Is bactibilia a predictor of poor outcome of pancreaticoduodenectomy?

Sivanpillay Mahadevan Sivaraj, Velayutham Vimalraj, Palanichamy Saravanaboopathy, Shanmugasundaram Rajendran, Sathyanesan Jeswanth, Palaniappan Ravichandran, Rosy Vennilla and Rajagopalan Surendran

Chennai, India

Original Article / Pancreas

Is bactibilia a predictor of poor outcome of pancreaticoduodenectomy?

Sivanpillay Mahadevan Sivaraj, Velayutham Vimalraj, Palanichamy Saravanaboopathy, Shanmugasundaram Rajendran, Sathyanesan Jeswanth, Palaniappan Ravichandran, Rosy Vennilla and Rajagopalan Surendran

Chennai, India

BACKGROUND:Although bile infection has been proposed to increase infective complications following pancreaticoduodenectomy, its association with infective complications and non-infective complications like pancreatic fistula is still controversial.

METHODS:Seventy-six patients who had undergone pancreaticoduodenectomy between July 2007 and December 2008 were included in a prospective database and their data analyzed. In all patients intraoperative bile from the bile duct was cultured. Preoperative, intra-operative, and post-operative variables were recorded and analyzed.

RESULTS:Bile culture showed positive growth in 35 patients and negative growth in 41. Twenty patients in the positive group underwent ERCP and stenting. The patients with a positive bile culture had a higher incidence of infective complications including intra-abdominal abscess (n=8), wound infection (n=27), bacteremia (n=10), and renal insufficiency (n=9). There was no increase in the rate of non-infective complications of pancreaticoduodenectomy including pancreatic fistula (n=7), delayed gastric emptying (n=9), and post-operative hemorrhage (n=3). The hospital stay was significantly prolonged in the patients with a positive bile culture (P=0.0002).

CONCLUSIONS:Pre-operative biliary drainage is significantly associated with bile infection, and bile infection increases the overall rates of infective complications and renalinsufficiency. Because of the high incidence of complications is associated with infected bile, routine intra-operative bile culture is recommended in patients undergoing pancreaticoduodenectomy. Pre-operative prophylaxis is dependent on sensitivity of cases to perioperative antibiotics and intraoperative bile culture report. Because of its significant association with infected bile, biliary stenting should be used in strictly selected cases.

(Hepatobiliary Pancreat Dis Int 2010; 9: 65-68)

bactibilia; Whipples pancreaticoduodenectomy; perioperative outcomes

Introduction

Although bile infection has been proposed to increase infective complications following pancreaticoduodenectomy,[1]its association with infective and non-infective complications like pancreatic fistula is still controversial.[2-8]Jagannath et al[4]in a study on the outcome of pancreaticoduodenectomy following stenting concluded that biliary stenting was not significantly associated with a positive culture. But others[2,3,5-8]suggested preoperative biliary drainage was associated with bile infection. Some studies[2,6-8]associated infected bile with increased incidence of post-operative infective complications, whereas other studies[3,5]did not record such an association. Recently few studies have related the higher incidence of pancreatic fistula with bile infection.[5]Hence, the aim of this study was to analyze the effect of bile infection in the immediate outcome of pancreaticoduodenectomy, both infective and non-infective.

Methods

Seventy-six patients who had undergone pancreatico-duodenectomy between July 2007 and December 2008 were included in a prospective database, and their data were analyzed. The patients were given prophylatic antibiotics. Intravenous injection of Cephazolin 2 g was given before induction of anesthesia. All patients underwent standard Whipple pancreaticoduodenectomy,[9]after which, the pancreatic remnant was mobilized proximally, a posterior gastrostomy was made, and a pancreaticogastrostomy was performed to invaginate the remnant into the stomach. Anastomosis was made with 3-0 polyglactin (vicryl). Gastrojejunostomy and hepaticojejunostomy were performed on the same jejunal loop. Two drains were placed to drain the pancreatic and biliary anastomosis. In all patients, intraoperative bile culture from the bile duct was collected.

The preoperative variables analyzed were age, gender, serum bilirubin, serum albumin, and diabetes mellitus, which are associated with post-operative complications.[5,8]Intra-operatively, the nature of the pancreatic remnant, the size of the main pancreatic duct, operative time, blood loss, and transfusions were recorded. Post-operatively, also recorded were death caused by complications, pancreatic fistula, hemorrhage, delayed gastric emptying, intra-abdominal abscess, wound infection, septicemia, renal insufficiency, and pulmonary complications. Post-operative hospital stay was also observed.

Pancreatic fistula was defined by the level of drained fluid amylase more than three times the level of serum amylase 3 days after operation.[10]Delayed gastric emptying was defined by drainage with a nasogastric tube for more than 10 days after operation with one of the following signs: emesis after removal of the nasogastric tube, reinsertion of a nasogastric tube, use of prokinetic agents after post-operative day 10, or failure to progress with diet.[11]Wound infection, intraabdominal abscess, and bacteremia were recognized as infectious complications, which were confirmed by microbial cultures. Complications other than wound infection (death, pancreatic fistula, hemorrhage, delayed gastric emptying, intra-abdominal abscess, bacteremia, renal insufficiency, and pulmonary complications) were considered as major complications.

Values were expressed as median and ranged appropriately. Discrete variables were analyzed statistically using the two-tailed Fisher's exact test, and continuous variables using Student'sttest. A difference was considered statistically significant whenP<0.05.

Results

Bile culture showed positive growth in 35 patients and negative one in 41. Twenty patients in the positive group underwent ERCP and stenting.

The mean age of patients was 53.42 years in the positive group and 52.24 in the negative group. No significant difference was seen in sex distribution in the two groups. The distribution of diabetes mellitus in both groups was not different significantly. No significant difference was observed in the levels of serum bilirubin and albumin between the two groups (Table 1).

Pre-operative biliary drainage

In our series, 20 patients underwent ERCP and sphincterotomy, 18 underwent the procedures before being refered to our centre; the indications were not unified. Of the 18 patients, 2 had a history of fever and rigor. Since preoperative drainage was performed selectively for those with cholangitis non-responding to medical management, only 2 patients underwent ERCP and stenting for cholangitis in our institution.

Intra-operative variables

All of our patients underwent a standard pancreaticoduodenectomy. Their median operative time and blood loss were not different. No blood transfusion was given. There was no significant difference in the nature of the pancreatic remnant and main pancreatic duct size between the two groups (Table 2).

Table 1. Demography and preoperative variables

Table 2. Intra-operative variables

Table 3. Post-operative complications

Table 4. Preoperative biliary drainage and complications

Mortality

One of the 35 patients died of pancreatic fistula and septicemia on postoperative day 35. One of the 41 patients died of polycystic kidney disease and chronic renal failure on postoperative day 16 after development of pulmonary edema (Table 3).

Morbidity

In 20 patients of the positive group one or more postoperative complications developed, and infectious complications were seen in 18 of them. They included intra-abdominal abscess (n=8), wound infection (n=27), bacteremia (n=10), and renal insuf ficiency (n=9). The rates of non-infective complications such as pancreatic fistula, delayed gastric emptying, and postoperative hemorrhage were not increased in patients after pancreaticoduodenectomy. Hospital stay was prolonged in the positive group (Table 3).

Table 5. Microorganisms isolated from bile cultures

Table 6. Antibiotic sensitivity pattern of organisms isolated from bile

The rates of complications such as wound infection, intra-abdominal abscess, and septicemia in the patients who had undergone ERCP and preoperative drainage were significantly higher than in those who had undergone ERCP and biliary drainage. Other complications including pancreatic fistula, hemorrhage, and pulmonary complications were not significantly different in both groups, but delayed gastric emptying was found in the patients with biliary drainage (Table 4).

Escherichia coli,Klebsiellawere commonly seen organisms. In stented patientsPsuedomonaswere isolated. About 91% of the isolates were sensitive to piperacillintazobactum, followed by amikacin, gentamicin, and ciprofloxacin. Only 6% of the organisms were sensitive to cefazolin (Table 5 and 6).

Discussion

In our study, we did not find an association of bile infection with preoperative comorbid illness, biochemical parameters, or pathological type of malignancy as reported elsewhere.[3]It was reported that bile infection was associated with pathological type,[2,8]age,[5]preoperative levels of serum bilirubin and albumin,[5]and coronary artery disease.[8]In the present study, bile infection was not significantly associated with pathologic types, because of few patients with ampullary carcinomas undergoing ERCP for diagnosis/drainage. During the operation, operative time and blood loss were not affected by bile infection. Postoperative mortality was not influenced bybile infection.[2,3,5,8]One study reported[4]positive intraoperative bile culture was related to operative mortality. The rate of infectious complications was significantly increased in the positive bile culture group,[2,4,6,8]but few studies showed this relation insignificant.[1,5]The specific complications of pancreaticoduodenectomy included pancreatic fistula, hemorrhage, and delayed gastric emptying, the rates of these complications were not increased by bile infection.[2,3-8]

The sensitivity of organisms may underscore the need for routine bile culture as most of them are resistant to the commonly used antibiotics. Before a culture, perioperative antibiotic therapy must be dependent on the sensitivity of antibiotics.

In our study, preoperative biliary drainage was significantly associated with bile infection, which increased the rates of overall complications, infective complications, and renal insufficiency. There was no increase in the incidence of pancreatic fistula, hemorrhage, or delayed gastric emptying, but ERCP and biliary stenting contribute to delayed gastric emptying. In view of the high incidence of complications associated with infected bile, it is thus recommended to avoid bile spillage, take a routine intra-operative bile culture in all patients undergoing pancreaticoduodenectomy, preoperative antibiotic prophylaxis, and peri-operative antibiotic treatment depending on bile culture. Since biliary stenting is significantly associated with infected bile, it should be used only in strictly selected cases of cholangitis inresponsible to medical management.

Funding:None.

Ethical approval:Not needed.

Contributors:SR proposed the study. SSM wrote the first draft. SSM and VV analyzed the data. All authors contributed to the design and interpretation of the study and to further drafts. SSM is the guarantor.

Competing interest:No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

1 Povoski SP, Karpeh MS Jr, Conlon KC, Blumgart LH, Brennan MF. Preoperative biliary drainage: impact on intraoperative bile cultures and infectious morbidity and mortality after pancreaticoduodenectomy. J Gastrointest Surg 1999;3:496-505.

2 Cortes A, Sauvanet A, Bert F, Janny S, Sockeel P, Kianmanesh R, et al. Effect of bile contamination on immediate outcomes after pancreaticoduodenectomy for tumor. J Am Coll Surg 2006;202:93-99.

3 Grizas S, Stakyte M, Kincius M, Barauskas G, Pundzius J. Etiology of bile infection and its association with postoperative complications following pancreatoduodenectomy. Medicina (Kaunas) 2005;41:386-391.

4 Jagannath P, Dhir V, Shrikhande S, Shah RC, Mullerpatan P, Mohandas KM. Effect of preoperative biliary stenting on immediate outcome after pancreaticoduodenectomy. Br J Surg 2005;92:356-361.

5 Isla AM, Griniatsos J, Riaz A, Karvounis E, Williamson RC. Pancreaticoduodenectomy for periampullary malignancies: the effect of bile colonization on the postoperative outcome. Langenbecks Arch Surg 2007;392:67-73.

6 Lermite E, Pessaux P, Teyssedou C, Etienne S, Brehant O, Arnaud JP. Effect of preoperative endoscopic biliary drainage on infectious morbidity after pancreatoduodenectomy: a case-control study. Am J Surg 2008;195:442-446.

7 Howard TJ, Yu J, Greene RB, George V, Wairiuko GM, Moore SA, Madura JA. Influence of bactibilia after preoperative biliary stenting on postoperative infectious complications. J Gastrointest Surg 2006;10:523-531.

8 Limongelli P, Pai M, Bansi D, Thiallinagram A, Tait P, Jackson J, et al. Correlation between preoperative biliary drainage, bile duct contamination, and postoperative outcomes for pancreatic surgery. Surgery 2007;142:313-318.

9 Rajarathinam G, Kannan DG, Vimalraj V, Amudhan A, Rajendran S, Jyotibasu D, et al. Post pancreaticoduodenectomy haemorrhage: outcome prediction based on new ISGPS Clinical severity grading. HPB (Oxford) 2008;10:363-370.

10 Bassi C, Dervenis C, Butturini G, Fingerhut A, Yeo C, Izbicki J, et al. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery 2005;138:8-13.

11 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;218:229-238.

June 30, 2009

Accepted after revision December 12, 2009

Author Affiliations: Institute of Surgical Gastroenterology and Liver Transplantation, New Gastroenterology Block, Government Stanley Medical College Hospital, Chennai 600 001, India (Sivaraj SM, Vimalraj V, Saravanaboopathy P, Rajendran S, Jeswanth S, Ravichandran P, Vennilla R and Surendran R)

Rajagopalan Surendran, Professor, Institute of Surgical Gastroenterology and Liver Transplantation, New Gastroenterology Block, Government Stanley Medical College, Royapuram, Chennai 600 001, India (Tel: 0091-44-25289595; Fax: 0091-44-25289595; Email: Stanleygastro@yahoo.com)

© 2010, Hepatobiliary Pancreat Dis Int. All rights reserved.