Secondary Logo

Journal Logo

Analysis of complications after Whipple's procedure using ERAS protocols

Aristizabal Linares, Juan Pabloa; Estrada Quiroz, José Juliána; Gómez, Carolina Hoyosb; Dávila Martínez, Diego Fernandoa; Palacios Rodríguez, Oscar Germána; Sánchez Zapata, Paolab

doi: 10.1097/CJ9.0000000000000140
CLINICAL RESEARCH
Open
SDC
Spanish Version

Background: The administration of perioperative fluids is a controversial issue that can be associated with the development of postoperative pancreatic fistula (POPF) after Whipple procedure.

Objective: To evaluate whether intraoperative fluid management along with Enhanced Recovery after Surgery (ERAS) protocols affect outcomes following major pancreatic resection.

Methods: A retrospective cohort study was conducted from January 2012 to January 2017, collecting all patients scheduled for duodenopancreatectomy (DP). Patients were divided into 2 groups according to the use of ERAS protocols and the use of a fluid therapy algorithm.

Results: A total of 67 patients were analyzed, 49.3% of which were females. The most frequent diagnoses were Pancreatic Cancer n:48 (71.6%), followed by intraductal papillary mucinous neoplasm n:6 (9%). The majority of patients were in the ERAS group n:46 (68.7%); 80.4% and 95.7% of them did not develop pancreatic fistula or delayed gastric emptying (DGE) respectively, and the incidence for both was 11.94%. Fluid therapy was below 5000 mL (P = 0.001) with blood loss less 300 mL (P = 0.001) in the ERAS group. The length of stay was shorter in the ERAS group (7 days, interquartilel range 5–12, P ≤ 0.001). No differences in 30 days mortality were found.

Conclusion: The implementation of ERAS protocols in DP did show a decrease in intraoperative blood loss, intravenous fluids therapy, need for transfusion, DGE, or total hospital stay. However, intraoperative fluid restriction in DP did not show a reduction in the development of POPF.

Resumen 

Introducción: La administración de fluidos durante el perioperatorio es un tema controvertido que puede asociarse a complicaciones como la presencia de fístula pancreática después de Whipple.

Objetivo: Evaluar si los protocolos de manejo de líquidos dentro de las recomendaciones de recuperación acelerada después de cirugía (ERAS) afectan los desenlaces después de cirugía pancreática mayor.

Materiales y métodos: Se realizó un estudio de cohorte retrospectivo de enero 2012 a enero 2017. Se recopilaron todos los pacientes llevados a duodenopancreatectomía. Se dividieron en dos grupos según el uso de protocolos ERAS y el uso de algoritmos para terapia hídrica.

Resultados: Se analizaron 67 pacientes, el 49,3% correspondió al género femenino. Los diagnósticos más frecuentes fueron Cáncer de páncreas n:48 (71.6%), seguido de Neoplasia mucinosa papilar intraductal n:6 (9%). La mayoría de los pacientes se encontraban en el Grupo ERAS n:46 (68,7%). En el grupo ERAS, el 80,4% y el 95,7% no desarrollaron fístula pancreática o retraso del vaciamiento gástrico y la incidencia fue del 11,94% respectivamente. La terapia hídrica estuvo por debajo de 5000 ml (p = 0,001) con una pérdida sanguínea inferior a 300 ml (p = 0,001) en el grupo ERAS. La estancia hospitalaria fue más corta en el grupo ERAS (7 días, rango intercuartílico 5–12, p =< 0,001). No hubo diferencias en la mortalidad a 30 días.

Conclusión: La implementación de protocolos ERAS en la duodenopancreatectomía mostró una menor pérdida sanguínea, menor terapia hídrica, menor necesidad de transfusión, menor retraso del vaciamiento gástrico y menor estancia hospitaria. Sin embargo, la terapia restrictiva hídrica no redujo el desarrollo de fístula pancreática postoperatoria.

aClínica CES, Medellín, Colombia

bCES University, Medellín, Colombia.

Correspondence: Clínica CES, Calle 58 N° 50C—2 Prado Centro, Medellín, Antioquia. E-mail: juanpablo.aristizabal@gmail.com

How to cite this article: Aristizabal Linares JP, Estrada Quiroz JJ, Gómez CH, Dávila Martínez DF, Palacios Rodríguez OG, Sánchez Zapata P. Analysis of complications after Whipple's procedure using ERAS protocols. Case report. Colombian Journal of Anesthesiology. 2019;00:000–000.

Read the Spanish version of this article at: http://links.lww.com/RCA/A901.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.www.revcolanest.com.co).

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Back to Top | Article Outline

Introduction

The primary goal of Enhanced Recovery after Surgery (ERAS) protocols is to optimize the recovery of patients with improved quality. This should be a multidisciplinary approach involving several specialties. Furthermore, among others tasks, the anesthesiologist plays a major role in fluid therapy during the perioperative period.

The use of optimal fluid therapy in the operating room in major surgeries is controversial. Some studies are in favor of a restrictive approach, specifically for duodenopancreatectomy (DP); however, there are contradictory literature reports with regards to which regimen must be used during the perioperative period. Furthermore, 2 of the more frequent complications after DP are postoperative pancreatic fistula (POPF) and delayed gastric emptying (DGE) which can be related to fluid therapy.

Some studies have suggested that intraoperative fluid overload could be associated with the development of POPF with an incidence between 10% and 40%.1 In contrast, DGE, has an incidence between 3.2% and 59%, although the causes for delayed gastric emptying remain elusive.2

Hence, we decided to compare 2 approaches for patients undergoing DP in our hospital. One with standard protocol and a second group using ERAS protocols and a fluid therapy algorithm.2,3 We hypothesized that implementation of ERAS strategies along with intraoperative fluid management could decrease the development of complications after DP. The objective of this study was to evaluate whether intraoperative fluid management along with ERAS protocols affect the outcomes after DP.

Back to Top | Article Outline

Methods

Patients selection

A retrospective cohort study was conducted, analyzing the data from 67 consecutive patients who underwent DP from January 2012 to January 2017, from the Department of Hepatopancreatobiliary (HPB) surgery. All patients scheduled for DP in whom total pancreatectomy was performed were excluded from this analysis. All of the surgical procedures analyzed were performed by the same surgical team made up by 2 HPB surgeons and 2 HPB anesthesiologists. Two groups were identified: No-ERAS group that included patients operated between January 2012 and December 2014, and ERAS group that included patients operated between January 2015 and January 2017.

Back to Top | Article Outline

Anesthesiologist protocols

Patients in which ERAS protocols were not applied (No-ERAS group), had an 8-hour fasting time for both liquids and solids. Carbohydrate loading was not administered. Basic patient education was given by surgeons and anesthesiologist. Intravenous fluids were administered liberally during the operation, without adhering to any particlar protocol and vasopressors were administered according to the opinion of the anesthesiologist.

Patients in ERAS protocols (ERAS group) followed the recommended guidelines of the ERAS society.4 A nutritional evaluation was performed 2 weeks before the operation. Ecoimmunonutrition, including pre-biotics and arginine supplements, were prescribed. Patient education was provided by surgeons and anesthesiologist. Pre-operative fasting time was 8 hours for solids and 2 hours for liquids. A load of Maltodextrins was offered 2 hours before surgery. A cardiac output monitor was used (EV1000; Edwards Lifescience, Irvine, California, US) to guide fluid therapy according to the following algorithm: All patients received balanced solutions (Isofundin; Bbraun, Melsungen, Germany) at an infusion rate of 2 mL/kg/h. The systolic volume variation (SVV) was measured and whenever this variation was below 13%, in addition to a cardiac index (CI) above 2.5 L/min/m2 the infusion rate was left unchanged. If the SVV was higher than 13%, a fluid bolus of balanced solutions was administered at a rate of 3 mL/kg every 5 minutes, until SVV reached its goal of 13%. Moreover, if the mean blood pressure (MBP) dropped more than 20% below the baseline value, and SVV was less than 13% with a CI above than 2.5 L/min/m2, noradrenaline titration was initiated to keep a systolic blood pressure above 90 mm Hg. If the MBP dropped more than 20% with a SVV below 13% but with a CI under 2.5 L/min/m2, dobutamine was initiated. Orotracheal intubation was performed in all patients. Balanced anesthesia was administered using remifentanil with target controlled infusion between 3 and 5 ng/mL and sevoflurane to maintain a MAC level of 0.8. Muscle relaxation was achieved with rocuronium. Mechanical ventilation was controlled with tidal volume at 8 mL/kg, respiratory rate 12–14/min and positive end expiratory pressure 5 mm Hg for achieving ETCO2 of 35 mm Hg. All patients were monitored with central venous line and arterial line. Thoracic epidural analgesia (T7–T8) was used in all patients administered at the end of the procedure, with a bolus of 10 mL of bupivacaine, followed with an infusion of bupivacaine 0.125%, between 6 and 8 mL/h for 3 days. Intraoperative arterial blood gases, lactate, and electrolytes were measured. Immediately after surgery, all patients were transferred to the intensive care unit.

Back to Top | Article Outline

Surgical protocols

Pancreatic anastomosis was performed according to risk factors for POPF,3 Double-layer invaginated pancreaticogastrostomy (PG) was performed in high-risk pancreas, and duct-to-mucosa pancreatojejunostomy (PJ) in low-risk pancreas.5

The definitions for POPF and DGE as reported by the International Study Group of Pancreatic Surgery were used for this study.6,7

Back to Top | Article Outline

Statistical protocols

Demographic, clinical, and intraoperative variables were retrospectively collected. Fluid therapy below 5000 mL and intraoperative bleeding above 600 mL were also recorded. Postoperative variables included hospital stay, and 30-day mortality and were also included in a multivariate analysis. Normality distribution was evaluated with the Shapiro–Wilk test. The Student t, Chi-square, Mann–Whitney U, and binary logistic regression tests were used where applicable, using SPSS version 24, IBM, US version 24 for Macintosh. Alpha values below 0.05 were considered statistically significant.

Back to Top | Article Outline

Ethical approval

Protocols for this study had the informed consent of, and were approved by, the institutional ethics committee, pursuant to the national guidelines and legal approval provided under resolution number 8430 which rated the research as risk-free.8,9

Back to Top | Article Outline

Results

A total of 67 patients were analyzed from July 2012 to January 2017. Of the sample 49.3% were female, with a median age of 58.2 years old (standard deviation 12.5 years). The most frequent diagnosis was pancreatic cancer n:48 (71.6%), followed by intraductal papillary mucinous neoplasm n:6 (9%) and duodenal adenocarcinoma n:4 (6%). ERAS group included 46 patients (68.7%).

The overall incidence of POPF and DGE was 11.94% and 11.94%, respectively (Table 1).

Table 1

Table 1

Table 1

Table 1

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).

Table 2

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).

Table 3

Table 3

Back to Top | Article Outline

Discussion

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.

Back to Top | Article Outline

Ethical responibilities

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.

Back to Top | Article Outline

Financial support

The authors declare no financial support.

Back to Top | Article Outline

Conflict of interests

The authors have no conflict of interests to disclose.

Back to Top | Article Outline

References

1. Kulemann B, Fritz M, Glatz T, et al. Complications after pancreaticoduodenectomy are associated with higher amounts of intra- and postoperative fluid therapy: a single center retrospective cohort study. Ann Med Surg 2017; 16:23–29.
2. Ahmad SA, Edwards MJ, Sutton JM, et al. Factors influencing readmission after pancreaticoduodenectomy: a multi-institutional study of 1302 patients. Ann Surg 2012; 256:529–537.
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 2013; 216:1–14.
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 2013; 37:240–258.
5. Sikora SS, Posner MC. Management of the pancreatic stump following pancreaticoduodenectomy. Br J Surg 1995; 82:1590–1597.
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 2017; 161:584–591.
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 2007; 142:761–768.
8. Ghooi R. The Nuremberg Code—a critique. Perspect Clin Res 2011; 2:72–76.
9. Ministerio de salud, República de Colombia. Resolución número 8430 de 1993 [Internet]. octubre 4 de 1993. [Cited 12 Sep 201]. Available from: https://www.minsalud.gov.co/sites/rid/Lists/BibliotecaDigital/RIDE/DE/DIJ/RESOLUCION-8430-DE-1993.PDF.
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 2003; 238:641–648.
11. Gan TJ, Soppitt A, Maroof M, et al. Goal-directed intraoperative fluid administration reduces length of hospital stay after major surgery. Anesthesiology 2002; 97:820–826.
12. Voldby AW, Brandstrup B. Fluid therapy in the perioperative setting—a clinical review. J Intensive Care 2016; 4:27.
13. Mythen MG, Swart M, Acheson N, et al. Perioperative fluid management: consensus statement from the enhanced recovery partnership. Perioper Med (Lond) 2012; 1:2.
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 2015; 19:261.
15. Navarro LHC, Bloomstone JA, Auler JOC, et al. Perioperative fluid therapy: a statement from the international Fluid Optimization Group. Perioper Med (Lond) 2015; 4:3.
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 2014; 18:584.
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 2018; 267:57–65.
18. Scott MJ, Miller TE. Pathophysiology of major surgery and the role of enhanced recovery pathways and the anesthesiologist to improve outcomes. Anesthesiol Clin 2015; 33:79–91.
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 2013; 100:1015–1024.
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 2016; 40:2441–2450.
21. Han IW, Kim H, Heo J, et al. Excess intraoperative fluid volume administration is associated with pancreatic fistula after pancreaticoduodenectomy: a retrospective multicenter study. Medicine (Baltimore) 2017; 96:e6893.
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) 2017; 96:e6858.
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 2010; 252:952–958.
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) 2014; 16:1062–1067.
25. Chen BP, Chen M, Bennett S, et al. Systematic review and meta-analysis of restrictive perioperative fluid management in pancreaticoduodenectomy. World J Surg 2018; 42:2938–2950.
26. Wang S, Wang X, Dai H, et al. The effect of intraoperative fluid volume administration on pancreatic fistulas after pancreaticoduodenectomy. J Invest Surg 2014; 27:88–94.
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 2009; 208:738–747.
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 2002; 9:733–737.
30. Dong Z, Xu J, Wang Z, et al. Stents for the prevention of pancreatic fistula following pancreaticoduodenectomy. Cochrane Database Syst Rev 2013; CD008914.
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 2011; 35:2290–2297.
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 2012; 105:81–84.
Keywords:

Pancreaticoduodenectomy; Fluid Therapy; Fistula; Complications; Palabras clave; Pancreatoduodenectomia; Terapia hídrica; Fistula; Complicaciones

Supplemental Digital Content

Back to Top | Article Outline
© 2019 by Lippincott Williams & Wilkins, Inc.