Acute pancreatitis is a sudden and often severe inflammation of the pancreas, the organ responsible for producing digestive enzymes and hormones like insulin, typically resulting from the premature activation of these enzymes that leads to autodigestion of pancreatic tissue.[1][2] It manifests abruptly with intense upper abdominal pain that may radiate to the back, accompanied by nausea, vomiting, fever, and elevated levels of pancreatic enzymes such as amylase and lipase in the blood.[3][4] While most cases are mild and resolve with supportive care within a few days, severe forms can lead to life-threatening complications like pancreatic necrosis, infection, or organ failure, with overall mortality ranging from 1-2% in mild cases to higher in severe ones.[2][1]The condition accounts for approximately 300,000 hospital admissions annually in the United States, with incidence rates increasing over recent decades, particularly among adults in their 40s to 60s, though cases in children and the elderly are also rising.[1][2][5] The two leading causes are gallstones, which account for 35-40% of cases by obstructing the pancreatic duct, and heavy alcohol consumption, responsible for 17-25% of episodes through toxic effects on pancreatic cells.[3][2] Other notable etiologies include hypertriglyceridemia (high blood fat levels), certain medications, trauma, infections, high calcium levels (hypercalcemia), and genetic factors such as mutations in genes like PRSS1 or CFTR.[4][2]Risk factors that elevate susceptibility include obesity (BMI ≥ 30), cigarette smoking (which triples the risk), diabetes, and a family history of pancreatitis or gallstones, with men and Black individuals facing higher incidence rates.[3][4] In severe cases, complications may involve systemic inflammatory response syndrome, acute respiratory distress, or pseudocysts, necessitating intensive care.[2] Initial management typically involves hospitalization for intravenous fluids, pain control, and nutritional support, with interventions like endoscopic procedures to remove gallstones or antibiotics for infections as needed.[6] Early recognition is critical, as prompt treatment improves outcomes and prevents progression to chronic pancreatitis in recurrent cases.[1]
Introduction
Definition and Classification
Acute pancreatitis is defined as a sudden inflammatory process of the pancreas characterized by reversible parenchymal injury and potential necrosis of peripancreatic fat, which typically resolves within six months without leading to permanent structural changes.[7] This condition arises from premature activation of pancreatic digestive enzymes, resulting in autodigestion of the gland and surrounding tissues, distinguishing it from chronic pancreatitis, which involves irreversible fibrosis.[2]The Revised Atlanta Classification, established in 2012 through an international consensus, provides a standardized framework for assessing the severity of acute pancreatitis based on the presence of organ failure and complications.[8] It categorizes the disease into three severity levels: mild acute pancreatitis, which lacks organ failure or local/systemic complications and generally resolves without intervention; moderately severe acute pancreatitis, characterized by transient organ failure lasting less than 48 hours or the presence of local or systemic complications without persistent failure; and severe acute pancreatitis, defined by persistent organ failure exceeding 48 hours, often associated with higher mortality risk.[8] This system divides the disease course into an early phase (first week, driven by systemic inflammatory response) and a late phase (after the first week, potentially involving local complications).[8]Morphologically, acute pancreatitis is classified into interstitial edematous pancreatitis, involving pancreatic parenchymal edema without necrosis, and necrotizing pancreatitis, which includes necrosis of the pancreatic parenchyma, peripancreatic tissues, or both.[8] Necrotizing pancreatitis is further subdivided into sterile necrosis, which does not involve infection, and infected necrosis, a critical complication that significantly worsens prognosis and often requires intervention.[8] These morphologic distinctions guide imaging and management decisions, with computed tomography commonly used to identify necrosis after 72 hours from onset.The evolution of classification systems reflects advances in understanding the disease's clinical and radiologic features, progressing from the 1963 Marseille classification—which distinguished acute edematous from acute necrotizing pancreatitis based primarily on pathology—to the 1984 Marseille update incorporating relapsing forms, and then to the 1992 Atlanta symposium's clinically oriented criteria emphasizing organ failure and local complications.[9] The 2012 revision of the Atlanta system incorporated evidence from prospective studies and refined definitions to improve prognostic accuracy and interobserver reliability, replacing outdated terms like "pancreatic abscess" with more precise descriptors of infected collections.[8]
Epidemiology
Acute pancreatitis affects an estimated 13 to 45 individuals per 100,000 population annually worldwide, with pooled global incidence rates from systematic reviews indicating approximately 34 cases per 100,000.[10] According to the Global Burden of Disease Study 2021, the number of incident cases reached approximately 2.75 million globally, reflecting an increase from 1.73 million in 1990, though age-standardized incidence rates have remained relatively stable around 34 per 100,000 due to population growth.[11] The increasing trends in case numbers are largely attributed to rising prevalence of risk factors such as obesity, gallstone disease, and alcohol consumption, which have driven a gradual upward trajectory over recent decades.[2]Demographic patterns reveal a higher overall incidence in men compared to women, with a male-to-female ratio of approximately 1.5:1 to 2:1, primarily due to alcohol as a predominant etiological factor in males.[2] In contrast, women experience elevated rates linked to gallstones, which account for a larger proportion of cases in this group.[12] The condition peaks in incidence between the ages of 40 and 60 years, though rates rise with advancing age, particularly beyond 75 years where biliary causes dominate.[2] Geographically, incidence rates are notably higher in developed countries, ranging from 30 to 50 cases per 100,000 in Europe and the United States, compared to lower figures of 5 to 20 per 100,000 in parts of Asia and Africa.[10] These disparities are tied to socioeconomic factors, including greater alcohol consumption and obesity prevalence in high-income regions, alongside differences in gallstone disease patterns influenced by diet and genetics.[11]
Clinical Presentation
Signs and Symptoms
The cardinal symptom of acute pancreatitis is severe epigastric pain that typically radiates to the back, often described as constant, deep, burning, or stabbing in nature, with sudden onset and worsening after eating; this pain usually persists for hours to days.[2][3] Patients commonly report associated symptoms including nausea, non-bilious vomiting, and anorexia, which contribute to dehydration and discomfort.[2][4]On physical examination, findings include abdominal tenderness in the epigastric region, often with guarding or mild rigidity, diminished bowel sounds suggestive of ileus, and possible abdominal distension in more severe presentations.[2]Vital signs may reveal fever and tachycardia, reflecting the inflammatory process; in severe cases, hypotension and altered mental status can indicate hemodynamic instability.[2][4] Rare hemorrhagic manifestations, such as Cullen's sign (periumbilical ecchymosis) or Grey Turner's sign (flank ecchymosis), occur in cases of retroperitoneal or intraperitoneal bleeding and are uncommon, appearing in fewer than 3% of patients.[2]In mild cases, symptoms typically resolve within 3 to 7 days with supportive care, representing about 80% of presentations.[2][13] Severe cases, however, may progress to systemic inflammatory response syndrome (SIRS), characterized by persistent fever, tachycardia, and leukocytosis, potentially leading to multi-organ involvement if untreated.[2]
Complications
Acute pancreatitis can lead to a range of local and systemic complications that significantly impact patient outcomes, with local complications occurring in approximately 10-20% of cases and systemic complications in 15-25%, though rates are substantially higher in necrotizing pancreatitis.[2]31310-6/fulltext) These complications often determine the transition from mild to moderately severe or severe disease, as defined by the revised Atlanta classification, and may require interventional management to prevent progression to multi-organ failure or death.[8]Local complications primarily involve peripancreatic structures and evolve over time based on the disease phase. Acute peripancreatic fluid collections (APFC) form within the first 4 weeks after onset and consist of homogeneous collections of enzyme-rich fluid adjacent to the pancreas in the setting of interstitial edematous pancreatitis, without non-viable pancreatic tissue; they are often asymptomatic but can cause pain or infection if persistent.[8][14] After 4 weeks, APFCs may mature into pancreatic pseudocysts, which are well-circumscribed, encapsulated collections of fluid devoid of solid necrotic debris, occurring in up to 10-20% of cases and potentially leading to symptoms such as abdominal pain, nausea, or rupture if untreated.[8][15] In necrotizing pancreatitis, acute necrotic collections (ANC) develop in the first 4 weeks as heterogeneous collections containing both fluid and non-viable pancreatic or peripancreatic tissue, carrying a risk of superinfection.[8] These can progress to walled-off necrosis (WON) after 4 weeks, forming encapsulated necrotic collections that are clinically significant due to their association with infection, hemorrhage, or disconnection of viable pancreatic tissue, often necessitating drainage.[8][16] Additional local issues include gastric outlet obstruction, resulting from inflammatory mass effect or pseudocyst compression on the duodenum, and portal vein thrombosis, arising from extrinsic compression or direct inflammatory extension, both of which can lead to gastrointestinal bleeding or portal hypertension.04916-3/fulltext)[17]Systemic complications arise from the inflammatory cascade and are more ominous, often defining severe disease. Persistent organ failure, lasting beyond 48 hours, commonly affects the respiratory system (e.g., via acute lung injury), cardiovascular system (e.g., shock), or renal system (e.g., acute kidney injury), occurring in about 20% of all cases and driving much of the 15-30% mortality in severe pancreatitis.[18]30102-7/fulltext) Infected pancreatic necrosis develops in 20-30% of severe cases, typically after the third week when gut bacteria translocate into necrotic tissue, manifesting as fever, worsening sepsis, and high mortality rates up to 30% despite antibiotics and debridement.[19][20]Complications are temporally divided into early and late phases to guide prognosis and intervention. Early complications, within the first week, include systemic inflammatory response syndrome (SIRS), characterized by widespread inflammation leading to fever, tachycardia, and leukocytosis, and acute respiratory distress syndrome (ARDS), which impairs gas exchange and requires ventilatory support in up to 20% of severe cases.[2][21] Late complications, beyond the first week, encompass multi-organ dysfunction syndrome (MODS), involving failure of two or more organ systems due to ongoing inflammation, and a persistent inflammatory response that exacerbates tissue damage and increases infection risk.[2][18] Overall, these early and late events highlight the need for vigilant monitoring, as persistent systemic issues portend worse outcomes compared to transient ones.[8]
Etiology
Common Causes
The two most common causes of acute pancreatitis are gallstones and alcohol consumption, accounting for the majority of cases worldwide.[22][23] Percentages vary by region; for example, alcohol accounts for a higher proportion (up to 40%) in Europe compared to 17-25% in the US.[2]Gallstone pancreatitis arises from the migration of gallstones into the common bile duct, causing transient biliary obstruction and subsequent reflux of bile into the pancreatic duct, which triggers premature activation of pancreatic enzymes and autodigestion of the gland.[24][25] This etiology accounts for 35 to 40 percent of acute pancreatitis cases, with higher prevalence in women over 50 years of age due to the demographic distribution of gallstone disease.[22][26] Key risk factors include obesity, female gender, rapid weight loss, and older age, though only 3 to 7 percent of individuals with gallstones develop pancreatitis.[27][28]Alcoholic pancreatitis results from chronic heavy alcohol use, involving mechanisms such as direct toxicity to acinar cells, oxidative stress from acetaldehydemetabolism, and dysfunction of the sphincter of Oddi leading to ductal hypertension and enzymeactivation.[29][30] It comprises 17 to 25 percent of cases and typically requires prolonged heavy consumption, such as more than 5 drinks per day for over 5 years, with binge drinking often serving as an acute precipitant.[2][31] This cause is more prevalent in men aged 30 to 50 years, and cigarette smoking synergistically increases risk by potentiating pancreatic injury.[32][29] In approximately 10 percent of cases, both gallstones and alcohol contribute to the etiology.[33]
Less Common Causes
Hypertriglyceridemia accounts for approximately 1-10% of acute pancreatitis cases, with higher incidences reported in certain populations. It typically occurs when serum triglyceride levels exceed 1000 mg/dL, though levels above 2000 mg/dL confer a substantially elevated risk of up to 10-20%. The mechanism involves the hydrolysis of triglycerides into free fatty acids, which exert direct toxic effects on pancreatic acinar cells, leading to inflammation. Management strategies include aggressive lipid-lowering therapies, such as insulin infusion or plasmapheresis, to rapidly reduce triglyceride levels and mitigate severity.Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis is an iatrogenic complication occurring in 3-10% of procedures, representing a notable procedural risk. Incidence rises with factors such as sphincterotomy, difficult biliary cannulation, or patient characteristics like female sex and younger age. Preventive measures, including rectal nonsteroidal anti-inflammatory drugs and adequate hydration, are recommended to lower this risk in high-susceptibility cases.Drug-induced acute pancreatitis is rare, comprising less than 2% of cases, and often results from idiosyncratic hypersensitivity reactions rather than dose-dependent toxicity. Commonly implicated medications include azathioprine, valproic acid, and statins, with early pharmacovigilance data raising concerns for glucagon-like peptide-1 receptor agonists such as liraglutide and semaglutide; however, 2025 analyses indicate no increased risk and suggest safe use even in patients with a history of pancreatitis.[34] High-risk drugs also encompass didanosine and mesalazine, necessitating immediate discontinuation upon suspicion and careful rechallenge assessment.Other less common etiologies include hypercalcemia, often secondary to primary hyperparathyroidism, which accounts for 1-7% of cases through calcium-mediated activation of pancreatic enzymes. Traumatic injury, such as blunt abdominal trauma, can precipitate pancreatitis via direct glandular disruption, though it is infrequent outside of surgical or accidental contexts. Infectious causes, including viral agents like mumps or coxsackievirus, are rare triggers, typically in pediatric or immunocompromised patients. Autoimmune pancreatitis, particularly IgG4-related disease, represents about 1-6% of chronic cases but can present acutely, characterized by lymphoplasmacytic infiltration responsive to corticosteroids.Idiopathic acute pancreatitis, where no etiology is identified after initial evaluation, comprises 10-30% of cases and may reflect occult biliary microlithiasis or sphincter of Oddi dysfunction upon further investigation. While gallstones and alcohol remain the predominant causes overall, these less common factors highlight the need for comprehensive etiological assessment to guide targeted interventions.
Acute pancreatitis is initiated by the premature activation of trypsinogen to trypsin within pancreatic acinar cells, which bypasses normal protective mechanisms such as trypsin inhibitor proteins and compartmentalization in zymogen granules.[35] This aberrant activation occurs intracellularly, often triggered by factors like lysosomal hydrolase cathepsin B or altered intracellular calcium signaling, leading to the loss of acinar cell integrity.[36] The activated trypsin then catalyzes the conversion of other proenzymes, including prophospholipase A2, proelastase, and prolipase, into their active forms, setting off a proteolytic cascade.[36]This local autodigestion process promotes the release of inflammatory mediators, including cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), from damaged acinar and immune cells.[37] These cytokines drive neutrophil infiltration into the pancreatic parenchyma, exacerbating microvascular injury through endothelial activation and increased vascular permeability.[38] Locally, the effects manifest as interstitial edema from fluid leakage, parenchymal necrosis due to ongoing enzymatic destruction, and fat saponification where activated lipases hydrolyze peripancreatic adipose tissue into soaps.[2] Systemically, the amplified inflammatory response creates a cytokine storm that induces systemic inflammatory response syndrome (SIRS), characterized by widespread endothelial dysfunction and activation of coagulation pathways.[39]The systemic inflammation further compromises distant organs, notably through gut barrier failure, where increased intestinal permeability allows bacterial translocation from the lumen into the bloodstream or peripancreatic spaces.[40] Recent 2025 research indicates that gut microbiotadysbiosis contributes to this process, worsening severity and infection risk in necrotizing cases through shifts in microbial composition.[41] This translocation contributes to multi-organ dysfunction, including acute respiratory distress syndrome and acute kidney injury, by perpetuating the inflammatory cascade.[42] Acute pancreatitis is classified into edematous (interstitial) and necrotizing forms; the latter involves pancreatic or peripancreatic tissue death and initially presents as sterile necrosis, but up to 30-40% progress to infected necrosis via bacterial translocation.[2] These pathophysiological processes result in characteristic histological appearances of acinar cell dropout and inflammatory infiltrates.[2]
Histopathology
Acute pancreatitis manifests histopathologically in two primary forms: interstitial edematous pancreatitis and necrotizing pancreatitis, distinguished by the extent of tissue damage and inflammation. In the edematous form, the milder variant, the pancreas exhibits diffuse interstitial edema with scant inflammatory infiltrates composed predominantly of neutrophils and macrophages, alongside acinar cell vacuolization but minimal necrosis and preservation of overall lobular architecture.[2]Fat necrosis is limited, and gross examination reveals a swollen, pale organ without significant hemorrhage.[2]The necrotizing form, indicative of severe disease, involves extensive coagulative necrosis of acinar cells and surrounding parenchyma, accompanied by prominent fat necrosis characterized by saponification—the formation of calcium soaps from lipid breakdown.[2] Microscopically, this is marked by dense leukocytic infiltrates, vascular thrombosis, and parenchymal destruction, while grossly, the tissue appears friable, dark red to black, and hemorrhagic in advanced cases.[2] These changes reflect the progression from localized injury to widespread tissue death.Histopathological evolution occurs in phases: early within hours, featuring premature enzyme activation and initial acinar disruption; intermediate over days, with apoptosis and necrosis dominating; and late over weeks, potentially leading to fibrosis and scarring if the inflammation persists unresolved.[43] Biopsy of pancreatic tissue is rarely performed due to risks, but when obtained, it reveals loss of lobular architecture, ductal disruption, and variable inflammatory patterns.[2]
Diagnosis
The diagnosis of acute pancreatitis requires at least two of the following three features according to the revised Atlanta classification: characteristic abdominal pain, serum amylase or lipase elevated to at least three times the upper limit of normal, and characteristic findings of acute pancreatitis on imaging.[2]
Laboratory Evaluation
Laboratory evaluation plays a crucial role in confirming the diagnosis of acute pancreatitis and assessing its severity through specific biomarkers and tests for organ dysfunction. The primary diagnostic enzymes are serum amylase and lipase, which should be elevated to at least three times the upper limit of normal (ULN) to support the diagnosis when combined with clinical features. Lipase is more specific than amylase for acute pancreatitis and remains elevated longer, typically for 8 to 14 days after symptom onset compared to 3 to 5 days for amylase. However, normal levels of these enzymes within the first 48 hours of symptom onset do not rule out the condition, as elevations may occur later.[44][45][46]Inflammatory markers provide prognostic information regarding disease severity. C-reactive protein (CRP) is the gold standard for predicting severe acute pancreatitis, with levels exceeding 150 mg/L at 48 hours after admission indicating a higher risk of complications. Procalcitonin (PCT) is useful for detecting infection, particularly in cases of pancreatic necrosis, where levels >1.0 ng/mL are associated with a higher risk of infected necrosis.[47][48][49]Evaluation of organ function involves several key tests to identify early signs of multiorgan involvement. Blood urea nitrogen (BUN) and creatinine levels assess renal function; an elevated BUN >20 mg/dL on admission is associated with severe disease and poor outcomes. A decrease in hematocrit from baseline, often >10%, signals significant fluid sequestration and hypovolemia. Hypocalcemia, typically with serum calcium <8 mg/dL, occurs in up to 20% of severe cases due to saponification of fats and is a marker of systemic inflammation.[50][44][51]Additional laboratory tests help identify etiology and monitor systemic effects. Elevated liver enzymes, particularly alanine aminotransferase (ALT) >3 times ULN (e.g., >150 IU/L), strongly suggest gallstone-related pancreatitis with a predictive probability of approximately 95%. Serum triglycerides >1000 mg/dL confirm hypertriglyceridemia as the causative factor in 1-4% of cases. Hematologic evaluation reveals leukocytosis, with white blood cell (WBC) count >12,000/mm³ contributing to the diagnosis of systemic inflammatory response syndrome (SIRS), while >16,000/mm³ indicates increased severity risk per Ranson's criteria.[52][53][54]
Imaging Modalities
Abdominal ultrasound serves as the first-line imaging modality in suspected acute pancreatitis, particularly for identifying gallstones as an underlying etiology, with a reported sensitivity of 70-90%.[55] However, its utility is constrained by overlying bowel gas, which often obscures direct visualization of the pancreas itself, limiting its role to etiological assessment rather than detailed pancreatic evaluation.[56]Contrast-enhanced computed tomography (CECT) is considered the gold standard for diagnosing and staging acute pancreatitis, providing comprehensive assessment of pancreatic inflammation, necrosis, and peripancreatic complications.[56] The Balthazar scoring system, integrated into the CT severity index, grades the degree of glandular and extrapancreatic involvement based on morphological changes such as edema, fluid collections, and tissue heterogeneity.[57]Necrosis is identified by lack of contrast enhancement in the pancreatic parenchyma, with severity graded as none (0%), <30% (2 points), 30-50% (4 points), or >50% (6 points) in the CT severity index, while fluid collections appear as non-enhancing areas surrounding the gland.[58] To optimize accuracy in detecting the full extent of necrosis and avoid early overestimation or underestimation of severity, CECT is typically performed at least 72 hours after symptom onset.[59]Magnetic resonance imaging (MRI), often combined with magnetic resonance cholangiopancreatography (MRCP), is particularly useful for evaluating pancreatic ductal abnormalities, such as disruptions or strictures, in equivocal cases or when radiation exposure is a concern.[60] MRCP excels in delineating the biliary tree and pancreatic duct without ionizing radiation, making it superior for confirming biliary etiologies like choledocholithiasis when ultrasound findings are inconclusive.[60] Its multiplanar capabilities also allow for better characterization of fluid collections and parenchymal changes compared to CT in select patients.[61]Endoscopic ultrasound (EUS) offers high-resolution imaging of the pancreas and surrounding structures, making it ideal for detecting subtle findings such as biliary microlithiasis or early necrotic changes in idiopathic or recurrent acute pancreatitis.[62] With its proximity to the gland via endoscopic access, EUS achieves superior sensitivity for microlithiasis—often missed by transabdominal ultrasound—and avoids radiation, though it requires sedation and expertise.[63] It is especially valuable in cases where noninvasive imaging is nondiagnostic, providing targeted evaluation of ductal variants or small tumors.[63]
Differential Diagnosis
The differential diagnosis for acute pancreatitis encompasses a range of intra-abdominal, thoracic, and systemic conditions that can present with acute epigastric or upper abdominal pain, nausea, vomiting, and systemic inflammatory signs, necessitating prompt evaluation to avoid misdiagnosis.[2] Distinguishing features often rely on clinical history, physical examination, targeted laboratory tests, and imaging to identify alternative pathologies while confirming or excluding pancreatic involvement.[64]Gastrointestinal conditions commonly mimic acute pancreatitis due to overlapping abdominal symptoms. Perforated peptic ulcer typically causes sudden, severe generalized abdominal pain with signs of peritonitis and is differentiated by the presence of free subdiaphragmatic air on upright chest radiography or computed tomography (CT).[65] Acute cholecystitis presents with right upper quadrant tenderness, fever, and a positive Murphy's sign on palpation; ultrasound revealing gallstones, pericholecystic fluid, or gallbladder wall thickening helps confirm this entity.[65] Appendicitis is suggested by right lower quadrant pain that may migrate from the periumbilical region, accompanied by anorexia and rebound tenderness, and is verified through clinical scoring systems like Alvarado criteria combined with CT findings of appendiceal inflammation.[65]Vascular disorders must be considered in patients with severe, atypical pain patterns. Aortic dissection often manifests as abrupt, tearing chest or back pain radiating to the abdomen, with pulse deficits or hypertension disparities; urgent CTangiography is diagnostic.[65] Mesenteric ischemia features disproportionate abdominal pain relative to physical examination findings, potentially with bloody diarrhea and elevated serum lactate; contrast-enhanced CT or mesenteric angiography identifies vascular occlusion.[65]Other mimics include cardiopulmonary and metabolic emergencies. Myocardial infarction may simulate epigastric discomfort, particularly in inferior wall involvement, but electrocardiographic changes (e.g., ST-segment elevation) and elevated cardiac troponins distinguish it.[65] Lower lobe pneumonia can refer pain to the upper abdomen via diaphragmatic irritation, with respiratory symptoms and chest X-ray infiltrates providing differentiation.[65]Diabetic ketoacidosis (DKA) presents with diffuse abdominal pain, dehydration, and vomiting in hyperglycemic patients; blood glucose exceeding 250 mg/dL, ketonemia, and arterial pH below 7.3 on blood gas analysis are confirmatory.[65]Key discriminators for acute pancreatitis include serum lipase levels elevated more than three times the upper limit of normal, which offers higher specificity than amylase for pancreatic origin, alongside imaging (e.g., CT) demonstrating pancreatic parenchymal inflammation or peripancreatic fluid without evidence of alternative pathologies.[21] Cases remaining undiagnosed after exhaustive exclusion of common etiologies are termed idiopathic acute pancreatitis.[2]
Management
Supportive Care
Supportive care forms the cornerstone of initial management for acute pancreatitis, focusing on stabilizing the patient through hydration, analgesia, and gastrointestinal rest while preventing complications from systemic inflammation. Fluid resuscitation is prioritized to address hypovolemia and maintain organ perfusion, with goal-directed therapy recommended to guide administration based on clinical response. According to the 2024 American College of Gastroenterology (ACG) guidelines, moderately aggressive hydration using lactated Ringer's solution at an initial rate of 1.5 mL/kg per hour for the first 24 hours is advised for most patients, with additional boluses of 10 mL/kg if hypovolemia is evident.[66] This approach has been shown to reduce the risk of persistent organ failure compared to less aggressive strategies.[67]Monitoring during fluid resuscitation is essential to ensure adequacy without excess, targeting urine output greater than 0.5 mL/kg per hour, a decrease in blood urea nitrogen (BUN), and hematocrit levels below 35-44%. Over-resuscitation should be avoided, as it can lead to complications such as abdominal compartment syndrome, particularly in severe cases.[68] Patients with predicted severe disease may require intensive care unit (ICU) admission for close hemodynamic monitoring, including vital signs and fluid balance.Pain management is critical given the severe abdominal discomfort associated with acute pancreatitis, typically achieved with intravenous opioids as first-line therapy. Morphine or fentanyl are preferred agents, administered via patient-controlled analgesia (PCA) pumps for titrated relief, while meperidine is avoided due to its neurotoxic metabolite normeperidine.[69] Adjunctive non-opioid analgesics, such as acetaminophen, can be used to minimize opioid requirements.[70]Patients are initially kept nil per os (NPO) to reduce pancreatic stimulation, but recent guidelines emphasize early oral feeding in mild cases to promote recovery. The 2025 International Association of Pancreatology (IAP) update recommends initiating oral intake within 24 hours if tolerated, rather than prolonged NPO, as this approach shortens hospital stays without increasing complications.[71] For those unable to tolerate oral feeding, a brief transition to enteral nutrition may be considered, but supportive care prioritizes resuming oral diet as soon as possible in non-severe presentations.
Interventional Therapies
Endoscopic retrograde cholangiopancreatography (ERCP) is recommended for acute pancreatitis patients with concomitant cholangitis or persistent biliary obstruction, with urgent intervention ideally performed within 24 hours for cholangitis and within 72 hours for obstruction without infection.[66] In contrast, routine early ERCP is not advised for predicted severe gallstone pancreatitis without cholangitis, as it does not improve outcomes and may increase the risk of complications.[66] These recommendations from the 2024 American College of Gastroenterology (ACG) guidelines emphasize targeted use to address specific biliary complications.[66]Prophylactic antibiotics are not recommended in severe acute pancreatitis or sterile necrosis, as they do not reduce infection rates or mortality and may promote resistant organisms.[66] Therapeutic antibiotics are indicated for confirmed or suspected infected pancreatic necrosis, with agents such as carbapenems (e.g., imipenem or meropenem) or piperacillin-tazobactam preferred due to their ability to penetrate necrotic tissue; selection should be guided by culture results and local resistance patterns.[72][73]Nutritional support is a key interventional component, with enteral nutrition preferred over parenteral to reduce infectious complications and length of stay in patients unable to tolerate oral intake.[67] Nasojejunal tube placement is considered if gastric feeding is not tolerated, while in mild cases, early oral feeding with a low-fat solid diet should begin within 24-48 hours as tolerated to promote recovery.[66] Parenteral nutrition is reserved for cases where enteral routes are contraindicated or ineffective.[67]For symptomatic peripancreatic fluid collections or walled-off necrosis, percutaneous drainage serves as an initial minimally invasive option in the step-up approach, particularly when infection is suspected, to alleviate symptoms and delay more invasive procedures.[67] Anti-emetic therapy, such as ondansetron, is commonly used to manage associated nausea and vomiting, with evidence suggesting improved short-term outcomes in hospitalized patients.[74] These targeted interventions complement foundational supportive care to address complications effectively.[66]
Surgical Interventions
Surgical interventions in acute pancreatitis are primarily reserved for complications in severe cases, particularly when conservative and interventional therapies fail to control infection or symptoms. The step-up approach, endorsed by the 2012 International Association of Pancreatology/American Pancreatic Association (IAP/APA) guidelines and reaffirmed in subsequent updates including the 2024 American College of Gastroenterology (ACG) guidelines, emphasizes delaying invasive procedures to allow necrosis to become walled-off, typically for at least 4 weeks in stable patients.[75] This strategy begins with percutaneous catheter drainage under radiological guidance for infected collections, followed by minimally invasive necrosectomy if drainage alone is insufficient.[20] Minimally invasive techniques, such as video-assisted retroperitoneal debridement (VARD), involve small incisions to access and remove necrotic tissue, reducing morbidity compared to traditional open methods.[76]Indications for surgical intervention include infected pancreatic necrosis that does not respond to antibiotics and percutaneous drainage, leading to persistent sepsis or organ failure.[20] Disconnected pancreatic duct syndrome, a complication of necrotizing pancreatitis, may necessitate surgery in symptomatic cases, such as recurrent fluid collections or pain unrelieved by endoscopic stenting.[77] Symptomatic pseudocysts larger than 6 cm persisting beyond 6 weeks, causing compression of adjacent structures like the stomach or bile duct, also warrant surgical drainage or resection if endoscopic approaches fail.01067-6/fulltext)Open necrosectomy, involving laparotomy for debridement of necrotic tissue followed by closed drainage or continuous lavage, is now reserved for cases where minimally invasive methods are not feasible or have failed, such as in patients with extensive anterior necrosis or hemodynamic instability requiring immediate source control.[75] This procedure carries higher risks, with mortality rates reported between 15% and 25% in contemporary series, largely due to postoperative complications like bleeding and enterocutaneous fistulas.[76] For etiology-specific management, laparoscopic cholecystectomy is recommended during the index admission for mild gallstone-related acute pancreatitis to prevent recurrence, as per the 2024 ACG guidelines.
Severity Assessment
Clinical Scoring Systems
Clinical scoring systems are essential bedside tools used to predict the severity of acute pancreatitis, stratify patients for intensive care, and guide therapeutic decisions early in the disease course. These systems integrate clinical, laboratory, and physiological parameters to estimate the risk of complications such as organ failure and mortality, allowing for timely intervention. Widely adopted systems include the Ranson score, APACHE II, BISAP, and Glasgow/Imrie score, each with distinct parameters and timing for assessment.[2]The Ranson score, developed in 1974, evaluates 11 parameters to prognosticate outcomes in acute pancreatitis. Five parameters are assessed at admission: age greater than 55 years, white blood cell count exceeding 16,000 cells/μL, blood glucose above 200 mg/dL, lactate dehydrogenase level greater than 350 IU/L, and aspartate aminotransferase greater than 250 IU/L. An additional six parameters are measured at 48 hours: hematocrit drop of more than 10%, blood urea nitrogen rise exceeding 5 mg/dL, serum calcium below 8 mg/dL, arterial partial pressure of oxygen less than 60 mmHg, base deficit greater than 4 mEq/L, and estimated fluid sequestration surpassing 6 L. A score of 3 or higher indicates severe disease with increased risk of mortality.[78][79]The APACHE II score, originally introduced in 1985 for general critical illness severity, has been validated for acute pancreatitis, particularly in intensive care settings. It comprises 12 physiological variables (including temperature, mean arterial pressure, heart rate, respiratory rate, oxygenation, arterial pH, serum sodium, serum potassium, creatinine, hematocrit, white blood cell count, and Glasgow Coma Scale), plus points for age and chronic health status. A score greater than 8 at admission or within 24 hours predicts severe pancreatitis and higher mortality risk, with advantages in dynamic monitoring over time.[80]The BISAP score is a simplified five-point system designed for early risk stratification within 24 hours of admission. It assigns one point each for blood urea nitrogen greater than 25 mg/dL, impaired mental status (Glasgow Coma Scale <15), presence of systemic inflammatory response syndrome (meeting ≥2 criteria), age over 60 years, and pleural effusion on imaging. A score of 3 or higher identifies patients at high risk for in-hospital mortality and severe disease, offering ease of use compared to more complex systems.[2]The Glasgow/Imrie score, a modification of earlier criteria introduced in 1984, uses eight parameters assessed at admission or within 48 hours to predict severity. These include age over 55 years, white blood cell count greater than 15,000 cells/μL, blood glucose above 180 mg/dL, serum calcium below 8 mg/dL, partial arterial oxygen pressure less than 60 mmHg, urea above 45 mg/dL, lactate dehydrogenase greater than 600 IU/L, and alanine aminotransferase greater than 100 IU/L. Similar to the Ranson score, a total of 3 or more points signifies severe acute pancreatitis with elevated complication rates.[79]
Imaging-Based Scoring
Imaging-based scoring systems for acute pancreatitis primarily rely on computed tomography (CT) findings to quantify pancreatic parenchymal damage, peripancreatic inflammation, necrosis, and extrapancreatic complications, providing prognostic information independent of clinical parameters. These scores help stratify patients into mild, moderate, or severe categories, guiding decisions on intensive care needs and intervention timing, with CT preferred due to its widespread availability and validated correlation with outcomes such as mortality and length of hospital stay. These imaging scores complement the Revised Atlanta classification, which primarily uses the presence and duration of organ failure (persistent >48 hours) to define severity: mild (no organ failure), moderately severe (transient or persistent organ failure without local complications, or local complications without organ failure), and severe (persistent organ failure).[81]The Balthazar CT severity index (CTSI), introduced in 1990, is a widely adopted 10-point scale combining pancreatic morphology (graded 0-4 points: grade A normal pancreas=0; grade B enlargement or contour abnormality=1; grade C glandular edema and mild peripancreatic inflammation=2; grade D single fluid collection=3; grade E two or more fluid collections or gas=4) with the extent of necrosis (0 points for none; 2 for <30%; 4 for 30-50%; 6 for >50%). Scores of 0-3 indicate mild disease, 4-6 moderate, and 7-10 severe, with scores greater than 5 associated with severe pancreatitis and increased mortality risk (up to 17% for scores 7-10). This index correlates strongly with clinical outcomes, including organ failure and infection, outperforming earlier grading systems alone.[82]The modified CT severity index (mCTSI), proposed in 2004, refines the original by simplifying scoring and incorporating extrapancreatic findings for a total of 10 points: pancreatic inflammation (0: normal pancreas; 2: focal or diffuse glandular abnormalities with or without peripancreatic inflammatory changes; 4: single or multiple fluid collections or gas in or adjacent to pancreas), necrosis (0: none; 2: ≤30%; 4: >30%), and extrapancreatic complications (2: one or more, e.g., pleural effusion, ascites, vascular or parenchymal complications). Mild disease scores 0-2, moderate 4-6, and severe 8-10, with severe scores indicating high risk for persistent organ failure, infection, and need for intervention. This update reduces interobserver variability and better predicts complications compared to the original CTSI.[83]Ultrasound and magnetic resonance imaging (MRI) lack fully standardized severity scores like CT but are valuable for assessing fluid collections and necrosis, particularly in contraindications to CT.[84]Ultrasound evaluates collection size and symptoms, with peripancreatic fluid collections >6 cm often indicating need for intervention if symptomatic or persistent beyond 4-6 weeks.[85] MRI, using T1- and T2-weighted sequences, can quantify necrosis and collections with high soft-tissue contrast, showing moderate correlation with clinical severity (e.g., MRSI scores 0-10 based on signal intensity and collections), though it is less routinely used due to cost and availability.[84]Optimal timing for contrast-enhanced CT is 48-72 hours after symptom onset to accurately assess necrosis development, as earlier scans may underestimate extent.[58]Necrosis involving >30% of the gland, visible on these scans, predicts higher infection risk and worse outcomes, prompting vigilant monitoring for infected pancreatic necrosis.[2]
Prognosis
Short-Term Outcomes
The short-term outcomes of acute pancreatitis are primarily determined by disease severity, with overall mortality rates ranging from 1% to 5%. In mild cases, mortality is less than 1%, while severe acute pancreatitis carries a 20% to 30% mortality risk, escalating to 15% to 35% in instances of infected pancreatic necrosis.[51][76][86] These rates reflect a substantial improvement from historical figures of 10% to 20%, attributable to advancements like the step-up approach, which prioritizes minimally invasive interventions over immediate open surgery.[76][87]Hospital length of stay differs markedly by severity: mild cases typically resolve within 3 to 7 days, whereas severe cases often extend to 4 to 8 weeks due to complications requiring intensive monitoring and support. Approximately 15% to 20% of patients face readmission within 30 days, most commonly for persistent symptoms or secondary issues like fluid collections.[88][89][90]Organ failure plays a critical role in prognosis, with transient failure (lasting under 48 hours) resolving successfully in about 80% of affected patients, often without long-lasting sequelae. In contrast, persistent organ failure beyond 48 hours strongly predicts adverse short-term outcomes, including higher mortality and prolonged recovery.[2][91]Early intervention strategies, as outlined in the 2025 International Association of Pancreatology guidelines, have been shown to reduce mortality by addressing complications promptly in high-risk cases.[71]Alcohol as an etiology is linked to worse short-term outcomes, including increased severity and higher rates of organ failure compared to biliary causes.[92] Severity assessment tools, such as those in the Revised Atlanta classification, aid in forecasting these outcomes by stratifying risk early in the disease course.[93]
Long-Term Consequences
Acute pancreatitis can lead to persistent exocrine pancreatic insufficiency in approximately 20-30% of survivors, manifesting as steatorrhea due to inadequate enzyme production and fatmalabsorption.[94] This condition often necessitates lifelong pancreatic enzyme replacement therapy to mitigate nutritional deficiencies and weight loss. The risk is notably elevated following necrosectomy in severe cases, where pancreatic tissue loss exacerbates insufficiency, with prevalence reaching up to 33% in severe acute pancreatitis compared to 19% in mild forms.[94]Endocrine dysfunction is another common long-term sequela, with new-onset diabetes mellitus developing in 10-50% of patients, particularly those with severe disease or extensive pancreatic resection such as total pancreatectomy, where rates approach 100%.[95] Impaired glucose tolerance may precede overt diabetes, contributing to metabolic complications that require ongoing monitoring and management. Additionally, recurrent acute pancreatitis occurs in 20-30% of cases if the underlying etiology remains unaddressed, such as gallstones without cholecystectomy, potentially evolving into chronic pancreatitis in about 10% of affected individuals.[96]Survivors may also experience chronic abdominal pain in 5-10% of cases, alongside pseudocyst recurrence that can necessitate repeated interventions. These issues contribute to a diminished quality of life, with studies showing reduced SF-36 scores across physical and mental health domains compared to general populations.[97] Recent 2024 reviews highlight an increased risk of pancreatic cancer following acute pancreatitis, with odds ratios ranging from 2 to 5, underscoring the need for vigilant long-term surveillance.[98]Long-term mortality among survivors is elevated compared to the general population. A 2025 population-based study found a cumulative mortality of 37.7% in acute pancreatitis patients versus 29.8% in matched controls over extended follow-up, attributed to increased risks of cardiovascular disease, infections, and malignancies.[99]