Management of acute pancreatitis

INTRODUCTION — 

The main principles of acute pancreatitis management are the assessment of disease severity, early intravenous fluids to promote pancreatic perfusion, pain control, and nutritional support. It is also important to identify and treat the underlying etiology and complications of pancreatitis.

This topic reviews the management of acute pancreatitis. Our recommendations are largely consistent with the American Gastroenterological Association, the American College of Gastroenterology, and the International Association of Pancreatology/American Pancreatic Association guidelines for the treatment of acute pancreatitis [1-4]. The etiology, clinical manifestations, diagnosis, prediction of severity, and outcome of acute pancreatitis are discussed separately.

●(See "Etiology of acute pancreatitis".)

●(See "Clinical manifestations, diagnosis, and natural history of acute pancreatitis".)

●(See "Predicting the severity of acute pancreatitis".)

CLASSIFICATION AND SEVERITY

Classification — There are two main classifications of pancreatitis. One is based on severity and the other on morphology. Both have prognostic and management implications.

●Severity-based classification

•Mild acute pancreatitis is characterized by the absence of organ failure and local or systemic complications.

•Moderately severe acute pancreatitis is characterized by transient organ failure (≤48 hours) and/or the development of local complications. (See 'Local complications' below.)

•Severe acute pancreatitis is characterized by persistent organ failure (>48 hours) of one or multiple organs, defined as shock, respiratory failure, or kidney failure; or modified Marshall score of ≥2 in at least one of the three accepted organ systems (table 1) [4].

●Morphology-based classification (revised Atlanta classification) [5]

•Interstitial edematous acute pancreatitis is characterized by acute inflammation of the pancreatic parenchyma and peripancreatic tissues, but without recognizable tissue necrosis. In the absence of organ failure and pancreatic necrosis, interstitial edematous acute pancreatitis correlates with mild disease.

•Necrotizing acute pancreatitis is characterized by inflammation associated with pancreatic parenchymal necrosis and/or peripancreatic necrosis. Necrotizing pancreatitis often correlates with moderately severe and severe disease [4].

Assessment of disease severity — Assessment of severity requires evaluation for organ failure (table 1), and local or systemic complications (see 'Local complications' below) [6]. The purpose is to identify patients requiring aggressive hydration, monitoring, and support who may benefit from monitored or intensive care. Close ongoing assessment is critical, especially over the first 72 hours.

It is reasonable to obtain the following laboratory tests at least every 24 hours in the first few days after onset of symptoms:

●Complete blood count (CBC)

●Comprehensive metabolic panel

●C reactive protein (CRP)

●Lactate

Serial measurements of serum amylase and lipase are not useful to assess or predict disease severity or prognosis, or for altering management, even though measurement is useful for the diagnosis of pancreatitis. (See "Clinical manifestations, diagnosis, and natural history of acute pancreatitis", section on 'Pancreatic enzymes and products'.)

In patients who fail to respond to initial treatment after 48 to 72 hours, computed tomography (CT) is recommended to evaluate for complications. The extent of pancreatic and peripancreatic necrosis may not become clear until 72 to 96 hours after the onset of symptoms [1]. (See "Clinical manifestations, diagnosis, and natural history of acute pancreatitis", section on 'Abdominal computed tomography' and "Predicting the severity of acute pancreatitis", section on 'CT scan'.)

Prediction of disease severity — While a small proportion of patients can be diagnosed with moderately severe or severe disease within the first 24 hours after symptom onset, many cannot be reliably classified as mild, moderate, or severe until 72 or 96 hours after presentation. Several scoring systems exist to predict the severity of acute pancreatitis based on initial clinical, laboratory, and radiologic risk factors, and serum markers. However, many can be used only 24 to 48 hours after disease onset and have not been consistently superior to assessment of systemic inflammatory response syndrome (SIRS) or the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. The prediction of disease severity in acute pancreatitis is discussed in detail, separately. (See "Predicting the severity of acute pancreatitis".)

Indications for intensive or monitored care — Admission or transfer to an intensive care unit is indicated for the following patients (table 2) [1,6,7]. Intensive care unit monitoring and support of pulmonary, renal, circulatory, and hepatobiliary function may minimize systemic sequelae [6].

●Patients with severe acute pancreatitis (See 'Classification' above.)

●Patients who do not meet criteria for severe disease but have one or more of the following parameters:

•Pulse <40 or >150 beats/minute

•Systolic arterial pressure <80 mmHg or mean arterial pressure <60 mmHg or diastolic arterial pressure >120 mmHg

•Respiratory rate >35 breaths/minute

•Serum sodium <110 mEq/L or >170 mEq/L

•Serum potassium <2.0 mEq/L or >7.0 mEq/L

•PaO₂ <50 mmHg

•pH <7.1 or >7.7

•Serum glucose >800 mg/dL (44 mmol/L)

•Serum calcium >15 mg/dL (3.75 mmol/L)

•Anuria

•Coma

Admission or transfer to a monitored or intensive care unit also may be considered in the following patients; however, centers with significant expertise in acute pancreatitis may manage such patients on general medical units [8]:

●Persistent (>48 hours) SIRS (table 3)

●Elevated hematocrit (>44 percent), blood urea nitrogen (BUN) (>20 mg/dL [1.77 mmol/L]), or creatinine (>1.8 mg/dL [0.16 mmol/L])

●Age >60 years

●Underlying cardiac or pulmonary disease, obesity

INITIAL MANAGEMENT

Fluid replacement — Numerous studies have evaluated intravenous hydration, including the type of fluid, rate, timing, and duration of treatment [9-11].

●Choice of fluid – We suggest lactated Ringer’s solution over normal saline in most patients with pancreatitis (except in cases due to hypercalcemia).  

In a meta-analysis, use of lactated Ringer’s reduced length of stay (-0.77 days; 95% CI -1.44 to -0.09, four randomized trials, 248 patients), and risk of intensive care admissions (relative risk [RR] 0.43, 95% CI 0.22-0.84) [12]. Mortality in acute pancreatitis is related to systemic inflammatory response syndrome (SIRS) and organ failure. Evidence on whether fluid resuscitation with lactated Ringer’s versus normal saline in acute pancreatitis reduces SIRS criteria is mixed [4,13-16]. In a meta-analysis of four randomized trials, the incidence of ≥2 SIRS criteria at 24 hours was lower with lactated Ringer’s versus normal saline, though this was not statistically significant (RR 0.69, 95% CI 0.32-1.51) [12]. However, hydration protocols were heterogenous between trials, and one trial showed reduction in SIRS criteria with lactated Ringer’s use. In this trial, fluid resuscitation with lactated Ringer's solution reduced the incidence of SIRS compared with normal saline (26 versus 4 percent reduction) at 24 hours from symptom onset [15].      

In rare patients with acute pancreatitis due to hypercalcemia, lactated Ringer's is avoided as it contains 3 mEq/L calcium. In these patients, normal saline may be used for volume resuscitation.

The use of hydroxyethyl starch containing fluids should be avoided given the absence of mortality benefit and possible risk of multiple organ failure [2,17]. (See "Intraoperative fluid management", section on 'Hydroxyethyl starches'.)

●Initial resuscitation amount – In general, we suggest using moderate intravenous hydration (an initial 10 mL/kg bolus in patients with hypovolemia, followed by 1.5 mL/kg/hour) with goal-directed therapy for fluid management in the first 24 to 48 hours after onset of symptoms [2,4,18].  

While previous guidelines recommended aggressive hydration initially (250 to 500 mL/hour of fluid during the first 24 to 48 hours [5 to 10 mL/kg/hour]), evidence from randomized trials suggests that a lower volume is safer in patients with mild acute pancreatitis [1,18-20]. In one trial, 249 patients were randomly assigned to aggressive fluid resuscitation (lactated Ringer's solution bolus of 20 mL/kg followed by 3 mL/kg/hour) versus moderate resuscitation (1.5 mL/kg/hour with a 10 mL/kg bolus only in patients with hypovolemia) [18]. Goal-directed resuscitation was adjusted at 12, 24, 48, and 72 hours based on volume status. Although there was no difference in the incidence of moderately severe or severe pancreatitis (22 versus 17 percent; adjusted RR [ARR] 1.30, 95% CI 0.78-2.18) or duration of hospitalization between the two groups, the trial was terminated early due to higher rates of fluid overload in the aggressive resuscitation group (20 versus 6 percent; ARR 2.85; 95% CI 1.36-5.94).

Appropriate fluid resuscitation early in the course of disease (within 24 hours after symptom onset) is important because it is associated with a reduction in morbidity and mortality [1,21-23]. This benefit is not observed when fluid resuscitation is delayed. In one retrospective study of 45 patients, late resuscitation (defined as less than one-third of cumulative 72-hour fluid administration given within the first 24 hours) was associated with increased mortality (18 versus 0 percent) [23]. The reason may be that third space losses early in the disease process lead to hemoconcentration and decreased perfusion of the pancreas, which can cause pancreatic cell death and the development of necrotizing pancreatitis. Necrotizing pancreatitis, in turn, worsens vascular permeability, third space losses, pancreatic hypoperfusion, and necrosis [1,4,18-20,24].

●Fluid titration – We reassess fluid administration at frequent intervals in the first six hours of admission and for the next 24 to 48 hours. Frequent reassessment of volume status is particularly important in older adults and those with a history of cardiac and/or kidney disease [4].

Adequate fluid replacement can be assessed by an improvement in vital signs (goal heart rate <120 beats/minute, mean arterial pressure between 65 to 85 mmHg), urine output (>0.5 to 1 mL/kg/hour) and reduction in hematocrit (goal 35 to 44 percent) and blood urea nitrogen (BUN) over 24 hours, particularly if they were high at the onset [1,25]. Elevated BUN at the time of admission and rising BUN during the first 24 hours of hospitalization predict mortality [26]. In patients whose BUN levels stay the same or increase, increasing fluid resuscitation should be considered. However, a low urine output could also reflect the development of acute tubular necrosis rather than persistent volume depletion. In this setting, aggressive fluid replacement can lead to peripheral and pulmonary edema without improving the urine output. (See "Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury in adults".)

Continued fluid resuscitation after 48 hours may not be beneficial, as overly vigorous fluid resuscitation is associated with increased risk of respiratory and kidney failure, and abdominal compartment syndrome [27-30].

Pain control — Abdominal pain should be treated, not only for patient comfort, but also because uncontrolled pain can contribute to hemodynamic instability. Attention to adequate fluid resuscitation should be the first priority in addressing abdominal pain as hypovolemia from vascular leak and hemoconcentration can cause ischemic pain and resultant lactic acidosis. (See 'Fluid replacement' above.)

●Mild pain – Opioids are the most frequently used agents for pain relief in pancreatitis in the United States. Oral opioids may be used for mild symptoms, though adequate pain control may still necessitate parenteral medications. Nonsteroidal anti-inflammatory drugs may be given instead of, or in addition to, an opioid in the absence of kidney failure, GI bleeding, or other contraindications [31-33].

●Moderate to severe pain – In moderate or severe acute pancreatitis, it may be more appropriate to initiate pain control with parenteral opioids. Hydromorphone or fentanyl are the most frequently used opioids, which may be administered as intravenous pushes as needed, or in cases of refractory pain, as a patient-controlled analgesia (PCA) pump. However, use of PCA pumps compared with standard physician-directed delivery of analgesia is associated with increased length of stay and higher likelihood of being discharged on opioids [34]. With clinical improvement, every effort should be made to wean opioids and discontinue as soon as possible after discharge.  

Fentanyl is being increasingly used due to its better safety profile, especially in kidney function impairment. It can be given both as a bolus from a PCA pump, as well as constant infusion in critically ill patients. When using fentanyl in a PCA pump, the typical dose for the bolus regimen ranges from 20 to 50 micrograms with a 10-minute lock-out period (time from the end of one dose infusion to the time the machine starts responding to another demand). As with other opioids, fentanyl can depress respiratory function. Patients on PCA pumps should be carefully monitored for side effects. (See "Pain control in the critically ill adult patient", section on 'Adverse effects of opioid analgesics'.)

Though meperidine was favored over morphine for analgesia in pancreatitis in the past, due to concern for morphine causing increased sphincter of Oddi pressure and hypothetical worsening of pain, both medications are now rarely used [35]. All opioids increase sphincter pressure, and meperidine has several disadvantages including neuromuscular side effects and, rarely, seizures in high doses or in those with kidney failure [36].  

Monitoring — All patients should be monitored closely in the first 24 to 48 hours. The majority of patients with mild pancreatitis require no further therapy and recover within three to seven days. Patients with moderately severe and severe pancreatitis require more intensive monitoring as they have transient (<48 hours) or persistent (>48 hours) organ failure and local or systemic complications.

●Vital signs and oxygen saturation – Monitor vital signs, including oxygen saturation, and administer supplemental oxygen to maintain arterial oxygen saturation of greater than 95 percent. Perform blood gas analysis if oxygen saturation is less than 90 percent or if clinically indicated. Hypoxia may be due to splinting, atelectasis, pleural effusions, opening of intrapulmonary shunts, or acute respiratory distress syndrome (ARDS).

Transfer patients with progressive hypoxia to an intensive care unit (ICU) for ongoing monitoring and respiratory support. (See "Acute respiratory distress syndrome: Clinical features, diagnosis, and complications in adults" and "Acute respiratory distress syndrome: Fluid management, pharmacotherapy, and supportive care in adults" and 'Indications for intensive or monitored care' above.)

Monitor urine output and titrate fluids to maintain urine output >0.5 to 1 mL/kg/hour [1]. (See 'Fluid replacement' above.)

●Electrolytes and kidney function – Monitor electrolytes frequently in the first 48 to 72 hours and especially with fluid resuscitation. Depending on the severity of disease and electrolyte imbalance, the frequency can range from every 4 hours to every 24 hours.

Monitor BUN and creatinine every 12 hours in the first 72 hours as they may predict mortality and development of pancreatic necrosis. (See "Predicting the severity of acute pancreatitis", section on 'Laboratory and radiologic predictors'.)

Hypocalcemia should be corrected if ionized calcium is low or if signs of neuromuscular irritability (Chvostek's or Trousseau's sign) are present. (See 'Assessment of disease severity' above and 'Indications for intensive or monitored care' above.)

Low magnesium levels can also cause hypocalcemia and should be corrected. (See "Treatment of hypocalcemia", section on 'Intravenous calcium dosing'.)

●Glucose – Monitor serum glucose levels hourly in patients with hyperglycemia (blood glucose greater than 180 to 200 mg/dL (10.0 to 11.1 mmol/L) and treat appropriately, as hyperglycemia can increase the risk of secondary pancreatic infections. Hyperglycemia may result from parenteral nutritional therapy, decreased insulin release, increased gluconeogenesis, and decreased glucose utilization. The management of hyperglycemia is discussed in detail separately. (See "Glycemic control in critically ill adult and pediatric patients", section on 'Our approach'.)

●Abdominal compartment syndrome – Monitor patients in the ICU for abdominal compartment syndrome with serial measurements of urinary bladder pressures [37]. (See 'Abdominal compartment syndrome' below.)

Nutrition — Nutrition is an important part of pancreatitis management. When possible, administer oral or enteral nutrition early to maintain gut mucosal integrity [4].

The presence of fluid collections or elevated pancreatic enzymes is not necessarily a contraindication to oral or enteral feeding. However, in a subgroup of patients with fluid collections, feeding is correlated with pain, recurrence of pancreatitis, or worsening of fluid collections. These patients often have disrupted pancreatic ducts with fluid collections. Drainage of fluid collections may allow resumption of oral intake. The diagnosis and management of pancreatic duct disruptions is discussed in detail, separately. (See "Pancreatic stenting at endoscopic retrograde cholangiopancreatography (ERCP): Indications, techniques, and complications", section on 'Pancreatic duct leakage'.)

Candidates for oral diet — Patients with mild pancreatitis who do not have nausea, vomiting, or paralytic ileus can resume an oral diet as soon as tolerated [1-3]. Oral feeding can be initiated early (within 24 hours) when patients are subjectively hungry. This contrasts with the historical approach of delayed feeding until resolution of abdominal pain and normalization of pancreatic enzymes.  

●In a 2017 systematic review (11 randomized trials, 948 patients with acute pancreatitis), early feeding (≤48 hours after hospitalization), as compared with delayed feeding, did not increase adverse effects or exacerbate symptoms [38]. In four of seven trials including patients with mild to moderate pancreatitis, early feeding was associated with a reduction in length of hospital stay. However, there was significant heterogeneity in feeding protocols and reported outcomes across studies, and a high risk of bias in several studies included in the systematic review.

●In another 2017 systematic review (eight randomized trials, 748 patients with mild to moderate pancreatitis), early feeding was associated with decreased length of stay and costs without increasing adverse events [39].

Some contributors start with a low-residue, low-fat, and soft diet and then advance the diet cautiously, as tolerated. Others may start with a clear liquid diet, especially in patients with heightened concern for oral intolerance. Although traditionally patients have been advanced from a clear liquid diet to solid food as tolerated, early refeeding with a solid, low-fat diet when patients are subjectively hungry appears to be safe [40-44].

Additional randomized trials are needed to define the benefits of early feeding in patients with acute pancreatitis.

Candidates for enteral versus parenteral nutrition — Nutritional support is often required in patients with moderate to severe pancreatitis if they cannot resume oral intake within five to seven days. Oral feeding may not be tolerated due to postprandial pain, nausea or vomiting related to gastroduodenal inflammation, extrinsic compression from fluid collections leading to gastric outlet obstruction, or in situations preventing nourishment by mouth (eg, transfer to an ICU, development of organ failure, or SIRS persisting for 48 hours). When complications start improving, nutritional support can be stopped, and oral feeding can be initiated and advanced as tolerated [38,39,45,46].

Enteral — We recommend enteral feeding, rather than parenteral nutrition, in patients with moderately severe and severe acute pancreatitis who do not tolerate oral feeding [1,3,19,47,48]. Enteral nutrition helps maintain the intestinal barrier, prevents bacterial translocation from the gut, and avoids the complications associated with parenteral nutrition, including those secondary to venous access and blood stream infections.

●Type of tube – In patients with predicted severe or necrotizing pancreatitis requiring enteral tube feeding, either nasogastric or nasojejunal routes may be used. Nasojejunal feeding is often the preferred route in resource-abundant settings because of the theoretical benefit of less pancreatic stimulation related to the ileal brake phenomenon (a physiologic feedback mechanism where the presence of nutrients in the ileum inhibits exocrine pancreatic stimulation). Enteral feeding via a nasojejunal route requires radiologic or endoscopic placement of a jejunal feeding tube beyond the ligament of Treitz [2]. Nasogastric tubes have been found to be noninferior to nasojejunal tubes in randomized trials [49-51], and thus nasogastric tubes may be utilized in resource-limited settings, given their ease of placement.  

●Rate – We start enteral feeds with a polymeric formulation at 25 cc per hour and advance as tolerated to at least 30 percent of the calculated daily requirement (25 kcal/kg ideal body weight), even in the presence of ileus [52]. Signs that the formula is not tolerated include increased abdominal pain, vomiting (with nasogastric feeding), bloating, or diarrhea (>5 watery stools or >500 mL per 24 hours with exclusion of Clostridioides difficile toxin and medication-induced diarrhea) that resolves if the feeding is held. (See "Nutrition support in critically ill adult patients: Enteral nutrition".)

●Evidence – Multiple meta-analyses of randomized trials demonstrate that enteral nutrition significantly reduces mortality, multiple organ failure, systemic infections, and the need for surgery as compared with parenteral nutrition [3,53-56]. In one representative meta-analysis of eight randomized trials including 348 participants, those who received enteral nutrition had reduced mortality (RR for death 0.5, 95% CI 0.28-0.91), risk for multiple organ failure (RR 0.55, 95% CI 0.37-0.81), and systemic infections (RR 0.39, 95% CI 0.23-0.65) compared with parenteral nutrition.

Parenteral — Parenteral nutrition should only be initiated in patients who do not tolerate enteral feeding, or if the target rate of enteral feeding is not achieved within 48 to 72 hours, as the use of parenteral nutrition as an adjunct to enteral feeding may be harmful [57,58].

●In a randomized trial, 4640 critically ill adults receiving enteral nutrition were assigned to supplemental parenteral nutrition initiated early (within 48 hours of ICU admission) or late (after the eighth day of ICU admission) [57]. Compared with the early-initiation group, patients in the late-initiation group had lower rates of ICU infections (23 versus 26 percent), and fewer mechanical ventilation and kidney replacement therapy days (relative risk reduction 10 percent). (See "Nutrition support in critically ill adult patients: Initial evaluation and prescription", section on 'Early parenteral nutrition'.)

●An observational study that included 2920 mechanically ventilated, critically ill adults compared 60-day mortality in patients who received enteral nutrition alone versus with early or late parenteral nutrition [58]. Enteral nutrition plus either early or late parenteral nutrition was associated with increased mortality as compared with enteral nutrition alone (35 versus 28 percent).

Role of antibiotics — Prophylactic antibiotics are not recommended in patients with acute pancreatitis without infection, regardless of the type (interstitial or necrotizing) or disease severity (mild, moderately severe, or severe) [2,3,19].

However, up to 20 percent of patients with acute pancreatitis develop an extrapancreatic infection (eg, bacteremia, pneumonia, and urinary tract infections) [59]. Extrapancreatic infections are associated with an increase in mortality [60]. If an extrapancreatic infection is suspected (fevers, rising leukocytosis, or new focal symptoms), empiric antibiotics covering gram positive and negative organisms (eg, vancomycin and cefepime) should be started while the source of the infection is being investigated. If cultures are negative and no source of infection is identified, then antibiotics should be discontinued.

The use of antibiotics in patients with suspected infected pancreatic necrosis or cholangitis is discussed separately. (See 'Infected necrosis' below and 'Gallstone pancreatitis' below.)

Therapies we do not recommend

●Prophylactic antifungals – Administration of prophylactic antifungal therapy (eg, fluconazole) along with prophylactic or therapeutic antibiotics is not recommended [3,19]. Fungal organisms have become increasingly isolated in infected pancreatic necrosis. Studies have reported infection rates of up to 30 percent in primary (without any intervention) and secondary (after intervention of fluid collections) infections in pancreatic necrosis [61]. However, it is not clear if they are associated with higher mortality [62].

●Pentoxifylline – Pentoxifylline is not recommended for acute pancreatitis. In a trial of 84 patients with acute pancreatitis randomized to pentoxifylline versus placebo, the difference between the primary composite outcome of death, pancreatic necrosis, persistent organ failure or SIRS, hospital stay length greater than four days, or need for intensive care was not statistically different. Patients receiving pentoxifylline had a longer length of stay and higher readmission rates [63].  

●Protease inhibitors – We do not use protease inhibitors. Evidence from clinical trials and a meta-analysis demonstrated only marginal reduction in mortality in patients with moderate to severe pancreatitis (pooled risk difference -0.07, 95% CI -0.13 to -0.01), and no difference in patients with mild pancreatitis [64-68]. Intra-arterial administration is another disadvantage.  

MANAGEMENT OF COMPLICATIONS

Identifying complications — Contrast-enhanced CT scan should be obtained in patients with moderately severe or severe acute pancreatitis, signs of sepsis, or clinical deterioration 72 hours after initial presentation, to evaluate for pancreatic or extra-pancreatic necrosis and local complications. In patients who have already had a CT on initial presentation, a repeat CT may be appropriate if there is otherwise unexplained clinical deterioration. Patients with persistent organ failure and extensive local complications should be transferred to centers of expertise [8]. (See 'Classification and severity' above.)

Local complications — Local complications include acute peripancreatic fluid collection, acute necrotic collection, pancreatic pseudocyst, and walled-off necrosis (table 4) [5].

●Early complications (<4 weeks after onset of pancreatitis)

•Acute peripancreatic fluid collection — Fluid collections usually develop in the early phase of pancreatitis. Acute peripancreatic fluid collections (APFC) do not have a well-defined wall, usually remain asymptomatic, and usually resolve spontaneously without the need for drainage (image 1). In a longitudinal study of patients with interstitial pancreatitis, most acute fluid collections resolved within 7 to 10 days, with only 6.8 percent of APFCs persisting beyond four weeks as pancreatic pseudocysts [69]. Most can be managed with supportive care.

•Acute necrotic collection — Necrotizing pancreatitis most commonly manifests as necrosis involving both the pancreas and peripancreatic tissues. Necrosis may result in an acute necrotic collection (ANC) that contains a variable amount of fluid and necrosis but lacks a definable wall (image 2). Management is discussed below. (See 'Complications of necrotizing pancreatitis' below.)

●Late complications (>4 weeks after onset of pancreatitis)

•Pancreatic pseudocyst — A pancreatic pseudocyst is an encapsulated collection of fluid with a well-defined inflammatory wall usually outside the pancreas with minimal or no necrosis (image 3). Pancreatic pseudocysts usually occur more than four weeks after the onset of interstitial edematous pancreatitis. It should be recognized that pancreatic pseudocysts are rare, as most acute peripancreatic fluid collections resolve spontaneously. Most patients diagnosed with "pseudocysts" actually have walled-off pancreatic or peripancreatic necrosis. The management of pancreatic pseudocysts is discussed in detail separately. (See "Approach to walled-off pancreatic fluid collections in adults".)

•Walled-off necrosis — Walled-off necrosis consists of a mature, encapsulated collection of pancreatic and/or peripancreatic necrosis that has developed a well-defined inflammatory wall. The management of walled-off pancreatic fluid collections is discussed in detail separately. (See "Approach to walled-off pancreatic fluid collections in adults".)

Complications of necrotizing pancreatitis — Management of early necrotizing pancreatitis (acute necrotic collection) is detailed below and in the algorithm (algorithm 1).

Infected necrosis — Acute necrotic collections are initially sterile but may become infected. The occurrence of infection in acute necrotizing pancreatitis is a leading cause of morbidity and mortality (image 4). Approximately one-third of patients with pancreatic necrosis develop infected necrosis [48]. There is no correlation between the extent of necrosis and the risk of infection. Although infection can occur early in the course of necrotizing pancreatitis, it is more often seen later in the clinical course (after 10 days) [70,71]. The majority of infections (approximately 75 percent) are monomicrobial with gut-derived organisms (eg, Escherichia coli, Pseudomonas, Klebsiella, and Enterococcus). However, the incidence of gram-positive, multidrug resistant, and fungal organisms is rising.

●Clinical suspicion and initial management – Infected necrosis (image 4) should be suspected in patients with pancreatic or extrapancreatic necrosis who deteriorate (clinical instability or sepsis physiology, increasing white blood cell count, fevers) or fail to improve after 7 to 10 days of hospitalization with conservative management. Clinical signs of infection and abdominal imaging demonstrating the presence of gas within the necrosis are reasonably suggestive of infection, and antibiotic therapy can be initiated without CT-guided aspiration and culture [1,4,19]. Elevated procalcitonin levels are also being increasingly used to diagnose infection in acute pancreatitis. If infected necrosis or infection are suspected, a broad work-up including blood cultures should be completed. Empiric antibiotics known to penetrate pancreatic necrosis (eg, piperacillin/tazobactam; cefepime combined with anaerobic agent; or a carbapenem alone) should be used. Occasionally, an antifungal agent may be utilized as well [72]. Local resistance patterns and patient characteristics are factors in antimicrobial selection. Though previously commonly utilized, the role of fine-needle CT-guided aspiration cytology of necrosis is now very limited, as decisions regarding intervention are primarily based on clinical and radiographic data as above.

●Conservative management versus drainage and/or necrosectomy – In patients who are stable or improve after 48 to 72 hours of antibiotics, we attempt to delay possible drainage or necrosectomy by continuing antibiotics for at least two to four weeks [4]. Routine immediate drainage once infected necrosis is diagnosed does not improve outcomes. Postponing intervention allows for wall formation and, more importantly, maturation, which is associated with less procedural complications if drainage or intervention is needed [73]. However, interim percutaneous drainage may be considered in patients with infected necrosis who exhibit clinical deterioration or fail to improve (but do not have a walled-off necrotic collection).

•Patients who deteriorate – In patients who deteriorate in 48 to 72 hours despite initiation of antibiotics, we first evaluate if antimicrobials can be tailored based on available cultures and sensitivities and provide intensive care support as appropriate. Reimaging with CT can also be performed every three to four days to assess for new complications. In patients who continue to deteriorate despite antibiotics and supportive management, we perform early percutaneous drainage or debridement (necrosectomy), even in the absence of a mature wall. Endoscopic drainage is also occasionally performed for retrogastric necrosis in these circumstances [74,75]. However, complications and mortality associated with early intervention may be high and such interventions are best performed only in specialist centers.

●Rationale for postponed drainage – A multicenter, randomized trial showed no difference in rate of complications or mortality between 104 patients who were randomly assigned to immediate drainage (55 patients), or postponed drainage (49 patients) when necrotic collections were largely walled-off but there was either clinical deterioration or lack of improvement [76]. No difference in the rate of complications or mortality between the two groups was detected; however, the mean number of interventions (catheter drainage and necrosectomy) was higher in the immediate drainage group compared with the postponed drainage group (4.4 versus 2.6, mean difference 1.8; 95% CI 0.6-3.0). Thirty-nine percent of patients with infected necrosis randomized to postponed drainage improved with antibiotics alone, without the need for any other intervention.

●Step-up approach versus up-front necrosectomy – Drainage or necrosectomy can be accomplished initially by a minimally invasive approach (endoscopic or percutaneous radiologic drainage; video-assisted retroperitoneal or laparoscopic necrosectomy). Open necrosectomy is rarely required and in the current era, surgical approaches are very rarely performed [1,77-79]. This “step-up” approach of stenting/drainage first and debridement later, if required, has become a common practice in patients requiring intervention [78]. However, a multicenter, randomized controlled trial in patients with infected pancreatic necrosis demonstrated safety as well as reduced number of interventions with upfront necrosectomy, compared with step-up approach [80]. The technique, efficacy, and complications associated with percutaneous, endoscopic, and surgical necrosectomy are discussed in detail separately. (See "Approach to walled-off pancreatic fluid collections in adults", section on 'Percutaneous drainage' and "Endoscopic interventions for walled-off pancreatic fluid collections" and "Pancreatic debridement".)

Sterile necrosis — The diagnosis of sterile necrosis is clinical, based on the absence of defining features of infected necrosis, such as clinical findings of infection, presence of gas in necrotic tissue, and positive blood cultures. CT-guided aspiration is not needed to diagnose sterile necrosis. In the absence of infected necrosis, usually there is no need for therapeutic or prophylactic antibiotics, or intervention. However, in select cases of sterile necrosis when there is gastrointestinal or biliary obstruction, persistent abdominal pain, inability to tolerate oral intake, or weight loss, delayed intervention of collections that have formed a wall may be considered.

Indications for intervention (radiological, endoscopic, or other minimally invasive) in a patient with sterile necrosis without signs of an infection (eg, fever, hypotension, leukocytosis) include [1,47]:

●Ongoing gastric outlet, intestinal, or biliary obstruction due to mass effect at least four weeks after the onset of acute pancreatitis.

●Persistent symptoms (eg, abdominal pain, nausea, vomiting, anorexia, or weight loss) >8 weeks after the onset of acute pancreatitis.

●Disconnected duct syndrome (full transection of the pancreatic duct) with persisting symptomatic collections with necrosis (eg, pain, obstruction) >4 weeks after the onset of acute pancreatitis.

Peripancreatic vascular complications

Splanchnic venous thrombosis — Splanchnic vein thrombosis (splenic, portal, and/or superior mesenteric veins) is incidentally found on imaging in 1 to 24 percent of patients with acute pancreatitis, depending on the disease severity and the imaging modality [81,82].

Most cases of splanchnic vein thrombosis occur in patients with necrotizing pancreatitis, and only occasionally in patients with interstitial pancreatitis. Despite the theoretical possibility of hemorrhage into pancreatic necrosis or fluid collections, therapeutic anticoagulation is initiated if there is extension of the clot into the portal or superior mesenteric vein. Meanwhile, anticoagulation is not initiated in cases of isolated splenic vein thrombosis. Most studies of anticoagulation in splanchnic vein thrombosis in acute pancreatitis showed no increased hemorrhagic complications, and higher rates of recanalization of the thrombus in patients treated with anticoagulation [83]. The duration of anticoagulation is three to six months and usually initiated with unfractionated or low-molecular-weight heparin during admission and transitioned to a direct oral anticoagulant (DOAC) at the time of clinical stability or hospital discharge.  

Delayed sequelae of splanchnic vein thrombosis include segmental portal hypertension, splenomegaly, isolated gastric varices, which may bleed, and hypersplenism. Endoscopic therapy for such gastric variceal bleeding and in some cases splenectomy, particularly if there is hypersplenism, may be required. In contrast with patients who have splenic vein thrombosis due to chronic pancreatitis, complications such as variceal bleeding are rare and therefore prophylactic splenectomy is not recommended [84]. (See "Recent portal vein thrombosis in adults: Clinical features, diagnosis, and management", section on 'Management'.)

Pseudoaneurysm — Pseudoaneurysms are a rare but serious complication that should be suspected with unexplained gastrointestinal bleeding, an unexplained drop in hematocrit, or sudden expansion of a pancreatic fluid collection. The diagnosis and management of pancreatic pseudoaneurysms are discussed separately. (See "Overview of the complications of chronic pancreatitis", section on 'Pseudoaneurysms' and "Angiographic control of nonvariceal gastrointestinal bleeding in adults".)

Abdominal compartment syndrome — Abdominal compartment syndrome is defined as sustained intra-abdominal pressure >20 mmHg with new onset organ failure [1]. Patients with severe pancreatitis are at increased risk for intra-abdominal hypertension and abdominal compartment syndrome due to tissue edema from aggressive fluid resuscitation, peripancreatic inflammation, ascites, and ileus [85]. Patients in the intensive care unit can be monitored for potential abdominal compartment syndrome with serial measures of urinary bladder pressures [37]. The clinical presentation, diagnosis, and management of abdominal compartment syndrome are discussed in detail separately. (See "Abdominal compartment syndrome in adults", section on 'Clinical presentation'.)

Long-term complications — Patients with acute pancreatitis are at increased risk for exacerbation of underlying comorbidities (eg, coronary artery disease, chronic lung disease). In addition to treating these exacerbations, patients should be treated for other complications including alcohol withdrawal and hyperglycemia.(See "Management of moderate and severe alcohol withdrawal syndromes" and "Glycemic control in critically ill adult and pediatric patients", section on 'Our approach'.)

MANAGEMENT OF UNDERLYING ETIOLOGIES — 

In addition to general initial management and treatment of associated complications, it is necessary to identify and address the underlying predisposing factors of pancreatitis during the index presentation.

Gallstone pancreatitis — In patients with gallstone pancreatitis, most stones pass into the duodenum without the need for intervention. However, in a small proportion of patients, obstructive stones in the biliary tract or ampulla of Vater can cause persistent biliary and pancreatic duct obstruction leading to acute pancreatitis and cholangitis. (See "Etiology of acute pancreatitis" and "Clinical manifestations, diagnosis, and natural history of acute pancreatitis".)

Endoscopic retrograde cholangiopancreatography — In patients with gallstone pancreatitis, those with cholangitis or persistent bile duct obstruction benefit from endoscopic retrograde cholangiopancreatography (ERCP) though the timing of intervention varies (algorithm 2).  

Patients with cholangitis — Antibiotics and intravenous fluids should be given in those with cholangitis, as discussed elsewhere. (See "Acute cholangitis: Clinical manifestations, diagnosis, and management", section on 'Antibiotics'.)

Additionally, in patients with gallstone pancreatitis and cholangitis, endoscopic retrograde cholangiopancreatography (ERCP) should be performed early in the course (within 24 to 48 hours of admission) [4]. In patients with cholangitis, urgent ERCP with papillotomy or surgical intervention to remove bile duct stones may lessen the severity of gallstone pancreatitis and reduce mortality [1,86,87]. In one representative meta-analysis of five trials including patients with cholangitis, early ERCP reduced mortality compared with conservative management (RR 0.20, 95% CI 0.06-0.68) as well as local (RR 0.45, 95% CI 0.20-0.99) and systemic (RR 0.37, 95% CI 0.18-0.78) complications as defined by the Atlanta Classification [87].  

Patients without cholangitis — In the absence of cholangitis, non-urgent indications for ERCP in gallstone pancreatitis include patients with ongoing biliary obstruction, ie, common bile duct (CBD) obstruction (visible stone on imaging), dilated CBD, or increasing liver tests prior to elective cholecystectomy (if suspicion of stone in the CBD is high) [4,88,89]. In these patients without cholangitis but with biliary obstruction, ERCP does not have to be done urgently (within 24 to 48 hours of admission) [2,3,87,90]. We often perform non-urgent ERCP during the same admission before an elective cholecystectomy, if there is a strong suspicion of stone in the bile duct; or postoperatively, if intra-operative cholangiogram demonstrates a stone [1,2]. In a systematic review of eight randomized trials, urgent ERCP in patients without cholangitis did not lead to a significant reduction in the risk of overall pancreatic complications, single organ failure, or mortality [3]. However, one trial demonstrated a reduction in the length of hospital stay with urgent ERCP.

In the absence of cholangitis and biliary obstruction, ERCP is not indicated for (mild or severe) gallstone pancreatitis [87,89]. When in doubt about the presence of bile duct obstruction, liver chemistries can be rechecked in 24 to 48 hours to assess for improvement. If liver chemistries improve significantly, we do not obtain further imaging or pursue intervention, unless otherwise clinically indicated. If liver chemistries remain persistently elevated or worsen, we then perform magnetic resonance cholangiopancreatography (MRCP) (unless contraindicated or unavailable; in which case endoscopic ultrasound (EUS) is performed) to assess for stones in the CBD. ERCP is then performed in cases where CBD stones are demonstrated.  

●Other indications for MRCP/EUS prior to ERCP in gallstone pancreatitis – MRCP (or EUS, if MRCP is contraindicated or unavailable) should be performed to confirm the presence of CBD stones and determine the need for ERCP in the following scenarios:

•Persistent elevation of liver tests and/or dilation of CBD, without overt cholangitis – Of note, liver chemistries may improve even if a biliary stone is present, so we have a very low threshold for performing MRCP (or EUS, as above).

•Pregnant patients – We perform MRCP in all pregnant patients with suspicion for CBD stones. If MRCP is contraindicated or unavailable, we perform EUS if liver chemistries remain persistently elevated or worsened after trending for 48 hours. If a CBD stone is demonstrated on MRCP or EUS, we proceed with ERCP since the risk of cholangitis and recurrent pancreatitis is high. ERCP is performed without routine use of fluoroscopy and with fetal monitoring after approximately 20 to 24 weeks of gestation with obstetrics support.  

•Altered anatomy, such as Roux-en-Y gastric bypass – ERCP is technically challenging in those with Roux-en-Y anatomy. MRCP is always performed to confirm the presence of stone, prior to attempting ERCP. The procedural approach in such patients is individualized and discussed in detail separately. (See "Endoscopic retrograde cholangiopancreatography (ERCP) in patients with Roux-en-Y anatomy".)

In patients who are found to have stones on MRCP or EUS, ERCP with sphincterotomy and stone extraction is necessary and decreases recurrent attacks of biliary pancreatitis. However, unless cholecystectomy is performed, these patients remain at risk for other biliary complications including acute cholecystitis, biliary colic, and gallbladder complications of cholelithiasis.

Cholecystectomy — Cholecystectomy should be performed after recovery in all patients with gallstone pancreatitis including those who have undergone an endoscopic sphincterotomy to reduce the risk of recurrent pancreatitis [91]. Failure to perform a cholecystectomy is associated with a 25 to 30 percent risk of recurrent acute pancreatitis, cholecystitis, or cholangitis within 6 to 18 weeks [92]. The risk of recurrent pancreatitis is highest in patients who have not undergone a sphincterotomy. (See "Endoscopic management of bile duct stones", section on 'ERCP-guided stone removal'.)

●Timing — In patients who have mild, interstitial gallstone pancreatitis, cholecystectomy can usually be performed safely in the same index hospitalization [4,93,94]. A randomized trial demonstrated a reduction in the composite outcome of mortality and readmissions for recurrent gallstone-related complications for patients undergoing same admission cholecystectomy compared with interval cholecystectomy within eight weeks (5 versus 17 percent; RR 0.28, 95% CI 0.12-0.66) [95].

However, in patients with necrotizing pancreatitis, interval cholecystectomy is advised after inflammation and fluid collections resolve or subside [96]. In a retrospective cohort study, patients who were initially diagnosed with interstitial gallstone pancreatitis but actually had unrecognized necrotizing pancreatitis and underwent same admission cholecystectomy had higher incidence of organ failure, infected necrosis, and longer hospital stay [97]. Leukocytosis ≥12 x 10⁹/L and the presence of ≥2 SIRS criteria were correlated with presence of unrecognized necrotizing pancreatitis.

●Patients with concurrent choledocholithiasis — If the clinical suspicion of CBD stones is high (eg, CBD stone on transabdominal ultrasound or cross-sectional imaging, acute cholangitis, or serum bilirubin greater than 4 mg/dL [68 micromol/L] and a dilated CBD on ultrasound), a preoperative ERCP is the best test as there is a high likelihood that therapeutic intervention (sphincterotomy, stone extraction) will be required. Patients at intermediate risk of a CBD stone (age >55 years, abnormal liver biochemical tests or dilated CBD on ultrasound or other imaging) should undergo MRCP or EUS to look for choledocholithiasis and, if present, a preoperative ERCP, sphincterotomy and stone extraction. Intraoperative cholangiography or ultrasound is also an alternative [98]. (See "Choledocholithiasis: Clinical manifestations, diagnosis, and management", section on 'Subsequent evaluation and management'.)

Biliary sludge — Most patients with biliary sludge are asymptomatic. However, biliary sludge is not uncommon in patients with acute pancreatitis without another obvious cause. On ultrasound, sludge appears as a mobile, low amplitude echo that layers in the most dependent part of the gallbladder and is not associated with shadowing. However, ultrasound has a low sensitivity for biliary sludge.

If the cause is not clear, we perform EUS, even after one attack, to look for microlithiasis in the gallbladder or bile duct. In a randomized trial, 85 patients were assigned to laparoscopic cholecystectomy or conservative watchful waiting after their first attack of idiopathic acute pancreatitis [99]. During a median follow-up of 36 months, significantly fewer patients who had undergone laparoscopic cholecystectomy had recurrent idiopathic acute pancreatitis as compared with controls (10 versus 30 percent). A total of five patients needed to be treated to prevent one episode of idiopathic acute pancreatitis. However, EUS was not performed to detect small gallstones or biliary sludge. Biliary stones or sludge were detected during surgery in 23 of 39 patients (59 percent) who underwent cholecystectomy. (See "Etiology of acute pancreatitis", section on 'Approach to establishing the underlying etiology' and "Etiology of acute pancreatitis", section on 'Biliary sludge and microlithiasis'.)

Alcohol-associated pancreatitis — Patients with alcohol-associated pancreatitis should receive brief alcohol intervention as inpatients for unhealthy alcohol use [2]. (See "Brief intervention for unhealthy alcohol and other drug use: Goals and components" and "Brief intervention for unhealthy alcohol and other drug use: Efficacy, adverse effects, and administration".)

Hypertriglyceridemia — The treatment of hypertriglyceridemic pancreatitis is discussed separately. (See "Hypertriglyceridemia-induced acute pancreatitis".)

Hypercalcemia — Hypercalcemia is a rare cause of acute pancreatitis. If present, treatment should be directed at normalizing serum calcium levels and determining the underlying etiology. (See "Etiology of hypercalcemia" and "Diagnostic approach to hypercalcemia" and "Treatment of hypercalcemia" and "Etiology of acute pancreatitis", section on 'Hypercalcemia'.)

Medication-induced pancreatitis — Medication-induced pancreatitis is overall rare, and all other causes of pancreatitis should be ruled out before implicating a medication as the cause. Drugs associated with acute pancreatitis may need to be discontinued. (See "Etiology of acute pancreatitis", section on 'Medications' and "Unique aspects of gastrointestinal disease in patients on dialysis", section on 'Acute pancreatitis'.)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute pancreatitis".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Acute pancreatitis (The Basics)")

●Beyond the Basics topics (see "Patient education: Acute pancreatitis (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Classification of acute pancreatitis – Acute pancreatitis is classified by morphology and severity, which have prognostic and management implications. (See 'Classification and severity' above.)

By morphology, pancreatitis is categorized as interstitial acute or necrotizing.

By severity:

•Mild acute pancreatitis is characterized by the absence of organ failure and local or systemic complications

•Moderately severe acute pancreatitis is characterized by no organ failure or transient organ failure (<48 hours) and/or local complications

•Severe acute pancreatitis is characterized by persistent organ failure (>48 hours) that may involve one or multiple organs

●Initial management – The main principles of management are the assessment of disease severity, early intravenous fluids to promote pancreatic perfusion, pain control, and nutritional support.

•Assessing disease severity – The severity of acute pancreatitis is determined by presence of organ failure (table 1) and local or systemic complications. (See 'Assessment of disease severity' above and "Predicting the severity of acute pancreatitis".)

Admission to a monitored or intensive care unit is indicated in patients with severe acute pancreatitis and in patients with acute pancreatitis who meet certain parameters (table 2) (see 'Indications for intensive or monitored care' above).

•Fluid replacement – In all patients, we suggest using moderate rather than aggressive intravenous hydration (Grade 2B). An initial 10 mL/kg bolus is administered in patients with hypovolemia and is followed by 1.5 mL/kg/hour with goal-directed therapy for fluid management in the first 24 to 48 hours after onset of symptoms. Moderate hydration is safer than aggressive hydration, with less risk of fluid overload.

In most patients, we suggest lactated Ringer’s solution over normal saline (Grade 2C). Lactated Ringer’s solution may reduce length of stay and risk of intensive care admission. (See 'Fluid replacement' above.)

•Pain control – Adequate pain control may require the use of intravenous opioids, such as hydromorphone and fentanyl. Nonsteroidal anti-inflammatory drugs may be given instead of, or in addition to, an opioid in the absence of acute kidney injury, gastrointestinal bleed, or other contraindications. (See 'Pain control' above.)

•Nutrition – In mild pancreatitis, oral feeding can be initiated early (within 24 hours) when patients are subjectively hungry and do not have nausea, vomiting, or paralytic ileus. We usually start with a low-residue, low fat, and soft diet. (See 'Nutrition' above.)

In moderately severe and severe pancreatitis, we recommend enteral nutrition rather than initiating parenteral nutrition in patients who do not tolerate oral feeding (Grade 1B). If the target rate of enteral nutrition is not achieved within 48 to 72 hours and severe acute pancreatitis is not resolved, supplemental parenteral nutrition should be provided. (See 'Candidates for enteral versus parenteral nutrition' above.)

●Indications for abdominal imaging – Contrast-enhanced computed tomography (CT) scan should be obtained in patients with moderately severe or severe acute pancreatitis, signs of sepsis, or clinical deterioration 72 hours after initial presentation to evaluate for pancreatic or extra-pancreatic necrosis and local complications. (See 'Management of complications' above.)

•Complications of acute pancreatitis – Local complications of acute pancreatitis include acute peripancreatic fluid collection, acute necrotic collection, pancreatic pseudocyst, and walled-off necrosis (table 4). Acute peripancreatic fluid collections and acute necrotic collections develop less than four weeks after the onset of pancreatitis, while pancreatic pseudocyst and walled-off necrosis usually occur more than four weeks after the onset of acute pancreatitis. (See 'Local complications' above.)

•Patients with infected necrosis – Both acute necrotic collection and walled-off necrosis are initially sterile but may become infected. Pancreatic infection is a leading cause of morbidity and mortality in acute necrotizing pancreatitis. Infected necrosis (image 4) should be suspected in patients with pancreatic or extra-pancreatic necrosis who deteriorate (clinical instability or sepsis physiology, increasing white blood cell count, fevers) or fail to improve after 7 to 10 days of hospitalization. In patients with suspected infected necrosis, we suggest empiric antibiotics rather than CT-guided fine needle aspiration (Grade 2C). (See 'Infected necrosis' above.)

Patients with infected necrosis who deteriorate may require pancreatic drainage or debridement. If possible, we attempt to delay intervention until at least two to four weeks after initial presentation to allow the infected necrosis to become walled off. Necrosectomy is performed with minimally invasive methods (endoscopic, percutaneous, laparoscopic) and open surgical debridement is only performed if minimally invasive methods are not possible or fail.

●Management of underlying etiologies – Underlying predisposing factors of pancreatitis should also be identified and addressed during the index presentation. (See 'Management of underlying etiologies' above.)

•Patients with gallstone pancreatitis – In patients with gallstone pancreatitis, those with cholangitis or persistent bile duct obstruction benefit from endoscopic retrograde cholangiopancreatography (ERCP) (algorithm 2).

In those with cholangitis, we recommend urgent (<24 to 48 hours) ERCP and duct decompression (Grade 1B). In patients with gallstone pancreatitis and persistent biliary obstruction (without cholangitis), we perform non-urgent ERCP.

Cholecystectomy should be performed after recovery from acute pancreatitis in all operable patients with gallstone pancreatitis or biliary sludge if no other cause is found. In patients who have mild, interstitial gallstone pancreatitis, cholecystectomy can usually be performed safely in the same index hospitalization. (See 'Gallstone pancreatitis' above.)