Chapter 55. Complications of Acute Pancreatitis (Including Pseudocysts)

Recovery from acute pancreatitis is now expected, with mortality less than 10%, which reflects improvements in the treatment of complications and intensive care management.1 A third of patients with acute pancreatitis develop complications and a quarter of these will die of them. These complications can be local, regional, or systemic. Most regional and systemic complications occur in association with severe acute pancreatitis. The most important determinants of severity in acute pancreatitis are infected local complications and multiple organ dysfunction.2 These regional and systemic complications provide the basis for defining four categories of severity (Table 55-1).3 This chapter will focus on the diagnosis and management of the important complications of acute pancreatitis.

Severe acute pancreatitis is associated with fluid collections and tissue necrosis in and around the pancreas.4 These local complications of acute pancreatitis were defined by the Atlanta Symposium in 1992 as pancreatic necrosis, pseudocyst, and abscess. These terms, however, have proven to be confusing and new terminology has been introduced in an attempt to reflect current understanding of the pathophysiology and morphology of the disease.5,6 In the revised Atlanta Classification, fluid collections less than 4 weeks after disease onset are termed either an acute fluid collection or a postnecrotic pancreatic or peripancreatic fluid collection.7 Over time changes in the morphology of the lesion occur, in particular the reaction of the surrounding tissue to the enzyme-rich fluid produces a wall, and this is usually well defined on CT scan after 4 weeks. A pancreatic pseudocyst is the term that has traditionally been applied to this lesion, but it is now appreciated that the contents may be anywhere on a continuum from entirely solid to entirely fluid.8 When a fluid collection has developed in association with pancreatic necrosis, the revised Atlanta Classification has suggested that this is termed “walled off necrosis” (WON). In addition to this variation in content (solid to fluid) local complications can also be sterile or infected, with the latter having significant prognostic significance.

Acute Fluid Collections

Description

Acute fluid collections have no solid component or wall, and typically exist adjacent to the pancreas confined by anatomical fascial planes (eg, anterior pararenal fascia).7 These collections occur in 30–50% of cases9,10 and contain a mixture of inflammatory exudates and/or enzyme-rich pancreatic secretions that are a consequence of breakdown of small peripheral ductal side branches. While they may be associated with parenchymal necrosis, their presence does not necessarily indicate necrosis or significant duct disruption. The pancreatic fluid can track widely and may take the form of peripancreatic fluid collections in the retroperitoneum and mediastinum, pancreatic ascites, and/or pleural effusions. The most common routes of extension are into the lesser sac, behind the pancreatic head, behind the left and right colons on the psoas muscle, and into the small bowel mesentery and bulging through the transverse mesocolon.

Diagnosis

Acute fluid collections are a common feature of acute pancreatitis, usually developing in the first 48–72 hours of the disease. Contrast-enhanced CT (CECT), magnetic resonance imaging (MRI) or endoscopic ultrasound (EUS) may be used to confirm the diagnosis and to differentiate acute fluid collections from other local complications (Fig. 55-1).

Management

Acute fluid collections usually remain sterile and resolve spontaneously.9,10 They are only important in and of themselves because they may be the precursor of pancreatic pseudocysts. If spherical or ovoid with sharp margins, suggesting that under some pressure from ongoing leakage, they are more likely to persist. Massive collections of fluid around or within the pancreas are more likely to be due to disruption of the main pancreatic duct and are more likely to persist for a number of weeks or continue to increase in size.

Acute fluid collections are rarely symptomatic and do not require active treatment. Intervention, by surgical or radiological drainage, risks introducing infection into a usually sterile collection. An asymptomatic fluid collection is managed by observation alone, and only in the presence of infection drainage is usually necessary. Medical therapy, such as with diuretics, is not indicated. Continuous peritoneal lavage does not alter the course of the disease and should not be a routine practice.11

Rarely, leakage from injury to the main pancreatic duct can be treated by endoscopic or surgical intervention. Endoscopic treatment uses a trans-sphincteric pancreatic duct stent, which can be placed across the sphincter of Oddi (to decrease ductal pressure and facilitate drainage), into the fluid collection through the disrupted duct (to drain the collection directly) or across the damaged duct (to redirect drainage from the collection to the duodenum and to stent the duct to reduce the risk of stricture formation). The operative approach is either a distal resection of the pancreas or internal drainage of the collection into a Roux-en-Y limb of jejunum. The latter can only be considered once the wall of the collection has matured (see later).

The drainage of pleural effusions in patients with acute pancreatitis should be considered if there is compromised respiratory function or inadequate oxygenation. Chronic pleural effusions as a result of an internal pancreatic fistula often are treated with a chest tube, nasojejunal tube feeding, and somatostatin. Persistence or recurrence will require identification of a pancreatic leak and either drainage into a Roux-en-Y limb of jejunum or distal resection of the pancreas.

Postnecrotic Pancreatic and Peripancreatic Fluid Collection

Description

Postnecrotic collections contain both solid and fluid components, and are not surrounded by a fibrous capsule during the first few weeks. These lesions arise from liquefaction of solid necrosis, but may also contain pancreatic secretions due to an associated pancreatic duct disruption. Over time necrotic tissue undergoes liquefaction and forms part of this fluid collection. As the lesion matures, a wall without an epithelial lining develops around the collection, and is termed WON. Postnecrotic collections are usually sterile but infection may ensue. The term pancreatic abscess is best abandoned as it might represent an infected fluid collection or an infected area of solid necrosis with little associated fluid. This differs from the original definition of a pancreatic abscess, which was defined as a collection of pus, usually in close proximity to the pancreas, containing little or no pancreatic necrosis.4

Diagnosis

Postnecrotic fluid collections are diagnosed with CECT, MRI, or EUS after the first week from disease onset. Infection may be identified on CT as extraluminal gas (Fig. 55-2), although definitive diagnosis requires image-guided fine-needle aspiration (FNA) for Gram's stain and culture. Endoscopic retrograde cholangiopancreatography (ERCP) can be used to determine whether there is any ductal communication associated with the lesion, but is rarely required and risks the introduction of infection.

Management

Management of postnecrotic collections is the same as that for pancreatic necrosis, which is described in detail later in this chapter.

Pseudocyst

A pseudocyst is a well-circumscribed fluid collection with no associated tissue necrosis that is present for 4 or more weeks after disease onset.7 In the original Atlanta Classification a pseudocyst was defined as a collection of pancreatic juice enclosed by a wall of fibrous tissue, and there was no mention of whether it could also contain a solid component. In practice the lesion is either a fluid collection that does not contain necrosum, which when mature (>4 weeks) is best termed a pseudocyst, or a postnecrotic collection that contains necrosum, which when mature (>4 weeks) is best termed WON.

Thus the pseudocyst precursor is the acute fluid collection, and it is differentiated from the former by the presence of a well-defined wall (capsule) without an epithelial lining (Fig. 55-3). This is in contrast to cystic neoplasms of the pancreas, which are characterised by an epithelial lining. However, this is not an absolute distinction as there may be discontinuous epithelium within cystic neoplasms (probably due to pressure atrophy) and partial epithelialization within chronic pseudocysts (facilitated by communication with the main pancreatic duct). In fewer than 20% of cases, more than one pseudocyst is present. Acute pseudocysts are located most often in close proximity to the pancreas, especially in the lesser sac (see Fig. 55-3) but also may be found in the pelvis, scrotum, mediastinum, or thorax. The extent and number of fluid collections are included in the Balthazar grading of the severity of acute pancreatitis CT scanning.12

Pathogenesis and Classification

The development of a pseudocyst requires pancreatic duct disruption, and this occurs in the context of acute pancreatitis (10–15% of cases), trauma, or duct obstruction in chronic pancreatitis (20–40% of cases).13,14 The leakage of enzyme-rich secretion incites a marked inflammatory reaction in the peritoneum, retroperitoneal tissue, and serosa of adjacent viscera. As a result, the fluid is contained by a developing layer of granulation tissue and fibrosis that matures over time. If the communication between pancreatic duct and pseudocyst persists, the pseudocyst can continue to enlarge, sometimes reaching 20–30 cm in diameter. The contents of the pseudocyst usually consist of a relatively clear watery fluid. However, with hemorrhage, it may contain clot and become xanthochromic. In the presence of infection, a pseudocyst will contain pus. If a collection of fluid develops following pancreatic necrosis, and it contains solid tissue, it should not be termed a pseudocyst but rather walled off necrosis (WON).

Pseudocysts secondary to blunt trauma tend to develop anterior to the neck and body of the gland because the duct is injured where it crosses the vertebral column. In chronic pancreatitis, pseudocysts are thought to develop secondary to obstuction of the pancreatic duct. The pseudocysts are usually located within the fibrotic gland, can be multiple and sometimes are difficult to distinguish from pancreatic retention cysts. The latter are formed by progressive dilatation of the pancreatic duct and tend to retain the epithelial lining of the duct.

A useful classification of pseudocysts was proposed by D'Egidio in 1991, which incorporates the key features discussed earlier (Table 55-2).15 Type I pseudocysts occur after an episode of acute pancreatitis and are associated with normal duct anatomy and rarely communicate with the pancreatic duct. Type II pseudocysts occur after an episode of acute or chronic pancreatitis and have a diseased but not strictured pancreatic duct, and there is often a communication between the duct and the pseudocyst. Type III pseudocysts occur in chronic pancreatitis, and are uniformly associated with a duct stricture and a communication between the duct and the pseudocyst.

Complications

With modern imaging practice, a higher proportion of asymptomatic pseudocysts are diagnosed. As a result the risk of pseudocyst complications is probably less than previously considered when pseudocysts were diagnosed on the basis of symptoms. Complications occur in about 10% of cases and the four main complications of pseudocysts are infection, rupture or internal fistulation, bleeding, and mass effect.16

Pseudocysts are initially sterile, but infection can occur in up to 25% of cases.16,17 The presence of sepsis due to an infected pseudocyst is an indication for drainage of the infected contents. This can be done by percutaneous drainage, with the risk of a persisting external pancreatic fistula, or by internal drainage to the stomach or small bowel.

The rupture of a pseudocyst can occur by erosion into the adjacent gastrointestinal tract, which may allow the pseudocyst to resolve or it may leave a cystoenteric fistula or pancreaticopleural/bronchial fistula. The term fistula is not strictly accurate in this setting as the communication is not between two epithelial-lined structures. Rupture into the gastrointestinal tract may be associated with significant haemorrhage, that is a sentinel bleed. Rupture into the peritoneum leads to pancreatic ascites and can be a dramatic presentation with acute abdominal pain and rigidity from chemical peritonitis.

Bleeding associated with a pancreatic pseudocyst can be a life-threatening complication. There are several causes of bleeding. Bleeding may occur secondary to erosion of the gut mucosa with the impending development of a cystoenteric fistula. This may produce hematemesis and melena. More ominous is the direct erosion of a significant visceral vessel, including the splenic, gastroduodenal, and middle colic vessels. The action of pancreatic enzymes (especially elastase) on the vessel wall can lead to thinning of the vessel wall with aneurysm and pseudoaneursym formation (Fig. 55-4). This situation carries a high mortality (~20%).18 The risk of bleeding is increased in the presence of local infection. If time and patient stability permit, emergency selective splanchnic angiography is performed to delineate the site of bleeding, and embolization is attempted (Fig. 55-5A, B). Otherwise, emergency surgery is required, consisting of oversewing of the bleeding vessels and internal or external drainage of the pseudocyst. Occasionally it is possible to resect the pseudocyst, which is effective in preventing recurrent hemorrhage.

A large pseudocyst may exert a mass effect, and thereby produce early satiety (stomach), partial or complete intestinal obstruction (duodenum, gastric outlet, esophagogastric junction, and rarely small or large bowel), cholestasis (bile duct), and venous thrombosis (portal, superior mesenteric, and splenic veins) leading to portal or segmental hypertension and varices. Mass effect is more likely when a pseudocysts is greater than 6 cm in diameter.16

Diagnosis

A pseudocyst should be suspected when a patient with acute pancreatitis fails to recover after a week of treatment or when, after initial improvement, symptoms return. Most patients with symptomatic pseudocysts have epigastric discomfort or pain. There may be anorexia, early satiety, nausea, mild fever, back pain, and a palpable mass. Signs of sepsis are not usually overt. In about half the patients there is failure of the serum amylase level to return to normal or a mild (2–4 times normal) secondary rise. However, often the early stages of pseudocyst formation are observed radiologically before symptoms develop, and this provides some forewarning.

The clinical suspicion of a pseudocyst may be investigated by CECT or MRI scan, where it appears as a rounded, low attenuation, fluid-filled structure within or adjacent to the pancreas (for diagnostic and treatment algorithm, see Fig. 55-6). While ultrasonography (US) is excellent for the detection of a pseudocyst, it is limited by operator skill, the patient's habitus, and overlying bowel gas. The advantage of ultrasonography is that it is better able to determine the extent of solid tissue within a fluid collection, and it is used often to guide FNA. EUS can be useful in distinguishing a pseudocyst from a cystic neoplasm because it often delineates internal septation better than CT scan.19 Compared with ultrasonography, CT scanning has an accuracy approaching 100% for the diagnosis of a pseudocyst, is not operator-dependent, and is more useful in planning therapy. It will demonstrate the key features of a pseudocyst (ie, size, shape, wall thickness, and contents), the nature of the pancreas (ie, presence and extent of necrosis, diameter of pancreatic duct, and features of chronic pancreatitis, including atrophy and calcification), and the relationship of these to the surrounding organs (see Fig. 55-3), which can be critical in planning internal surgical drainage. Triphasic helical CT scanning will delineate the regional arteries (to look for pseudoanuerysm formation) and veins (to look for thrombosis, cavernous transformation, and formation of varices). More recently, MRI is excellent at characterising the morphological features of the lesion and in particular outlining the solid component of the lesion.7

ERCP is not routinely required as part of the diagnostic workup for pseudocysts. In symptomatic cases where treatment is likely, it may be useful to plan further management. The advantage of ERCP is that it has both diagnostic and therapeutic roles. Because of the risks of exacerbating pancreatitis, perforation, bleeding, and introducing infection, it is preferably done within 48 hours of any planned drainage procedure. Over 90% of patients with a pseudocyst have some abnormality of the pancreatic duct. The unique diagnostic contribution of ERCP is to accurately delineate a communication between the main pancreatic duct and the pseudocyst, which occurs in over 60% of patients. A communication of this type is a relative contraindication to external drainage of a pseudocyst.20 The classification of the main pancreatic duct by ERCP has been shown to assist in selecting the type of treatment, where the presence or absence of a stricture, communication, and obstruction is an important feature to note.21 Magnetic resonance cholangiopancreatography (MRCP) may be used to assess pancreatic and biliary duct morphology instead of ERCP and in some centers has replaced ERCP in its diagnostic role and has the advantage of being noninvasive with similar diagnostic accuracy to ERCP, but has no therapeutic role.22

The clinical diagnosis of a complication of a known pseudocyst is usually straightforward. The rupture of a pseudocyst into the peritoneal cavity is associated with the onset of acute abdominal pain and signs of peritonitis. This is in contrast to the spontaneous decompression of a pseudocyst into an adjacent organ, which usually results in the relief of symptoms. Infection of a pseudocyst is accompanied by signs of sepsis. Infection can be confirmed with image-guided FNA for Gram's stain and bacterial culture. Bleeding usually results in an increase in abdominal pain and possible syncope, tachycardia, and hypotension. A drop in hemoglobin concentration is expected.

Although cystic neoplasms are rare, they can be mistaken for pseudocysts. Absence of an antecedent history of acute pancreatitis, elevation of carcinoembryonic antigen (CEA) or carbohydrate antigen (CA) 19-9, and/or the presence of internal septation should suggest this diagnosis. If EUS is available, it will enable the identification of septations (microscopic characteristics of serous lesions or macrocystic characteristic of mucinous lesions), mural nodules, echogenic debris, and calcification, and it may also allow aspiration of fluid content for analysis. Pseudocysts usually contain fluid with elevated amylase (>5000 U/mL) and an absence of tumor markers, but this should not be relied on for a definitive diagnosis.23

Management

The natural history of a pseudocyst is not easy to predict. Spontaneous resolution occurs frequently and usually within 6 weeks. When larger than 6 cm in diameter, and when it continues to enlarge during the first month, a pseudocyst is more likely to persist and develop complications. Size alone is a poor predictor because resolution can occur even with very large pseudocysts. Persistence is also more likely if there is a distal stricture of the main pancreatic duct and a proximal communication between the main pancreatic duct and the pseudocyst. Although not directly correlated, a large pseudocyst is more likely to cause discomfort and pain.

The two principal indications for treating pancreatic pseudocysts are to relieve symptoms and to treat complications. In the absence of symptoms or evidence of enlargement, conservative management is usually reasonable. A traditional approach that dictated treatment of all pseudocysts that have been present for more than 4–6 weeks is no longer justified.24 The decision as to whether a pseudocyst in a particular patient requires active intervention can be difficult. The desire to allow time for spontaneous resolution to occur must be balanced against the risk of complications while waiting for cyst wall maturity. The traditional indications for treatment were the complications of a pseudocyst. Now the focus is on preventing complications. In many centers it has become less common to treat a pseudocyst solely on the grounds of a failure to resolve. An enlarging asymptomatic pseudocyst that has been present for 6 weeks is usually treated. A natural-history study from India indicates that asymptomatic pseudocysts less than 7.5 cm in diameter and without internal debris will resolve spontaneously at an average of 5 months.25 In modern series, the mean diameter of pseudocysts requiring treatment is approximately 9 cm.26,27 At the same time as this trend toward conservatism, there has been an increase in the number of treatment modalities, including open surgical, laparoscopic, endoscopic, and radiological.

There are two important rules in the treatment of pseudocysts. The first is that a cystic neoplasm must not be treated as a pseudocyst. The second is that elective external drainage of a pseudocyst must not be done if there is downstream and unrelieved pancreatic ductal obstruction because of the high risk of an external pancreatic fistula. The approach to treatment (Table 55-3) depends on the nature of the pseudocyst, the pancreatic duct, and the fitness of the patient. Also important is the level of available expertise and experience with the various treatment modalities.

The following general features of a pseudocyst are important in considering the most appropriate treatment:

• The thickness of the pseudocyst wall, which is usually a function of the duration of the pseudocyst. This is important because the operative drainage of a pseudocyst requires that it safely accept sutures or staples. After 6 weeks the fluid collection is fully walled off in a fibrous capsule.28
• The location of the pseudocyst. If adherent to the stomach or duodenum, the options are different than if the pseudocyst is deep within the retroperitoneum and covered by bowel loops.
• The contents of the pseudocyst. The presence of blood may indicate the need for prior embolization of a pseudoanuerysm. Pus will require drainage, either internally or externally. The presence of solid necrosum suggests the lesion is in fact WON and may require some form of necrosectomy.
• The number of pseudocysts. If multiple pseudocysts are present, then minimally invasive approaches may not be feasible. Conservative management is not recommended with symptomatic multiple pseudocysts.
• The etiology of the pseudocyst. Lesions arising from acute-on-chronic pancreatitis may require different treatment to those arising from the first episode of acute pancreatitis.
• The main pancreatic duct anatomy and degree of disruption. The pancreas and the pancreatic duct need separate consideration in planning the treatment of a pseudocyst. The pancreas may warrant treatment in its own right, especially if there is a ductal stricture, a dilated duct, or regional disease warranting resection.

Open Surgical Treatment.

There is no single surgical procedure that is appropriate for all pseudocysts. The most important factor dictating the mode of treatment is local expertise.29 In principle, drainage procedures are preferred to resection because they preserve pancreatic function, are technically easier, and have a lower mortality rate. Despite the many alternatives and less invasive approaches, it is important to emphasize that the most effective and reliable means of treating a pseudocyst is internal drainage by an open surgical approach (see Table 55-3). The complication and mortality rates of internal drainage are half those of external drainage.

A D'Egidio type II pseudocyst is best treated by internal drainage or resection, particularly when ductal disruption or stricture is present. When there is a mature wall, internal drainage is the best surgical option. Recurrence rates should be less than 5%, and mortality should be less than 2%. The pseudocyst can be drained into the stomach, the duodenum, or the jejunum. The choice of surgical procedure depends on the location of the pseudocyst and its relationship to these organs. A cystogastrostomy is ideal when the pseudocyst is adherent to the posterior stomach and indenting it (Fig. 55-7). A longtitudinal anterior gastrostomy is followed by the stepwise excision of a disk (>2 cm diameter) of stomach with subjacent pseudocyst wall. The tissue is sent for frozen section in all cases to exclude cystic neoplasia. Sutures are placed in stages to reduce the risk of edge bleeding as the disk is excised. Prior confirmation of the location of the pseudocyst may be required by needle aspiration, although it is usually obvious. The stoma should be large enough to allow transgastric débridement of any necrotic tissue within the pseudocyst cavity. A laparoscope can be used after open débridement to confirm that the cavity it clear of debris. The disadvantage of the cystogastrostomy is that it is not a dependent stoma, may act as a sump, and when the pseudocyst is large can accumulate gastric debris. Where access permits, a Roux-en-Y cystojejunostomy is ideal for internal drainage (Fig. 55-8) and is particularly suited to drainage of pseudocysts arising from the body and tail of the pancreas, or not adherent to the stomach or bulging through the left transverse mesocolon.

Combining internal drainage of a pseudocyst with a lateral pancreaticojejunostomy should be considered in patients with chronic pancreatitis and a dilated pancreatic duct because it will improve outcome without increasing the risk of the procedure. The blind end of the Roux limb should be placed toward the tail of the pancreas because this allows the head of the pancreas to be drained and the bile duct to be bypassed using the same limb.

Distal pancreatic resection has a role, particulary when the head of the pancreas is relatively preserved. An endoscopic retrograde pancreatogram will help to define the extent of resection. Provided that there is no pancreatic duct obstruction, the recurrence and fistula rates are very low. Specific ligation of the pancreatic duct will decrease the fistula rate.

External drainage of a pseudocyst has a limited role but is useful in the critically ill patient and where a controlled external fistula is an acceptable goal. Other rare indications for external drainage at the time of laparotomy include the control of an immature ruptured pseudocyst and for some bleeding pseudocysts where there has been under-running of the bleeding point. An external fistula may resolve more rapidly with placement of a transpapillary stent and with the use of a long-acting somatostatin analogue.

Radiological Treatment.

The first description of direct percutaneous aspiration and external drainage using radiologic guidance was in the early 1980s.30–33 This technique has become widely practiced with a reported morbidity of between 10 and 30%. It can be used with an immature pseudocyst wall, although the risk of complications is higher in this setting. Percutaneous drainage is best suited to D'Egidio type I pseudocysts in which there is no significant underlying duct abnormality or communication between the duct and pseudocyst. In the setting of acute pancreatitis, catheter drainage may not be helpful because of small catheter size and the inability to allow the drainage of necrotic and viscous material. In the setting of chronic pancreatitis, the downstream obstruction of the duct gives rise to a high recurrence rate and/or an external fistula along the catheter tract. In simple, uncomplicated pseudocysts, percutaneous drainage is usually successful, but not necessary since this is the group with the fewest symptoms, the lowest complication rate, and the best chance of spontaneous resolution.

The introduction of a transgastric approach to percutaneous drainage has almost abolished the problem of external pancreatic fistulas (Fig. 55-9A, B).34 This produces a percutaneous cystogastrostomy but requires an initial period of external transgastric drainage, clamping at 3 days, and then internalization at 2 weeks. Internalization can be helped with a concurrent endoscopic view, especially using double pigtail catheters. The endoscopic approach is also used for the subsequent removal of the catheters. A well-matched population-based study comparing percutaneous (n = 8121) with open surgical drainage (n = 6409) in 14,914 patients with pancreatic pseudocysts revealed a longer length of hospital stay and twice the mortality (5.9 vs 2.8%) for the former35 (ie, percutaneous). Currently there is limited use of percutaneous pseudocyst drainage, unless there is an underlying medical problem or cyst complication.

Endoscopic Treatment.

There has been significant activity in the endoscopic treatment of pseudocysts over the last decade. Endoscopic transpapillary techniques include stenting the sphincter of Oddi to lower ductal pressures. The stent also can be advanced via the pancreatic duct into the pseudocyst when there is a demonstrable communication. Endoscopic transmural drainage is also possible and involves identifying the bulge into stomach or duodenum caused by the pseudocyst. The cyst generally is entered using a diathermy needle knife. Prior endoscopic ultrasonography allows greater accuracy and safety by confirming the anatomic route, and Doppler can be used to help avoid larger blood vessels. A number of pigtail stents can be inserted. The tract also can be dilated with a balloon catheter and the endoscope itself inserted into the cavity of the pseudocyst for direct visualization and retrieval of the cyst contents and wall biopsy (to rule out a cystic neoplasm).

These endoscopic methods are still evolving but have a reported success rate of up to 90% with experienced practitioners. But it must be remembered that the reports generally are in carefully selected patients. Caution needs to be exercised because of the risks of perforation, peritonitis, and infection through inadequate internal drainage. This is also a less reliable means of obtaining a large tissue sample to exclude cystic neoplasia and there is also an increased risk of bleeding. The risk of bleeding is significantly reduced when the initial puncture is guided by EUS. The real complication rate probably is higher than the reported 20%, many related to catheter plugging or being dislodged and subsequent sepsis.

Minimally Invasive Surgery.

All the open surgical techniques have been undertaken using a laparoscopic approach.36 Intraluminal laparoscopic surgery, where the trocars are placed through the abdominal and stomach walls, has been successful. The cystogastrostomy can be performed with a stapler or by suture. A more recent modification of this approach is the minilaparoscopic cystogastrostomy using a 2-mm intraluminal laparoscope. The view is augmented by the insertion of a flexible endoscope per os, which also can be used to explore the cyst cavity.

The balloon dilatation of a percutaneous catheter track using a similar approach to that used for percutaneous nephrolithotomy is feasible in many cases. It is worth considering this when the initial radiologic attempts have failed to bring resolution. The placement of a sheath then allows the insertion of an operating nephroscope to enable débridement of the pseudocyst and removal of organized pancreatic necrosis and infected necrosum. This procedure can be repeated and allows the placement of a soft large-bore external drain.

Summary of Treatment for Pseudocysts.

The treatment of choice for pancreatic pseudocysts depends on a number of factors, including size, number, and location of pseudocysts; whether the main pancreatic duct is obstructed or communicates with the pseudocyst; and whether there are complications of the pseudocyst. The clinical context is important (see Table 55-2). With the range of approaches to treatment and the variation in the availability of equipment and expertise, it is necessary to develop a rational treatment algorithm that is appropriate for the clinical setting and the patient (see Fig. 55-6). In practice, type I pseudocysts can usually be managed conservatively. Percutaneous drainage should be considered if the pseudocyst becomes symptomatic or infected. Type II pseudocysts are best managed by internal drainage, especially when there is communication between duct and pseudocyst. Endoscopic, laparoscopic, and radiologic approaches have an emerging role in expert hands.37 With type III pseudocysts, consideration needs to be given to decompression of the pancreatic duct and relieving the stricture at the same time as drainage of the pseudocyst.

Pancreatic Necrosis

Necrosis may involve the pancreatic parenchyma and/or the peripancreatic tissue, and involvement of either of these tissues differentiates necrotizing pancreatitis from edematous pancreatitis.7 Over time the solid necrosis gradually liquefies and becomes surrounded by a capsule, such that after 4 weeks it is termed WON. This partially solid and partially fluid, encapsulated lesion has been described in the literature by a range of terms, including organised necrosis, necroma, and pancreatic sequestrum. The extent of tissue necrosis is not fixed and may progress as the disease evolves during the first 2 weeks of the disease. The necrotizing process can extend widely to involve retroperitoneal fat, small and large bowel mesentery, and the retrocolic and perinephric compartments. The presence of necrosis usually determines a more protracted course lasting weeks to months. From a clinical viewpoint, the development of necrosis is the most important event in the course of acute pancreatitis because subsequent complications, both local and systemic, are associated with it.

Epidemiology

The incidence of acute pancreatitis exhibits marked regional differences, and has been reported to from 5 to 80/100,000.38,39 The proportion of patients with acute pancreatitis that develop pancreatic necrosis is approximately 20%, and of these 25–70% will develop infected necrosis.40,41 The risk of infection is higher when necrosis is more extensive (ie, >30% of the gland).42 In addition, the risk of infection increases with time, from 24% by the end of the first week of illness, to 36% at the end of the second week, and to 71% by the end of the third week.43 The overall mortality of edematous pancreatitis is 1% or less, that of sterile necrosis is 5%, and that of infected necrosis is 10–25% in the best published series.44

Pathogenesis

Of the patients who develop pancreatic necrosis, 70% have evidence of it by 48 hours of the onset of abdominal pain, and all of them by 96 hours.43 The premature activation of proteolytic enzymes within the acinar cells and interstitium of the lobule results in extensive necrosis of pancreatic tissue and the substantial accumulation and activation of leukocytes. There are a number of factors that contribute to the failure of the pancreatic microcirculation, which is evident histologically as stasis and/or thrombosis of intrapancreatic vessels. The failure of the pancreatic microcirculation leads to ischemia, which compounds the enzymatic and inflammatory injury and leads to the full syndrome of necrotizing pancreatitis. During this first week or so, in the so-called early or vasoactive phase, there is the release of proinflammatory mediators that contribute to the pathogenesis of pulmonary, cardiovascular, and renal insufficiency. This early systemic inflammatory response and multiorgan dysfunction are frequently present with evidence of pancreatic infection. In the septic or late phase, which occurs in most patients after 3–4 weeks, these systemic events usually occur as a consequence of infected pancreatic necrosis.

During mild edematous pancreatitis, the surface of the pancreas may show spotty fat necrosis and be larger and firm due to edema,45 usually without hemorrhage or parenchymal necrosis. Early during necrotizing pancreatitis, there is obvious necrosis of the peripancreatic fatty tissue while the parenchyma of the gland may appear less affected. The surface of the pancreas typically demonstrates considerable heterogeneity, with areas of mineralised fat necrosis (saponification) mixed with areas of superficial hemorrhage. There may also be disseminated areas of necrosis in the omentum, mesentery, retroperiotoneum, or other regions of the abdomen. Within the parenchyma of the pancreas there may be only a few foci of hemorrhage associated with fat necrosis between lobules, although in more severe cases lobules are also affected, transforming large areas into necrosis. In severe cases, necrosis of the pancreatic duct or its tributaries may be present, resulting in significant extravasation of pancreatic enzymes. The distribution of parenchymal necrosis is extremely variable, with some patients having necrosis affecting only a portion of the gland (eg, head or tail) and others having confluent necrosis affecting most of the gland.

On histopathological examination there are large areas of peripancreatic fat necrosis and within the pancreas there is evidence of interstitial edema along with necrosis of the parenchyma. This necrosis is initially present in the interlobular fatty tissue, and may be more severe when there is more fatty tissue present. Islets are usually only affected in lobules that are mostly or entirely necrotic. Granulocytes and macrophages are present at the periphery of necrotic areas.

Mild edematous pancreatitis does not usually progress to necrotizing pancreatitis, implying that pathophysiological events soon after the onset of the disease are decisive in determing the course of the disease.45 While edema usually resolves within a few days, the resolution of fat necroses is more variable, depending on the size and location of the lesions. Foci of necrosis less than 1 cm in diameter on the surface of the pancreas usually resolve entirely. This occurs by phagocytosis of necrotic material by macrophages, and these areas may later be replaced by fibrotic scar tissue. Larger foci of necrosis, 2–4 cm in diameter, are demarcated by macrophages that slowly phagocytose the necrotic material. The inner contents of the foci become liquefied. Large foci of necrosis, greater than 5 cm in diameter, do not resolve spontaneously. Macrophages rich in hemosiderin, along other immune cells, form a thin layer of granulation tissue around the lesion by 10–20 days after disease onset. After 20–30 days this becomes a fibrous capsule which gradually increases in thickness.46 As with the smaller lesions, the contents slowly liquefy or organize over time. The contents may also contain high levels of pancreatic enzymes, suggesting the presence of communications with pancreatic ducts. Necrotic lesions are most likely to permit entry of bacteria when they are demarcated by only a thin rim of granulation tissue (4–20 days). Over time necrotic areas slowly resolve and are replaced by fibrotic scar tissue (necrosis-fibrosis sequence).47–49

Microbiology of Infected Necrosis

There are five routes by which bacteria are thought to be able to infect pancreatic necrosis: (1) hematogenous, (2) transpapillary reflux of duodenal content into the pancreatic duct, (3) translocation of intestinal bacteria and toxins via the mesenteric lymphatics to the systemic circulation via the thoracic duct, and possibly directly to the pancreas via lymphatic connections between the intestine and pancreas, (4) reflux of bacteriobilia via a disrupted pancreatic duct into the necrotic parenchyma, and (5) transperitoneal spread.

Cultures of infected pancreatic necrosis are polymicrobial in approximately one-third of patients and monomicrobial in two-thirds of patients.50 Gram-negative aerobic bacteria are the most common organisms identified (eg, Escherichia coli, Pseudomonas, Proteus, and Klebsiella), followed by gram-positive bacteria (eg, Enterococcus, Staphylococcusaureus). Anaerobic bacteria are identified in only around 5% of positive cultures, although this may reflect inadequate culture techniques. Fungi may also be cultured, and are more common after use of prophylactic antibiotics.51,52 The spectrum of bacteria cultured from infected necrosis demonstrates that enteric bacteria dominate, suggesting bacterial translocation is an important event in the pathogenesis of infected pancreatic necrosis.41 Pancreatic necrosis is most likely to become infected during the late phase of acute pancreatitis, with a median time from hospital admission to infection of 26 days.42

Prediction and Diagnosis

There are no specific symptoms or signs that are indicative of pancreatic necrosis. The presentation is usually nonspecific with abdominal pain, distension, guarding and associated low-grade fever, and tachycardia. The severity of pain and the extent of hyperamylasemia do not correspond with the severity of acute pancreatitis. Patients presenting late with severe disease will often have established multiorgan dysfunction. The classic skin signs of retroperitoneal necrosis, including discoloration of the navel (Cullen's sign), the flanks (Grey-Turner's sign), and the inguinal region (Fox's sign), are rare and often not seen until the second or third week after disease onset. The diagnosis of pancreatic necrosis requires more than just clinical acumen.

Predicting the severity of acute pancreatitis and the presence of pancreatic necrosis remains an imprecise science. Scoring systems, such as Ranson, Glascow, APACHE II, or “bedside index for severity in acute pancreatitis” (BISAP), are often used for severity stratification, but the derived scores are not accurate with high false-positive and negative rates.53 Patients with predicted severe disease and high likelihood of pancreatic necrosis require radiological confirmation of the presence and extent of necrosis, which is conventionally categorized as less than 30%, 30–50%, and greater than 50% of the pancreas.54 Dynamic contrast-enhanced CT (CECT) is the gold standard for diagnosing pancreatic necrosis and other local complications (see Fig. 55-2), but is not usually indicated within the first 48–72 hours after the onset of acute pancreatitis.55–57 Pancreatic hypoperfusion is usually established by about 72 hours and imaging before then probably underestimates the extent of necrosis and the ultimate disease severity.57 CECT can also be used to score the severity by the CT severity index as proposed by Balthazar.12,55

Current guidelines recommend that CECT is indicated for patients with persisting organ failure, signs of sepsis, or clinical deterioration 6–10 days after admission.55 There has been concern that contrast used for the CT might worsen the necrosis and/or exacerbate existing renal failure.55,56,58–60 A range of alternative modalities have been developed to diagnose the extent of pancreatic necrosis, including MRI and echo-enhanced ultrasound (EEU), which are at least as accurate as CECT in diagnosing and determining the extent of pancreatic necrosis.61,62 In practice, the indications to diagnose and determine the extent of pancreatic necrosis by CECT are predicted severe acute pancreatitis (usually during the second week), when a patient fails to improve with initial resuscitation and/or when the CRP has crossed the diagnostic threshold (see later). The CECT scan can also be used to grade the severity of acute pancreatitis (CT severity index [CTSI]) based on the extent of extrapancreatic changes and pancreatic necrosis.12 It is important to recognize the limitations of CECT, where a pseudocyst and WON can be difficult to distinguish. Imaging by MR or EUS, which better delineate the solid components within a lesion, may be employed when the diagnosis of necrosis is uncertain.

In the absence of a specific marker of pancreatic necrosis, many serum predictors have been proposed. An ideal predictor or prognostic indicator should be simple, cheap, reproducible, valid, available on admission, and specific for necrosis. While a full discussion of markers is beyond the scope of this chapter, there are several that fulfill most of these criteria, compare favorably with CT scanning, and have an established role in routine clinical practice.

C-reactive protein (CRP) is the most widely used predictor of pancreatic necrosis and is useful as a daily monitor of disease progress. The accuracy in detecting necrosis is about 85%, but it requires 3–4 days after the onset of the disease to reach a diagnostic level. The threshold values depend on the assay and the study used. A commonly used threshold is greater than 120 mg/L.63 Other prognostic markers, none of which has been shown to outperform CRP, include interleukin-6 (IL-6) (threshold >14 pg/mL) which peaks a day earlier than CRP; polymorphonuclear elastase (threshold >120 μg/L), which peaks early and reflects neutrophil activation and degranulation; and phospholipase A2 type II (threshold >15 U/L). Urinary trypsinogen-activating peptide has also been proposed as a predictor of necrosis, but is not the major advance that was first anticipated.64 Procalcitonin has been proposed as a sensitive and specific marker for infected necrosis but it has not become part of routine management.41–43

The importance of determining the severity of acute pancreatitis is the need to initiate early intensive care management, and this may necessitate transfer of the patient to a tertiary unit. The initiation of prophylactic antibiotics has been the subject of considerable debate.65–67. The concerns with this approach relate to the increased risk of invasive fungemia, which increases mortality, and of the development of multiresistant organisms.68,69 The current consensus is that there is not a routine role for prophylactic antibiotics.56

The diagnosis of infected necrosis is very important because it is generally considered an indication for intervention. Rarely, the early invasion of gas-forming organisms, such as Clostridium perfringens, makes the diagnosis of infection on CT scanning straightforward.70 It is more usual to suspect pancreatic infection with rapidly progressive disease or a secondary deterioration after 2 or 3 weeks of admission. This is often heralded by a significant rise in CRP. A CT scan will usually confirm the presence of a tense collection with rim enhancement arising from the region(s) of pancreatic necrosis. The presence of gas within the tissues confirms infection, with an “air bubble” appearance (see Fig. 55-2), but this is present in the minority of cases.

Infected necrosis is best diagnosed by image-guided (CT or ultrasound) fine-needle aspiration (FNA) for Gram staining and/or bacterial culture.55,56 The UK guidelines recommended all patients with greater than 30% necrosis and persistent symptoms, and those with smaller areas of necrosis and clinical suspicion of infected necrosis, should undergo image-guided FNA.1 There is now considerable debate over this recommendation, with some authorities suggesting that in addition to significant and secondary clinical deterioration, patients should have a rise in serum markers (eg, CRP, procalcitonin) to increase the index of suspicion for infected necrosis.71 The decision to intervene is one of the most difficult decisions in clinical practice.

There has been some concern that FNA is associated with a potential risk of secondary infection.72 However, clinical practice guidelines are consistent in their recommendation to use FNA as the gold standard test to diagnose infected necrosis.1,4,8,15,46,56,73–79 The rationale for early diagnosis of infected necrosis with FNA is to allow prompt treatment with antibiotics and invasive intervention. Over the last 20 years this has been the prevailing approach to reduce the morbidity and mortality associated with infected necrosis.80 More recently the debate surrounding FNA has been reopened, with the understanding that surgical intervention should be delayed as long as possible or even avoided completely with the judicious use of radiological drainage. When surgical intervention is clinically indicated (by nonresponse to antibiotics and intensive care management) the results of the FNA will not alter patient management because surgery might be undertaken even in the absence of FNA-confirmed infection.71 In summary it is better to view FNA of pancreatic necrosis as an adjunctive measure and one that is only undertaken in a patient in whom there is already a strong clinical suspicion of infection and in whom confirmation of infection will result in intervention.

Indications for Intervention

The indications for intervention in patients with pancreatic necrosis are evolving such that infected pancreatic necrosis, of itself, is no longer considered an absolute indication for surgery in many centres. However, infected necrosis, confirmed by culture-positive FNA, is the strongest indication for intervention, particularly in a deteriorating patient receiving maximum intensive care. Where radiological drainage has been attempted, failure of drainage and/or persistent sepsis from infected necrosis are also clear indications for intervention. Any necrotizing process, regardless of the infectious status, that causes massive hemorrhage or bowel perforation (eg, duodenum or transverse colon) is an indication, albeit rare, for surgical intervention. The indications for surgery in the absence of infection are very limited. Amongst patients with sterile necrosis, only those who are clinically deteriorating despite maximal supportive care and who have a clear target lesion to drain or debride should be considered for surgery.81,82 Surgery is rarely indicated in some patients who “fail to thrive,” but this remains controversial.82 These patients may have documented sterile necrosis, abdominal symptoms, and intolerance to oral feeding more than 4 weeks after disease onset, although the vast majority of patients with sterile necrosis can and should be managed without surgery.

Timing of Intervention

Historically, surgical intervention for pancreatic necrosis was during the first week after disease onset. Early surgery was advocated in order to remove the dead tissue, the focus of infection, and terminate the inflammatory process. We now know that the inflammatory cascades are not easily switched off and are exacerbated by the surgical procedure. Early surgery is more difficult and dangerous because the necrotic tissue is immature, poorly demarcated and not easily separated from viable tissue, resulting in a significant risk of bleeding. Additionally, early surgery may cause infection of sterile necrosis. With mortality rates of up to 65%, the trend for early intervention was called into question.73 In recent years the timing of surgical intervention has become progressively later, such that the current concept for timing of intervention is that it should be undertaken as late as possible after disease onset (preferably >4 weeks), when the necrotic process has stopped extending, there is clear demarcation between viable and nonviable tissues, and infected necrotic tissues have become organized and “walled off.”1,56,73 Such a delay allows time for stabilization of the patient, and decreases the risk of bleeding and pancreatic insufficiency through the unnecessary removal of viable tissue.

Once a diagnosis of infected necrosis has been established, it is now quite common practice to undertake percutaneous catheter drainage of infected fluid.83 This often results in some improvement in the patient's overall clinical status, or an arrested decline. The type and timing of further intervention is dictated by a number of factors, including the patient's condition and comorbidities, local expertise, and the anatomical location and complexity of the lesion. There are two main approaches in regards to repeated surgical intervention. With “programmed intervention,” surgery is repeated according to a set schedule (eg, every second day). With “on demand intervention,” surgery is repeated only if and when it is clinically indicated, by a failure to improve or with secondary deterioration.82

Type of Intervention

There are many different interventions and the challenge is to select the intervention that is appropriate for the particular local complication, taking into account the anatomical location, infection status and complexity of the target lesion(s), the physiological status, comorbidity of an individual patient, and the availability of expertise with the type of intervention. A review of current guidelines highlights the absence of level 1 evidence to guide decision making regarding the types of intervention.84 There are two broad philosophies regarding the type of intervention used. Some experts state that open surgical drainage and necrosectomy remains the gold standard in the management of infected pancreatic necrosis, and reserve less invasive interventions for subsequent complications. These include percutaneous and endoscopic drainage of residual fluid complications. Such a step-down approach contrasts with the step-up approach, which advocates the use of less invasive interventions initially (eg, percutaneous or endoscopic drainage) and only employing open surgical techniques later in the disease course in those who fail to respond. These two approaches have been subjected to a randomized controlled trial in the PANTER trial.85 This demonstrated that a minimally invasive approach, as compared with open necrosectomy, reduced the rate of the composite end point of major complications or death. Mortality itself was not decreased, but new onset multiple organ failure occurred less often in patients assigned to the step-up approach. Another important finding was that a third of patients who would have previously undergone an open necrosectomy were managed by radiological percutaneous drainage alone.

There is a need to standardize the description of invasive interventions to facilitate communication between clinicians, comparison of techniques, and controlled clinical trials. Interventions can be classified based on the method of visualization of the lesion, the anatomical route taken to reach the lesion, and the purpose of the intervention.86

The possible visualization modalities include open procedures where the operative site is exposed through the skin incision, endoscopic procedures where the operative site is visualized with an endoscope (eg, gastroscope, laparoscope, or nephroscope), radiological procedures where CT, ultrasound, or fluoroscopy are used to visualize the lesion during the procedure, and hybrid procedures that combine endoscopic and radiological techniques.

The routes taken by these interventions are defined by the external route into the body (skin or external orifice) and the internal route into the lesion. The internal routes used to reach the target lesion might pass through the gastrointestinal wall, peritoneum, or retroperitoneum.

The overall purpose of treatment is to eliminate areas of necrotic and infected tissue and/or fluid, as well as inflammatory and enzyme-rich exudates. However, the way in which this is achieved varies considerably, with some procedures being considerably more aggressive than others. Therefore, the purpose of individual interventions may be to effect simple drainage alone, lavage of the necrotic cavity to assist drainage of necrotic debris, fragmentation of necrotic tissue to facilitate its drainage, débridement of necrotic tissue, and excision or resection of the pancreas. The overall purpose of intervention is to control the focus of sepsis combined with preservation of vital tissue. Drainage procedures involve allowing fluid and solid necrotic to drain externally out of the body or internally into the gastrointestinal tract. Lavage describes flushing away solid necrotic matter with fluid to facilitate external or internal drainage. Fragmentation is a method used to break down solid necrotic matter by instrumental or mechanical disruption to facilitate drainage. Débridement, which is often termed “necrosectomy,” involves taking or cutting out solid necrotic matter (typically with blunt dissection), and may or may not include postoperative lavage. Débridement may involve removal of all or only some of the necrotic tissue, although normal tissue is never intentionally removed. Only during excision or resection of the pancreas is normal tissue intentionally removed along with devitalised tissue. Such an approach is no longer recommended.

General Principles for Intervention

Figure 55-10 is an algorithm for clinicians who are faced with the management of patients with infected necrosis. The general principles for intervention are the removal of all infected and necrotic tissue and fluid, preservation of vital tissues, and avoidance of intraoperative hemorrhage. Infected necrotic tissue and fluid should be sent for bacterial culture, in order to confirm the causative organisms and rationalize antibiotic therapy. All fluid collections identified on the preoperative CECT must be identified, opened, and evacuated. Débridement of necrotic tissue is performed bluntly, usually with digital dissection, careful use of instruments, and lavage. Only loosely adherent necrotic tissue should be removed and this is easier if there has been a significant delay between onset of disease and surgery. Use of a systematic approach, such as examining in turn the retroperitoneum behind the transverse, ascending, and descending colon, helps to ensure all areas of necrotic tissue are identified and removed. If multiple procedures are planned, the first necrosectomy provides the best exposure and therefore the most complete débridement that is safe should be accomplished at this time. The thoroughness of the initial débridement is the most important factor in determining the need for subsequent reoperation.87The need for complete débridement has been questioned and it has been suggested that incomplete débridement may be sufficient if adequate drainage and lavage is established.88

A key point is to avoid sharp dissection in order to prevent major hemorrhage. Adherent necrotic tissue should be left in situ, as this will subsequently demarcate and become loose. Strands of tissue forming bridges across the cavity may be vessels and should not be avulsed. This is important, because bleeding from inflamed vessels within the retroperitoneum is difficult to control and may require formal packing.

Following débridement, extensive irrigation is used to flush away necrotic debris, inflammatory exudates, and residual bacteria. A gentle hydrodissection device can be used for this purpose. Postoperative lavage may be employed, and this can be either intermittent or continuous (Fig. 55-11).89,90 The fluids most commonly used for this purpose are normal saline and peritoneal dialysis fluid, although there is no evidence to support any specific fluid type or flow rate in this setting.

The choice of operation is determined by the location, extent, and maturity of the necrotic material; status of the infection; the patient's condition; the degree of organ dysfunction; and the preference and experience of the surgeon.41 A number of different approaches have been described (Table 55-4), some of which are only of historical interest. Interventions are complex, fraught with potentially life-threatening complications, and should only be performed by experienced surgeons in referral centers.

Open Surgical Procedures

The role of open surgical treatment of infected pancreatic necrosis is diminishing with the accumulating evidence for the less invasive approaches.85 There are three broad approaches to open necrosectomy: (1) open necrosectomy with open or closed packing; (2) open necrosectomy with continuous closed postoperative lavage; and (3) programmed open necrosectomy. While the débridement technique for all the approaches is similar, they differ in terms of how they provide exit routes for infected fluid, debris, and tissue. The abdomen is best entered though a bilateral subcostal incision since this allows better access to the extremities of the gland and less contamination of the greater peritoneal sac if there are subsequent procedures. The pancreas is exposed by dividing the gastrocolic omentum (Fig. 55-12) or gastrohepatic omentum to access the pancreas through the lesser sac. The body and tail of the pancreas can be exposed by elevating the transverse colon and gaining access to the lesser sac via the transverse mesocolon (Fig. 55-13). Inflammatory adhesions may exist between the pancreas and stomach or transverse mesocolon, and great care is required during exposure. It is generally useful to take down both the hepatic and splenic flexures, if possible, as this will facilitate exposure and reduce the risk of colonic fistula secondary to drain erosion. When the process involves the head of the pancreas, access might require medial mobilization of the duodenum.

Open Necrosectomy with Closed Packing.

The goal of necrosectomy with closed packing is to perform a single operation, with thorough débridement and removal of necrotic and infected tissue, and to avoid or minimize the need for reoperation or subsequent drainage.82 Once the necrotic cavity is opened, fluid collections are evacuated and all areas of necrosis debrided. Some units use gauze stuffed Penrose drains placed via separate stab incisions, but there are many variations in practice with regards to the type and number of drains. With the Penrose drain technique, the intention is to fill the cavity and provide compression rather than facilitate external drainage per se, and between two and twelve drains are usually placed. Additional silicon drains (eg, Jackson-Pratt) are placed in the pancreatic bed and lesser sac to drain fluid from the area. Primary closure of the abdomen is routine with this approach. The stuffed Penrose drains are removed once every other day, starting 5–7 days postoperatively. The silicon drains are removed last. Packing techniques are probably best reserved to control hemorrhage as it is associated with an increased risk of enteric fistulae.

Open Necrosectomy with Open Packing.

The difference with this approach to closed packing is that the abdomen is left open after débridement and packing of the abdomen.91 An alternative form of open packing uses a 20-cm flank incision instead of an anterior laparotomy.92 Open packing techniques have been reported to have higher incidences of fistulae, bleeding, and incisional hernias, as well as a slightly higher mortality rate.93 However, it should be noted there are no prospective trials comparing open packing with any other techniques.

Open Necrosectomy with Continuous Closed Postoperative Lavage.

In this technique débridement is followed by continuous peripancreatic lavage to remove infected necrotic debris, peripancreatic exudates, and extravasated pancreatic exocrine fluid.82,86 Drainage catheters, usually two on each side, are placed with their tips at the head and tail of the pancreas behind the ascending and descending colon. Placement of sump drains (20–24F) with two lumens allows inflow of lavage fluid and outflow of drainage fluid. Larger silicon drains (28–32F) allow evacuation of larger necrotic debris. During closure, a closed peripancreatic compartment is attempted by resuturing the gastrocolic and duodenocolic ligaments. Postoperative continuous lavage is instituted at 1–10 L per day, and is usually continued until the effluent is clear and the patient shows improvement in clinical and laboratory parameters.82,94 There is no evidence as to the best irrigation fluid, the optimal number or calibre of drains, or the duration of irrigation.

Programmed Open Necrosectomy.

The principle of this approach is to be more conservative with débridement, particularly if the necrosis has not fully demarcated, with the intention of performing repeat procedures until débridement is no longer required.82 Following necrosectomy, the pancreatic bed is packed and drains are placed on top of the packing. The abdominal wall is closed with a zipper or mesh sewn to the fascia. This allows easy repeated access to the abdomen and helps to prevent wound retraction. Reoperation is repeated every 48 hours until there is no further necrotic tissue to remove. In a proportion of patients primary closure is not possible and healing by secondary intention is allowed to occur. This procedure may be modified with the addition of intra-abdominal vacuum sealing (negative pressure 50–75 mm Hg) in order to encourage granulation of the pancreatic bed.95

Endoscopic Techniques.

In 1996 Gagner described the first true endoscopic treatment of necrotizing pancreatitis, where the pancreas was debrided using a laparoscopic approach.96 Over the last decade a wide range of endoscopic approaches for pancreatic necrosectomy have been described, including infracolic laparoscopy, transgastric laparoscopy, hand-assisted laparoscopy, retroperitoneal laparoscopy, transgastric flexible endoscopy, flexible endoscopy via a percutaneous endoscopic gastrostomy, and retroperitoneal nephroscopy.97–103 This array of endoscopic techniques may be classified by the type of scope that is used: laparoscope, nephroscope, or flexible endoscope.104 While some endoscopic procedures do not utilize radiological modalities, many are hybrid procedures using fluoroscopy or EUS.

Laparoscopic Techniques.

Most laparoscopic techniques are minimally invasive versions of open surgical techniques, and use an anterior or lateral approach. In Gagner's original description of laparoscopic necrosectomy, two anterior routes (retrogastric retrocolic and transgastric) and one lateral route were described.96 In the retrogastric retrocolic route, a 30-degree laparoscope is introduced through the umbilical port following CO2 insufflation. Placement of additional ports depends on the position of the necrosis. Large drains are placed in the necrotic beds and continuous lavage may be established. In the transgastric route, the stomach is opened anteriorly and posteriorly. Endoluminal ports are used, which maintain the tip of the port inside the stomach. Débridement is performed internally through the posterior stomach wall. It is also possible to use a transduodenal route for necrosis of the pancreatic head. No drains are left in the stomach, although a drain might be placed over the incision in the anterior gastric wall. With the retroperitoneal route, the patient is placed in the left (or right) lateral position and a small flank incision made. The three muscle layers of the abdominal wall are split and a trocar is inserted. Using a 0-degree laparoscope and CO2 insufflation, a tract is made to access the pancreas. Once the necrotic areas have been identified, necrosectomy proceeds as when approached via a retrogastric retrocolic route.

These techniques have subsequently been modified. Of the lateral approaches, one of the most widely used laparoscopic techniques is “videoscopic-assisted retroperitoneal débridement” (VARD).101,105 The purpose of this procedure differs from those of open necrosectomy. Rather than performing complete removal of all infected and necrotic tissue, its goal is to facilitate percutaneous drainage. In this technique radiological drainage of the lesion is first instituted. Following this, a 4–5 cm incision is made in the left flank at the site of the drain. A finger is used to probe and confirm entry into the necrotic cavity. Fluid and loose necrotic debris are removed by suction, and two ports (10–12 mm) are inserted through the incision. The incision is sealed with wet sponges and towel clips to allow insufflation with CO2. Débridement of necrotic tissue is performed with hydrodissection and 10 mm forceps. Drains are placed for postoperative continuous lavage. A 10F red rubber drain is brought through a separate anterolateral incision, and two Penrose drains are placed in the original skin incision. An ostomy bag is then positioned over the flank incision and Penrose drains, and continuous lavage is performed through the red rubber drain at 200 mL/h for 5 days or until the effluent is clear.

Variations on the anterior laparoscopic approaches are well described. In addition to the retrogastric, recolic, and transgastric routes, a transmesocolic route may be used. The transverse colon is elevated to expose the pancreatic lesion in the lesser sac.98 Laparoscopic ultrasound may be used to confirm the position of the lesion, and transverse mesocolon is usually opened to the left of the middle colic vessels. Two or more drains are placed in the pancreatic bed for postoperative lavage. Anterior approaches may also incorporate a hand-assist device (hand-assisted laparoscopic surgery—HALS).100

Nephroscopic Techniques.

Nephroscopic techniques utilize warmed fluid to expand the necrotic cavity and maintain a clear visual field. Use of a nephroscope for necrosectomy was termed “percutaneous necrosectomy” in the unit that pioneered this approach.106 Its principle is the same as for open necrosectomy—debridement of devitalized tissue and establishment of a system for continuous postoperative lavage—although with reduced physiological stress on the patient. Percutaneous necrosectomy may only be used when the area of necrosis is accessible to percutaneous puncture, and is contraindicated in the presence of bowel ischemia, perforated viscus, or significant preoperative hemorrhage.82 The first step is to insert a drainage catheter under CT guidance into the pancreatic lesion. The preferred path for drainage is between the lower pole of the spleen and the splenic flexure, although in right-sided necrosis a path through the gastrocolic omentum (anterior to the duodenum) may occasionally be used. The patient is then transferred to the operating room and positioned in the left (or right for right-sided necrosis) lateral position. The drain tract is then dilated to allow insertion of a 34F Amplatz sheath. A nephroscope is inserted through the sheath into the cavity, and lavage is used to clear away debris and suppurative fluid (Fig. 55-14). Following necrosectomy, a 32F soft drainage tube is left in the cavity. An additional catheter may be used to allow continuous postoperative lavage. Repeat procedures are often required after 2–10 days.82,107

Flexible Endoscopic Techniques.

Peroral flexible endoscopic techniques follow an internal route through either the gastric or duodenal wall or duodenal papilla, and some authors consider this to be a form of natural orifice transluminal endoscopic surgery (NOTES).108 Initial descriptions of flexible endoscopic treatment of pancreatic necrosis used lavage and drainage without instrumental débridement.109 A more aggressive approach was subsequently introduced, which demonstrated necrotic tissue could be debrided with baskets, snares, forceps, and suction.110,111 Endoscopic retrograde cholangiopancreatography (ERCP) may be used to diagnose any communication between the duct and cavity or duct stenosis or disruption, and transpapillary stenting might be employed to decompress the duct. Puncture of the posterior gastric wall into the pancreatic lesion is performed at the point of maximal bulging, although confirmation of the location with EUS helps achieve correct placement of the perforation and avoid injury to vessels. The injection of contrast with fluoroscopy can be used to determine the extent of the cavity. The gastric perforation is dilated with balloons up to 20 mm. For lavage and drainage, a 7F nasocystic (lavage) and a 10F pigtail drain (drainage) are placed in the cavity. Necrosectomy may be performed with endoscopic instruments (eg, Dormia basket or polypectomy snare), and introduction of a forward-viewing endoscope into the necrotic cavity can be used for better visualization during the necrosectomy. Multiple necrosectomy procedures are usually required to clear the cavity of necrotic tissue.

Other techniques using flexible endoscopy through skin incisions have been described. Following percutaneous necrosectomy with a nephroscope, subsequent débridement may be undertaken using a flexible endoscope (sinus tract endoscopy).106 A similar technique has been described following open necrosectomy via a translumbar incision, where a flexible endoscope is inserted into the cavity for débridement of ongoing necrosis.112 Usually multiple débridement procedures are required, typically 8–10 sessions. The wide range of endoscopic approaches to necrosectomy and the absence of formal comparison make a recommendation for the optimal approach difficult. The selection of an endoscopic technique will be influenced by training, experience, and the availability of equipment, but it will also be determined by the location and complexity of the target lesion and the clinical status of the patient.

The first randomized controlled trial comparing two different minimally invasive approaches to the treatment of infected pancreatic necrosis has now been published (PENGUIN).112 In this study endoscopic transgastric necrosectomy was found to be superior compared with VARD. There was a reduction in the incidence of the predefined composite endpoint (new onset multiple organ failure, intra-abdominal bleeding, enterocutaneous fistula, and/or pancreatic fistula) or death. There was a decrease in the incidence of new onset of multiple organ failure, supported by the finding that there was a significantly lower proinflammatory response after the procedure, and a reduction in the incidence of pancreatic fistulation.

Radiological Techniques.

Since solid pancreatic necrosis is commonly associated with a fluid component (postnecrotic pancreatic or peripancreatic fluid collection or walled-off pancreatic necrosis), interventional radiological techniques are assuming greater importance, particularly for initial sepsis control to allow a delay in definitive necrosectomy.113 Ultrasound, fluoroscopy, or CT are used to guide the interventional radiologist into the pancreatic lesion. These radiological modalities are then used to define the extent and composition of the lesion, visualize the position of instruments used, and determine the efficacy of the treatment procedure. The purpose of radiological techniques may be to achieve either drainage (with or without lavage) or débridement.

Radiological Drainage Techniques.

Image-guided percutaneous catheter drainage may be used as a primary treatment for pancreatic necrosis, as a secondary treatment to manage postsurgical accumulation of fluid and residual necrosis, or to delay more definitive treatment until the patient has stabilized clinically or to allow the target lesion to mature.83 Most collections are located in the lesser sac, anterior pararenal space, and other parts of the retroperitoneum.114 The available internal routes into the target lesion are multiple but are most commonly retroperitoneal or transperitoneal. Transmural (transgastric or transduodenal) and transhepatic routes have been described, although these are less common.83 While transgressing the stomach poses little infection risk, gastric peristalsis may dislodge the catheter over time. Transgressing the liver carries increased theoretical risk of bleeding, but in practice this is generally safe. Routes should avoid colon, small bowel, spleen, and kidney to minimize the risk of hemorrhage and bacterial contamination. A retroperitoneal approach that avoids the peritoneal cavity is the preferred route, as this prevents contamination of the peritoneal cavity and possible peritonitis.114

Appropriate catheter selection is required to ensure adequate drainage and to maximize catheter patency. Typically catheters should have multiple side holes and a minimum diameter of 12–14F (4.0–4.7 mm).83 Often multiple catheters are required, especially for large or complex lesions. Lavage can be employed to reduce the concentration of digestive enzymes and proinflammatory mediators in the lesion, and to remove solid necrotic debris from the cavity.115 Lavage may also help ensure catheters remain patent. There have been theoretical concerns that lavage may spread infection, either from infected fluid spilling over into previously sterile cavities, or from the increased intracavity pressure resulting in translocation of bacteria into surrounding tissues. However, this is not been demonstrated as a major concern clinically, most likely because the pancreatic lesion is walled off in a fibrous capsule 4 to 6 weeks after the onset of acute pancreatitis.28

The efficacy of drainage procedures is limited by the contents of the target lesion, with purely solid lesions less likely to be amenable to radiological drainage. In patients with pancreatic necrosis treated with percutaneous catheter drainage, approximately half will be successful and not require surgical intervention.116,117 Indications for surgical intervention in patients who have undergone percutaneous catheter drainage include persistent systemic or local manifestation of infected necrosis, physiological deterioration despite drain patency, persistent abdominal pain, and intolerance of oral intake after the systemic inflammatory response syndrome has resolved.116

Radiological DéBridement Techniques.

In some specialized centers, radiological techniques have been used to debride pancreatic necrosis. These procedures are similar to percutaneous catheter drainage as described earlier, but also include removal of necrotic material with snares, baskets, or by applying suction to a catheter during its removal.89,118,119 Necrotic tissue may be fragmented with wires before attempting its extraction.89 Use of lavage is essential to flush away the loosened necrotic debris.

Prognosis

The prognosis of patients with necrotizing pancreatitis depends on the extent of necrosis and the onset of infection. The overall mortality associated with infected pancreatic necrosis is around 25%,44 while that associated with sterile necrosis is much lower (<5%).120 Most deaths are in the context of multiorgan failure.121

Pancreatic Abscess

The term pancreatic abscess was defined by the Atlanta Symposium as a circumscribed intra-abdominal collection of purulent material containing little or no pancreatic necrosis.4 This term has been used in very different ways including infected acute fluid collection or pancreatic pseudocyst, and a collection of infected fluid arising from infected necrosis. Due to the confusion surrounding this term, it has been abandoned by the revised Atlanta Classification. In units or publications where use of this term persists, the principles guiding management of the lesion are the same as those for infected WON: elimination of infected tissue and/or fluid.

Vascular Complications

Venous Thrombosis

Venous thrombosis is a rare complication of acute pancreatitis and one that usually develops a few weeks after the onset. The etiology is multifactorial, but extrinsic compression of the vein by the swollen pancreas and/or fluid collection is important. Other factors include hypercoagulability and hemoconcentration. The consequences of splenic vein thrombosis are splenomegaly with discomfort and possible hypersplenism. Segmental venous hypertension may result in upper gastrointestinal bleeding from gastric varices. Because the risk of gastric variceal bleeding from pancreatitis-induced splenic vein thrombosis is low (5% for CT-identified varices and 18% for endoscopically identified varices) routine splenectomy is no longer recommended.122 Portal vein thrombosis occurs insidiously and often is discovered after gastrointestinal hemorrhage has occurred. The consequences of acute superior mesenteric vein thrombosis are venous ischemia and infarction of the intestine. CT scanning with contrast material is helpful in the diagnosis of venous thrombosis and may show features of impaired mucosal enhancement, edematous swelling of the vessel wall, and most commonly filling defects within the vein. The goal of the initial treatment of venous thrombosis is to reduce extrinsic compression of the vein by drainage and/or débridement. The role of acute anticoagulation is controversial because of the risk of bleeding. If thrombosis occurs later in the disease course, anticoagulation can be prescribed with less trepidation. Thrombolytic therapy and surgical thrombectomy have no established role in the context of acute pancreatitis. Acute venous thrombosis is associated with a 25% recurrence rate without anticoagulant therapy and a 30% mortality. Anticoagulant therapy combined with surgery is associated with the lowest recurrence rate (3–5%).

Bleeding

Bleeding associated with severe acute pancreatitis is usually, but not always, due to a pseudoaneursym related to a pancreatic pseudocyst. The splenic artery is the most commonly affected artery (30–50%) because of its proximity to the pancreas, followed by the gastroduodenal artery (10–15%), the inferior and superior pancreaticoduodenal arteries (10%), and all others to a lesser extent.

Pathogenesis.

The disruption of the pancreas by necrosis and the damage to pancreatic ducts leads to the accumulation of activated proteolytic enzymes (eg, elastase), weakens the vessel wall, and promotes aneurysmal dilatation. This process is accelerated in the presence of infection. The contained rupture of the aneurysm is a pseudoaneurysm, an extravascular hematoma communicating with the intravascular space.

Diagnosis.

Patients usually present with hypovolemic shock or with an unexplained drop in hemoglobin concentration. Bleeding may occur into a pseudocyst and tamponade, preventing any overt evidence of bleeding. Very rarely the diagnosis will be made in a patient with a known pseudocyst who develops an abdominal bruit.

Selective mesenteric angiography is the best way to make the diagnosis of pseudoanuerysm (see Fig. 55-5A, B), although it can often be detected on the arterial phase of CT scan. Angiography identifies the location of the pseudoanuerysm and its relationship to named vessels. The majority of patients will require surgical management, and the angiogram provides a useful guide.

Treatment.

Pancreatic or peripancreatic bleeding is one of the most formidable and life-threatening complications of pancreatitis. The standard of care in dealing with pseudoaneurysms has been surgical intervention; however, many interventional radiologists have reported excellent outcomes after angioembolization. The approach to treatment depends on the hemodynamic stability of the patient. If the patient is anemic but stable, then transarterial catheter angioembolization of the pseudoaneurysm (see Fig. 55-5A, B) will be considered. If subsequent surgery is required, it can be performed under better conditions, with less risk of torrential hemorrhage. Success with embolization is operator-dependent but success approaches 90% in leading centers. Failure results from an inability to selectively cannulate the bleeding vessel or the poor placement of embolization material. This approach is less likely to succeed with diffuse bleeding, bleeding from the pancreatic head, and bleeding after necrosectomy. Recurrent bleeding occurs in fewer than 40% of patients, and the overall mortality is under 20%.

If emergency laparotomy is required for bleeding, it may not be possible to arrange prior angioembolization. The lifesaving surgery may involve under-running the bleeding vessel (inside or outside the pseudocyst) and/or pancreatic resection. The mortality rate following surgical treatment of arterial hemorrhage during the acute phase of pancreatitis ranges from 28 to 56% and is higher when bleeding from the head of the pancreas. The mortality rate following surgical treatment of massive hemorrhage is usually over 50%.

Intestinal Complications

Paralytic Ileus

The proximity of the inflamed pancreas to the intestine commonly results in regional self-limiting paralytic ileus affecting the duodenum, proximal jejunum, or transverse colon. Another factor which may contribute to the ileus is the relative splanchnic ischemia secondary to the reflex vasoconstriction in reponse to systemic hypotension. An ileus gives rise to the classic “sentinel loop” and “colon cutoff” signs on plain radiographs.

Intestinal Ischemia and Necrosis

Subclinical mucosal ischemia is common in acute pancreatitis, particularly during the early phase, and occurs in response to the hypovolemia and reflex splanchnic vasoconstriction. Intestinal ischemia might be compounded by abdominal compartment syndrome, nonselective inotropes, and the demands of early and continuous enteral feeding. Full-thickness necrosis is rare and probably involves venous and/or arterial thrombosis at sites proximal to the inflammatory process. The middle mesocolic vessels and the transverse colon are mostly at risk.

Intestinal Obstruction

Mechanical obstruction rarely complicates acute pancreatitis. The mechanism is usually inflammatory stenosis which presents very late. It is unusual to require surgery.

Cholestasis

Biochemical and clinical jaundice occur in approximately 20% of patients with acute pancreatitis, often during their hospital course. Mild cholestasis is more common and has been attributed to periductal edema and cholangitis. Long-term total parenteral nutrition will contribute to abnormal liver tests. Extrahepatic bile duct obstruction most often is due to choledocholithiasis or compression by a pseudocyst or pancreatic abscess.

Systemic Inflammatory Response Syndrome

The systemic inflammatory response syndrome (SIRS) is common with acute pancreatitis and encompasses the hallmarks of a proinflammatory state (ie, tachycardia, tachypnea or hyperpnea, hypotension, hypoperfusion, oliguria, leukocytosis or leukopenia, pyrexia or hypothermia, and the need for volume infusion) but without end-organ damage, identifiable bacteremia, or the need for pharmacologic support. SIRS is distinct from sepsis (where there is an identified pathogen) and septic shock (where there is associated hypotension). SIRS is best regarded as an exuberant host inflammatory response and the consequence of hypoperfusion.

There is no single trigger for SIRS. Instead, it represents a whole-organism response to a variety of quite different challenges. Theories on the drivers for SIRS include the immunologic dissonance theory (where there is imbalance between the pro- and anti-inflammatory responses)123 and the gut motor theory (where decreased intestinal perfusion and subsequent damage to the mucosal and immunologic barriers may allow the translocation of endogenous bacteria or their products into the systemic circulation).124 More recently, the intestinal mucosa has been considered another source of inflammatory mediators activated by hypoperfused mucosa. Measurement of intramucosal pH (tonometry) can stratify mortality risk in acute pancreatitis.125

The mediation of SIRS is due to a number of well-described cytokines responsible for the proinflammatory state, a full description of which is beyond the scope of this chapter. In many patients with acute pancreatitis, SIRS progresses to multiple organ dysfunction syndrome (MODS) and possible end-organ damage. Occasionally, patients will be admitted with fulminant or early severe acute pancreatitis, often with respiratory and renal impairment from the outset, and these patients are responsible for early deaths. Organ failure on admission, which occurs in 30–40% of patients with necrotizing pancreatitis, is a very poor prognostic sign, doubling intensive care stay and increasing the mortality rate to fourfold.43 Early aggressive volume resuscitation has an important role in attenuating the systemic inflammatory response.125

Multiple Organ Dysfunction Syndrome

The development of MODS is common in severe acute pancreatitis. It has been defined as the presence of altered organ function in a severely ill patient such that homeostasis cannot be maintained without intervention.126 Many patients with early organ failure respond rapidly to supportive treatment and appear to have an otherwise uncomplicated outcome. These patients are said to have transient organ dysfunction, if it resolves within 48 hours. Recently, it has been shown that organ failure in the first week of admission is a dynamic process and that the progression of early organ failure was attended by a mortality rate in excess of 50%. The response to the initial intensive care is an important determinant of outcome (Fig. 55-15).127

The sequence of organ dysfunction in acute pancreatitis has not been defined. Initial pulmonary insufficiency and renal impairment are often followed by circulatory failure and then metabolic dysfunction and liver failure.

Many potential predictors of organ failure early in the course of admission have been studied. MODS can be predicted with reasonably high accuracy at the time of hospital admission using a combination of the anti-inflammatory cytokine IL-10 (an early marker of systemic inflammation) and serum calcium (an early marker of organ dysfunction).128

MODS scoring systems can be classified using general physiologic critical care scores, that is, the Acute Physiologic and Chronic Health Evaluation (APACHE) score, the Simplified Acute Physiology Score (SAPS), the Mortality Probability Model (MPM), a specific organ score to describe dysfunction (Multiple Organ Dysfunction Score [MODS])], developed by Bernard and colleagues as a descriptor of clinical outcome in MODS, the Sepsis-related Organ Failure Assessment (SOFA), and the Logistic Organ Dysfunction System (LODS). The specific organ dysfunction scores classify organs as failed (yes or no) or dysfunctional using an ordinal scale (graded score). The aggregate score quantitates severity in any one organ and the overall severity of organ dysfunction. The aggregate score then can be interpreted as the likelihood of predicted mortality based on the observed mortality in those study patients used to construct the original scoring system.

There exists no rationale to favor one scoring system over another. The scoring systems do not tell the clinician when specific organ dysfunction is reversible or irreversible. Practically, a simple count of organs affected and the duration of the dysfunction will stratify mortality within broad ranges between 60 and 98% depending on age, with dysfunction in three or more organs for at least a week.

Respiratory Complications

Respiratory impairment can result from several causes, including atelectasis, pleural effusion, pneumonia, mediastinal pseudocyst or abscess, and/or adult respiratory distress syndrome (ARDS). Tachypnea, mild respiratory alkalosis, and mild hypoxemia are common within 2 days of the onset of acute pancreatitis. These clinical features usually can be corrected with analgesia, supplemental oxygen, and chest physiotherapy. A pleural effusion may require a chest drain. Impending respiratory failure is suggested when the arterial PO2 remains less than 60 mm Hg despite high-flow oxygen by mask. These patients should be considered for mechanical ventilation. Lung-protection ventilation strategies, with low tidal volumes for patients with ARDS, are recommended.129 ARDS may occur within a few days of admission or after the development of infected necrosis and septicemia. ARDS results from the release of activated pancreatic enzymes, vasoactive lysosomal enzymes, and especially phospholipase A2 (which destroys surfactant). Parenchymal injury appears to be due primarily to oxidative damage from the activated neutrophils in the lung.

Renal Complications

Renal impairment is usually due to both hypovolemia (prerenal failure) and direct nephrotoxicity from the mediators of acute pancreatitis. Activation of the renin-angiotensin system may contribute to reduced renal perfusion. This manifests as oliguria (<30 mL/h) or anuria and as an increased serum concentration of creatinine and urea. The initial approach is aggressive intravenous crystalloid administration (of up to 10 L/24 h). Then diuretics (furosemide 20–200 mg/24 h) and dopamine infusion (4 μg/kg/min) should be considered. Further deterioration will necessitate continuous hemofiltration and/or hemodialysis.

Cardiovascular Complications

These include arrhythmias, pericardial effusion, impaired myocardial contractility, reduced peripheral vascular resistance, and increased permeability. Hypovolemia, from third-space fluid loss, is common during the first 12 hours and may be up to 30% in severe acute pancreatitis. This problem should be anticipated with aggressive intravenous fluid therapy in the first 24–48 hours. Circulatory failure (mean arterial pressure [MAP] <70 mm Hg) requires prompt, aggressive fluid resuscitation plus or minus inotropic support. SIRS is characterized by decreased peripheral vascular resistance and is the reason for the preferred use of norepinephrine to increase vascular tone and blood pressure (dose 0.05–0.2 μg/kg/min). Epinephrine (dose 0.05–0.2 μg/kg/min) also may be used to support cardiac output. Unfortunately, these inotropes will compound splanchnic vasoconstriction.

If the patient with infected necrosis meets the criteria for severe sepsis, he or she should be managed by current sepsis guidelines.130 Although not widely adopted, there is the evidence for the use of recombinant human activated protein C and low-dose corticosteroids for vasopressor-dependent shock.131,132 There is evidence that glycemic control is important in patients with severe sepsis, although very tight control is associated with hypoglycemia and possibly increased mortality.133,134

Metabolic Complications

Hypocalcemia is the most frequent metabolic disturbance, and it usually occurs during the first week. Low serum albumin will make the hypocalcemia appear worse, and therefore, replacement should be based on ionized calcium. There are several factors likely to be responsible for low calcium. Primarily, calcium is sequestered in areas of fat necrosis by the process of saponification. In addition, there is probably a contribution from altered calcium-regulating hormones (eg, calcitonin, parathyroid hormone, and glucagon). Hypomagnesemia may inhibit parathyroid hormone and contribute to the hypocalcemia.

Hyperglycemia is a frequent finding and usually corrects without the need for treatment. It is an adverse prognostic sign in itself. There are three contributing factors to hyperglycemia, including a stress-induced increase in cortisol and catecholamines, hyperglucagonemia, and probably most important, an insulin deficiency that may reflect necrosis of the islet cells. Glucose intolerance, if not insulin-dependent diabetes, occurs in up to half of patients who have had severe necrotizing pancreatitis.

Disseminated intravascular coagulopathy is not common, but there is a well recognized tendency toward hypercoagulability in acute pancreatitis. Other rare complications include subcutaneous fat necrosis and polyarthritis, which are also seen in patients with acinar cell carcinoma of the pancreas and thought to be due to increased serum lipase. There have also been reports of osteolysis and rhabdomyolysis in severe acute pancreatitis.

Protein-calorie malnutrition is a complication of acute pancreatitis, especially when it is severe and associated with infected necrosis. These patients have a significantly elevated resting energy expenditure, and it has been shown that total parenteral nutrition is unable to reverse this hypercatabolic insult on body protein (Fig. 55-16).135 The importance of and the approaches to nutritional support in patients with severe acute pancreatitis are discussed in Chap. 54.

Encephalopathy

Pancreatic encephalopathy is a rare complication of acute pancreatitis. Clinical features include focal neurologic signs and acute onset of dementia. This picture can fluctuate over time; cyclic progression with remission and relapses has been described. Although the exact mechanisms are unclear, postmortem examination reveals amylase in the cerebrospinal fluid. MRI of the brain may be helpful. Patchy white matter signal abnormalities resembling the plaques seen in multiple sclerosis may reflect the lesions that are found in the cerebral white matter of postmortem-confirmed cases. Treatment is supportive. Any patient with suspicious or unusual neurologic symptoms and signs associated with possible malnutrition, hyperemesis, or malabsorption should be given intravenous thiamine to avoid the potential morbidity and mortality associated with undiagnosed Wernicke's encephalopathy.

The many and varied complications of acute pancreatitis present a considerable clinical challenge and highlight the need for the treatment of patients with severe disease in centers able to offer expertise in a wide range of disciplines including intensive care, surgery, endoscopy, radiology, infectious disease, and nutrition. The two primary goals of research in the field of acute pancreatitis should be aimed at preventing infected pancreatic necrosis and reducing the frequency and severity of multiple organ dysfunction. In the meantime the clinician caring for patients with acute pancreatitis must remain vigilant to detect the development of local, regional, and systemic complications of this protean disease, and be well versed in the considerable recent progress in the treatment of local complications. Of note is the more conservative approach to the simple pseudocyst, the judicious primary use of percutaneous drainage for infected local complications, and the evolution of minimally invasive techniques, which if required should result in improved outcomes in these patients with limited physiological reserve.