The development of POPF grade B or C was 15.2% (n:7) in ERAS group and 4.8% (n:1) in No-ERAS group being statistically non-significant (P = 0.41; odds ratio [OR] 1.7, 95% confidence interval [CI] 0.32–9.0). Moreover, the development of DGE was 4.3% (n:2) in ERAS group and 28.5% (n:6) in No-ERAS group, with no statistical significance (P = 0.009; OR 0.1, 95% CI 0.02–0.62).
A step by step forward binary logistic regression analysis was conducted using the Hosmer–Lemeshow test, including the variables described in the literature with biological plausibility. In addition, we analyzed the coefficient of determination (R squared of Nagelkerke) and found that 20% of the fistulas of the selected sample could be accounted for by the variables included in the model. However, none of the variables were statistically significant under the explanatory model for the development of fistulas (Table 2).
Moreover, the risk of experiencing bleeding of more than 600 mL, requiring more than 7500 mL of fluid therapy and need for transfusion was higher in the No-ERAS group (P = 0.001, 0.001, <0.001, respectively). The use of vasopressors did not show any differences between both groups. The total length of stay was higher in the No-ERAS group with 14 days (interquartilel range 8–20, P ≤ 0.001). No differences in 30 days mortality were found (Table 3).
Fluid therapy is a significant challenge for the anesthesiologist during surgery. The therapy must be guided by algorithms aimed at physiological objectives, knowing that a hyper or hypovolemic status increases the risk of complications.1,10,11 Moreover, fluid therapy should be administered when the patient is a responder to volume according to the Frank–Starling curve, achieving adequate tissue perfusion in the microcirculation.12–14 Navarro et al15 recommend the use of protocols and fluid therapy governed by goals based on the measurement of dynamic variables (such as stroke volume variation: SVV, pulse pressure variation) in major surgeries.16
Since the introduction of the ERAS guidelines, their multimodal approach and strategies are meant to reduce the length of stay, morbidity, and improve the functional capacity of patients.17 From the perspective of the anesthesiologist, these strategies are aimed at achieving better pain control leading to an early mobilization; better fluid control, starting from the pre-operative period with shorter fasting times for liquids and decreased net fluid balance.18 The end result is that patients included in enhanced recovery programs have faster hospital discharges, less medical complications, and lower hospital costs, compared with the standard perioperative treatment groups.19,20
Recently, the administration of intravenous fluids in the perioperative period has received growing attention due to its impact on patient recovery.21 There are several international studies comparing liberal vs restrictive administration of intravenous fluids in DP. The importance of this study that it presents our results considering that there are not studies about this topic in the Latin America population.2,3
DP is one of the most challenging intra-abdominal procedures. Nevertheless, even the most uneventful DP may be associated with the development of POPF.22 The exact pathophysiological mechanism explaining the development of a pancreatic fistula is unclear. It has been suggested that the excessive administration of intravenous fluids in the perioperative period may result in pancreatic parenchymal edema, and in general, edema of the entire gastrointestinal tract that could compromise the healing of the anastomosis. In addition, this predisposes to suture dehiscence due to increased intestinal pressure of the submucosa, decreased oxygenation, decreased mesenteric blood flow, and intramural acidosis.23
Studies have suggested that the adequate and restrictive administration of intravenous fluids reduces the complications, recovery time, and hospital stay of patients undergoing major gastrointestinal surgery, specifically DP; while on the contrary, the liberal administration of fluids is associated with an increased mortality and the development of complications such as POPF, with an incidence ranging between 10% and 40% according to the literature.1,21,24 However, Chen et al25 concluded that there are very few studies to be able to draw conclusions about this matter. Wang et al26 concluded in their studies that complications in pancreatic anastomosis were more significant in patients with high intraoperative fluid volumes (≥8.2 mL/kg/h) (P = 0.035). We were however unable to ascertain the association between high rates of intraoperative fluid therapy and the presence of POPF.
Kulemann et al1 in a retrospective study concluded that a duration of surgery beyond than 420 minutes predisposes the patient to receiving increasing amounts of intravenous fluids and lead to more significant complications in the postoperative period (P < 0.001) with the development of pancreatic fistula B/C (P < 0.005). In our study, patients who presented POPF were mostly type B or C and were part of the ERAS group (P = 0.556) but the non-significant results of the variables that might explain the development of fistulae may be accounted for by the low frequency of this complication in the sample; therefore, larger samples are needed to find a model that can indicate which are the variables that best explain the development of POPF.
Multiple strategies have been developed trying to reduce the incidence of POPF after DP, including modifications in the technique used for the pancreatic stump anastomosis, such as end-to-side PJ, PG, dunking PJ, or pancreatic duct occlusion27–29 among others, also associated with or without the use of a plastic stent in the pancreatic duct.30 However, the evidence in favor of one technique versus the others to reduce the incidence of POPF after DP is not conclusive.28,30 This study failed to show a difference in the incidence of POPF based on the pancreatic reconstruction technique used. However, a higher incidence of postoperative upper gastrointestinal bleeding was observed in PG, as shown in other reports.31
We were able to show that patients using ERAS protocols had less intraoperative bleeding, less transfusional needs, and a shorter hospital stay, and this was similar to the results reported by Melis et al32 in their group with less intraoperative fluid administration (<6000 mL).
Our study has its own limitations due to the retrospective observational and single-center design method. The number of patients in the ERAS group was twice the number in the No-ERAS group and the total incidence of POPF is very low, which hinders the statistical analysis.
In conclusion, intraoperative fluid restriction in DP did not show a significant effect on the incidence of POPF; however, the implementation of ERAS protocols in HPB surgery decreases the number of complications such as DGE, while reducing blood loss, the need for transfusion, fluid therapy, and most of all, shortens the length of stay.
Protection of persons and animals. The authors declare that no experiments have been made in humans or animals for this research.
Confidentiality of the information. The authors claim to have followed their institutional protocols for disclosure of patient information.
Right to privacy and informed consent. The authors declare that no patient data have been disclosed in this article.
The authors declare no financial support.
Conflict of interests
The authors have no conflict of interests to disclose.
1. Kulemann B, Fritz M, Glatz T, et al. Complications
are associated with higher amounts of intra- and postoperative fluid therapy
: a single center retrospective cohort study. Ann Med Surg
2. Ahmad SA, Edwards MJ, Sutton JM, et al. Factors influencing readmission after pancreaticoduodenectomy
: a multi-institutional study of 1302 patients. Ann Surg
3. Callery MP, Pratt WB, Kent TS, et al. A prospectively validated clinical risk score accurately predicts pancreatic fistula
after pancreatoduodenectomy. J Am Coll Surg
4. Lassen K, Coolsen MME, Slim K, et al. Guidelines for perioperative care for pancreaticoduodenectomy
: Enhanced Recovery after Surgery (ERAS®) Society recommendations. World J Surg
5. Sikora SS, Posner MC. Management of the pancreatic stump following pancreaticoduodenectomy
. Br J Surg
6. Bassi C, Marchegiani G, Dervenis C, et al. The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula
: 11 years after. Surgery
7. Wente MN, Bassi C, Dervenis C, et al. Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS). Surgery
8. Ghooi R. The Nuremberg Code—a critique. Perspect Clin Res
10. Brandstrup B, Tønnesen H, Beier-Holgersen R, et al. Effects of intravenous fluid restriction on postoperative complications
: comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial. Ann Surg
11. Gan TJ, Soppitt A, Maroof M, et al. Goal-directed intraoperative fluid administration reduces length of hospital stay after major surgery. Anesthesiology
12. Voldby AW, Brandstrup B. Fluid therapy
in the perioperative setting—a clinical review. J Intensive Care
13. Mythen MG, Swart M, Acheson N, et al. Perioperative fluid management: consensus statement from the enhanced recovery partnership. Perioper Med (Lond)
14. Cannesson M, Ramsingh D, Rinehart J, et al. Perioperative goal-directed therapy and postoperative outcomes in patients undergoing high-risk abdominal surgery: a historical-prospective, comparative effectiveness study. Crit Care
15. Navarro LHC, Bloomstone JA, Auler JOC, et al. Perioperative fluid therapy
: a statement from the international Fluid Optimization Group. Perioper Med (Lond)
16. Benes J, Giglio M, Brienza N, et al. The effects of goal-directed fluid therapy
based on dynamic parameters on post-surgical outcome: a meta-analysis of randomized controlled trials. Crit Care
17. Visioni A, Shah R, Gabriel E, et al. Enhanced recovery after surgery for noncolorectal surgery?: a systematic review and meta-analysis of major abdominal surgery. Ann Surg
18. Scott MJ, Miller TE. Pathophysiology of major surgery and the role of enhanced recovery pathways and the anesthesiologist to improve outcomes. Anesthesiol Clin
19. Jones C, Kelliher L, Dickinson M, et al. Randomized clinical trial on enhanced recovery versus standard care following open liver resection: enhanced recovery following open liver resection. Br J Surg
20. Joliat GR, Labgaa I, Hübner M, et al. Cost–benefit analysis of the implementation of an enhanced recovery program in liver surgery. World J Surg
21. Han IW, Kim H, Heo J, et al. Excess intraoperative fluid volume administration is associated with pancreatic fistula
: a retrospective multicenter study. Medicine (Baltimore)
22. Pedrazzoli S. Pancreatoduodenectomy (PD) and postoperative pancreatic fistula
(POPF): a systematic review and analysis of the POPF-related mortality rate in 60,739 patients retrieved from the English literature published between 1990 and 2015. Medicine (Baltimore)
23. Fischer M, Matsuo K, Gonen M, 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
24. Khalil JA, Mayo N, Dumitra S, et al. Pancreatic fistulae after a pancreatico-duodenectomy: are pancreatico-gastrostomies safer than pancreatico-jejunostomies? An expertise-based trial and propensity-score adjusted analysis. HPB (Oxford)
25. Chen BP, Chen M, Bennett S, et al. Systematic review and meta-analysis of restrictive perioperative fluid management in pancreaticoduodenectomy
. World J Surg
26. Wang S, Wang X, Dai H, et al. The effect of intraoperative fluid volume administration on pancreatic fistulas after pancreaticoduodenectomy
. J Invest Surg
27. Berger AC, Howard TJ, Kennedy EP, et al. Does type of pancreaticojejunostomy after pancreaticoduodenectomy
decrease rate of pancreatic fistula
? A randomized, prospective, dual-institution trial. J Am Coll Surg
28. Tran K, Van Eijck C, Di Carlo V, et al. Occlusion of the pancreatic duct versus pancreaticojejunostomy: a prospective randomized trial. Ann Surg
2002; 236:422–428. discussion 428.
29. Z’graggen K, Uhl W, Friess H, et al. How to do a safe pancreatic anastomosis. J Hepatobiliary Pancreat Surg
30. Dong Z, Xu J, Wang Z, et al. Stents for the prevention of pancreatic fistula
. Cochrane Database Syst Rev
31. Yang SH, Dou KF, Sharma N, et al. The methods of reconstruction of pancreatic digestive continuity after pancreaticoduodenectomy
: a meta-analysis of randomized controlled trials. World J Surg
32. Melis M, Marcon F, Masi A, et al. Effect of intra-operative fluid volume on peri-operative outcomes after pancreaticoduodenectomy
for pancreatic adenocarcinoma: intra-operative fluids and pancreatectomy. J Surg Oncol
Pancreaticoduodenectomy; Fluid Therapy; Fistula; Complications; Palabras clave; Pancreatoduodenectomia; Terapia hídrica; Fistula; Complicaciones
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