Acute Pancreatitis: Five Things to Know

Acute pancreatitis is the third most common gastrointestinal condition associated with hospitalization in the United States and is the primary diagnosis in hundreds of thousands of emergency department visits each year.

The incidence of acute pancreatitis has steadily increased across most countries in the Western world since the 1960s. This trend is perhaps due to a corresponding increase in metabolic syndrome and obesity, which are associated with gallstone formation, the leading cause of acute pancreatitis.

After first experiencing acute pancreatitis, nearly a quarter of patients develop recurrent episodes, and 10% develop chronic pancreatitis. Although most patients with acute pancreatitis have its mild form, some develop moderate or severe acute pancreatitis, both of which include serious complications and an increased risk for death.

Several recent developments could have implications for identifying the cause of acute pancreatitis, predicting its progression, and improving treatment.

Here are five things to know about acute pancreatitis.

1. Relevant clues can help identify the common underlying causes.

The diagnosis of acute pancreatitis requires the patient to meet two of the following three criteria: Abdominal pain consistent with acute pancreatitis (acute onset of persistent, severe epigastric pain often radiating to the back), serum lipase or amylase levels at least three times above the upper limit of normal, and characteristic features of acute pancreatitis on contrast-enhanced CT, MRI, or transabdominal ultrasonography.

Because acute pancreatitis has several etiologies, clinicians must identify the root cause or causes to design an appropriate treatment plan once the diagnosis is made.

The four most common etiologies of acute pancreatitis are gallstones (40%), heavy alcohol use (30%), hypertriglyceridemia (2%-7%), and certain medications (< 5%), according to a May 2024 review.

Sometimes the etiology is clear at diagnosis, as when imaging shows gallstones, which are a more common cause of pancreatitis in women than in men. The passage of gallstones through the common bile duct is a common cause of acute pancreatitis, and transabdominal ultrasound can reveal an associated dilation of this region of the biliary system. Elevated liver chemistries raise the possibility of gallstone etiology. Alanine aminotransferase levels offer the most clinically useful parameter, with a 95% specificity for gallstone pancreatitis when they are elevated by approximately threefold.

Alcohol-related acute pancreatitis is more common in men and is associated primarily with prolonged and heavy alcohol consumption vs binge drinking or social alcohol intake. Alcohol can also exacerbate pancreatic injury from genetic and environmental factors. Therefore, it’s important that a careful history include documentation of patients’ alcohol use in order to identify it as a possible etiology.

Hypertriglyceridemia-related acute pancreatitis is initially identified by triglyceride levels (> 1000 ng/mL). However, subsequent recurrences can be initiated by much smaller elevations.

Several drugs may induce acute pancreatitis, with the strongest associations found with didanosine, asparaginase, azathioprine, valproic acid, 6-mercaptopurine, and mesalamine. However, causality is difficult to determine. Identifying this as a source can require stopping the drug and observing whether symptoms reoccur upon rechallenge in the absence of other possible causes.

The recent approval of glucagon-like peptide 1 (GLP-1) receptor agonists for obesity may add another drug to that list. A 2022 retrospective study found that patients taking GLP-1 have a higher risk for acute pancreatitis, especially if they have a history of type 2 diabetes, stage III or higher chronic kidney disease, or tobacco use.

However, because a history of acute pancreatitis was not associated with an increased risk for subsequent episodes, the investigators advised against discontinuing the use of GLP-1s in these patients, given the glycemic, cardiovascular, and weight loss benefits.

Additional but less common acute pancreatitis etiologies include endoscopic retrograde cholangiopancreatography, pancreatic trauma, and infectious viruses and parasites.

2. Current tools for predicting severity are limited.

Acute pancreatitis is classified into three severity categories: Mild (no organ failure or complications), moderately severe (transient organ failure, local complications, or exacerbation of comorbid disease), and severe (persistent organ failure > 48 hours). Among the condition’s possible complications are pancreatic necrosis, pseudocyst formation, acute respiratory distress syndrome, and acute renal failure.

Around 80% of patients with acute pancreatitis have the mild form and usually improve within 48 hours of hospitalization. The other 20% of patients develop moderately severe or severe acute pancreatitis and require higher levels of care and specific interventions to manage existing complications and prevent further deterioration or death. In severe or necrotizing acute pancreatitis, mortality rates have been reported to range from 20% to as high as 50%.

Predicting which patients will develop more severe forms of acute pancreatitis is important to improve their outcomes; however, doing so can be challenging for clinicians.

Clinical factors associated with an increased risk for complications and death (eg, obesity and long-term heavy alcohol use) aren’t reliable predictors of an individual’s risk of developing severe acute pancreatitis. Laboratory markers primarily assess the degree of inflammation or intravascular volume status rather than predict severity. Cross-sectional imaging can identify severe acute pancreatitis but only after a patient has clinically declined.

While various scoring systems that combine these factors have been introduced over the past 40 years, none has emerged as superior in terms of sensitivity and specificity.

However, according to a May 2024 review, an easily adaptable marker of progression is systemic inflammatory response syndrome. As part of this review, the authors also highlighted the potential of a novel panel that measures five cytokines (angiopoietin 2, hepatocyte growth factor, interleukin 8, resistin, and soluble tumor necrosis factor receptor 1A). The panel, developed to predict persistent organ failure early in the disease course, significantly outperformed existing laboratory tests and clinical scores, researchers found.

3. Acute pancreatitis can lead to a diabetes subtype with serious complications.

Many patients who experience even one bout of acute pancreatitis can go on to develop diabetes mellitus. A meta-analysis of 24 prospective studies involving 1102 patients with their first acute pancreatitis episode found that 15% developed newly diagnosed diabetes within 12 months and that they had a 2.7-fold increased risk over 5 years. This risk was not influenced by factors such as acute pancreatitis severity, etiology, age, or gender.

Although commonly misdiagnosed as type 2 diabetes, this condition represents a secondary diabetes known as post-pancreatitis diabetes mellitus (PPDM). Several other terms are used to describe diabetes that follows pancreatic disease, including post-acute pancreatitis diabetes mellitus, diabetes of the exocrine pancreas, and type 3c diabetes.

The pathogenesis behind PPDM remains unclear, although pro-inflammatory cytokine-induced lipolysis has been suggested. The American Diabetes Association identifies PPDM as being distinguished by concurrent pancreatic exocrine insufficiency, pathologic findings on pancreatic imaging, and the absence of type 1 diabetes-associated autoimmunity.

Patients with PPDM have worse glycemic control, require more insulin, and have a higher risk for hospitalization and mortality from cancer, infectious disease, and gastrointestinal disease than those with type 2 diabetes. PPDM may also be an early sign of pancreatic malignancy.

Recent research suggests that statins may protect against PPDM development.

A large cohort study of 118,479 patients without preexisting diabetes mellitus followed for a median of 3.5 years after their first acute pancreatitis episode found that regular statin usage prior to the episode lowered the risk of developing PPDM by 42% compared with nonuse of statins. Similar benefits were observed regardless of statin dose, the patient’s sex, and acute pancreatitis etiology and severity. The researchers suggested that, with further study, statins could emerge as a therapy for PPDM.

4. A procalcitonin-based algorithm may reduce antibiotic overuse.

Patients who are hospitalized with acute pancreatitis are susceptible to infectious complications, such as infected necrosis, bacteremia, and pneumonia.

That susceptibility, along with the difficulty clinicians face in distinguishing between infection and inflammation in patients with worsening acute pancreatitis, makes overuse of antibiotics common in this population. Current guidelines recommend against the use of prophylactic antibiotics, in part to avoid fostering multidrug-resistant organisms.

An algorithm incorporating procalcitonin levels may help clinicians identify which patients need antibiotics and reduce unnecessary use. In a 2022 randomized controlled trial, UK researchers compared procalcitonin-guided care, in which antibiotics were initiated or continued in patients whose procalcitonin levels were ≥ 1.0 ng/mL, with usual care among patients hospitalized for acute pancreatitis.

Investigators reported that procalcitonin-guided care significantly reduced the number of patients receiving antibiotics compared with usual care (45% vs 63%, respectively) without affecting length of hospital stay, infection rates, adverse events, or death.

5. Moderate fluid resuscitation is considered ‘new standard of care’.

Patients with acute pancreatitis can experience intravascular volume depletion and third-space fluid sequestration, which initiates a cascading effect that can eventually cause renal and circulatory failures, progression of acute pancreatitis, and pancreatic necrosis.

It was previously believed that early, aggressive fluid resuscitation was the best strategy to combat this. The approach was dealt a blow with the 2022 publication of results from the WATERFALL trial, in which researchers at 18 centers worldwide enrolled 249 patients to randomly receive aggressive or moderate resuscitation with lactated Ringer’s solution.

Aggressive fluid resuscitation consisted of a bolus of 20 mL/kg of body weight, followed by 3 mL/kg/h. Moderate fluid resuscitation consisted of a bolus of 10 mL/kg in patients with hypovolemia or no bolus in patients with normovolemia, followed by 1.5 mL/kg/h in all patients in this group. Patients were assessed at 12, 24, 48, and 72 hours, with fluid resuscitation adjustment made as necessary.

The trial was halted early when investigators uncovered that fluid overload occurred in 20.5% of those in the aggressive resuscitation group, compared with just 6.3% in the moderate resuscitation group. There was no significant difference observed between the aggressive and moderate groups in the incidence of moderately severe or severe acute pancreatitis (22.1% vs 17.3%, respectively).

WATERFALL investigator Enrique de-Madaria, MD, PhD, told Medscape Medical News that the trial’s results indicated that aggressive fluid resuscitation in acute pancreatitis “should be abandoned,” with the moderate strategy now considered “a new standard of care in the early management of acute pancreatitis.”

John Watson is a freelance writer in Philadelphia.