THE ROLE OF THE INFECTIOUS DISEASE SPECIALIST IN PANCREATIC SURGERY

Abstract

Fever and leukocytosis of unknown cause are the reasons for most infectious disease consultations. They are common in pancreatitis and pancreatic malignancy as a result of complications of the diseases or subsequent surgical treatment. After surgery, fever or leukocytosis that does not abate within 72 hours develops in 30% to 50% of patients. Fever preceding surgery often is related to biliary obstruction, and cholangitis is common in periampullary malignancy. Cholangitis develops when pressure in the bile duct exceeds sinusoidal pressure in the liver, causing back-diffusion of bacteria and endotoxin, chills, and fever; biliary obstruction causes jaundice. The causes of postoperative fever are myriad and include the “usual” medical problems that occur after other abdominal surgical procedures. There are some complications specific to pancreatic surgery, and this article focuses predominantly on them.

Morbidity after pancreatic resection is significant. Postoperative complications develop in at least 30% of patients. Many are trivial and spontaneously subside, whereas others are more significant. Common postoperative complications include wound infections (5%–15% of cases)4, 5, 7; intra-abdominal abscesses (≥ 10% of cases); cholangitis (5% of cases if biliary obstruction recurs)4, 5, 7; and pancreatic fistula and bile leaks, which cause fever in as many as 25% of patients. Thus, the evaluation of postoperative pancreatic surgical patients with fever includes exclusion of the usual postoperative causes and inclusion of those specific to pancreatic resection.

There are multiple predisposing factors for complications after pancreatic resection. Pancreaticoduodenectomy, which involves three or four anastomoses, a lengthy surgical procedure in a jaundiced or compromised host, commonly is associated with fistula after anastomotic disruption. The pancreatic enteric anastomosis is notorious for this complication and, depending on definition, accounts for a fistula occurrence rate of 4% to 30%. Bile, pancreatic fluid, or small bowel drainage in compromised and antibiotic-treated hosts is likely to contain altered pathogenic flora. In addition, patients undergoing pancreaticoduodenectomy for cancer commonly are malnourished and may exhibit cachexia and cholangitis before surgery. Patients with pancreatic malignancy commonly have multiple hospitalizations, with antimicrobial exposure in the course of their evaluation when the diagnosis has been elusive. Many of these patients are likely to be colonized with resistant Enterobacteriaceae; methicillin-resistant Staphylococcus aureus; and enterococci, including vancomycin-resistant strains. Most patients with pancreatic cancer are elderly (60% are > 80 years of age) with diminished reticuloendothelial cell function; these factors contribute to a diminished immune status. Thus, under the best of circumstances, patients undergoing pancreaticoduodenectomy for malignancy are at a greater risk for a priori infection and other complications that patients with other malignancies avoid.

In the postoperative period, common causes of fever, such as pneumonia, catheter-related infections, urinary tract infections, and pseudomembranous colitis, should be ruled out before a more intensive evaluation for intra-abdominal abscesses or deep wound infections is performed.

Ultrasonography and CT scanning generally can diagnose or assist in the detection of intra-abdominal abscesses, which develop in as many as 10% of patients after pancreatic duct resection (PDR). With an obvious abscess, CT is very accurate (≥ 90%); with fever and a suspected, occult abscess, all tests commonly are wanting. Dilatation of the biliary tree postoperatively suggests continued biliary obstruction, perhaps from edema of the anastomosis, but cholangitis is uncommon and is manifest by a persistently elevated alkaline phosphatase level, chills, and fever. Postoperative CT scans commonly are unable to distinguish postoperative fluid collections from abscess collections, particularly when barium or contrast medium does not fill a loop of bowel because of a Roux anastomosis or delayed gastric emptying. There is, however, almost no role for blind repeat exploration in febrile but hemodynamically stable patients. The author favors initial right upper quadrant sonography, which is sensitive for fluid collections near the liver. These fluid collections usually develop near the drain or tract placed at the time of pancreaticoduodenal resection and, when present, drain spontaneously. Detection of fluid in this area, not accessible to operatively placed drains, or that which develops after drains are removed, can be treated at the bedside under sonographic guidance. The author uses CT only if the sonogram is unrevealing and fever persists without an obvious source. Sonography has been most helpful in examining interfaces between solid organs, and least helpful in the mid abdomen, where fluid collections can develop between loops of bowel. When radiologic tests do not disclose the fluid collection, it is best to follow up patients closely for an additional 7 to 10 days and reexamine them by repeat imaging tests. A fluid collection, if now detected and accessible, may be drained percutaneously. The author rarely has found patients to deteriorate during this waiting period. In some patients, fever resolves spontaneously, or collections drain spontaneously.

Wound infections are sometimes difficult to detect. This seems unlikely despite daily wound examination but occurs particularly in elderly or debilitated patients who may be incapable of mounting a strong inflammatory response. Not infrequently, the wound drains spontaneously or a wound collection is first detected on CT scanning in the absence of the usual signs and symptoms.

Patients with cholangitis are usually acutely and transiently ill, with positive blood cultures. This is not a common postoperative problem but is a common cause of fever and infection preoperatively. If a jaundiced patient is treated by endoscopic stent placement, the obstruction is relieved; if the stent occludes, bacteremia may develop from colonization of the biliary tree by the stent. These patients are jaundiced and have a classic history of chills and fever. In the presence of a stent, stent occlusion should be the first thought. Pending culture results, patients generally are placed on broad-spectrum antimicrobial therapy directed toward Enterobacteriaceae and aerobic and anaerobic streptococci. Gram-negative anaerobes, common in the lower gastrointestinal tract, rarely are encountered in the biliary tree.

The most significant postoperative complication is the development of biliary and pancreatic drainage detected through a drain site. This situation most often is associated with fever and leukocytosis. If adequate egress of the fistula is provided, abscess formation is unlikely. The fistula invariably closes spontaneously. Concern as to whether drains may increase the risk for infection and fever persists. Randomized studies have shown no benefit to routine drainage.² The author's view is that there is no disadvantage to a closed drainage system and every reason to avoid the occasional patient who presents with overwhelming sepsis and hypotension from an abscess, particularly in surgical procedures with a fistula occurrence rate of 16%.

Less common causes of postoperative fever include hepatic and splenic infarcts, liver abscesses, deep venous thrombosis, and pancreatitis. Although the author's intention is to discuss only those postoperative complications specific to pancreatic surgery, because of the rapidly increasing prevalence of Clostridium difficile colitis in the patient population at the author's institution and in hospitalized patients in general, this problem deserves discussion. Pseudomembranous colitis, a result of colonization of the colon with toxin-producing C. difficile, accounts for approximately 20% to 30% of cases of antibiotic-associated diarrhea³ and a smaller percentage of cases of diarrhea after pancreatic surgery (e.g., patients in whom diarrhea also may result from enteral hyperalimentation). This high prevalence is not surprising because patients undergoing pancreatic surgery have several risk factors for C. difficile colitis, including advanced age, severe illness, gastrointestinal surgery, and alterations in gastrointestinal motility caused by pharmacologic agents, especially second- and third-generation cephalosporins and extended spectrum penicillins. Because leukocytosis and fever commonly accompany postoperative complications of pancreatic surgery (intra-abdominal abscesses and diarrhea may be common for reasons mentioned earlier), physicians caring for these patients must maintain a high index of suspicion to promptly recognize this disorder.

Similar to C. difficile colitis, yeast infections have become an increasing problem in hospitalized patients. Although fungemia is uncommon in patients at the author's institution because of the relatively short length of hospital stay, aggressive avoidance of prolonged central venous catheterization, and limited use of antimicrobial agents, yeast commonly is isolated from cultures of drain sites in febrile patients and may present a treatment dilemma. Limited medical literature exists to provide guidance on this subject, but the author believes that, in most instances, treatment is unnecessary. Exceptions include patients who are critically ill, and patients who are persistently febrile, in whom yeast is isolated from multiple sites, such as urine or sputum. The presence of other risk factors for fungemia, including heavy previous antimicrobial exposure and underlying diabetes mellitus, may tip the equation in favor of treatment.

The choice of antimicrobial agents for treating infectious complications in patients undergoing pancreatic surgery depends largely on the known local resistance patterns of the organisms commonly associated with intra-abdominal abscesses and cholangitis and the susceptibilities of organisms isolated from blood and other sterile sites. In high-volume tertiary care centers, many of the common gram-negative organisms may be resistant to second- and third-generation cephalosporins, and the extended-spectrum penicillins, and vancomycin-resistant enterococci may be a common problem.