Recommendations

Key Recommendations

Acute pancreatitis has two distinct phases that require different management approaches: the early phase (1 week), characterized by systemic inflammatory response syndrome (SIRS) and/or organ failure and the late phase (>1 week), characterized by local complications including sterile or infected pancreatic necrosis and pseudocysts.[8] In most patients, the disease is mild and improves rapidly within 3-7 days with fluid resuscitation, management of pain and nausea, and early oral feeding, while around 20% to 30% of patients develop severe disease, with a hospital mortality rate of around 15%.[28]

Initial management

All patients need to be treated with intravenous hydration for the first 24 hours and monitored closely for early fluid losses, hypovolemic shock, and symptoms suggestive of organ dysfunction in the first 48-72 hours from presentation.[8][71] A steady rate of initial resuscitation is recommended, with close monitoring and addition of a fluid bolus only if there is evidence of hypovolemia.[71][72]​​​ Clinicians should recognize that patients with acute pancreatitis may develop hypovolemia rapidly after admission and require fluid boluses and/or increases in the rate of hydration.[8] Previously, aggressive early rehydration was recommended for all patients with acute pancreatitis but evidence now supports a moderate approach with close attention to vital signs, especially heart rate, with BUN and hematocrit evaluation at frequent intervals (within 6 hours of presentation and for the following 24-48 hours).[8][71][73]​​​​​ It may not be possible to predict which patients with acute pancreatitis will develop severe disease: severity scoring tools such as APACHE II and Glasgow have limited value early in the course of the disease. While early laboratory testing of hematocrit and renal function is important to determine intravascular fluid losses and early renal insufficiency, no laboratory test has been shown to be consistently accurate in predicting later disease severity.[8][74] No patient should be classified as having mild disease until at least 48 hours after symptom onset, as some patients who go on to develop severe disease present without signs of organ failure or local complications.[8]

It is critical to recognize the importance of organ failure in determining disease severity.[8] In the presence of SIRS-associated organ dysfunction, additional monitoring and organ support may be necessary (e.g., oxygen supplementation and/or ventilatory support for respiratory failure). Signs of cardiovascular, respiratory, or renal dysfunction may be present. Patients with organ failure and/or persisting SIRS should be admitted to an intensive care unit whenever possible.[8][28]

The definition of SIRS is met by the presence of at least two of the following criteria:[49]

  • Pulse >90 beats per minute

  • Respiratory rate >20 per minute or partial pressure of carbon dioxide (PaCO₂) <32 mmHg

  • Temperature >100.4°F or <96.8ºF

  • WBC count >12,000 or <4000 cells/mm³, or >10% immature neutrophils (bands)

The presence of persistent (>48 hours) single- or multi-organ failure defines acute pancreatitis as severe according to the revised Atlanta criteria.[8][28] In everyday clinical practice, the following criteria (original Atlanta criteria) may be used to establish organ failure:[8]

  • Shock: systolic blood pressure <90 mmHg

  • Pulmonary insufficiency: partial pressure of oxygen (PaO₂) ≤60%

  • Renal failure: creatinine >2 mg/dL

  • Gastrointestinal bleeding: >500 mL blood loss in 24 hours

Early intravenous hydration

The initial treatment of acute pancreatitis requires early intravenous hydration.[1][5][71][75][76][77][78][79] Clinicians should focus on a steady rate of initial resuscitation (no more than 1.5 mL/kg/hour) and should administer a bolus of 10 mL/kg only if there are signs of hypovolemia.[72]​​

A balanced crystalloid (such as Ringer's lactate [Hartmann solution] or Plasma-Lyte®) may have benefits compared with normal saline, and guidelines generally recommend use of a balanced crystalloid for patients with acute pancreatitis.[8][28][46][47][80][81] Normal saline given in large volumes may lead to the development of a non-anion gap hyperchloremic metabolic acidosis.[8] This has particular relevance in acute pancreatitis where low pH may trigger premature trypsinogen activation and exacerbate the symptom of abdominal pain. However, high-quality evidence on choice of fluid specific to patients with acute pancreatitis is lacking, and results from randomized controlled trials of critically unwell patients in general (not specifically people with acute pancreatitis) have reached conflicting conclusions.[82][83][84]

A rising blood urea nitrogen (BUN) and/or hematocrit in the first 24-48 hours indicates inadequate rehydration and has been associated with the risk of developing organ failure and pancreatic necrosis. Rapid intravenous hydration sufficient to decrease hematocrit (i.e., hemodilution) and/or BUN (i.e., increased renal perfusion) has been shown to decrease morbidity and mortality.[8][56][85]​​ Studies have shown that these benefits appear at 24 hours.[86][87] Measurement of BUN and hematocrit within 6-8 hours of admission is therefore recommended so that timely adjustments in the rate of hydration can be made.[8] Conversely, close observation of clinical parameters such as heart rate, blood pressure, and urine output is needed to guard against the risk of excessive intravenous hydration, particularly in certain patient groups such as older individuals and those with a history of cardiac and/or renal disease.[8] Large volume resuscitation may worsen third-space losses characteristic of acute pancreatitis, worsening pulmonary edema and/or leading to abdominal compartment syndrome.[8] One multicenter randomized controlled trial published in 2022 showed that aggressive early hydration resulted in a higher incidence of fluid overload compared with moderate hydration, without improvement in clinical outcomes.[71]

The rationale for early hydration arises from multiple factors causing hypovolemia including vomiting, reduced oral intake, "third spacing" of fluids, increased respiratory losses, and diaphoresis. A combination of microangiopathic effects and edema in the inflamed pancreas may impede blood flow, leading to increased cellular death, tissue necrosis, and ongoing release of pancreatic enzymes, further activating inflammatory cascades. Inflammation increases vascular permeability leading to increased third-space fluid losses, and worsening pancreatic hypoperfusion. Hypoperfusion of the pancreas leads to further necrosis. Early intravenous fluid resuscitation provides micro- and macrocirculatory support to prevent pancreatic necrosis and reduce the risk of other serious complications.[85]​​

Gallstone pancreatitis

Patients with mild gallstone pancreatitis should have a cholecystectomy during the initial admission, after the acute symptoms have resolved. Cholecystectomy is typically delayed for patients with severe disease; these patients require complex decision-making between the surgeon and gastroenterologist.[8][47]

Patients with gallstone pancreatitis complicated by concurrent cholangitis benefit from early endoscopic retrograde cholangiopancreatography (ERCP). The benefit is seen in patients with sepsis and organ failure who undergo the procedure within the first 24 hours from admission.[8][47][88][89] Although gallstones in the common bile duct are a common cause of acute pancreatitis, most gallstones readily pass to the duodenum and are lost in the stool. Persistent choledocholithiasis can lead to persistent pancreatic duct and/or biliary tree obstruction, leading to necrosis and/or cholangitis. Removal of obstructing gallstones from the biliary tree in patients with acute pancreatitis should reduce the likelihood of complications.

Cholangitis should be suspected in the presence of the Charcot triad (jaundice, fever and rigors, right upper quadrant pain). ERCP is not indicated for either mild or severe gallstone pancreatitis without cholangitis.[64]​​[85]​​ The risks of the procedure outweigh any potential benefits in this patient population.

Analgesia and antiemesis

Pain control with opioids may reduce the need for multimodal analgesia.[90] [ Cochrane Clinical Answers logo ] [Evidence C]​​

Fentanyl or morphine can be used, either for breakthrough pain or as patient-controlled analgesia. In mild cases, the standard World Health Organization pain ladder can be used to inform the selection, monitoring, and adjustment of analgesia. Ketorolac, a nonsteroidal anti-inflammatory drug, can be used in patients with intact renal function. It should not be used in older patients because of the risk of adverse gastrointestinal effects.[91]

Nausea and/or vomiting is a presenting symptom in 70% to 80% of patients. Ondansetron is the most commonly used antiemetic.

Nutrition

Nutrition in mild to moderate acute pancreatitis

In mild acute pancreatitis, oral intake should be restored quickly and usually no nutritional intervention is needed. Although the timing of refeeding remains controversial, recent studies have shown that immediate oral feeding in patients with mild disease appears safe.[92] Both the American College of Gastroenterology and the American Gastroenterological Association recommend oral feeding within 24 hours, if tolerated, in patients with acute pancreatitis.[8][85]​​

Earlier guidelines had recommended withholding oral feeding ("pancreatic rest") until resolution of pain and/or normalization of pancreatic enzymes or evidence of resolution of inflammation from imaging. However, current evidence shows early oral feeding leads to better outcomes.[93][94][95] One systematic review of 11 randomized studies showed no association between early feeding (≤48 hours after hospitalization; studies assessed oral, nasogastric, and nasojejunal routes) and increased risk of adverse events compared with delayed feeding; and patients with mild to moderate pancreatitis receiving early feeding benefited from a reduced length of hospital stay.[93]

Nutrition in severe acute pancreatitis

In patients who are unable to feed orally, enteral tube nutrition should be used; parenteral nutrition should be avoided.[96] There have been multiple randomized trials showing that total parenteral nutrition is associated with infectious and other line-related complications. Enteral feeding maintains the gut mucosal barrier, prevents disruption, and prevents the translocation of bacteria to seed pancreatic necrosis.[97][98][99] Continuous enteral infusion is preferred over cyclic or bolus administration.[8] Small peptide-based medium chain triglyceride formulas can be used if standard formulas are not tolerated.[96]

Nasogastric tube feeding is recommended in preference to the nasojejunal route for most patients.[8][96] One systematic review describing 92 patients from 4 studies on nasogastric tube feeding found that it was safe and well tolerated in patients with predicted severe acute pancreatitis.[100] Patients at increased risk of aspiration should be put in a more upright position and placed on aspiration precautions.[8] Nasojejunal tube placement requires interventional radiology or endoscopy and thus has resource implications, but has no proven benefit over nasogastric tube feeding in terms of safety or effectiveness.[8][101][102] Oral nutrition should resume as soon as pain and any nausea/vomiting begin to subside. A randomized trial showed that an oral diet after 72 hours was just as effective compared with early nasoenteric tube feeding in reducing the rate of infection or death in patients with acute pancreatitis at high risk of complications.[94] No specific enteral nutrition formulation has been proven to be better than another in patients with acute pancreatitis.[103]

Infectious complications

Many patients with acute pancreatitis who develop severe disease have infectious complications, including cholangitis, urinary tract infections, infected pseudocysts, fluid collections, and infected pancreatic necrosis. Fever, tachycardia, tachypnea, and leukocytosis are associated with the SIRS that may occur early in the course of acute pancreatitis. This clinical picture may be indistinguishable from sepsis. When an infection is suspected, antibiotics should be given while the source of the infection is being investigated. However, once blood and other cultures are found to be negative and no source of infection is identified, antibiotics should be discontinued. Despite the risk of infectious complications, the American College of Gastroenterology and the American Gastroenterology Association recommend against the use of prophylactic antibiotics in patients with severe acute pancreatitis (or predicted severe acute pancreatitis).[8][85]​​

Pancreatic necrosis

In most patients, necrosis is associated with moderately severe or severe disease.[85]​ Pancreatic necrosis is defined as diffuse or focal areas of nonviable pancreatic parenchyma >3 cm in size or >30% of the pancreas.[8]

Sterile necrosis

Early in the course of the disease, areas of necrotic pancreas form a diffuse solid/semi-solid inflammatory mass. Endoscopic, surgical, and/or radiologic intervention should be avoided within the first 4 weeks, unless a patient is deteriorating. After approximately 4 weeks, a fibrous wall develops around the necrotic area, making it more amenable to intervention. At this stage, drainage or necrosectomy/debridement may be considered.[47]

Prophylactic antibiotics to prevent infection are not recommended for patients with sterile necrosis (even for those predicted as having severe disease).[8] Although early unblinded trials suggested that administration of antibiotics may prevent infectious complications in patients with sterile necrosis, subsequent higher-quality trials have consistently failed to confirm an advantage.[8][104] One meta-analysis of 11 prospective randomized trials demonstrated that the number-needed-to treat was 1429 for one patient to benefit from the use of prophylactic antibiotics in severe acute pancreatitis.[105]

Infected necrosis

Necrotic collections become infected in around one third of patients.[88] This is thought to occur as a result of bacterial translocation from the gut.[88] When compared with patients with sterile necrosis, patients with infected pancreatic necrosis have a higher mortality rate (mean 30%, range 14% to 69%).[8]

Antibiotics should be used judiciously in patients with necrotizing acute pancreatitis if an infection is suspected. Antibiotics with good pancreatic penetration are recommended, such as a carbapenem (e.g., imipenem/cilastatin), a fluoroquinolone (e.g., ciprofloxacin), or metronidazole.[8][28]

Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behavior.[106]

  • Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, and unavailability).

  • Consult your local guidelines and drug information source for more information on suitability, contraindications, and precautions.

Historically, all patients with infected pancreatic necrosis were subject to prompt surgical debridement. This is no longer recommended unless the patient is clinically unstable.[18][107][108][109] In patients who are clinically stable, the initial management of infected necrosis for patients should be a 30-day course of antibiotics to allow the inflammatory reaction to become better organized.[8] At this time, when the necrosis has become fully walled off, a decision can be made regarding the preferred method of drainage, which may include endoscopic, radiologic, and/or minimally invasive surgical intervention.[8][47][110][111] If there is no prompt response to antibiotics or if the clinical situation deteriorates, necrosectomy/debridement should be performed.[8]

[Figure caption and citation for the preceding image starts]: Walled off pancreatic necrosisGut. 2017 Nov;66(11):2024-32; used with permission [Citation ends].Walled off pancreatic necrosis[Figure caption and citation for the preceding image starts]: Infected necrotic collection, not fully encapsulated, on day 20 after disease onsetGut. 2017 Nov;66(11):2024-32; used with permission [Citation ends].Infected necrotic collection, not fully encapsulated, on day 20 after disease onset

Pseudocysts

Pseudocysts are common and do not appear until at least 2-4 weeks after the onset of an episode of acute pancreatitis.[18] Early in the course of acute pancreatitis, large volumes of fluid may leave the intravascular compartment and form fluid collections in the abdomen. Most of this fluid is reabsorbed in the first few weeks.[18] However, in almost one third of patients, the fluid collections will persist and develop a fibrous nonepithelialized wall, becoming a pseudocyst. "Pseudocysts" diagnosed at initial presentation are likely to represent alternative pathology: either a patient with chronic pancreatitis, an old walled-off area of pancreatic necrosis, or a pancreatic cystic neoplasm.

Pancreatic necrosis, especially walled-off pancreatic necrosis (WOPN), cannot be differentiated from a pseudocyst by computed tomography. This is important as the treatment of a symptomatic or infected pseudocyst (abscess) and pancreatic necrosis are quite different. The differentiation between pancreatic necrosis and pseudocysts can only be made by the location of the cyst in relation to the pancreas. Whereas pseudocysts are located outside the parenchyma of the pancreas or adjacent structures, pancreatic necrosis will always involve the pancreas. Magnetic resonance imaging and endoscopic ultrasound (with fine needle aspiration) can determine the presence of tissue in WOPN but these imaging modalities are not used routinely.

Historically, patients with pseudocysts greater than 6 cm or enlarging on serial imaging underwent drainage. However, there is now a consensus that regardless of size, pseudocysts can be managed conservatively, with no intervention.[18][112]

If a pseudocyst becomes infected it is best described as an abscess, which requires antibiotics and drainage. Pseudocysts can become painful, or cause early satiety and weight loss when their size affects the stomach and bowel; drainage of these pseudocysts is recommended for symptom relief, regardless of infection.[8][18] Depending on expertise available, drainage can be performed via endoscopic, radiologic, or surgical techniques.

Use of this content is subject to our disclaimer