods: This retrospective cohort study enrolled 567 patients who underwent open pancreaticoduodenectomy, and the demographic, laboratory, and medical data were recorded. All patients were categorized into four groups according to quartiles of intraoperative fluid balance. Multivariate logistic regression and restricted cubic splines (RCSs) were used to analyze the relationship between intraoperative fluid balance and POPF. Results: The intraoperative fluid balance of all patients ranged from -8.47 to 13.56 mL/kg/h. A total of 108 patients reported POPF, and the incidence was 19.0%. After adjusting for potential confounders and using restricted cubic splines, the dose‒response relationship between intraoperative fluid balance and POPF was found to be statistically insignificant. The incidences of bile leakage, postpancreatectomy hemorrhage, and delayed gastric emptying were 4.4%, 20.8%, and 14.8%, respectively. Intraoperative fluid balance was not associated with these abdominal complications. BMI≥25kg/m 2 , preoperative blood glucose<6 mmol/L, long surgery time, and lesions not located in the pancreas were independent risk factors for POPF. Conclusion: The study did not find a significant association between intraoperative fluid balance and POPF. Well-designed multicenter studies are necessary to explore the association between intraoperative fluid balance and POPF. pancreaticoduodenectomy intraoperative fluid balance postoperative pancreatic fistula risk factors postoperative complications Figures Figure 1 Background From the perspective of anesthesiologists, perioperative fluid management is an important part of their anesthesia scheme. The fluid management strategies vary among anesthesiologists. In recent years, the classical perioperative fluid balance described in textbooks has been challenged. Fluid overload was reported to increase cardiopulmonary complications and impair the recovery of gastrointestinal function ( 1 ). Restrictive fluid management has been thought to be beneficial for decreasing postoperative complications and improving prognosis for patients who underwent intraabdominal surgery ( 2 ). A meta‑analysis suggested that patients receiving restricted fluid therapy were associated with rapid recovery and shorter length of hospital stay compared with liberal management during abdominal surgery ( 3 ). In the consensus on the perioperative care of colorectal surgery patients, restrictive fluid management was recommended in the protocol of enhanced recovery after surgery (ERAS) ( 4 ). Nevertheless, due to the limited quantity and quality of research, restrictive fluid management has been controversial during major abdominal surgery. Pancreaticoduodenectomy (PD), as one of the most complex and traumatic abdominal operations, is associated with many postoperative abdominal complications, including pancreatic fistula, bile leak (BL), postpancreatectomy hemorrhage (PPH), delayed gastric emptying (DGE), and intra-abdominal infection ( 5 ). Postoperative pancreatic fistula (POPF) is a critical complication with an incidence ranging from 10–34% ( 6 ). If timely and effective treatment is not available, patients with POPF could experience intra-abdominal infection, intra-abdominal bleeding, and even death, consequently extending the length of hospital stay and exacerbating the medical burden ( 7 ). We used to hold the opinion that whether POPF occurred depended largely on the technique and experience of surgeons. Some previous studies have clarified multiple perioperative factors related to POPF ( 8 – 10 ). However, only a few studies have analyzed the correlation between intraoperative fluid management and POPF. Whether restrictive fluid management lowers the risk of POPF remains unclear. Therefore, we conducted a retrospective cohort study to clarify the impact of intraoperative fluid balance on the development of POPF. In addition, we performed exploratory analysis to investigate risk factors for POPF and the relationship between intraoperative fluid balance and other abdominal complications after PD. Methods Study Design and Patient After approval by the institutional ethics board of Peking Union Medical College Hospital (K1522, 28 June 2022), the study created a retrospective cohort of patients who underwent open pancreatoduodenectomy between July 2016 and July 2021 at Peking Union Medical College Hospital. The surgeries were performed by an experienced surgical team. Indications for the surgery were tumors and other disorders of the pancreas, duodenum, bile duct, and adjacent other organs. The standard procedure of PD involved the removal of the pancreatic head, duodenum, first 15 cm of the jejunum, common bile duct, gallbladder, partial gastrectomy, and the reconstruction of gastrointestinal continuity. An end-to-side anastomosis was adopted in pancreaticojejunostomy, biliary-enteric anastomosis or gastrointestinal anastomosis. Modified PD, pylorus-preserving pancreaticoduodenectomy (PPPD) which preserves the gastric antrum, pylorus, and proximal 3 to 4 cm of the duodenum has been gradually used in the hospital for gastrointestinal continuity. The inclusion criteria were as follows: 1) older than 18 years; 2) ASA I–Ⅲ; 3) patients who underwent elective open PD (including bowel resection, anastomosis, ostomy, partial vascular resection or reconstruction). The exclusion criteria were as follows: 1) patients who underwent total pancreatectomy and duodenectomy and 2) patients who lacked fluid records. Intraoperative Fluid Balance According to the Chinese conventional infusion regimen, the intraoperative fluid volume was calculated by subtracting the total fluid output (preoperative loss during fasting, physiological required volume, urine output, blood loss, third space fluid loss) from the total fluid input (crystalloids, colloids, blood products). Specifically speaking, we evaluated preoperative loss during fasting and physiological required volume using the “4-2-1” calculation. The third space fluid loss was calculated by 6mL/kg/h ( 11 ). Finally, the intraoperative fluid balance was equal to the intraoperative fluid volume divided by the patients’ weight and anesthesia time. The patients were categorized into 4 groups according to intraoperative fluid balance quartiles: Q1≤-1.62, -1.61 < Q2 ≤ 0.80, -0.79 < Q3 ≤ 0.02, Q4 ≥ 0.03 mL/kg/h. Endpoints The primary endpoint was clinically relevant POPF. In 2016, the International Study Group of Pancreatic Surgery (ISGPS) updated the POPF definition and grading system, which has been widely recognized and used. A clinically relevant POPF is defined as a drain output of any measurable volume of fluid with amylase level greater than 3 times the upper institutional normal serum amylase level, associated with a clinically relevant development/condition related directly to the POPF. Biochemical leakage no longer belonged to the category of POPF. Grade B was accompanied by a clinical change in the postoperative management or persistent drainage > 3 weeks, while Grade C required reoperation or led to organ failure or death ( 12 ). The secondary endpoints included Grade B POPF, Grade C POPF, BL, PPH, and DGE. Likewise, the definitions of BL and PPH are derived from the ISGPS ( 13 , 14 ). Yeo et al provided a clear definition of DGE in their prospective, randomized, and placebo-controlled trial. We chose to use the same definition for our study ( 15 ). Study Variables We collected demographic, laboratory, and medical data via the electronic medical record system and surgical anesthesia system of Peking Union Medical College Hospital. The baseline characteristics included age, sex, BMI, and comorbidities. BMI was expressed as a continuous variable as well as a categorical variable, and BMI was categorized into two groups: < 25kg/m 2 , ≥ 25kg/m 2 . The preoperative variables consisted of abdominal surgery history, lesions site, ASA classification, preoperative fluid infusion, and laboratory data (preoperative albumin, bilirubin and blood glucose). The grouping thresholds of the laboratory data were determined by the medical reference value. The intraoperative variables were comprised of the anesthetic mode, surgery option, surgery time, and intraoperative fluid management (blood loss, urine output, red blood cells, fresh frozen plasma, crystalloid/colloid volume). PD and PPPD are two surgical options. Statistical Analyses All participants were categorized into four groups according to quartiles of intraoperative fluid balance. Continuous variables were presented as the mean ± standard deviation or medians and interquartile ranges where appropriate. Categorical data are shown as numbers and percentages. Univariate and multivariate nonconditional logistic regression analyses were performed to assess the association between the fluid balance quartiles and primary outcome. Variables potentially associated with POPF or clinically important were selected for logistic regression. Odds ratios (ORs) and 95% confidence intervals (95% CIs) across the fluid balance quartiles (the lowest quartile as a reference) were calculated. Based on a multivariate logistic regression model, we used restricted cubic splines (RCSs) to explore the nonlinear dose‒response relationship between intraoperative fluid balance and POPF, with three knots defined at the 10th, 50th, and 90th percentiles of intraoperative fluid balance ( 16 ). Data were analyzed using SPSS version 25.0 (SPSS, Inc., Chicago, IL, USA). The restricted cubic spline analysis and the related figure were conducted with R version 4.2.0 (R Foundation for Statistical Computing, Vienna, Austria) using the rms and ggplot2 packages. All tests were 2-sided, and all tests were conducted at the 5% significance level. Results Demographics We collected 595 patients who underwent elective open PD between July 2016 and July 2021 at Peking Union Medical College Hospital, and 567 patients were finally included for statistical analysis. A total of 336 (59.3%) of the patients were male. The patients were divided by their intraoperative fluid balance, ranging from − 8.47 to 13.56 mL/kg/h, according to the quartiles. The demographic characteristics based on the four groups are shown in Table 1 . The mean age of the enrolled patients was 58.68 ± 10.87 years old, and there was no significant difference in the patients’ ages among the groups. As the intraoperative fluid balance increased, the proportion of overweight patients decreased. Table 1 Cohort Characteristics by Fluid Balance Quartiles Variables All patients Q1 Q2 Q3 Q4 (n = 567) (n = 142) (n = 142) (n = 142) (n = 141) Baseline characteristics Age, mean (SD), years 58.68 ± 10.87 58.46 ± 10.23 58.44 ± 10.38 58.81 ± 10.69 58.99 ± 12.17 Sex, male, n (%) 336 (59.3%) 77 (54.2%) 100 (70.4%) 84 (59.2%) 75 (53.2%) BMI, mean (SD), kg/m 2 22.75 ± 3.28 24.26 ± 3.06 23.5 ± 3.04 22.52 ± 3.06 20.73 ± 2.88 BMI ≥ 25 kg/m 2 , n (%) 134 (23.6%) 53 (37.3%) 39 (27.5%) 29 (20.4%) 13 (9.2%) Comorbidities Smoking history, n (%) 214 (37.7%) 48 (33.8%) 64 (45.1%) 56 (39.4%) 46 (32.6%) Alcohol intake, n (%) 179 (31.6%) 44 (31%) 55 (38.7%) 40 (28.2%) 40 (28.4%) Hypertension, n (%) 168 (29.6%) 53 (37.3%) 46 (32.4%) 43 (30.3%) 26 (18.4%) Diabetes mellitus, n (%) 128 (22.6%) 35 (24.6%) 34 (23.9%) 31 (21.8%) 28 (19.9%) Coronary artery disease, n (%) 44 (7.8%) 12 (8.5%) 9 (6.3%) 15 (10.6%) 8 (5.7%) Preoperative characteristics Abdominal surgery history, n (%) 164 (28.9%) 38 (26.8%) 39 (27.5%) 36 (25.4%) 51 (36.2%) Lesion site, pancreas, n (%) 356 (62.8%) 90 (63.4%) 90 (63.4%) 91 (64.1%) 85 (60.3%) ASA classification Class I–II, n (%) 477 (84.1%) 120 (84.5%) 122 (85.9%) 121 (85.2%) 114 (80.9%) Class III, n (%) 90 (15.9%) 22 (15.5%) 20 (14.1%) 21 (14.8%) 27 (19.1%) Pre-ALB, mean (SD), g/L 39.98 ± 4.77 40.92 ± 4.4 40.14 ± 4.29 39.6 ± 4.89 39.26 ± 5.32 Pre-ALB < 35 g/L, n (%) 78 (13.8%) 10 (7%) 12 (8.5%) 25 (17.6%) 31 (22%) Pre-TBIL, median (IQR), µmol/L 18.6 (11.4 ~ 69.5) 17.9 (11.5 ~ 67.68) 18.75 (11.78 ~ 72.88) 19.6 (11.25 ~ 64.88) 18.5 (11.1 ~ 88.8) Pre-TBIL > 17.1 µmol/L, n (%) 303 (53.4%) 74 (52.1%) 75 (52.8%) 78 (54.9%) 76 (53.9%) Pre-GLU, mean (SD), mmol/L 6.53 ± 2.39 6.38 ± 2.18 6.46 ± 2.03 6.83 ± 2.87 6.47 ± 2.38 Pre-GLU > 6 mmol/L, n (%) 244 (43.0%) 57 (40.1%) 69 (48.6%) 61 (43%) 57 (40.4%) Preoperative fluid infusion, n (%) 200 (35.3%) 32 (22.5%) 42 (29.6%) 55 (38.7%) 71 (50.4%) Intraoperative characteristics Total intravenous anesthesia, n (%) 50 (8.8%) 11 (7.7%) 9 (6.3%) 9 (6.3%) 21 (14.9%) Surgery time, mean (SD), h 5.87 ± 1.38 5.86 ± 1.29 6.02 ± 1.42 5.89 ± 1.42 5.7 ± 1.38 PPPD, n (%) 76 (13.4%) 20 (14.1%) 24 (16.9%) 20 (14.1%) 12 (8.5%) Blood transfusion, n (%) 301 (53.1%) 40 (28.2%) 64 (45.1%) 84 (59.2%) 113 (80.1%) Blood loss, median (IQR), L 0.46 (0.3 ~ 0.7) 0.4 (0.3 ~ 0.6) 0.4 (0.3 ~ 0.7) 0.41 (0.3 ~ 0.8) 0.5 (0.4 ~ 0.9) Red blood cells, median (IQR), units 0 (0 ~ 3) 0 (0 ~ 0) 0 (0 ~ 2) 2 (0 ~ 2) 4 (1 ~ 4) Fresh frozen plasma, median (IQR), L 0 (0 ~ 0.4) 0 (0 ~ 0.05) 0 (0 ~ 0.4) 0.2 (0 ~ 0.4) 0.4 (0 ~ 0.4) Crystalloid, median (IQR), L 3 (2.4 ~ 3.7) 2.45 (2.1 ~ 2.73) 2.85 (2.5 ~ 3.4) 3.3 (2.7 ~ 3.9) 3.4 (2.8 ~ 4.3) Colloid, median (IQR), L 1 (0.5 ~ 1) 0.5 (0.5 ~ 1) 1 (0.5 ~ 1) 1 (0.5 ~ 1) 1 (0.5 ~ 1.5) Pre, Preoperative; SD, standard deviation; IQR, interquartile range; ALB, albumin; TBIL, total bilirubin; GLU, blood glucose; PPPD, pylorus-preserving pancreaticoduodenectomy Intraoperative Fluid Balance And Popf Among the 567 patients, 108 were diagnosed with POPF, and the incidence was 19.0%. Among them, 80 patients were categorized into Grade B while 28 patients belonged to Grade C. There were 22 patients with POPF in the Q3 group of intraoperative fluid balance, which was lower than the other three groups. First, we used intraoperative fluid balance as a categorical variable and the lowest quartile as the reference to conduct a univariate analysis. The results showed no statistically significant relationship between intraoperative fluid balance and POPF. Then, multivariate logistic regression was performed after adjusting for potential confounding factors, including age, sex, BMI, abdominal surgery history, preoperative bilirubin, preoperative blood glucose, ASA classification, anesthetic mode, surgery option, and lesion site. The outcome did not change. Furthermore, we took into account the differentiation between grade B and grade C POPF, the outcome kept the same. The results are summarized in Table 2 . Furthermore, we adjusted for the same potential confounders and modeled the association between intraoperative fluid balance and POPF using restricted cubic splines. The AIC value for the model with a 3-knot RCS function was less than those for the models with a 4-knot or 5-knot, suggesting that the model with a 3-knot RCS function was more adequate. The results are presented in Fig. 1 . According to the OR curve, when the intraoperative fluid balance level was approximately − 0.7 mL/kg/h, the risk of POPF was minimal. When the intraoperative fluid balance level became more positive or negative, the risk of POPF increased. Nevertheless, the value of the test for the overall association between intraoperative fluid balance and POPF was insignificant, which means that regardless of the shape of this curve, there was no significant association between intraoperative fluid balance and POPF. Table 2 Associations Between Fluid Balance and Outcomes Q1 Q2 Q3 Q4 (n = 142) (n = 142) (n = 142) (n = 141) Primary Outcome POPF, n (%) 29 (20.42%) 29 (20.42%) 22 (15.49%) 28 (19.86%) Adjusted OR95%CI 1 1 (0.56,1.78) 0.71 (0.39,1.32) 0.97 (0.54,1.73) P value 0.668 Adjusted OR95%CI † 1 1.15 (0.62,2.11) 0.86 (0.45,1.63) 1.3 (0.69,2.46) P value † 0.618 Secondary Outcomes Grade B POPF, n (%) 21 (14.79%) 24 (16.90%) 15 (10.56%) 20 (14.18%) Adjusted OR95%CI † 1 1.38 (0.7,2.72) 0.92 (0.44,1.92) 1.31 (0.63,2.7) P value † 0.62 Grade C POPF, n (%) 11 (7.75%) 4 (2.82%) 5 (3.5%) 8 (5.63%) Adjusted OR95%CI † 1 0.68 (0.22,2.08) 0.73 (0.23,2.27) 1.25 (0.42,3.69) P value † 0.698 BL, n (%) 7 (4.9%) 5 (3.5%) 7 (4.9%) 6 (4.3%) Adjusted OR95%CI † 1 0.61 (0.18,2.02) 0.99 (0.33,2.98) 0.95 (0.29,3.06) P value † 0.841 PPH, n (%) 27 (19%) 29 (20.40%) 25 (17.60%) 37 (26.20%) Adjusted OR95%CI † 1 1.15 (0.62,2.12) 0.97 (0.52,1.81) 1.86 (1.01,3.43) P value † 0.115 DGE, n (%) 24 (16.90%) 14 (9.90%) 22 (15.50%) 24 (17.00%) Adjusted OR95%CI † 1 0.55 (0.27,1.13) 0.99 (0.51,1.89) 1.22 (0.63,2.36) P value † 0.187 † adjusted by age, sex, BMI, abdominal surgery history, preoperative bilirubin, preoperative blood glucose, ASA classification, anesthetic mode, surgery option, and location of lesion. the lowest quartile as the reference. POPF, postoperative pancreatic fistula; BL, bile leakage; PPH, postpancreatectomy hemorrhage; DGE, delayed gastric emptying; OR, odds ratio; CI, confidence interval. Other Complications And Risk Factors For Popf The incidences of BL, PPH, and GED were 4.4%, 20.8%, and 14.8%, respectively. We found that the association between intraoperative fluid balance and these abdominal complications was not statistically significant. For risk factors for POPF, after univariate regression analysis, we included the variables with P < 0.1 in the multivariate regression analysis, and the results are shown in Table 3 . We found that BMI, preoperative blood glucose, surgery time, and lesion site were related to POPF. In contrast to the patients without POPF, the surgeries (OR: 1.29, 95% CI: 1.08–1.55) were longer, and the proportion of overweight patients (OR: 2.45, 95% CI: 1.54–3.91) was higher in the group of patients who developed POPF. However, preoperative hyperglycemia (blood glucose > 6 mmol/L, OR: 0.61, 95% CI: 0.38–0.97) and lesions located in the pancreas (OR: 0.43, 95% CI: 0.27–0.67) were protective factors for POPF. Table 3 Risk factors for POPF based on logistic regression analysis Univariate Multivariate OR95%CI P value OR95%CI P value BMI ≥ 25 kg/m 2 2.54 (1.62,3.98) < 0.001 2.45 (1.54,3.91) 6 mmol/L 0.6 (0.39,0.94) 0.025 0.61 (0.38,0.97) 0.038 Surgery time, h 1.26 (1.09,1.46) < 0.001 1.29 (1.08,1.55) 0.006 Blood loss, L 1.37 (1.01,1.87) 0.046 1.09 (0.75,1.58) 0.659 Preoperative fluid infusion 0.62 (0.39,0.99) 0.043 0.73 (0.45,1.19) 0.208 Lesion site, pancreas 0.45 (0.3,0.69) < 0.001 0.43 (0.27,0.67) < 0.001 GLU, blood glucose; OR, odds ratio; CI, confidence interval. Discussion Fluid management is complex and variable. Some studies tend to support restrictive fluid management, but the controversy over fluid management has never ceased. Zhang et al. enrolled 301 patients for a retrospective study, and the results showed that higher postoperative fluid balance appeared to be associated with morbidity after PD, systemic inflammatory response syndrome (SIRS), acute respiratory distress syndrome (ARDS), bleeding, and heart failure ( 17 ). However, Meyhoff et al. performed an international, randomized trial among adult patients with septic shock in the ICU and found that intravenous fluid restriction did not decrease mortality at 90 days compared with standard intravenous fluid therapy ( 18 ). The relationship between intraoperative fluid balance and the specific abdominal complication of POPF is also ambiguous. Some studies have demonstrated that the incidence of POPF in the high fluid volume group was higher than that in the low fluid volume group during PD, and intraoperative fluid excess was also considered a risk factor for POPF ( 19 – 23 ). Nevertheless, in 2017, a meta-analysis evaluated the relationship between the perioperative fluid balance and postoperative complications of PD (including POPF), and no significant correlation was found ( 24 ). Similarly, a meta-analysis published in 2018 demonstrated that intraoperative fluid balance did not affect the occurrence of POPF ( 25 ). Interestingly, a retrospective cohort study showed that intraoperative fluid balance did not affect the incidence of POPF, but the higher cumulative fluid balance per body weight (FBPBW) at postoperative day 3 was an independent risk factor for CR-POPF ( 26 ). Other studies have also demonstrated that patients with a high postoperative fluid balance presented a higher incidence of POPF ( 27 – 29 ). Although the related mechanisms have not been thoroughly studied, there are some plausible claims. Trauma of the pancreatic surface in the PD procedure and leakage of a pancreatic-enteric anastomosis are the main reasons for POPF ( 12 ). Fluid overload could cause pancreatic parenchyma and intestinal edema, increase the distance between capillaries and cells, impair gas exchange, and then lead to dysfunction or disruption of the pancreatojejunostomy ( 30 , 31 ). The study consecutively enrolled 567 patients who underwent PD surgery, and they were divided into four groups by the quartiles of intraoperative fluid balance to explore any difference in POPF between the four groups. Then, intraoperative fluid balance was regarded as a continuous variable, and we used restricted cubic splines to analyze whether a dose‒response relationship existed between intraoperative fluid balance and POPF. Finally, the relationship was found to be statistically insignificant. In addition, we did not find an association between intraoperative fluid balance and BL, DEG, or PPH. Identically, Braga et al. grouped patients undergoing PD according to whether they received a comprehensive ERAS protocol or standard perioperative care. A comprehensive ERAS protocol contained many items, such as a lack of bowel preparation and shortening of the preoperative fasting period, and the intravenous fluid infusion rate was lower in the ERAS group. The results showed that the incidence of POPF was similar in the two groups, as were BL, DGE, and PPH ( 32 ). Sex, BMI, fasting blood glucose level, pancreatic texture, pancreatic duct, pancreatojejunostomy anastomosis technique, and tumor location were related risk factors for POPF. Our study found that BMI ≥ 25kg/m 2 , preoperative hypoglycemia (blood glucose ≤ 6 mmol/L), long surgery time, and lesion not located in the pancreas were risk factors for POPF. Preoperative hypoglycemia, lesions not located in the pancreas, and BMI might lead to a softer pancreas, thereby influencing the occurrence of POPF ( 7 – 10 ). In addition, when the operation was complicated and difficult, the surgery took longer, and there was a tendency to develop related postoperative complications. As the most critical complication of PD, the treatment and prevention of POPF have been the main concerns for pancreatic surgeons. Besides early identification of related risk factors for POPF, other contemporary mitigation strategies include the use of abdominal drains, prophylactic somatostatin analogues, modified anastomotic techniques, and anastomotic stents ( 33 ). Recently, a study showed that coronary artery stent (CAS) positioning in PJ anastomosis could be a novel mitigation strategy in the prevention of POPF ( 34 ). The definition of POPF is relatively uniform in many studies, but the calculation of perioperative fluid balance or fluid management varies. There is no uniform standard for the definition of perioperative fluid balance or fluid management, especially for the cutoff values, which can vary ( 20 – 23 ), and this makes it difficult to integrate and summarize the results of current clinical studies. Relevant research results should be treated with caution. Many anesthesiologists still use the conventional infusion regimen described in textbooks when formulating plans before major surgery. Our definition of fluid balance was based on that. However, the conventional infusion regimen took the patient’s perioperative physiological needs and the third space fluid loss into account; patients were thought to be relatively hypovolemic and therefore required relatively more aggressive fluid replacement. This explains why many patients received a negative intraoperative balance in our study. Our definition of intraoperative fluid balance consisted of the surgery time and patient weight, which helped to reduce the impact of the surgery time and patient weight on intraoperative fluid balance. The intraoperative RBC and colloid infusion in Q3 and Q4 was higher than that in Q1 and Q2. However, intraoperative fluid balance was an integrated variable, and it was difficult for us to explain whether the intraoperative RBC and colloid infusion affected the incidence of POPF. Moreover, we did not consider the difference in the volume effect of crystalloids and colloids when calculating the intraoperative fluid balance. Many anesthesiologists formulate the intraoperative fluid management plans in advance based on the patient’s physiological needs. In fact, the intraoperative fluid management is affected by many factors, such as intraoperative bleeding, patient cardiovascular function, depth of anesthesia, and use of vasoactive drugs in a major surgery such as PD. Therefore, many anesthesiologists often use invasive monitoring methods in combination with other hemodynamic parameters to evaluate the patient's volume status and adjust their fluid management plan in a timely manner. As a result, the concept of goal-directed fluid therapy (GDFT) may be the most reasonable fluid management strategy available. Limitation The present study had some limitations. First, this study analyzed the association between intraoperative fluid balance and the incidence of POPF but did not further analyze the effect of intraoperative fluid balance on the severity of POPF. Second, it was a retrospective analysis in which our data lacked some variables involved in the operation. Confounding factors such as pancreatic texture and pancreatic duct played an influential role in whether pancreatic fistula occurred. Third, all the patients were treated at a single center. To validate the effect of intraoperative fluid balance on POPF, a multicenter study with a larger number of patients is needed in the future. Conclusions Our study failed to find a significant association between intraoperative fluid balance and POPF. Furthermore, the correlations between fluid balance and other abdominal complications were statistically insignificant. On the other hand, the findings of this study indicated that BMI, blood glucose, surgery and lesion site were closely related to POPF. It is necessary to unify the definition of fluid balance and develop well-designed studies to validate the optimal fluid strategy and reduce abdominal complications such as POPF. Until then, the intraoperative fluid management plan of PD should be individualized and adjusted according to the actual situation. Abbreviations POPF, Postoperative pancreatic fistula; PD, pancreaticoduodenectomy; RCS, restricted cubic splines; ERAS, enhanced recovery after surgery; BL, bile leak; PPH, postpancreatectomy hemorrhage; DGE, delayed gastric emptying; PPPD, pancreaticoduodenectomy; ISGPS, International Study Group of Pancreatic Surgery; OR, odds ratio; CI, confidence interval; SIRS, systemic inflammatory response syndrome; ARDS, acute respiratory distress syndrome; FBPBW, cumulative fluid balance per body weight; CAS, coronary artery stent; GDFT, goal-directed fluid therapy. Declarations Ethics approval and consent to participate The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and approved by the institutional ethics board of Peking Union Medical College Hospital (K1522, 28 June 2022). As a retrospective study, it did not impair the patients’ legal rights and interests because we only collected data in the electronic medical record system and surgical anesthesia system of Peking Union Medical College Hospital and did not utilize any forms of personally identifiable data in the study. Therefore, the Peking Union Medical College Hospital Institutional Review Board approved our application of waiving informed consent. Consent for publication Not applicable. Availability of data and materials The datasets generated and/or analyzed during the current study are not publicly available due to the fear of improper use but are available from the corresponding author on reasonable request Competing interests The authors declare that they have no competing interests. Funding This work was supported by the This research was funded by National High Level Hospital Clinical Research Funding and National Key Research and Development Program of China (2020YFC2008401-1). Authors' contributions SL and ZL designed the study; ZL collected and analyzed clinical data and wrote this manuscript; SL and ZYL reviewed and revised the manuscript. All authors read and approved the final manuscript. Acknowledgments Not applicable. References Bundgaard-Nielsen M, Secher NH, Kehlet H. Kehlet. 'Liberal' vs. 'restrictive' perioperative fluid therapy–a critical assessment of the evidence. Acta Anaesthesiol Scand. 2009;53:843–51. Nisanevich V, Felsenstein I, Almogy G, Weissman C, Einav S, Matot I. Effect of intraoperative fluid management on outcome after intraabdominal surgery. Anesthesiology. 2005;103:25–32. Jia FJ, Yan QY, Sun Q, Tuxun T, Liu H, Shao L. Liberal versus restrictive fluid management in abdominal surgery: a meta-analysis. Surg Today. 2017;47:344–56. Lassen K, Soop M, Nygren J, Cox PB, Hendry PO, Spies C, et al. Consensus review of optimal perioperative care in colorectal surgery: Enhanced Recovery After Surgery (ERAS) Group recommendations. 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World J Gastroenterol. 2016;22:7797–805. Ellis RJ, Brock Hewitt D, Liu JB, Cohen ME, Merkow RP, Bentrem DJ, et al. Preoperative risk evaluation for pancreatic fistula after pancreaticoduodenectomy. J Surg Oncol. 2019;119:1128–34. Miller RD, Eriksson LI, Fleisher LA, Wiener-Kronish JP, Young WL. Miller’s Anesthesia. 7th ed. In: White, Paul, editors. Intravascular Fluid Electrolyte Physiology. New York: Churchill Livingstone; 2009. p.1705-37 Bassi C, Marchegiani G, Dervenis C, Sarr M, Abu Hilal M, Adham M, et al. The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 Years After. Surgery. 2017;161:584–91. Koch M, Garden OJ, Padbury R, Rahbari NN, Adam R, Capussotti L, et al. Bile leakage after hepatobiliary and pancreatic surgery: a definition and grading of severity by the International Study Group of Liver Surgery. Surgery. 2011;149:680–8. Wente MN, Veit JA, Bassi C, Dervenis C, Fingerhut A, Gouma DJ, et al. Postpancreatectomy hemorrhage (PPH): an International Study Group of Pancreatic Surgery (ISGPS) definition. Surgery. 2007;142:20–5. Yeo CJ, Barry MK, Sauter PK, Sostre S, Lillemoe KD, Pitt HA et al. Erythromycin accelerates gastric emptying after pancreaticoduodenectomy. A prospective, randomized, placebo-controlled trial.Ann Surg. 1993;218:229 – 37; discussion 37 – 8. Desquilbet L, Mariotti F. Dose-response analyses using restricted cubic spline functions in public health research. Stat Med. 2010;29:1037–57. Zhang H, Feng Y, Suolang D, Dang C, Qin R. Postoperative fluid balance and outcomes after Pancreaticoduodenectomy: a retrospective study in 301 patients. Langenbecks Arch Surg. 2022;407:1537–44. Meyhoff TS, Hjortrup PB, Wetterslev J, Sivapalan P, Laake JH, Cronhjort M, et al. Restriction of Intravenous Fluid in ICU Patients with Septic Shock. N Engl J Med. 2022;386:2459–70. Fischer M, Matsuo K, Gonen M, Grant F, Dematteo RP, D'Angelica MI, et al. Relationship between intraoperative fluid administration and perioperative outcome after pancreaticoduodenectomy: results of a prospective randomized trial of acute normovolemic hemodilution compared with standard intraoperative management. Ann Surg. 2010;252:952–8. Han IW, Kim H, Heo J, Oh MG, Choi YS, Lee SE, et al. Excess intraoperative fluid volume administration is associated with pancreatic fistula after pancreaticoduodenectomy: A retrospective multicenter study. Med (Baltim). 2017;96:e6893. Bruns H, Kortendieck V, Raab HR, Antolovic D. Intraoperative Fluid Excess Is a Risk Factor for Pancreatic Fistula after Partial Pancreaticoduodenectomy. HPB Surg. 2016; 2016:1601340. Wang S, Wang X, Dai H, Han J, Li N, Li J. The effect of intraoperative fluid volume administration on pancreatic fistulas after pancreaticoduodenectomy. J Invest Surg. 2014;27:88–94. Cao X, Wang X, Zhao B, Kong L, Zhou L, Zhu W, et al. Correlation between Intraoperative Fluid Administration and Outcomes of Pancreatoduodenectomy. Gastroenterol Res Pract. 2020;2020:8914367. Huang Y, Chua TC, Gill AJ, Samra JS. Impact of perioperative fluid administration on early outcomes after pancreatoduodenectomy: A meta-analysis. Pancreatology. 2017;17:334–41. Chen BP, Chen M, Bennett S, Lemon K, Bertens KA, Balaa FK, et al. Systematic Review and Meta-analysis of Restrictive Perioperative Fluid Management in Pancreaticoduodenectomy. World J Surg. 2018;42:2938–50. Lapisatepun W, Wongsa W, Chanthima P, Junrungsee S, Lapisatepun W. Higher cumulative fluid following a pancreaticoduodenectomy as a single modifiable factor for post-operative pancreatic fistula: An analysis of risk factor. Asian J Surg. 2022;45:401–6. Winer LK, Dhar VK, Wima K, Lee TC, Morris MC, Shah SA, et al. Perioperative Net Fluid Balance Predicts Pancreatic Fistula After Pancreaticoduodenectomy. J Gastrointest Surg. 2018;22:1743–51. Weinberg L, Wong D, Karalapillai D, Pearce B, Tan CO, Tay S, et al. The impact of fluid intervention on complications and length of hospital stay after pancreaticoduodenectomy (Whipple's procedure). BMC Anesthesiol. 2014;14:35. Jeon HJ, Kwon HJ, Hwang YJ, Kim SG. Unfavorable effect of high postoperative fluid balance on outcome of pancreaticoduodenectomy. Ann Surg Treat Res. 2022;102:139–46. Shin CH, Long DR, McLean D, Grabitz SD, Ladha K, Timm FP, et al. Effects of Intraoperative Fluid Management on Postoperative Outcomes: A Hospital Registry Study. Ann Surg. 2018;267:1084–92. Brandstrup B. Fluid therapy for the surgical patient. Best Pract Res Clin Anaesthesiol. 2006;20:265–83. Braga M, Pecorelli N, Ariotti R, Capretti G, Greco M, Balzano G, et al. Enhanced recovery after surgery pathway in patients undergoing pancreaticoduodenectomy. World J Surg. 2014;38:2960–6. Marchegiani G, Bassi C. Prevention, prediction, and mitigation of postoperative pancreatic fistula. Br J Surg. 2021;108:602–4. Huscher C, Perri G, Lazzarin G, Marchegiani G, Malleo G, Salvia R, et al. Coronary Artery Stent for Securing High-risk Pancreatico-jejunal Anastomosis After Pancreatoduodenectomy: A Pilot Series. Ann Surg. 2022;275:e665–8. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 13 Apr, 2023 Read the published version in BMC Surgery → Version 1 posted Editorial decision: Major revision 03 Mar, 2023 Reviews received at journal 02 Mar, 2023 Reviewers agreed at journal 26 Feb, 2023 Reviewers agreed at journal 13 Feb, 2023 Reviewers invited by journal 10 Feb, 2023 Editor assigned by journal 10 Feb, 2023 Editor invited by journal 15 Jan, 2023 Submission checks completed at journal 15 Jan, 2023 First submitted to journal 10 Jan, 2023 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 Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2465372","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":167946421,"identity":"3099f7e0-6120-4887-bb5b-47567ec03094","order_by":0,"name":"Le Zhang","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Le","middleName":"","lastName":"Zhang","suffix":""},{"id":167946423,"identity":"b45ce962-2bc4-4735-8877-0a94e2cf93f7","order_by":1,"name":"Yuelun Zhang","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yuelun","middleName":"","lastName":"Zhang","suffix":""},{"id":167946424,"identity":"40681946-e4a3-44b5-89fe-01d5abd11339","order_by":2,"name":"Le Shen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0klEQVRIiWNgGAWjYJACZgaGAwwM7AyMDxIqakjRwszAbPDgzDHStLBJPmxhJqzcXCI78XPBnzty5szMxyoSG9gY+Nu7E/BqsZyRu1l6ZtszY8tmtrQbiTtkGCTOnN2AV4vBjdxtzLwNhxM3HOYxu5F4ho3BQCKXCC08fw7XbzjM/60gsY2ZWC1shxMMDvOwMRClxbLn7WZp3rbDhhsOsxlLJJw5xkPQL+bsuRs/Ax0mb3C8+eHHHxU1cvztvQQchi7Ag1c5Vi2jYBSMglEwCjAAAEgnSktavl5PAAAAAElFTkSuQmCC","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Le","middleName":"","lastName":"Shen","suffix":""}],"badges":[],"createdAt":"2023-01-11 04:29:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2465372/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2465372/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12893-023-01978-9","type":"published","date":"2023-04-13T20:29:06+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":31693328,"identity":"b87307ad-7a2d-4fab-b985-6db9ed31f015","added_by":"auto","created_at":"2023-01-17 15:57:08","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":87925,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAdjusted ORs of postoperative pancreatic fistula according to intraoperative fluid balance\u003c/strong\u003e. Odds ratios and 95% confidence intervals derived from restricted cubic spline regression, with knots placed at the 10th, 50th, and 90th percentiles of intraoperative fluid balance.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-2465372/v1/dead547db19818b66857a980.png"},{"id":44724907,"identity":"f6507526-1c0f-4722-baa6-1d0bbe8a6b04","added_by":"auto","created_at":"2023-10-16 20:37:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":738029,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2465372/v1/7b98d50e-84e7-4bd6-8e96-0158cb215724.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effects of Intraoperative Fluid Balance During Pancreatoduodenectomy on Postoperative Pancreatic Fistula: An Observational Cohort Study","fulltext":[{"header":"Background","content":"\u003cp\u003eFrom the perspective of anesthesiologists, perioperative fluid management is an important part of their anesthesia scheme. The fluid management strategies vary among anesthesiologists. In recent years, the classical perioperative fluid balance described in textbooks has been challenged. Fluid overload was reported to increase cardiopulmonary complications and impair the recovery of gastrointestinal function (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Restrictive fluid management has been thought to be beneficial for decreasing postoperative complications and improving prognosis for patients who underwent intraabdominal surgery (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). A meta‑analysis suggested that patients receiving restricted fluid therapy were associated with rapid recovery and shorter length of hospital stay compared with liberal management during abdominal surgery (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). In the consensus on the perioperative care of colorectal surgery patients, restrictive fluid management was recommended in the protocol of enhanced recovery after surgery (ERAS) (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Nevertheless, due to the limited quantity and quality of research, restrictive fluid management has been controversial during major abdominal surgery.\u003c/p\u003e \u003cp\u003ePancreaticoduodenectomy (PD), as one of the most complex and traumatic abdominal operations, is associated with many postoperative abdominal complications, including pancreatic fistula, bile leak (BL), postpancreatectomy hemorrhage (PPH), delayed gastric emptying (DGE), and intra-abdominal infection (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Postoperative pancreatic fistula (POPF) is a critical complication with an incidence ranging from 10\u0026ndash;34% (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). If timely and effective treatment is not available, patients with POPF could experience intra-abdominal infection, intra-abdominal bleeding, and even death, consequently extending the length of hospital stay and exacerbating the medical burden (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWe used to hold the opinion that whether POPF occurred depended largely on the technique and experience of surgeons. Some previous studies have clarified multiple perioperative factors related to POPF (\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). However, only a few studies have analyzed the correlation between intraoperative fluid management and POPF. Whether restrictive fluid management lowers the risk of POPF remains unclear. Therefore, we conducted a retrospective cohort study to clarify the impact of intraoperative fluid balance on the development of POPF. In addition, we performed exploratory analysis to investigate risk factors for POPF and the relationship between intraoperative fluid balance and other abdominal complications after PD.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Patient\u003c/h2\u003e \u003cp\u003e After approval by the institutional ethics board of Peking Union Medical College Hospital (K1522, 28 June 2022), the study created a retrospective cohort of patients who underwent open pancreatoduodenectomy between July 2016 and July 2021 at Peking Union Medical College Hospital. The surgeries were performed by an experienced surgical team. Indications for the surgery were tumors and other disorders of the pancreas, duodenum, bile duct, and adjacent other organs. The standard procedure of PD involved the removal of the pancreatic head, duodenum, first 15 cm of the jejunum, common bile duct, gallbladder, partial gastrectomy, and the reconstruction of gastrointestinal continuity. An end-to-side anastomosis was adopted in pancreaticojejunostomy, biliary-enteric anastomosis or gastrointestinal anastomosis. Modified PD, pylorus-preserving pancreaticoduodenectomy (PPPD) which preserves the gastric antrum, pylorus, and proximal 3 to 4 cm of the duodenum has been gradually used in the hospital for gastrointestinal continuity. The inclusion criteria were as follows: 1) older than 18 years; 2) ASA I\u0026ndash;Ⅲ; 3) patients who underwent elective open PD (including bowel resection, anastomosis, ostomy, partial vascular resection or reconstruction). The exclusion criteria were as follows: 1) patients who underwent total pancreatectomy and duodenectomy and 2) patients who lacked fluid records.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eIntraoperative Fluid Balance\u003c/h3\u003e\n\u003cp\u003eAccording to the Chinese conventional infusion regimen, the intraoperative fluid volume was calculated by subtracting the total fluid output (preoperative loss during fasting, physiological required volume, urine output, blood loss, third space fluid loss) from the total fluid input (crystalloids, colloids, blood products). Specifically speaking, we evaluated preoperative loss during fasting and physiological required volume using the \u0026ldquo;4-2-1\u0026rdquo; calculation. The third space fluid loss was calculated by 6mL/kg/h (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Finally, the intraoperative fluid balance was equal to the intraoperative fluid volume divided by the patients\u0026rsquo; weight and anesthesia time. The patients were categorized into 4 groups according to intraoperative fluid balance quartiles: Q1\u0026le;-1.62, -1.61\u0026thinsp;\u0026lt;\u0026thinsp;Q2\u0026thinsp;\u0026le;\u0026thinsp;0.80, -0.79\u0026thinsp;\u0026lt;\u0026thinsp;Q3\u0026thinsp;\u0026le;\u0026thinsp;0.02, Q4\u0026thinsp;\u0026ge;\u0026thinsp;0.03 mL/kg/h.\u003c/p\u003e\n\u003ch3\u003eEndpoints\u003c/h3\u003e\n\u003cp\u003eThe primary endpoint was clinically relevant POPF. In 2016, the International Study Group of Pancreatic Surgery (ISGPS) updated the POPF definition and grading system, which has been widely recognized and used. A clinically relevant POPF is defined as a drain output of any measurable volume of fluid with amylase level greater than 3 times the upper institutional normal serum amylase level, associated with a clinically relevant development/condition related directly to the POPF. Biochemical leakage no longer belonged to the category of POPF. Grade B was accompanied by a clinical change in the postoperative management or persistent drainage\u0026thinsp;\u0026gt;\u0026thinsp;3 weeks, while Grade C required reoperation or led to organ failure or death (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). The secondary endpoints included Grade B POPF, Grade C POPF, BL, PPH, and DGE. Likewise, the definitions of BL and PPH are derived from the ISGPS (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Yeo et al provided a clear definition of DGE in their prospective, randomized, and placebo-controlled trial. We chose to use the same definition for our study (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eStudy Variables\u003c/h3\u003e\n\u003cp\u003eWe collected demographic, laboratory, and medical data via the electronic medical record system and surgical anesthesia system of Peking Union Medical College Hospital. The baseline characteristics included age, sex, BMI, and comorbidities. BMI was expressed as a continuous variable as well as a categorical variable, and BMI was categorized into two groups: \u0026lt; 25kg/m\u003csup\u003e2\u003c/sup\u003e, \u0026ge;\u0026thinsp;25kg/m\u003csup\u003e2\u003c/sup\u003e. The preoperative variables consisted of abdominal surgery history, lesions site, ASA classification, preoperative fluid infusion, and laboratory data (preoperative albumin, bilirubin and blood glucose). The grouping thresholds of the laboratory data were determined by the medical reference value. The intraoperative variables were comprised of the anesthetic mode, surgery option, surgery time, and intraoperative fluid management (blood loss, urine output, red blood cells, fresh frozen plasma, crystalloid/colloid volume). PD and PPPD are two surgical options.\u003c/p\u003e\n\u003ch3\u003eStatistical Analyses\u003c/h3\u003e\n\u003cp\u003eAll participants were categorized into four groups according to quartiles of intraoperative fluid balance. Continuous variables were presented as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or medians and interquartile ranges where appropriate. Categorical data are shown as numbers and percentages. Univariate and multivariate nonconditional logistic regression analyses were performed to assess the association between the fluid balance quartiles and primary outcome. Variables potentially associated with POPF or clinically important were selected for logistic regression. Odds ratios (ORs) and 95% confidence intervals (95% CIs) across the fluid balance quartiles (the lowest quartile as a reference) were calculated. Based on a multivariate logistic regression model, we used restricted cubic splines (RCSs) to explore the nonlinear dose‒response relationship between intraoperative fluid balance and POPF, with three knots defined at the 10th, 50th, and 90th percentiles of intraoperative fluid balance (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Data were analyzed using SPSS version 25.0 (SPSS, Inc., Chicago, IL, USA). The restricted cubic spline analysis and the related figure were conducted with R version 4.2.0 (R Foundation for Statistical Computing, Vienna, Austria) using the rms and ggplot2 packages. All tests were 2-sided, and all tests were conducted at the 5% significance level.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eDemographics\u003c/h2\u003e \u003cp\u003eWe collected 595 patients who underwent elective open PD between July 2016 and July 2021 at Peking Union Medical College Hospital, and 567 patients were finally included for statistical analysis. A total of 336 (59.3%) of the patients were male. The patients were divided by their intraoperative fluid balance, ranging from \u0026minus;\u0026thinsp;8.47 to 13.56 mL/kg/h, according to the quartiles. The demographic characteristics based on the four groups are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The mean age of the enrolled patients was 58.68\u0026thinsp;\u0026plusmn;\u0026thinsp;10.87 years old, and there was no significant difference in the patients\u0026rsquo; ages among the groups. As the intraoperative fluid balance increased, the proportion of overweight patients decreased.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCohort Characteristics by Fluid Balance Quartiles\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll patients\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eQ1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eQ2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eQ3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eQ4\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;567)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;142)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;142)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;142)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;141)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge, mean (SD), years\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58.68\u0026thinsp;\u0026plusmn;\u0026thinsp;10.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58.46\u0026thinsp;\u0026plusmn;\u0026thinsp;10.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58.44\u0026thinsp;\u0026plusmn;\u0026thinsp;10.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e58.81\u0026thinsp;\u0026plusmn;\u0026thinsp;10.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e58.99\u0026thinsp;\u0026plusmn;\u0026thinsp;12.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex, male, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e336 (59.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77 (54.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100 (70.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e84 (59.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e75 (53.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI, mean (SD), kg/m\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.75\u0026thinsp;\u0026plusmn;\u0026thinsp;3.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.26\u0026thinsp;\u0026plusmn;\u0026thinsp;3.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22.52\u0026thinsp;\u0026plusmn;\u0026thinsp;3.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20.73\u0026thinsp;\u0026plusmn;\u0026thinsp;2.88\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI\u0026thinsp;\u0026ge;\u0026thinsp;25 kg/m\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e, \u003cb\u003en (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e134 (23.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53 (37.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39 (27.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29 (20.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13 (9.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComorbidities\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSmoking history, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e214 (37.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 (33.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64 (45.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e56 (39.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e46 (32.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAlcohol intake, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e179 (31.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44 (31%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e55 (38.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40 (28.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e40 (28.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHypertension, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e168 (29.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53 (37.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46 (32.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e43 (30.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e26 (18.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDiabetes mellitus, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e128 (22.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (24.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34 (23.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31 (21.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e28 (19.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCoronary artery disease, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 (7.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (8.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (6.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15 (10.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8 (5.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePreoperative characteristics\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAbdominal surgery history, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e164 (28.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (26.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39 (27.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36 (25.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e51 (36.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLesion site, pancreas, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e356 (62.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90 (63.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e90 (63.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e91 (64.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e85 (60.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eASA classification\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClass I\u0026ndash;II, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e477 (84.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e120 (84.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e122 (85.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e121 (85.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e114 (80.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClass III, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90 (15.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (15.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 (14.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21 (14.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e27 (19.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePre-ALB, mean (SD), g/L\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39.98\u0026thinsp;\u0026plusmn;\u0026thinsp;4.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40.92\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40.14\u0026thinsp;\u0026plusmn;\u0026thinsp;4.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e39.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e39.26\u0026thinsp;\u0026plusmn;\u0026thinsp;5.32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePre-ALB\u0026thinsp;\u0026lt;\u0026thinsp;35 g/L, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e78 (13.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (8.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25 (17.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e31 (22%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePre-TBIL, median (IQR), \u0026micro;mol/L\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.6 (11.4\u0026thinsp;~\u0026thinsp;69.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.9 (11.5\u0026thinsp;~\u0026thinsp;67.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18.75 (11.78\u0026thinsp;~\u0026thinsp;72.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19.6 (11.25\u0026thinsp;~\u0026thinsp;64.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18.5 (11.1\u0026thinsp;~\u0026thinsp;88.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePre-TBIL\u0026thinsp;\u0026gt;\u0026thinsp;17.1 \u0026micro;mol/L, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e303 (53.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74 (52.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75 (52.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e78 (54.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e76 (53.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePre-GLU, mean (SD), mmol/L\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.53\u0026thinsp;\u0026plusmn;\u0026thinsp;2.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.38\u0026thinsp;\u0026plusmn;\u0026thinsp;2.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.46\u0026thinsp;\u0026plusmn;\u0026thinsp;2.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.83\u0026thinsp;\u0026plusmn;\u0026thinsp;2.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.47\u0026thinsp;\u0026plusmn;\u0026thinsp;2.38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePre-GLU\u0026thinsp;\u0026gt;\u0026thinsp;6 mmol/L, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e244 (43.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57 (40.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e69 (48.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e61 (43%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e57 (40.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePreoperative fluid infusion, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e200 (35.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (22.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42 (29.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e55 (38.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e71 (50.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIntraoperative characteristics\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal intravenous anesthesia, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 (8.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (7.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (6.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9 (6.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21 (14.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSurgery time, mean (SD), h\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.87\u0026thinsp;\u0026plusmn;\u0026thinsp;1.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.86\u0026thinsp;\u0026plusmn;\u0026thinsp;1.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.02\u0026thinsp;\u0026plusmn;\u0026thinsp;1.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.89\u0026thinsp;\u0026plusmn;\u0026thinsp;1.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePPPD, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76 (13.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (14.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24 (16.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20 (14.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12 (8.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBlood transfusion, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e301 (53.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40 (28.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64 (45.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e84 (59.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e113 (80.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBlood loss, median (IQR), L\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.46 (0.3\u0026thinsp;~\u0026thinsp;0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.4 (0.3\u0026thinsp;~\u0026thinsp;0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.4 (0.3\u0026thinsp;~\u0026thinsp;0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.41 (0.3\u0026thinsp;~\u0026thinsp;0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.5 (0.4\u0026thinsp;~\u0026thinsp;0.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRed blood cells, median (IQR), units\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0\u0026thinsp;~\u0026thinsp;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0\u0026thinsp;~\u0026thinsp;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0\u0026thinsp;~\u0026thinsp;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (0\u0026thinsp;~\u0026thinsp;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4 (1\u0026thinsp;~\u0026thinsp;4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFresh frozen plasma, median (IQR), L\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0\u0026thinsp;~\u0026thinsp;0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0\u0026thinsp;~\u0026thinsp;0.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0\u0026thinsp;~\u0026thinsp;0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.2 (0\u0026thinsp;~\u0026thinsp;0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.4 (0\u0026thinsp;~\u0026thinsp;0.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCrystalloid, median (IQR), L\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (2.4\u0026thinsp;~\u0026thinsp;3.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.45 (2.1\u0026thinsp;~\u0026thinsp;2.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.85 (2.5\u0026thinsp;~\u0026thinsp;3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.3 (2.7\u0026thinsp;~\u0026thinsp;3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.4 (2.8\u0026thinsp;~\u0026thinsp;4.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eColloid, median (IQR), L\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.5\u0026thinsp;~\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5 (0.5\u0026thinsp;~\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.5\u0026thinsp;~\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (0.5\u0026thinsp;~\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (0.5\u0026thinsp;~\u0026thinsp;1.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003ePre, Preoperative; SD, standard deviation; IQR, interquartile range; ALB, albumin; TBIL, total bilirubin; GLU, blood glucose; PPPD, pylorus-preserving pancreaticoduodenectomy\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eIntraoperative Fluid Balance And Popf\u003c/h3\u003e\n\u003cp\u003eAmong the 567 patients, 108 were diagnosed with POPF, and the incidence was 19.0%. Among them, 80 patients were categorized into Grade B while 28 patients belonged to Grade C. There were 22 patients with POPF in the Q3 group of intraoperative fluid balance, which was lower than the other three groups. First, we used intraoperative fluid balance as a categorical variable and the lowest quartile as the reference to conduct a univariate analysis. The results showed no statistically significant relationship between intraoperative fluid balance and POPF. Then, multivariate logistic regression was performed after adjusting for potential confounding factors, including age, sex, BMI, abdominal surgery history, preoperative bilirubin, preoperative blood glucose, ASA classification, anesthetic mode, surgery option, and lesion site. The outcome did not change. Furthermore, we took into account the differentiation between grade B and grade C POPF, the outcome kept the same. The results are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Furthermore, we adjusted for the same potential confounders and modeled the association between intraoperative fluid balance and POPF using restricted cubic splines. The AIC value for the model with a 3-knot RCS function was less than those for the models with a 4-knot or 5-knot, suggesting that the model with a 3-knot RCS function was more adequate. The results are presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. According to the OR curve, when the intraoperative fluid balance level was approximately \u0026minus;\u0026thinsp;0.7 mL/kg/h, the risk of POPF was minimal. When the intraoperative fluid balance level became more positive or negative, the risk of POPF increased. Nevertheless, the value of the test for the overall association between intraoperative fluid balance and POPF was insignificant, which means that regardless of the shape of this curve, there was no significant association between intraoperative fluid balance and POPF.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociations Between Fluid Balance and Outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eQ1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eQ2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eQ3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eQ4\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;142)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;142)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;142)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;141)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary Outcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePOPF, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (20.42%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29 (20.42%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22 (15.49%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e28 (19.86%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAdjusted OR95%CI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (0.56,1.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.71 (0.39,1.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.97 (0.54,1.73)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eP\u003c/span\u003e \u003cb\u003evalue\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.668\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAdjusted OR95%CI\u003c/b\u003e\u003csup\u003e\u003cb\u003e\u0026dagger;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.15 (0.62,2.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.86 (0.45,1.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.3 (0.69,2.46)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eP\u003c/span\u003e \u003cb\u003evalue\u003c/b\u003e\u003csup\u003e\u003cb\u003e\u0026dagger;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.618\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSecondary Outcomes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGrade B POPF, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (14.79%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e24 (16.90%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e15 (10.56%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e20 (14.18%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAdjusted OR95%CI\u003c/b\u003e\u003csup\u003e\u003cb\u003e\u0026dagger;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.38 (0.7,2.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.92 (0.44,1.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.31 (0.63,2.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eP\u003c/span\u003e \u003cb\u003evalue\u003c/b\u003e\u003csup\u003e\u003cb\u003e\u0026dagger;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGrade C POPF, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (7.75%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (2.82%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5 (3.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8 (5.63%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAdjusted OR95%CI\u003c/b\u003e\u003csup\u003e\u003cb\u003e\u0026dagger;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.68 (0.22,2.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.73 (0.23,2.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.25 (0.42,3.69)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eP\u003c/span\u003e \u003cb\u003evalue\u003c/b\u003e\u003csup\u003e\u003cb\u003e\u0026dagger;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.698\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBL, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (4.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (3.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7 (4.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAdjusted OR95%CI\u003c/b\u003e\u003csup\u003e\u003cb\u003e\u0026dagger;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.61 (0.18,2.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.99 (0.33,2.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.95 (0.29,3.06)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eP\u003c/span\u003e \u003cb\u003evalue\u003c/b\u003e\u003csup\u003e\u003cb\u003e\u0026dagger;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.841\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePPH, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (19%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29 (20.40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25 (17.60%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e37 (26.20%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAdjusted OR95%CI\u003c/b\u003e\u003csup\u003e\u003cb\u003e\u0026dagger;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.15 (0.62,2.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.97 (0.52,1.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.86 (1.01,3.43)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eP\u003c/span\u003e \u003cb\u003evalue\u003c/b\u003e\u003csup\u003e\u003cb\u003e\u0026dagger;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDGE, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (16.90%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14 (9.90%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22 (15.50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e24 (17.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAdjusted OR95%CI\u003c/b\u003e\u003csup\u003e\u003cb\u003e\u0026dagger;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.55 (0.27,1.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.99 (0.51,1.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.22 (0.63,2.36)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eP\u003c/span\u003e \u003cb\u003evalue\u003c/b\u003e\u003csup\u003e\u003cb\u003e\u0026dagger;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.187\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003e\u003cb\u003e\u0026dagger;\u003c/b\u003e\u003c/sup\u003eadjusted by age, sex, BMI, abdominal surgery history, preoperative bilirubin, preoperative blood glucose, ASA classification, anesthetic mode, surgery option, and location of lesion. the lowest quartile as the reference. POPF, postoperative pancreatic fistula; BL, bile leakage; PPH, postpancreatectomy hemorrhage; DGE, delayed gastric emptying; OR, odds ratio; CI, confidence interval.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eOther Complications And Risk Factors For Popf\u003c/h3\u003e\n\u003cp\u003eThe incidences of BL, PPH, and GED were 4.4%, 20.8%, and 14.8%, respectively. We found that the association between intraoperative fluid balance and these abdominal complications was not statistically significant. For risk factors for POPF, after univariate regression analysis, we included the variables with P\u0026thinsp;\u0026lt;\u0026thinsp;0.1 in the multivariate regression analysis, and the results are shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. We found that BMI, preoperative blood glucose, surgery time, and lesion site were related to POPF. In contrast to the patients without POPF, the surgeries (OR: 1.29, 95% CI: 1.08\u0026ndash;1.55) were longer, and the proportion of overweight patients (OR: 2.45, 95% CI: 1.54\u0026ndash;3.91) was higher in the group of patients who developed POPF. However, preoperative hyperglycemia (blood glucose\u0026thinsp;\u0026gt;\u0026thinsp;6 mmol/L, OR: 0.61, 95% CI: 0.38\u0026ndash;0.97) and lesions located in the pancreas (OR: 0.43, 95% CI: 0.27\u0026ndash;0.67) were protective factors for POPF.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRisk factors for POPF based on logistic regression analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUnivariate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMultivariate\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR95%CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOR95%CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI\u0026thinsp;\u0026ge;\u0026thinsp;25 kg/m\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.54 (1.62,3.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.45 (1.54,3.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePreoperative GLU\u0026thinsp;\u0026gt;\u0026thinsp;6 mmol/L\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.6 (0.39,0.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.61 (0.38,0.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSurgery time, h\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.26 (1.09,1.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.29 (1.08,1.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBlood loss, L\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.37 (1.01,1.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.046\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.09 (0.75,1.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.659\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePreoperative fluid infusion\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.62 (0.39,0.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.043\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.73 (0.45,1.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.208\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLesion site, pancreas\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.45 (0.3,0.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.43 (0.27,0.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eGLU, blood glucose; OR, odds ratio; CI, confidence interval.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eFluid management is complex and variable. Some studies tend to support restrictive fluid management, but the controversy over fluid management has never ceased. Zhang et al. enrolled 301 patients for a retrospective study, and the results showed that higher postoperative fluid balance appeared to be associated with morbidity after PD, systemic inflammatory response syndrome (SIRS), acute respiratory distress syndrome (ARDS), bleeding, and heart failure (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). However, Meyhoff et al. performed an international, randomized trial among adult patients with septic shock in the ICU and found that intravenous fluid restriction did not decrease mortality at 90 days compared with standard intravenous fluid therapy (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe relationship between intraoperative fluid balance and the specific abdominal complication of POPF is also ambiguous. Some studies have demonstrated that the incidence of POPF in the high fluid volume group was higher than that in the low fluid volume group during PD, and intraoperative fluid excess was also considered a risk factor for POPF (\u003cspan additionalcitationids=\"CR20 CR21 CR22\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Nevertheless, in 2017, a meta-analysis evaluated the relationship between the perioperative fluid balance and postoperative complications of PD (including POPF), and no significant correlation was found (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Similarly, a meta-analysis published in 2018 demonstrated that intraoperative fluid balance did not affect the occurrence of POPF (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Interestingly, a retrospective cohort study showed that intraoperative fluid balance did not affect the incidence of POPF, but the higher cumulative fluid balance per body weight (FBPBW) at postoperative day 3 was an independent risk factor for CR-POPF (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Other studies have also demonstrated that patients with a high postoperative fluid balance presented a higher incidence of POPF (\u003cspan additionalcitationids=\"CR28\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). Although the related mechanisms have not been thoroughly studied, there are some plausible claims. Trauma of the pancreatic surface in the PD procedure and leakage of a pancreatic-enteric anastomosis are the main reasons for POPF (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Fluid overload could cause pancreatic parenchyma and intestinal edema, increase the distance between capillaries and cells, impair gas exchange, and then lead to dysfunction or disruption of the pancreatojejunostomy (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe study consecutively enrolled 567 patients who underwent PD surgery, and they were divided into four groups by the quartiles of intraoperative fluid balance to explore any difference in POPF between the four groups. Then, intraoperative fluid balance was regarded as a continuous variable, and we used restricted cubic splines to analyze whether a dose‒response relationship existed between intraoperative fluid balance and POPF. Finally, the relationship was found to be statistically insignificant. In addition, we did not find an association between intraoperative fluid balance and BL, DEG, or PPH. Identically, Braga et al. grouped patients undergoing PD according to whether they received a comprehensive ERAS protocol or standard perioperative care. A comprehensive ERAS protocol contained many items, such as a lack of bowel preparation and shortening of the preoperative fasting period, and the intravenous fluid infusion rate was lower in the ERAS group. The results showed that the incidence of POPF was similar in the two groups, as were BL, DGE, and PPH (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSex, BMI, fasting blood glucose level, pancreatic texture, pancreatic duct, pancreatojejunostomy anastomosis technique, and tumor location were related risk factors for POPF. Our study found that BMI\u0026thinsp;\u0026ge;\u0026thinsp;25kg/m\u003csup\u003e2\u003c/sup\u003e, preoperative hypoglycemia (blood glucose\u0026thinsp;\u0026le;\u0026thinsp;6 mmol/L), long surgery time, and lesion not located in the pancreas were risk factors for POPF. Preoperative hypoglycemia, lesions not located in the pancreas, and BMI might lead to a softer pancreas, thereby influencing the occurrence of POPF (\u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). In addition, when the operation was complicated and difficult, the surgery took longer, and there was a tendency to develop related postoperative complications. As the most critical complication of PD, the treatment and prevention of POPF have been the main concerns for pancreatic surgeons. Besides early identification of related risk factors for POPF, other contemporary mitigation strategies include the use of abdominal drains, prophylactic somatostatin analogues, modified anastomotic techniques, and anastomotic stents (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). Recently, a study showed that coronary artery stent (CAS) positioning in PJ anastomosis could be a novel mitigation strategy in the prevention of POPF (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe definition of POPF is relatively uniform in many studies, but the calculation of perioperative fluid balance or fluid management varies. There is no uniform standard for the definition of perioperative fluid balance or fluid management, especially for the cutoff values, which can vary (\u003cspan additionalcitationids=\"CR21 CR22\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e), and this makes it difficult to integrate and summarize the results of current clinical studies. Relevant research results should be treated with caution. Many anesthesiologists still use the conventional infusion regimen described in textbooks when formulating plans before major surgery. Our definition of fluid balance was based on that. However, the conventional infusion regimen took the patient\u0026rsquo;s perioperative physiological needs and the third space fluid loss into account; patients were thought to be relatively hypovolemic and therefore required relatively more aggressive fluid replacement. This explains why many patients received a negative intraoperative balance in our study. Our definition of intraoperative fluid balance consisted of the surgery time and patient weight, which helped to reduce the impact of the surgery time and patient weight on intraoperative fluid balance. The intraoperative RBC and colloid infusion in Q3 and Q4 was higher than that in Q1 and Q2. However, intraoperative fluid balance was an integrated variable, and it was difficult for us to explain whether the intraoperative RBC and colloid infusion affected the incidence of POPF. Moreover, we did not consider the difference in the volume effect of crystalloids and colloids when calculating the intraoperative fluid balance.\u003c/p\u003e \u003cp\u003eMany anesthesiologists formulate the intraoperative fluid management plans in advance based on the patient\u0026rsquo;s physiological needs. In fact, the intraoperative fluid management is affected by many factors, such as intraoperative bleeding, patient cardiovascular function, depth of anesthesia, and use of vasoactive drugs in a major surgery such as PD. Therefore, many anesthesiologists often use invasive monitoring methods in combination with other hemodynamic parameters to evaluate the patient's volume status and adjust their fluid management plan in a timely manner. As a result, the concept of goal-directed fluid therapy (GDFT) may be the most reasonable fluid management strategy available.\u003c/p\u003e\n\u003ch3\u003eLimitation\u003c/h3\u003e\n\u003cp\u003eThe present study had some limitations. First, this study analyzed the association between intraoperative fluid balance and the incidence of POPF but did not further analyze the effect of intraoperative fluid balance on the severity of POPF. Second, it was a retrospective analysis in which our data lacked some variables involved in the operation. Confounding factors such as pancreatic texture and pancreatic duct played an influential role in whether pancreatic fistula occurred. Third, all the patients were treated at a single center. To validate the effect of intraoperative fluid balance on POPF, a multicenter study with a larger number of patients is needed in the future.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOur study failed to find a significant association between intraoperative fluid balance and POPF. Furthermore, the correlations between fluid balance and other abdominal complications were statistically insignificant. On the other hand, the findings of this study indicated that BMI, blood glucose, surgery and lesion site were closely related to POPF. It is necessary to unify the definition of fluid balance and develop well-designed studies to validate the optimal fluid strategy and reduce abdominal complications such as POPF. Until then, the intraoperative fluid management plan of PD should be individualized and adjusted according to the actual situation.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003ePOPF, Postoperative pancreatic fistula; PD, pancreaticoduodenectomy; RCS, restricted cubic splines; ERAS, enhanced recovery after surgery; BL, bile leak; PPH, postpancreatectomy hemorrhage; DGE, delayed gastric emptying; PPPD, pancreaticoduodenectomy; ISGPS, International Study Group of Pancreatic Surgery; OR, odds ratio; CI, confidence interval; SIRS, systemic inflammatory response syndrome; ARDS, acute respiratory distress syndrome; FBPBW, cumulative fluid balance per body weight; CAS, coronary artery stent; GDFT, goal-directed fluid therapy.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and approved by the institutional ethics board of Peking Union Medical College Hospital (K1522, 28 June 2022).\u0026nbsp;As a retrospective study, it did not impair the patients’ legal rights and interests because we only collected data in the electronic medical record system and surgical anesthesia system of Peking Union Medical College Hospital and did not utilize any forms of personally identifiable data in the study. Therefore, the Peking Union Medical College Hospital Institutional Review Board approved our application of waiving informed consent.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available due to the fear of improper use but are available from the corresponding author on reasonable request\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the This research was funded by National High Level Hospital Clinical Research Funding and National Key Research and Development Program of China (2020YFC2008401-1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSL and ZL designed the study; ZL collected and analyzed clinical data and wrote this manuscript; SL and ZYL reviewed and revised the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cspan\u003eBundgaard-Nielsen M, Secher NH, Kehlet H. Kehlet. \u0026apos;Liberal\u0026apos; vs. \u0026apos;restrictive\u0026apos; perioperative fluid therapy\u0026ndash;a critical assessment of the evidence. Acta Anaesthesiol Scand. 2009;53:843\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eNisanevich V, Felsenstein I, Almogy G, Weissman C, Einav S, Matot I. Effect of intraoperative fluid management on outcome after intraabdominal surgery. Anesthesiology. 2005;103:25\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eJia FJ, Yan QY, Sun Q, Tuxun T, Liu H, Shao L. Liberal versus restrictive fluid management in abdominal surgery: a meta-analysis. Surg Today. 2017;47:344\u0026ndash;56.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eLassen K, Soop M, Nygren J, Cox PB, Hendry PO, Spies C, et al. Consensus review of optimal perioperative care in colorectal surgery: Enhanced Recovery After Surgery (ERAS) Group recommendations. Arch Surg. 2009;144:961\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eKarim SAM, Abdulla KS, Abdulkarim QH, Rahim FH. The outcomes and complications of pancreaticoduodenectomy (Whipple procedure): Cross sectional study. Int J Surg. 2018;52:383\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003ePulvirenti A, Ramera M, Bassi C. Modifications in the International Study Group for Pancreatic Surgery (ISGPS) definition of postoperative pancreatic fistula. Transl Gastroenterol Hepatol. 2017;2:107.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eChen JS, Liu G, Li TR, Chen JY, Xu QM, Guo YZ, et al. 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Excess intraoperative fluid volume administration is associated with pancreatic fistula after pancreaticoduodenectomy: A retrospective multicenter study. Med (Baltim). 2017;96:e6893.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBruns H, Kortendieck V, Raab HR, Antolovic D. Intraoperative Fluid Excess Is a Risk Factor for Pancreatic Fistula after Partial Pancreaticoduodenectomy. HPB Surg. 2016; 2016:1601340.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eWang S, Wang X, Dai H, Han J, Li N, Li J. The effect of intraoperative fluid volume administration on pancreatic fistulas after pancreaticoduodenectomy. J Invest Surg. 2014;27:88\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eCao X, Wang X, Zhao B, Kong L, Zhou L, Zhu W, et al. Correlation between Intraoperative Fluid Administration and Outcomes of Pancreatoduodenectomy. 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Effects of Intraoperative Fluid Management on Postoperative Outcomes: A Hospital Registry Study. Ann Surg. 2018;267:1084\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBrandstrup B. Fluid therapy for the surgical patient. Best Pract Res Clin Anaesthesiol. 2006;20:265\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBraga M, Pecorelli N, Ariotti R, Capretti G, Greco M, Balzano G, et al. Enhanced recovery after surgery pathway in patients undergoing pancreaticoduodenectomy. World J Surg. 2014;38:2960\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eMarchegiani G, Bassi C. Prevention, prediction, and mitigation of postoperative pancreatic fistula. Br J Surg. 2021;108:602\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eHuscher C, Perri G, Lazzarin G, Marchegiani G, Malleo G, Salvia R, et al. 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Ann Surg. 2022;275:e665\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\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":"bmc-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bsur","sideBox":"Learn more about [BMC Surgery](http://bmcsurg.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bsur/default.aspx","title":"BMC Surgery","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"pancreaticoduodenectomy, intraoperative fluid balance, postoperative pancreatic fistula, risk factors, postoperative complications","lastPublishedDoi":"10.21203/rs.3.rs-2465372/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2465372/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Perioperative fluid management during major abdominal surgery has been controversial. Postoperative pancreatic fistula (POPF) is a critical complication of pancreaticoduodenectomy (PD). We conducted a retrospective cohort study to analyze the impact of intraoperative fluid balance on the development of POPF\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e This retrospective cohort study enrolled 567 patients who underwent open pancreaticoduodenectomy, and the demographic, laboratory, and medical data were recorded. All patients were categorized into four groups according to quartiles of intraoperative fluid balance. Multivariate logistic regression and restricted cubic splines (RCSs) were used to analyze the relationship between intraoperative fluid balance and POPF.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e The intraoperative fluid balance of all patients ranged from -8.47 to 13.56 mL/kg/h. A total of 108 patients reported POPF, and the incidence was 19.0%. After adjusting for potential confounders and using restricted cubic splines, the dose‒response relationship between intraoperative fluid balance and POPF was found to be statistically insignificant. The incidences of bile leakage, postpancreatectomy hemorrhage, and delayed gastric emptying were 4.4%, 20.8%, and 14.8%, respectively. Intraoperative fluid balance was not associated with these abdominal complications. BMI≥25kg/m\u003csup\u003e2\u003c/sup\u003e, preoperative blood glucose\u0026lt;6 mmol/L, long surgery time, and lesions not located in the pancreas were independent risk factors for POPF.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThe study did not find a significant association between intraoperative fluid balance and POPF. Well-designed multicenter studies are necessary to explore the association between intraoperative fluid balance and POPF.\u003c/p\u003e","manuscriptTitle":"Effects of Intraoperative Fluid Balance During Pancreatoduodenectomy on Postoperative Pancreatic Fistula: An Observational Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-01-17 15:57:02","doi":"10.21203/rs.3.rs-2465372/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2023-03-03T07:23:13+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-03-02T08:52:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"bef77a50-84a1-4c15-99d1-37cba3980e6c","date":"2023-02-26T22:14:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"147bc5b0-c778-4d22-8f4a-1aa5997a5e34","date":"2023-02-14T00:22:53+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-02-10T08:31:47+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-02-10T08:27:04+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2023-01-16T04:38:46+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-01-16T04:31:43+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Surgery","date":"2023-01-11T04:19:57+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bsur","sideBox":"Learn more about [BMC Surgery](http://bmcsurg.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bsur/default.aspx","title":"BMC Surgery","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"acc25fd9-1866-4824-b883-be701de66bf8","owner":[],"postedDate":"January 17th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-10-16T20:32:50+00:00","versionOfRecord":{"articleIdentity":"rs-2465372","link":"https://doi.org/10.1186/s12893-023-01978-9","journal":{"identity":"bmc-surgery","isVorOnly":false,"title":"BMC Surgery"},"publishedOn":"2023-04-13 20:29:06","publishedOnDateReadable":"April 13th, 2023"},"versionCreatedAt":"2023-01-17 15:57:02","video":"","vorDoi":"10.1186/s12893-023-01978-9","vorDoiUrl":"https://doi.org/10.1186/s12893-023-01978-9","workflowStages":[]},"version":"v1","identity":"rs-2465372","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2465372","identity":"rs-2465372","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}