Management of acute pancreatitis and pancreatitis-related complications

Acute pancreatitis

Acute pancreatitis (AP) is common with an incidence of 15 to 45 per 100,000 population per year. This has increased over the last two decades largely because of a rising prevalence of obesity and gallstone disease. Recurrent AP represents a subgroup of patients who have had at least two distinct episodes of pancreatitis with complete resolution in between and no evidence of chronic pancreatitis (CP). This may occur in up to 20% of patients, 35% of whom develop recurrent AP and will go on to develop features of CP.

AP is a potentially life-threatening illness. It may result in a prolonged hospital admission associated with significant morbidity and mortality; however, for the majority, it is a self-limiting disease. Successful management of pancreatitis relies on the early recognition of the high-risk subgroup and a multidisciplinary approach to manage complications of pancreatitis under the supervision of a pancreatic specialist. For the majority of patients who have mild uncomplicated attacks of pancreatitis, management is centered around early supportive care until resolution followed by appropriate measures to alleviate the precipitating cause and minimize further attacks, including lifestyle modification.

AP as defined by the revised Atlanta Classification 2012 requires two or more of the following: (1) abdominal pain characteristic of pancreatitis, (2) serum levels of amylase/lipase more than three times the upper limit of normal, and/or (3) imaging characteristics of pancreatitis (see Chapters 54 and 55 ). There are several causes of a solitary hyperamylasemia, especially in critical care patients. These include chronic renal failure, severe burns, liver failure, diabetic ketoacidosis, or after transplant or neurosurgery, and therefore results must be interpreted in context with clinical findings. Gallstones and alcohol are the two most common etiologic factors responsible for AP and their relative importance differs between populations across the world. There is an overall lifetime risk of AP in asymptomatic gallstones and heavy drinkers of 2% to 3%. ^,

Historically, pancreatitis was categorized into mild and severe groups with the emphasis being placed on clinical scoring systems and “predictive” indicators that would allow early triage into one category or another. ^, This overly simplistic classification, however, has been recognized and reflected in the revised Atlanta criteria where an additional category of “moderately severe” pancreatitis is defined to accommodate those patients who experience transient organ failure ( Table 56.1A and B ; Atlanta Classification). The importance of early systemic organ dysfunction and multiple organ failure is key to determining disease severity and outcome, and the management of local complications is heavily influenced by the degree of systemic disturbance.

TABLE 56.1A

Local Complications in Acute Pancreatitis

TIME SCALE	NECROSIS ABSENT	NECROSIS PRESENT
<4 weeks	Acute peripancreatic fluid collection (peripancreatic fluid associated with interstitial edematous pancreatitis with no associated peripancreatic necrosis)	Acute necrotic collection (a collection containing variable amounts of both fluid and necrosis; the necrosis can involve the pancreatic parenchyma or the extrapancreatic tissues)
>4 weeks	Pancreatic pseudocyst (an encapsulated collection of fluid with a well-defined inflammatory wall usually outside the pancreas with minimal or no necrosis)	Walled-off necrosis (a mature, encapsulated collection of pancreatic or extrapancreatic necrosis that has developed a well-defined inflammatory wall)
Infection	Each collection type may be sterile or infected

TABLE 56.1B

Grades of Severity (2012 Revised Atlanta Classification)

Mild acute pancreatitis

No organ failure
No local or systemic complications

Moderately severe acute pancreatitis

Organ failure that resolves within 48 hours (transient organ failure)
and/or
Local or systemic complications without persistent organ failure

Severe acute pancreatitis

Persistent organ failure (>48 hours)

Single organ failure
Multiple organ failure

Pancreatitis is a dynamic illness, and its severity may change during the course of the disease. Two distinct phases are seen in AP that correlate with two recognized peaks in mortality. Early death (defined as within two weeks of onset) occurs as a consequence of progressive multiple organ failure driven by cytokine cascades and systemic inflammatory response syndrome (SIRS). ^, Later mortality is often a consequence of local pancreatic complications because of pancreatic necrosis and therefore only manifests in those with moderate to severe pancreatitis.

Although intervention during the early phase of illness is usually counterproductive, timely and appropriate intervention for local complications in the late phase can be lifesaving and significantly alter the course of the illness. The incidence of AP has been rising but the overall mortality has been falling for several decades, and despite mortality rates in patients with severe AP being disproportionately high, we have seen a downward trend in recent years. This decrease in mortality can be attributed to widespread improvements in intensive care management, the use of minimally invasive approaches to treat complications, advances in interventional and vascular radiologic methods, better and more aggressive nutritional support, and, most importantly, the adoption of a multidisciplinary approach to this systemic disease through the development of specialist centers. The main impact of these improvements is that patients are given more optimal support, earlier and for longer periods during the early phase of the illness, allowing interventions for local complications to be carried out later and by less invasive methods.

Despite multiple randomized control trials (RCTs), there are no effective drug therapies that have shown any significant benefit in preventing organ failure through the use of agents such as glucagon, gabexate, somatostatin, or lexipafant. Although it is recognized that acinar cellular injury underpins the pathophysiology of the disease process, there have been very few trials targeting this and a distinct lack of translational studies.

Initial management

Management of AP requires a multimodal approach that is addressed in a number of national and international guidelines, with the most cited being the American Pancreatic Association (APA)/International Association of Pancreatology (IAP) guidelines of 2013.

Analgesia

Pain is a cardinal feature of AP and should be managed along similar lines to pain caused by other intraabdominal emergencies to improve the patient’s immediate quality of life. Most patients will require parenteral opiate analgesia after hospital admission, but the duration and severity of pain is variable. The choice of analgesic is largely dependent on local protocols, physician preference, and patient’s prior drug histories because no single approach has been shown to be beneficial. Historically, opiates, and morphine in particular, were thought to induce sphincter of Oddi spasm, thereby potentially exacerbating the severity or duration of AP. These were once contraindicated, but there is little evidence to support this. A Cochrane review in 2013 of five RCTs comparing different analgesics in AP found no evidence of increased complications relating to opioid use.

Several RCTs have been conducted comparing different analgesic modalities in AP. Collectively these have shown no contraindications to opiate-based drugs, no benefit from parenteral local anaesthetic agents, and although transdermal and rectal analgesia may be effective, no trials have compared them directly with conventional routes. Administration of opioids by patient-controlled analgesia (PCA) is recommended for patients with protracted and severe pain.

There has been growing interest in the potential role of epidural analgesia, particularly in patients with severe AP, because of their known effects on splanchnic perfusion and tissue oxygenation in experimental models as well as potential improvements in respiratory complications and shock. One RCT has shown that epidural analgesia has better analgesic coverage than parenteral intravenous (IV) opioids, improves pancreatic perfusion, and trends toward a reduced rate of necrosectomy, but the latter failed to reach statistical significance. Further larger trials are ongoing. However, epidural analgesia carries a risk of infective complications and systemic physiologic disturbances such as hypotension, which may be counterproductive in those who experience large fluid shifts, and thus this approach to analgesia is not often used.

Fluid therapy and resuscitation

Current guidelines for managing AP strongly recommend early and appropriate fluid therapy within the first 12 to 24 hours of admission to reduce the incidence of persistent SIRS and subsequent organ failure. Rapid and effective restoration of circulating volume is the single intervention most likely to improve outcome and reduce mortality and morbidity. There is limited evidence to support the fluid type, volume, rate of delivery, and markers to confirm adequate restoration of perfusion. Volume resuscitation as a fundamental principle remains the Holy Grail of critical care.

The choice of initial resuscitation fluid is becoming less contentious, although the lack of high-quality evidence leads to wide variations in practice worldwide. The colloid versus crystalloid debate is moving in favor of crystalloids after the SAFE trial. The American Gastroenterological Association (AGA) makes no specific recommendation over whether normal saline or Ringer’s lactate is better and instead recommends goal-directed therapy. RCTs have been conducted comparing Ringer’s lactate and normal saline in relation to local complications (necrosis, infection), systemic complications (renal failure, shock, respiratory failure, and persistent organ dysfunction) and mortality. Two of these trials demonstrated a clinical benefit with Ringer’s lactate in reducing SIRS in the first 24 hours, but it made no difference to SIRS or mortality at 48 hours. ^, These outcomes are consistent with the known proinflammatory effect of normal saline, which should be used cautiously because it can also cause hyperchloraemic metabolic acidosis when used in large volumes during resuscitation. Evidence, however, remains low quality and there is a lack of any well-designed RCTs.

The addition of hydroxyl ethyl starch (HES) has demonstrated theoretical benefits when used in the resuscitation of patients with AP by reducing intraabdominal hypertension (IAH) and the subsequent need for mechanical ventilation. ^, However, the use of HES in severe sepsis in intensive care has been shown, in several large multicenter studies, to increase the need for renal replacement therapy and overall mortality. Interestingly, a meta-analysis of nonseptic critical care patients has shown that HES does not increase mortality and morbidity in the same way ; however, the studies included were small and there is sufficient concern to recommend against the use of HES in resuscitation of AP.

The volume and rate of fluid resuscitation are similarly not well defined, but several liters may be required in the first 24 hours and there is a move away from rapid fluid infusions toward a more controlled approach with goal-directed therapy. Studies have demonstrated an adverse effect with large volumes of resuscitation fluids (>4 L) in the first 24 hours associated with more respiratory complications, acute collections, persistent organ failure, and a higher mortality.

Current evidence supports a rate of 5 to 10 mL/kg/h, demonstrating a decreased requirement for mechanic ventilation, abdominal compartment syndrome, sepsis, and mortality with this fluid regimen compared with patients assigned to lower infusion rates. ^, An initial fluid bolus of 20 mL/kg before commencing fluid infusions to deliver 3 L to 4 L over the first 24 hours has been recommended in a few studies and closely correlates with fluid resuscitation guidelines in septic shock.

There are no recommended national or international algorithms for the recommended fluid resuscitation in AP. It is crucial that patients have tailored fluid regimens delivered in a closely monitored environment, with frequent reviews by specialists with the aim of maintaining end organ perfusion and restoring physiologic homeostasis. Early identification and treatment of organ failure is key. This can be achieved using adjuncts such as a urinary catheter, arterial line and central venous line to allow monitoring of these variables. More advanced and invasive techniques to determine stroke volume variation or intrathoracic blood volume are only suitable for critically ill patients who are in an intensive care unit.

Critical care and the management of systemic complications

Patients with uncomplicated mild AP can be safely managed in a ward environment with close monitoring and regular clinical reviews to ensure high-risk patients, who may deteriorate, are identified early. Those with persistent or worsening organ dysfunction should be managed in a critical care environment, either in a high-dependency unit (HDU) or an intensive care unit (ICU). In general, an HDU will provide enhanced monitoring and single organ support, whereas an ICU provides multiorgan support and the ability to invasively ventilate (see Chapter 26 ). Critical care is not a treatment per se, but it provides organ support until the pathologic process driving organ failure improves. This may be achieved either with time or by using an additional treatment modality (e.g., surgery) or managing sepsis with source control and antibiotics. It should be noted that critical care requires significant physiologic reserve from the patient and should be used appropriately; not all patients have the reserve to survive critical illness, particularly if they have severe comorbid disease or increased frailty.

The need for critical care may manifest early in the disease course reflecting acute physiologic changes occurring as a result of the inflammatory process from the pancreatitis triggering organ failure. Admission to critical care later in the disease process is usually because of superimposed infective complications and sepsis. Systemic complications, including organ failure, are not binary processes but rather a dynamic continuum with the potential for rapid deterioration; hence early discussion with the critical care team is recommended. This is driven by the patient’s pathophysiology and not the anatomy of the disease process, and therefore close monitoring in all pancreatitis patients is recommended. The management of severe pancreatitis requiring critical care should involve a multidisciplinary team including surgeons, ICU clinicians, radiologists, microbiologists, physiotherapists, and dieticians.

Organ failure

Respiratory, cardiovascular, renal, and gastrointestinal (GI) dysfunction are the most common systemic complications encountered in AP and careful monitoring of each of these systems is key to determining medium- and long-term outcomes for these patients. Respiratory failure usually mandates transfer to the critical care unit, either for maximizing noninvasive support such as continuous positive airway pressure (CPAP) or high-flow nasal cannula or intubation and mechanical ventilation with lung protective strategies.

Cardiovascular collapse is managed primarily by volume resuscitation and vasoactive agents if necessary. This should be guided by invasive monitoring and goal-directed therapy as previously described. Renal failure usually occurs in the context of severe AP as a result of prolonged renal hypoperfusion causing renal tubular necrosis, IAH or nephrotoxic drugs, or computed tomography (CT) contrast. Management involves restoration of circulating volume, ensuring there is adequate blood pressure to provide renal perfusion. Despite this, renal failure may still occur and renal replacement therapy may be required. Recovering renal function is a useful marker of global physiologic improvement.

GI failure also occurs as a result of reduced perfusion, and the use of vasopressors for cardiovascular support can exacerbate the splanchnic vasoconstriction that occurs in these critically ill patients. It manifests as nausea, vomiting, and abdominal distension. The two most clinically relevant consequences of this phenomenon are failure to tolerate enteral nutrition (EN), and the breakdown of the intestinal barrier function with subsequent bacterial translocation, bacteremia, and ultimately infected pancreatic necrosis. Adequate nutrition is extremely important for patients with pancreatitis because a nutritional debt will rapidly develop with muscle wasting and an increased risk of additional complications, particularly respiratory ones.

Intraabdominal hypertension and abdominal compartment syndrome

Raised intraabdominal pressure (IAP) contributes to organ dysfunction and represents a growing area of interest in the management of patients with severe AP. IAH is defined as a persistently raised IAP of 12 mm Hg or higher (Grade I: 12–15 mm Hg; Grade II: 16–20 mm Hg; Grade III: 21–25 mm Hg; Grade IV: >25 mm Hg). Abdominal compartment syndrome (ACS) occurs when IAP is sustained at greater than 20 mm Hg and is associated with failure of at least one organ. The majority of the literature on ACS refers to trauma patients, but it is a recognized complication of severe AP and has been reported to occur in approximately 15% of these patients. When present, there is an associated 49% mortality.

IAH is an indicator of disease severity, organ failure, and mortality, but raised IAP may simply be a surrogate marker indicating a poor outcome and there are no data to suggest that this risk of mortality is improved by surgical decompression. Although controversial, international consensus guidelines advocate the following approach: First, measurement of IAP should be considered in mechanically ventilated patients with severe AP, especially in the context of clinical deterioration. Second, the mainstay of treatment is medical intervention to target the most important contributors to IAH (hollow viscera volume, careful attention to intravascular and extravascular volume status and abdominal wall compliance). Finally, and most controversially given the lack of evidence, invasive treatment for ACS in AP should only be considered after a multidisciplinary discussion for patients with a sustained IAP greater than 25 mm Hg and new-onset organ failure refractory to medical therapy and nasogastric/rectal tube decompression. Invasive treatment options include percutaneous catheter drainage of ascites, laparostomy, or subcutaneous linea alba fasciotomy. The major challenges of the surgical approach include the risk of infecting previously sterile pancreatic necrosis and the difficulty of managing the significant fluid losses that may ensue with an open abdomen. It cannot be overemphasized that these recommendations lack a solid evidence base and high-quality RCTs are required to determine the benefit, if any, of this approach.

Referral to a specialist unit

It is strongly recommended that patients with severe AP should be discussed with, but not necessarily transferred to, a specialist pancreatic unit at an early stage. Increasingly, these patients are managed “remotely” by the base hospital in conjunction with the specialist unit. This is particularly relevant during the early phase of the illness, where specialist intervention is rarely required, to avoid overwhelming the resources of the regional unit. Current guidelines advocate transfer to a specialist unit when patients with severe AP require radiologic, endoscopic, or surgical intervention.

Nutrition

AP is associated with a hypercatabolic state and despite the historic practice of dietary restriction, recent evidence supports that early oral nutrition or EN is beneficial and should be commenced within 24 to 72 hours of admission ^, (see Chapter 26 ). Those with clinically mild AP do not usually require additional nutritional support and may be maintained on a normal diet. Patients with severe AP, however, commonly require additional nutritional support.

The enteral route is preferred over parenteral nutrition (PN) in these patients for several reasons. Enteral feeding maintains normal gut integrity, stimulates intestinal motility, reduces bacterial translocation, and increases splanchnic blood flow, which all potentially reduce the incidence of infected pancreatic necrosis and organ failure. Gastric colonization by pathogenic bacteria, which may also increase the risk for septic complications, is reduced with EN support. PN is associated with more complications (e.g., line sepsis, trace element deficiencies, and liver dysfunction). EN is also significantly cheaper.

There are several RCTs and meta-analyses that support the use of EN over PN in AP. EN is associated with a reduction in systemic infections (including infected pancreatic necrosis), multiorgan failure, need for surgical intervention, and mortality. ^, Some studies have also shown a trend towards shorter length of stay (LOS) in patients who are enterally fed, although this fails to reach statistical significance. ^, A meta-analysis of 20 RCTs also supports the use of any EN formula and did not find any benefit with immuno-nutrition.

The benefits of EN over PN are well recognized, but there has been a long-standing debate regarding the best mode of delivery of EN. Nasogastric (NG) feeding is tolerated in up to 85% of patients and should be tried preferentially to nasojejunal (NJ) feeding. NG tubes are easier to place and are also more convenient and cheaper. Patients who do not tolerate NG feeding usually suffer with delayed gastric emptying, and NJ feeding can work well for these patients.

Contraindications for EN include prolonged paralytic ileus, ACS, and mesenteric ischemia, and a relative contraindication may include enteric fistulae. PN should be reserved for patients in whom the enteral route is not tolerated or inappropriate and although it may be used on its own, it is often used in conjunction with EN to allow patients to adequately meet their nutritional requirements. Glutamine supplementation has been found to be beneficial and is advised where PN is needed; two recent meta-analyses demonstrated elevated serum albumin, reduced C-reactive protein (CRP), less infective complications, shorter LOS, and lower mortality when used. ^,

There is no evidence to support the use of probiotics in the management of AP. Pancreatic enzyme replacement therapy (PERT) is not currently recommended for routine use in AP unless there is evidence of pancreatic exocrine insufficiency (PEI) by testing fecal elastase or demonstrated as malabsorption with steatorrhea. This has been evaluated in two small RCTs: one showed a slightly better outcome with PERT in patients with obvious PEI only and the other showed no difference. ^,

Antibiotics

In patients who survive the early systemic complications of AP, secondary infection of pancreatic necrosis leads to a second peak in mortality between 2 to 4 weeks after disease onset. It can be difficult to differentiate infection from inflammation, although markers such as procalcitonin have shown promise. However, the outcomes of a large RCT, PROCAP, which may help guide antibiotic use in AP, are still awaited. In the absence of a sufficiently specific and sensitive test, the decision to commence antibiotics is based on a variety of factors, including patient trajectory.

Infection occurs in some 40% of patients with pancreatic necrosis and the potential prevention of this by prophylactic antibiotic therapy has been the subject of much research interest. Mortality in this subgroup of patients with co-existing organ failure have a 2-fold increase in their overall mortality. However, there is no evidence to suggest that the routine use of prophylactic antibiotics alters the incidence of infected pancreatic necrosis or overall mortality. ^, ^, A Cochrane review of 7 RCTs and a meta-analysis of 14 studies have found no benefit from routine antibiotic prophylaxis either in mortality or in the incidence of infected pancreatic necrosis, and current international guidelines are clear in advising against routine antibiotic use.

Antibiotic treatment (as opposed to prophylaxis) is indicated in those with proven sepsis. This may occasionally occur at presentation because of co-existing cholangitis, and these patients require urgent relief of biliary obstruction, as discussed later in the next section. In the absence of cholangitis, antibiotics should be reserved for those patients with proven or strongly suspected sepsis because many patients may exhibit signs of SIRS in the absence of infection. In the event that antibiotics are commenced, they should ideally be targeted by culture and sensitivity results, and the duration should be limited to avoid antibiotic resistance.

Endoscopic retrograde cholangiopancreatography

An urgent endoscopic retrograde cholangiopancreatography (ERCP; <24 hrs after presentation) is indicated in gallstone pancreatitis in the presence of cholangitis (see Chapters 30 and 43 ). True cholangitis (jaundice, rigors, and pyrexia) is extremely rare, and a more common scenario is abnormal liver function tests in the context of pancreatitis, and these patients do not benefit from early intervention.

The first RCT of ERCP in pancreatitis was published in 1988 and reported fewer complications and shorter hospital LOS in patients randomized to early ERCP with sphincterotomy and stone extraction if stones were present. A second trial from Hong Kong suggested early ERCP was mainly effective in reducing the incidence of biliary sepsis rather than the severity of AP, and subsequent trials, meta-analyses, and reviews have drawn conflicting conclusions. The most recent Cochrane review of the five RCTs suggested that ERCP done within 72 hours may be associated with a nonsignificant trend toward a reduction in local and systemic complications. A retrospective study compared the outcomes in 73 patients with AP and no cholangitis who underwent urgent ERCP (<24 hours) or early ERCP (24–72 hours) and found that there was no difference in LOS or development of complications from pancreatitis or directly because of the ERCP. Being a small and retrospective study, however, its application is limited and highlights the need for an adequately powered RCT.

In the absence of cholangitis, for patients in whom bilirubin levels persist or rise, magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound (EUS) may be an alternative to ERCP to determine the presence of ductal stones. Given that in the majority of cases, most stones will pass spontaneously, identification of stones before performing ERCP is warranted.

Nontherapeutic ERCP in this group of patients should be avoided and, in a RCT of ERCP, was associated with a higher complication rate than EUS. The APEC trial, undertaken by the Dutch Pancreatitis Study Group, was a multicenter RCT whose aim was to determine if early nontherapeutic ERCP and sphincterotomy was better than conservative management in patients with severe acute biliary pancreatitis without cholangitis. They concluded that early ERCP was not associated with better outcomes with regard to developing organ failure, pancreatic necrosis, pancreatic endocrine, exocrine insufficiency, or pneumonia/bacteremia. In the group who underwent ERCP, however, they observed a reduction in what they described as cholangitis, although this was not defined by conventional cholangitic criteria.

Imaging (see Chapter 17 )

At initial presentation, the primary focus is on resuscitation, and early imaging rarely influences management. An urgent CT is indicated only in cases of diagnostic uncertainty. The role of CT thereafter is in the assessment and follow-up of local complications. Although upper abdominal ultrasound (US) is indicated to determine the presence of gallstones, this does not influence early management and should be performed after the patient has been adequately resuscitated. If the initial US is negative, this should be repeated before discharge because there are many factors that may contribute to false negative results (i.e., operator experience, stones <3 mm, patient body habitus).

In patients with proven gallstones, MRCP, EUS, or intraoperative cholangiography (IOC) may be indicated to evaluate the extrahepatic biliary tree as clinically appropriate. In patients with negative biliary imaging, no alcohol history, or alternative etiology, EUS may be helpful to exclude microlithiasis ( Fig. 56.1 ; see Chapter 22 ) or neoplastic pancreatic pathology. If the latter is expected, cross-sectional imaging should be performed, particularly in the older patient or in a patient with other symptoms suggestive of pancreatic malignancy such as significant pre-incident weight loss.

FIGURE 56.1, Endoscopic ultrasound (EUS) confirming gallbladder microlithiasis as a cause for acute pancreatitis.

Management of necrosis

As previously discussed, there is consensus advocating a principle of early targeted organ support, with nutritional optimization, ideally by the enteral route where possible. In previous editions of this chapter, the focus has been on the timing of open necrosectomy, the role of bacterial fine-needle aspiration to facilitate early intervention, and the management of the post-debridement cavity as described by Bradley, Warshaw, and Beger. This approach has since been largely superseded by the concept of minimally invasive intervention within a “step-up” framework.

The 2012 revision of the Atlanta Classification has taken account of these changes and provides guidelines on how to structure the management of what are invariably complex and individual management algorithms (see Chapter 54 ). This classification divides AP into three categories: mild, moderately severe, and severe disease. A subsequent paper suggested an additional category of “critical pancreatitis” to recognize those patients with sepsis and organ failure, which was associated with the highest mortality.

These categories are based on the absence or presence of local and/or systemic complications. In addition to disease severity, early mortality is strongly associated with age and comorbidity. The classification further categorizes local complications on the basis of time from presentation (< or > 4 weeks) and on the presence of necrosis ( Table 56.1 ). The vast majority of acute fluid collections (AFC) without necrosis ( Fig. 56.2 ) will resolve within 4 weeks and a persistent fluid collection with minimal or no necrotic component (“acute pancreatic pseudocyst”) is very rare, with the majority having at least a small amount of necrosis. In addition, collections may be sterile or infected.

FIGURE 56.2, Acute fluid collection with normal pancreatic attenuation of contrast-enhanced computed tomography (CECT).

The majority of peripancreatic complications are therefore related to either acute necrotic collections (<4 weeks) or walled-off pancreatic necrosis (WOPN; >4 weeks; Fig. 56.3 A–B). This temporal separation is somewhat arbitrary because the clinical management and surgical approach is determined by multifactorial individual patient factors. Where possible, it is recommended that any planned intervention for necrosis be delayed until at least 4 weeks after presentation.

FIGURE 56.3, A, Acute necrotic collection (ANC). B, Walled-off pancreatic necrosis (WOPN).

The systemic clinical course does not always correlate with the presence or severity of the local complications. One in five cases, however, will develop organ failure with or without local complications, a setting that defines severe AP. Half of the deaths attributable to AP occur within the first 7 days of admission, with the majority in the first 3 days. Patients with severe AP who survive this first phase of illness, particularly those with persistent SIRS or organ failure, ^, ^, are particularly at risk for developing secondary infection of pancreatic necrosis. Mortality in patients with infected necrosis and organ failure may reach 20% to 30%.

Acute fluid collections

These are common within the first few days and are identified radiologically as poorly demarcated fluid in the vicinity of the pancreas. Patients with this finding may be monitored with serial imaging but do not usually require intervention. These immature collections tend to resolve spontaneously in the majority of patients. They reflect local peripancreatic edema, and failure of resolution is probably related to the presence of parenchymal necrosis and duct disruption.

Intervention for acute necrotic collections or walled-off pancreatic necrosis

There is clearly some degree of overlap between the early and late patient populations, and most studies in the literature include heterogeneous groups. There have been repeated attempts to compare different approaches to the management of pancreatic necrosis, either within cohort series or RCTs. The Holy Grail of identifying a single superior technique is, however, a flawed approach because the heterogeneity of presentation, anatomy, and physiology has a much greater influence on outcome than any differences in the technique of intervention. The choice of intervention is guided by the clinical picture, anatomic position of the collection, and local expertise. All of the described approaches can have their role, but increasingly the choice lies between endoscopic or minimally invasive surgical drainage.

Indications include:

1.
Infection/sepsis, either suspected radiologically or as a part of the clinical picture
2.
Nutritional failure
3.
Persistent abdominal pain
4.
Management of complications

Indications for intervention vary with time from onset, initially being limited to the management of early complications, a middle phase focusing on sepsis control, and lastly addressing failure to thrive or late-onset complications. Surgical intervention for necrosis in the first 2 weeks carries a high risk for morbidity and mortality and is therefore to be avoided in the absence of specific complications, such as bleeding or ischemia. Although intervention may be eventually required for a persistent symptomatic walled-off necrotic (WON) collection, intervention for an acute necrotic collection before it has matured sufficiently to become encapsulated is usually only indicated in the presence of secondary infection. This may be evidenced by a secondary clinical and biochemical deterioration, coupled with CT evidence of infection such as a small pockets of gas. The identification of gas within a collection is not in itself an indication for intervention because spontaneous enteric discharge of a collection may be associated with clinical improvement. In this situation, there is often a gas/fluid level ( Fig. 56.4 ), and therefore any imaging result needs to be interpreted within the overall clinical context.

FIGURE 56.4, Spontaneous duodenal discharge of a walled-off necrosis (WON) collection resulting in clinical improvement.

Once a decision is made that intervention is required, these pancreatic (and peripancreatic) collections can be managed by a variety of approaches. Freeny and colleagues showed in the 1990s that aggressive percutaneous sepsis control would promote recovery in the absence of formal necrosectomy, although 50% required subsequent surgical intervention. A number of minimally invasive approaches have been described, including percutaneous necrosectomy (MIRP), video-assisted retroperitoneal debridement (VARD), endoscopic cystgastrostomy, and laparoscopic cystgastrostomy. Laparoscopic direct necrosectomy was described in the 1990s but failed to gain popularity because of its technical difficulty. Dual-modality drainages are commonly employed during a disease episode. There is evidence that minimal access techniques may pose less of a challenge to the patient’s systemic inflammatory response and, in our own experience, patients have reduced requirements for the intensive care management. Connor and colleagues reported half as many deaths in patients treated with a minimal access approach when compared with those having laparotomy.

Although a number of differing minimally invasive techniques had been described in cohort series showing benefit of historical controls, the PANTER trial from the Dutch Pancreatitis Study Group provided randomized data regarding the management of infected pancreatic necrosis (IPN). Patients with IPN were randomized to either open necrosectomy or a “step-up” approach based on endoscopic or percutaneous drainage as the initial intervention, with progression to retroperitoneal debridement with lavage if no improvement was observed. The composite endpoint of death or major complication demonstrated a significant benefit with the step-up approach. Indeed, 35% were successfully managed with percutaneous drainage alone and did not require subsequent debridement. There is now a consensus advocating a principle of early organ support and nutritional optimization, followed ideally by delayed minimally invasive intervention within a “step-up” framework where possible.

The choice of one approach over another is determined by the clinical condition of the patient, local experience and expertise, anatomic position/content of the collection, and the time from presentation/maturation of the wall of the collection. There is an acceptance that because of the complexity of presentation, no single technique is applicable in all circumstances. The optimal approach is developing through an evolution of the management concepts introduced over the last decade and has been informed by the publication of two RCTs comparing percutaneous and endoscopic intervention. The TENSION trial, again by the Dutch Pancreatitis Study Group, compared a step-up endoscopic drainage with a VARD-based surgical approach and is discussed in more detail later in this chapter. The MISER trial compared an endoscopic step-up approach with a primary laparoscopic cystgastrostomy intervention, although 19% were managed by VARD, and the trial design failed to recognize that laparoscopic cystgastrostomy is more suited to management of organized WON, with only 20% of interventions occurring more than 6 weeks from presentation.

The choice of initial percutaneous or endoscopic drainage is now largely based on the position of the collection relative to the stomach, colon, liver, spleen, and kidney. Although both the aforementioned trials can be critiqued as having biased intervention protocols, the results favored endoscopic intervention and, where available, this has become the primary intervention of choice. Furthermore, the ability to perform EUS-guided puncture within an ICU setting, without moving the patient to the radiology department for CT-guided drainage, may influence the management decision where a patient is in extremis.

In general, our practice has been to approach lateral collections and those extending behind the colon from the left or right flank percutaneously and to prefer endoscopic drainage for those medial collections where a percutaneous route may be compromised by overlying bowel, spleen, or liver. The route of percutaneous drainage should ideally take into account the probability of subsequent “step-up” escalation, siting the drain as lateral and inferior as possible and avoiding the costal margin, but the initial priority must be sepsis control. If the initial drain placement is suboptimal, secondary alternative access can be obtained, sometimes involving a combination of percutaneous and endoscopic techniques.

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