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Intra-Abdominal Sepsis Following Pancreatic Resection: Incidence, Risk Factors, Diagnosis, Microbiology, Management, and Outcome/ DISCUSSION

August 29, 2008

By Behrman, Stephen W Zarzaur, Ben L

Intra-abdominal sepsis (IAS) following pancreatectomy is associated with the need for therapeutic intervention and may result in mortality. We retrospectively reviewed patients developing IAS following elective pancreatectomy. Risk factors for the development of sepsis were assessed. The microbiology of these infections was ascertained. The number and type of therapeutic interventions required and infectious-related mortality were recorded. One hundred ninety-six patients had a pancreatectomy performed, 32 (16.3%) of who developed IAS. Infected abdominal collections were diagnosed and therapeutically managed at a mean of 11.8 days after the index procedure (range, 4-33). Eleven of 32 (34%) of these infections were diagnosed on or before postoperative day 6, 10 of who had Whipple procedures. Statistically significant risk factors included an overt pancreatic fistula (18.8% vs 5.5%) and a soft pancreatic remnant (74.2% vs 42.3%), but not the lack of intra-abdominal drainage, an antecedent immunocompromised state, postoperative hemorrhage, or the preoperative placement of a biliary stent. Fifty-five per cent had polymicrobial infections and 26 per cent of isolates were resistant organisms. Nineteen per cent and 48 per cent of patients had an isolate positive for fungus and a Gram-positive organism, respectively. Fortyseven therapeutic interventions were used, including 10 reoperations. Length of stay was significantly prolonged in those with IAS (28.5 vs 15.2 days) and mortality was higher (15.6% vs 1.8%). We conclude: 1) septic morbidity after pancreatectomy is associated with a soft pancreatic remnant and an overt pancreatic fistula and in this series resulted in a prolonged length of stay and a significant increase in procedure-related mortality; 2) infected fluid collections may occur very early in the postoperative period before frank abscess formation, and an early threshold for diagnostic imaging and/or therapeutic intervention should be entertained in those with clinical deterioration; and 3) these infections are often polymicrobial and frequently include resistant and nonenteric organisms. MORBIDITY FOLLOWING PANCREATIC resection remains common and has been reported in up to 50 per cent of patients in recent series.1-4 Pancreatic and biliary fistulae as well as delayed gastric emptying are most prevalent and have been the focus of study in the majority of the literature.1, 5-10 While these complications increase hospital length of stay, they rarely require further diagnostic and/or invasive therapeutic procedures and mortality is exceptional. Intraabdominal sepsis occurs less frequently but remains important.1-8, 11 In contrast to other morbidity following pancreatectomy, abscess and/or other infected abdominai fluid collections are most often associated with the need for nonoperative and operative intervention, a prolonged hospital length of stay, and an increase in mortality. The pathogenesis and microbiology associated with these infections has received relatively little attention. Furthermore, management and outcome that impact so significantly on this patient population, most of who have carcinoma, have been poorly described. We reviewed our experience with intra-abdominal sepsis following pancreatic resection with a focus on the diagnosis, bacteriology, and management of this problematic and sometimes catastrophic complication in hopes of improving future patient outcome and survival.

Methods

The records of patients developing intra-abdominal sepsis following elective pancreatic resection at the University of Tennessee, Memphis, affiliated hospitals from 1997 to 2007 were retrospectively reviewed. Data examined included disease process and type of resection. Risk factors for the development of intraabdominal abscess or intra-abdominal sepsis (IAS), including preoperative biliary stenting, a pre-existing immunocompromised state (other than carcinoma), the presence or absence of intraperitoneal drainage, the need for blood transfusion, the development of a pancreatic fistula, postoperative hemorrhage, and the consistency of the remnant pancreas, were examined. An immunocompromised state included diabetes, steroid use, and a history of neoadjuvant therapy. Blood transfusions were recorded within the first 24 hours of surgery. A pancreatic fistula was defined according to the International Study Group of Pancreatic Fistula consensus.12 The time from operation until the clinical development of intra-abdominal sepsis was noted. We specifically focused on the offending microbiologic pathogens recovered during treatment and note was made of resistant organisms or unexpected flora if present. The type (operative vs nonoperative) and number of invasive procedures used in an attempt to eradicate the septic focus were evaluated critically. The impact of postoperative IAS is on hospital length of stay and procedure-related mortality was assessed.

For the purposes of this study, IAS was categorized as follows. An intra-abdominal abscess was defined as a discrete, rim-enhancing fluid collection with or without the presence of gas occurring on or after postoperative day 7. An infected fluid collection was considered as ill-defined, localized, or diffuse, nonrimenhancing fluid noted on or before postoperative day 6. Peritonitis was defined as diffuse abdominal tenderness with rebound on physical examination within the clinical context of sepsis. Patients with a frank pancreaticoenteric anastomotic breakdown (Grade C fistula defined by the International Study Group of Pancreatic Fistula) were included as a result of the ensuing sepsis that developed.

All patients received routine prophylactic perioperative antibiotics for 24 to 48 hours at the time of the index procedure. In addition, during the last 3 years, we have maintained rigid glucose control (80 to 120 mg/dL) in the operating room with hourly blood glucose monitoring. Such levels are maintained in the postoperative period with the use of an insulin drip in the intensive care unit if necessary.

Comparisons between groups were made using Student’s t test for continuous variables and chi^sup 2^ analysis for discrete variables. Significance was assessed at the 95m percentile. Univariate and multivariate logistic regression analysis was used to determine the relationship between potential risk factors and the development of IAS following elective pancreatic resection. Potential risk factors were first assessed with univariate logistic regression. Risk factors with a P

Results

One hundred ninety-six patients underwent pancreatic resection during the 10-year time period with 32 patients (16.3%) developing postoperative IAS (Table 1). Of those with infections, 24 had Whipple procedures with seven and one having distal and total pancreatectomy, respectively. Twenty-four of 32 patients (75%) developing postoperative sepsis had operations performed for carcinoma or premalignant conditions, and this was not different from those avoiding infectious sequelae. The mean age of those with postoperative abdominal infection was 58.3 years and was not different from those without sepsis. Those developing infectious complications had a female predominance in contrast to those without postoperative sepsis; however, this difference was not significant.

Risk factors for the development of postoperative IAS were analyzed by univariate analysis (Table 2). Postoperative infection was not associated with age, operating time, the need for blood transfusion, preoperative biliary stenting, the presence or absence of abdominal drainage, perioperative hemorrhage, the type of procedure performed (distal vs proximal resection), or a preoperative immunocompromised state. In addition, there was no decrease in the incidence of postpancreatectomy sepsis with the institution of rigid glucose control (Fig. 1). In contrast, a pancreatic fistula and a soft pancreatic remnant were predictive of future infectious complications. Pancreatic duct stenting, fibrin glue application to the pancreaticoenteric anastomosis, and the perioperative use of octreotide did not prevent the development of postoperative sepsis. Only the development of a pancreatic fistula following elective pancreatic resection was associated with IAS on multivariate analysis.

TABLE 1. Patient Demographics

TABLE 2. Risk Factors for the Development of Intra-abdominal Sepsis

FIG. 1. Number of pancreatic resections and intra-abdominal sepsis per year.

Intra-abdominal infections were diagnosed at a mean of 11.8 days following the index procedure. Clinical and laboratory findings at the time of diagnosis of IAS are presented in Table 3. Notably, peritonitis and abdominal pain were uncommon. In contrast, more subtle findings such as oliguria, mental status changes, and an increase in the percentage of bands on differential analysis of the white blood cell count were not unusual. Eleven of 32 (34%) patients developing infectious sequelae were diagnosed on or before postoperative day 6 before the development of a frank abscess. This included three patients with a Class C pancreatic fistula. Ten of these 11 with infected fluid collections had Whipple procedures. Six of the 11 patients (55%) developing early infection ultimately required open surgical drainage to eradicate the septic focus versus four of 21 (19%) developing infection (abscess) on or after postoperative day 7. TABLE 3. Clinical Assessment and Laboratory Analysis Prompting Intervention

Fifty-eight pathogens were recovered on culture from these 32 patients (Table 4). Twenty-eight (48%) of these isolates were Gram- positive organisms. Eleven of 58 pathogens (19%) were fungi. Fifteen isolates (26%) comprised resistant organisms, including methicillin- resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis, and extendedspectrum beta-lactamase-producing Gram- negative bacteria. Fifty-four per cent of patients with IAS had polymicrobial infections. Four of 32 patients developing postoperative infections had placement of a preoperative biliary stent. There was no correlation between stent placement and the development of nonenteric or resistant organisms on final culture.

Forty-seven therapeutic interventions were used in an attempt to eradicate the septic focus on this study population (Table 5). Procedures used included percutaneous drainage of infected collections (26 of 32 [81%]) and open surgical drainage (10 of 32 [31%]). Up-front surgical drainage was used in six patients. Four of these six had Whipple procedures and required repeat laparotomy for severe sepsis before postoperative day 6 (including two with Class C fistulas). Two patients having up-front surgery developed subphrenic abscesses following distal pancreatectomy that were not amendable to percutaneous drainage. Twenty-one of 32 patients had one procedure alone, but 11 patients (34%) required multiple procedures. Four of 11 patients requiring multiple therapeutic interventions had open surgical drainage following failed percutaneous drainage. These four patients all had infected fluid collections diagnosed on or before postoperative day 6, including one with a Class C fistula. In total, only four of 26 patients (15%) developing IAS following pancreatic resection failed initial percutaneous, non-operative drainage. Six patients avoiding reoperation required more than one percutaneous drain placement for definitive eradication of sepsis.

TABLE 4. Microbiology of Intra-abdominal Sepsis (n = 32)

TABLE 5. Therapeutic Interventions (n = 47)

Length of stay was significantly prolonged in those who developed IAS versus those who did not (28.5 vs 15.2 days; P

Discussion

Mortality following pancreatic resection has diminished significantly in the past decade, especially when performed in high- volume centers with multispecialty expertise.13-15 In contrast, morbidity following pancreatectomy remains substantial ranging from approximately 30 per cent to 60 per cent in recent series with the vast majority involving an intra-abdominal process. The surgical literature has primarily focused on the incidence, management, and sequelae of pancreatic anastomotic complications as well as delayed gastric emptying. 9, 10, 16 While important in terms of a prolongation in length of stay and a delay in recovery, in the absence of a Class B or C pancreatic fistula, which are uncommon, these complications infrequently require invasive therapeutic intervention or result in mortality.12 Intra-abdominal sepsis following pancreatic resection has received relatively little attention. While less common than other complications, postoperative septic fluid collections or frank abscess formation mandate therapeutic drainage either by the percutaneous route or, not infrequently, repeat laparotomy.1, 4, 5, 11, 16 In addition, the development of IAS increases the cost associated with pancreatic resection, delays recovery, and has a distinct associated mortality rate, especially if reoperation is required in an attempt to eliminate the septic focus.1, 5, 16

The incidence of IAS ranges from 5 per cent to 16 percent inclusive of this study.1, 2, 5, 6, 11, 16, 17 Unfortunately, this rate of infection has not changed significantly in the last two decades despite a myriad of refinements and technical adjuncts involved in pancreatic resection and reconstruction. While a Class C pancreatic fistula remains uncommon, it is almost universally associated with sepsis that requires aggressive nonoperative and operative management.12, 18 In this scenario, sepsis results not so much from leakage of pancreatic juice, but from leakage of enteric contents within the peritoneal cavity. Three of 32 patients in this series developed a Class C fistula as defined by the International Study Group of Pancreatic Fistula classification scheme. All occurred after reconstruction to a soft gland. These patients became septic very early in their postoperative course (before day 6) and all required reoperation (including one after failed percutaneous drainage) for definitive control of their infection. Aggressive intervention failed to prevent one death in this group.

The use of preoperative biliary stenting and the lack of peritoneal drainage following pancreatectomy have been associated with infectious morbidity in some but not all studies and their relationship to septic morbidity remains controversial.2, 19-21 In this study, LAS was not associated with either the preoperative placement of a bile duct stent or the lack of peritoneal drainage. Other risk factors, including intraoperative blood loss, the need for perioperative blood transfusion, and a preoperative immunocompromised state, were not associated with IAS in this study. Only a soft pancreatic remnant and the development of a postoperative pancreatic fistula were significantly associated with the development of IAS by univariate analysis and just the development of a fistula by multivariate analysis. This finding is in common with most, but not all, studies in the literature.1-3, 5, 6, 10, 11, 16, 22

Measures potentially protective of the pancreatic anastomosis such as stenting, fibrin glue application, and the perioperative use of octreotide had no impact on the prevention of septic complications. Despite mese latter results, we continue to use these adjuncts to pancreatic reconstruction in those with a soft pancreatic remnant. Finally, data from the general and cardiac literature suggest that rigid glucose control in the perioperative period reduces infectious morbidity and indeed, this has become a quality initiative monitored by the Center for Medicare and Medicaid Services.23, 24 Despite the implementation of a rigid protocol for normalization of glucose in the perioperative period in the last 3 years, we did not appreciate any decrease in the incidence of IAS in this study. It may be that a 5 per cent to 15 per cent risk of postoperative IAS is inevitable following pancreatectomy with reconstruction to, or closure of, a soft gland. We feel further study might better focus on the early diagnosis of intra-abdominal infections, the recognition of commonly encountered pathogens, and the application of aggressive therapeutic intervention.

The diagnosis of IAS can usually be suspected based on clinical criteria, including fever and tachycardia. Abdominal tenderness and/ or peritonitis may or may not be present, especially if sepsis occurs early in the postoperative period. In addition, more subtle clues such as mental status changes and evidence of renal failure were noted in older patient populations in our review. When suspected, a manual differential has been particularly helpful demonstrating a shift to immature forms even in the face of a normal or depressed white blood cell count. We have been impressed with the rapidity with which these infections develop in the postoperative period. One-third of our patients developed infected fluid collections documented by percutaneous aspiration or reoperation on or before postoperative day 6. The development of an early infected fluid collection following pancreatic resection prior to frank abscess formation (7 to 10 days) has been suggested by others.11, 22 Our three Class C pancreatic fistulas occurred in this group suggesting that when these fistulas occur, they do so early in the postoperative period. Ten of 11 infected fluid collections developing early occurred following reconstruction to a soft gland and in all but one case following a Whipple procedure. Thus, early sepsis, especially following pancreaticoduodenectomy and reconstruction to a soft pancreas, should mandate immediate diagnostic imaging. Our review of patient records for mis study was noteworthy for the frequency with which early sepsis following pancreatic resection was mistakenly attributed to other etiologies such as atelectasis, pneumonia, line sepsis, and urinary tract infection by the treating surgeon as a result of the absence of abdominal physical findings. Our data suggest that if sepsis occurs early in the postoperative period, it is imperative mat an intra- abdominal source should be excluded with early CT scan. In patients with postresection sepsis, we recommend that any free fluid noted on CT be treated with at least percutaneous drainage.

To our knowledge, no prior study has specifically addressed the pathogens associated witii abdominal infections developing after elective pancreatic resection. In contrast to enteric pathogens that might be anticipated in these infections, over one-half of isolates obtained from our 32 patients included either a Gram-positive or fungal organism with no correlation noted between early and late infections or the preoperative placement of a biliary stent. Furthermore, the early presence of resistant organisms was not uncommon. The flora encountered in this study are more common in those developing tertiary peritonitis following laparotomy for secondary peritonitis.25, 26 All of our patients received prophylactic perioperative antibiotics alone, suggesting mat there was little selection pressure for these tertiary padiogens. One- fourth of isolates from patients with postoperative sepsis were resistant organisms and one-half had polymicrobial infections. Importantly, of the five deaths in those with IAS, three patients had fungal pathogens and one had methicillin-resistant S. aureus. We believe mat confirmation of these results from other centers performing pancreatic resection is clearly necessary. However, in the absence of further data and although it is difficult to speculate that earlier treatment would positively impact on outcome, we recommend the institution of broad-spectrum antibacterial coverage, including empiric antifungal therapy and treatment directed at methicillin-resistant S. aureus in those witii postpancreatectomy sepsis until final cultures are obtained. Not unexpectedly, all patients in this series developing postoperative IAS required therapeutic intervention. Although the vast majority of abscesses/fluid collections were amendable to percutaneous drainage, approximately one-tiiird of these infections ultimately required repeat laparotomy and open drainage as has been reported by other centers.1, 11, 16 Six of seven patients avoiding reoperation required more than one drain placement in common with results reported by Sohn et al.11 This was most often necessary as a result of noncontiguous fluid collections. We are aggressive in monitoring clinical improvement after drain placement as well as performing early follow-up CT scans to identify those that might require more than one percutaneous intervention. Four of 32 patients (12.5%) failed initial percutaneous drainage, greater than the 0.5 per cent reported by Sohn. This may simply reflect the smaller number of patients in this study. Open drainage was uniformly required in the three patients with Class C pancreatic fistulas, one after failed percutaneous drainage. Seven of 10 patients requiring reoperation had a pancreaticoduodenectomy as their index procedure, five of whom had reconstruction to a soft gland.

As might be anticipated, length of stay was prolonged in those developing IAS following pancreatic resection and in this study was nearly double that of those who did not have an infectious complication. This prolongation in hospitalization was not different than that previously reported in a series of patients requiring postoperative radiologic intervention for a variety of complications, including IAS following the Whipple procedure.11 More disturbing was a significant increase in procedure-related mortality in those with infectious complications. Our death rate related to infectious morbidity following pancreatic resection was slightly higher than that reported elsewhere.11, 16

The need for therapeutic intervention, the exaggerated length of stay, and the increase in mortality following the development of IAS after pancreatectomy emphasizes the need for early recognition and aggressive treatment of these infections. Based on our data and that of others, one must anticipate infectious complications, especially if a soft pancreas is managed or if a clinically relevant pancreatic fistula develops following surgical excision. Septic morbidity may develop very early in the postoperative period with subtle clinical and laboratory signs before the time period typical of abscess formation. We recommend the institution of early diagnostic imaging in those with clinical deterioration in the early perioperative period. Urgent operative and nonoperative intervention to drain intra-abdominal fluid collections should be used even if there is not a suggestion of frank abscess formation. Our review of the microbiology of these infections suggests a significant per cent is associated with nonenteric and resistant organisms. Early diagnosis, broad initial antimicrobial coverage, and prompt intervention to eradicate septic foci will hopefully ameliorate the morbidity and mortality associated with intra-abdominal infections after pancreatic resection.

REFERENCES

1. Yeo CJ, Cameron JL, Sohn TA, et al. Six hundred fifty consecutive pancreaticoduodenectomies in the 1990′s. Ann Surg 1997;226:248-57.

2. Conlon KC, Labow D, Leung D, et al. Prospective randomized clinical trial of the value of intraperitoneal drainage after pancreatic resection. Ann Surg 2001;234:419-29.

3. Satoi S, Takai S, Matsui Y, et al. Less morbidity after pancreaticoduodenectomy of patients with pancreatic cancer. Pancreas 2006;33:45-52.

4. Behrman SW, Rush BT, Dilawari RA. A modern analysis of morbidity after pancreatic resection. Am Surg 2004;70:675-82; discussion 682-3.

5. Miedema BW, Sarr MG, van Heerden JA, et al. Complications following pancreaticoduodenectomy. Arch Surg 1992;127: 945-50.

6. Grace PA, Pitt HA, Tompkins RK, et al. Decreased morbidity and mortality after pancreatoduodenectomy. Am J Surg 1986; 151:141-9.

7. Trede M, Schwall G. The complications of pancreatectomy. Ann Surg 1998;207:39-47.

8. Stephens J, Kuhn J, O’Brien J, et al. Surgical morbidity, mortality and long-term survival in patients with peripancreatic cancer following pancreaticoduodenectomy. Am J Surg 1997;174: 600- 4.

9. Yeo CJ, Lillemoe KD, Sauter PK, et al. Does prophylactic octreotide really decrease the rates of pancreatic fistula and other complications following pancreaticoduodenectomy? Ann Surg 2000;232:419-29.

10. Yeo CJ, Cameron JL, Maher MM, et al. A prospective randomized trial of pancreaticogastrostomy versus pancreaticojejunostomy after pancreaticoduodenectomy. Ann Surg 1995;222: 580-8.

11. Sohn TA, Yeo CJ, Cameron JF, et al. Pancreaticoduodenectomy: Role of interventional radiologists in managing patients and complications. J Gastrointest Surg 2003;7:209-19.

12. Bassi C, Dervenis C, Buttarmi G, et al. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery 2005;138:8-13.

13. Birkmeyer JD, Warshaw AL, Finlayson SR, et al. Relationship between hospital volume and late survival after pancreaticoduodenectomy. Surgery 1999;126:178-83.

14. Sosa JA, Bowman HM, Gordon TA, et al. Importance of hospital volume in the overall management of pancreatic cancer. Ann Surg 1998;228:429-38.

15. Rosemurgy AS, Bloomston M, Serafini FM, et al. Frequency with which surgeons undertake pancreaticoduodenectomy determines length of stay, hospital charges and in-hospital mortality. J Gastrointest Surg 2001;5:21-6.

16. Buchler MW, Wagner M, Schmied BM, et al. Changes in morbidity after pancreatic resection. Arch Surg 2003;138:1310-4.

17. Crist DW, Sitzmann JV, Cameron JL. Improved hospital morbidity, mortality and survival after the Whipple procedure. Ann Surg 1987;206:358-65.

18. Pratt WB, Maithel SK, Vanounou T, et al. Clinical and economic validation of the International Study Group of Pancreatic Fistula (ISGPF) classification scheme. Ann Surg 2007;245: 443-51.

19. Howard TJ, Yu J, Greene RB, et al. Influence of bactibilia after biliary stenting on postoperative infectious complications. J Gastrointest Surg 2006;10:523-31.

20. Pisters PW, Hudec WA, Hess KR, et al. Effect of preoperative biliary decompression on pancreaticoduodenectomy-associated morbidity in 300 consecutive patients. Ann Surg 2001; 234:47-55.

21. Povoski SP, Karpeh MS, Conlon KC, et al. Preoperative biliary drainage: Impact on intraoperative bile cultures and infectious morbidity and mortality after pancreaticoduodenectomy. J Gastrointest Surg 1999;5:496-505.

22. Grobmyer SR, Pieracci FM, Allen PJ, et al. Pancreaticoduodenectomy: Use of a prospective complication grading system. J Am Coll Surg 2007;204:356-64.

23. Pomposelli JJ, Baxter JK III, Babineau TJ, et al. Early postoperative glucose control predicts nosocomial infection rate in diabetic patients. J Parenter Enteral Nutr 1998;22:77-81.

24. Furnary AP, Zerr KJ, Grandemeier GL, et al. Continuous intravenous insulin infusion reduces the incidence of deep sternal wound infection in diabetic patients after cardiac surgical procedures. Ann Thorac Surg 1999;67:352-60.

25. Evans HL, Raymond DP, Pelletier SJ, et al. Tertiary peritonitis (recurrent diffuse or localized disease) is not an independent predictor of mortality in surgical patients with intraabdominal infection. Surg Infect (Larchmt) 2001;2:255-63.

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STEPHEN W. BEHRMAN, M.D., BEN L. ZARZAUR, M.D., M.P.H.

From the Department of Surgery, University of Tennessee, Memphis, Tennessee.

Presented at the Annual Scientific Meeting and Postgraduate Course Program, Southeastern Surgical Congress, Birmingham, AL, February 9-12, 2008.

Supported in part by the Herb Kosten endowment for pancreatic cancer research and care at the University of Tennessee, Memphis.

Address correspondence and reprint requests to Stephen W. Behrman, M.D., F.A.C.S., Associate Professor of Surgery, University of Tennessee, Memphis, Department of Surgery, 910 Madison Avenue, Suite 208, Memphis, TN 38163. E-mail: sbehrman@ utmem.edu.

DISCUSSION

JOHN R. GALLOWAY, M.D. (Atlanta, GA; Opening Discussion): This single institution review of 196 elective pancreatectomies for both benign and malignant diseases focused on the postoperative intra- abdominal sepsis that occurred in 16 per cent. Soft pancreas is identified as a major risk factor for postoperative leak and postoperative infection. Fever, tachycardia, altered mental status, oliguria, and hemodynamic changes are signs of developing intraabdominal sepsis. The authors appropriately advocate early CT imaging to effectively diagnose and treat infected fluid collections and abscesses. Based on their analysis, the bacterial flora obtained from such collection, the early institution of broadspectrum antimicrobial antibiotics against methicillinresistant S. aureus, Gram-negative rods, and antifungal agents are recommended. This is certainly in keeping with the sepsis protocol guidelines put forth by the Society of Critical Care Medicine. The authors accurately note the valuable role of CT drainage using multiple drains, if necessary, and the early follow-up CT scan to document efficacy. In those patients who cannot be safely drained or fail drainage, they advocate the expeditious role of surgical intervention.

Despite this aggressive program of management, postpancreatectomy intra-abdominal sepsis remains a terrible, devastating problem for the patient. Length of stay in the successfully treated patients is more than doubled, and mortality increases from 2 per cent to 16 per cent. Short of never cutting into the soft pancreas, are there any other ways to prevent this complication?

The authors state their own data does not support the use of intraoperative drainage, stenting of the pancreaticojejunostomy, fibrin glue application, or the use of perioperative octreotide. Nevertheless, in their discussion, when confronted with a soft pancreas, they do indeed use these techniques. Do these measures aid in preventing sepsis in a soft gland? How do you handle the cut edge of the pancreas in your patient with distal pancreatectomy?

STEPHEN W. BEHRMAN, M.D. (Memphis, TN; Closing Discussion): Other series, as well as our own results, suggest with a soft pancreas, a 10 per cent to 15 per cent leak rate will occur. My approach is to do everything in a soft gland: fibrin glue, octreotide, omentum, and so on.

I will typically invaginate those anastomoses. With a cut edge, I will individually ligate the duct of Wirsung and then place vertical mattress sutures across the cut edge. In addition, I will place fibrin glue and omentum over it.

JOSE J. DIAZ, JR., M.D. (Nashville, TN): Have you looked at any intraoperative differences during those cases that did and did not develop an intra-abdominal infection (that is, periods of hypotension, length of operation, perioperative antibiotic, timing, redosing during the procedure, and so on)?

STEPHEN W. BEHRMAN, M.D. (Memphis, TN; Closing Discussion): In the uni- and multivariate analyses, we did not find any difference. We have not been able to get our rate of sepsis below the 10 per cent to 15 per cent level.

TAD KIM, M.D. (Gainesville, FL): Do abscesses occur despite having intraperitoneal drains placed intraoperatively?

STEPHEN W. BEHRMAN, M.D. (Memphis, TN; Closing Discussion): I stopped draining pancreatic resections approximately 3 to 4 years ago. One of the things I wanted to look at was whether that made an impact on whether or not these patients developed sepsis. In our analysis, it had no impact on the development of this complication after pancreatectomy.

ROBERT MAXWELL, M.D. (Chattanooga, TN): I would like to get your thoughts on the soft gland and ligating or stapling the gland off.

STEPHEN W. BEHRMAN, M.D. (Memphis, TN; Closing Discussion): That has been reported in the surgical literature; the pancreatic fistula rate is higher when stapled versus hand-sewn.

GARY C. VITALE, M.D. (Louisville, KY): I think if you can convert these to a fistula, you are less likely to have sepsis that leads to death. Does it not make sense even though placing drains may promote fistulization and you end up with a higher fistula rate, that it might lead to less sepsis collections that need to be reoperated early? Could you comment about those in whom you did place drains and whether there was a little higher fistula rate but lower sepsis and collection rate?

STEPHEN W. BEHRMAN, MD. (Memphis, TN; Closing Discussion): I noted in the abstract that the sepsis postoperative sepsis rate was higher in mose who did not have intraperitoneal drains placed. I was very disturbed by that. For the subsequent follow up, I then placed drains in the 16 patients who I added to this series. The data showed there was no difference whether or not they had placement of intraperitoneal drains. My preference is to still not drain these patients because the drains are not effective in evacuating these fluid collections.

DAVID FELICIANO, M.D. (Atlanta, GA): Would it not be safer to put a JP drain in? I may be naive because I do not do pancreatic resections everyday, but although there is a fixed leak rate, I am not convinced that everyone has a high rate of abscesses.

STEPHEN W. BEHRMAN, M.D. (Memphis, TN; Closing Discussion): I have tried all sorts of drainage, and I have still not found one that works. I still place drains occasionally, but I am not sure if the intraperitoneal drain is the panacea to preventing this underlying complication. In all of our patients, the fistula probably occurred before postoperative day 6. We are really aggressive in investigating these patients early, so perhaps we are detecting collections earlier than we had in the past. These are not frank abscesses, but appear to be ascites or postoperative fluid that can accumulate after any operation. Because of the clinical condition of the patient, we are very aggressive with early percutaneous drainage.

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