Acute pancreatitis is common and is the leading cause of hospitalization amongst gastrointestinal disorders in the United States. The severity of the disease varies widely, from mild disease needing conservative treatment to severe and complicated disease with high morbidity and mortality. The diagnosis of acute presentation is easy, but the major challenge is predicting progression of disease course and outcome. This is important to determine the level of care. 
In the majority of cases, alcohol use, gallstones, and hypertriglyceridemia cause acute pancreatitis. The rate of occurrence of each etiology of acute pancreatitis varies across geographic regions and socio-economic strata. Common etiologies of acute pancreatitis are listed below.
Overall, the frequency of acute pancreatitis has been noted to be rising in the United States and the rest of the world. Whether this trend is related to a true increase in incidence or simply increased detection is difficult to determine. The rise in incidence is considered, in part, due to increased hypertriglyceridemia and metabolic syndrome with multiple reports showing an increase in acute pancreatitis secondary to hypertriglyceridemia. Despite the increased incidence, mortality has decreased in the United States with most recent studies citing mortality of approximately 2%. The peak age of incidence of acute pancreatitis occurs in the fifth and sixth decades; however, mortality increases with age. Incidence has been thought to differ across geographic regions and socio-economic regions and is likely related to differences in use of alcohol and occurrence of biliary calculi, the two major causes of acute pancreatitis. In the United States, population incidence has been most recently cited as 600 to 700 per 100,000 people with 200,000 to 250,000 discharges occurring per year for acute pancreatitis. 
The pathophysiology of pancreatitis incorporates both the localized destruction in the pancreas and systemic inflammatory response. The inciting event is the premature activation of trypsinogen to trypsin within the acinar cell as opposed to in the duct lumen. It is postulated that this can be caused by elevated ductal pressures (such as in duct obstruction) as well as problems with calcium homeostasis and pH. Because calcium transport is an ATP driven process, particularly for sequestration in the smooth endoplasmic reticulum, it is suspected that many toxins responsible for pancreatitis (including alcohol) involve ATP depletion resulting in elevated intra-acinar calcium concentrations that stimulate early activation of trypsinogen to trypsin, which activates enzymes such as elastase and phospholipases. Early activation of these zymogens leads to localized tissue damage and release of Damage Associated Molecular Patterns (DAMPs). The release of DAMPs causes recruitment of neutrophils and initiation of the inflammatory cascade. This inflammatory cascade is responsible for the systemic manifestations of acute pancreatitis and can ultimately lead to increase capillary permeability and damage of endothelium with microvascular thrombosis that causes multiorgan dysfunction syndrome (MODS), the main cause of morbidity and mortality in acute pancreatitis.
More recently, it has become apparent that there is also a genetic predisposition for pancreatitis in some individuals. These patients often suffer from recurrent acute pancreatitis and a progression to chronic pancreatitis. Not surprisingly, associated genes are involved in the activation of trypsin. The cystic fibrosis transmembrane conductance regulator (CFTR) gene involved in bicarbonate secretion into pancreatic ductules, cationic trypsinogen gene (PRSS1) gain of function mutations, mutations in pancreatic secretory trypsin inhibitor (SPINK1), and trypsin degrading enzyme, chymotrypsin C (CTRC), all play a role in recurrent pancreatitis. Furthermore, they are involved in the increasingly acknowledged spectrum of disease from acute to chronic pancreatitis.
The patient will commonly describe moderate to severe abdominal pain located in the epigastrium with nausea and anorexia. The nature of the pain can vary, often depending on whether the etiology is a biliary obstruction or a metabolic/toxicologic cause. Biliary etiology is more often described as a sharper pain, which radiates through to the back with more of an acute onset; whereas, metabolic and toxicologic causes, such as alcohol, often have a more indolent onset with more dull and generalized pain. A thorough history regarding alcohol use and medications should be gathered, keeping in mind that over five years of heavy alcohol use is often needed to induce alcohol-related pancreatitis. Smoking history is also important as a risk factor for acute pancreatitis. Family history should be reviewed, particularly when more common etiologies appear less likely, as there are rare genetically related cases of familial pancreatitis. A physical exam is often significant for elevated temperature, tachycardia and in severe cases, hypotension. The abdominal exam will typically reveal epigastric tenderness with possible guarding and rigidity and decreased bowel sounds. In severe cases where retroperitoneal bleeding has occurred, Grey-Turners sign may be present, as ecchymosis at the flanks while Cullen's sign appears as periumbilical ecchymosis secondary to peritoneal hemorrhage.
The diagnosis of acute pancreatitis has been defined by the Revised Atlanta Classification and requires at least 2 of 3 criteria be met: 1) a lipase or amylase level that is three times the upper limit of normal 2) abdominal pain that is consistent with pancreatitis 3) abdominal imaging consistent with acute pancreatitis. Initial evaluation of suspected acute pancreatitis involves laboratory abnormalities are suggesting biliary cholestasis, hypercalcemia or severe hyperlipidemia will help in determining the etiology of pancreatitis. An abdominal ultrasound is recommended in all the patients to assess for choledocholithiasis and bile duct dilatation. A chest radiograph is also often obtained in moderate to severe cases to evaluate for pleural effusions, which is an indication of the higher severity of disease with elevated mortality. In cases where the diagnosis is equivocal, but pancreatitis is still suspected, computed tomography (CT) with intravenous contrast is obtained to establish or rule out the diagnosis. CT is also recommended in cases where the patient has failed to improve or to worsen despite appropriate fluid resuscitation over 48 hours to determine the presence of necrosis.
When no cause for pancreatitis is forthcoming with the evaluation mentioned above, consultation of a gastroenterology specialist is often required for further evaluation with magnetic resonance cholangiopancreatography (MRCP), or endoscopic ultrasound (EUS). As MRCP is non-invasive, there is no perioperative risk. MRCP is non-invasive, doesn’t require contrast but lacks sensitivity for detection of biliary stones less than 3 mm and chronic pancreatitis and EUS is preferred. Diagnostic ERCP is reserved for recurrent episodes of acute pancreatitis.
The foundation of management for acute pancreatitis remains early aggressive fluid resuscitation. Lactated Ringer's solution is the recommended fluid of with an initial bolus of 15 to 20 mL/kg and following rates of 3 mL/kg per hour (usually approximately 250 to 500 mL per hour) for the first 24 hours if no other contraindications are present. The fluid resuscitation is monitored with a combination of blood urea nitrogen, hematocrit, and urine output, monitoring every 4 to 6 hours in first 24 hours of resuscitation to adjust the fluid rate. Continued non-response indicates a high likelihood of ensuing MODS and is grounds for upgrading the level of care.
Another important issue is nutrition. Common practice is to keep nothing by mouth until abdominal pain, nausea, vomiting, appetite, and ileus improve. Early feeding in mild pancreatitis is safe and does not exacerbate symptoms. Soft, low residue, low-fat diet is recommended for initial feeding and advanced to regular consistency as tolerated. In cases of severe pancreatitis or where peroral intake is not tolerated, nesojejunal feeding is superior to parenteral nutrition as it helps to minimize bacterial translocation by maintaining the intestinal barrier.
Prophylactic antibiotics are not needed. If infection is suspected, empirical antibiotics are appropriate until cultures results are back. Indication for antibiotic is limited to presence of infected necrosis.
Further management depends upon the etiology of pancreatitis. In gallstone pancreatitis, early cholecystectomy is strongly recommended. Early ERCP (within 24 hours of presentation) is of benefit in cases of concurrent cholangitis and obvious biliary obstruction. In cases of mild or spontaneously resolving biliary pancreatitis, ERCP is reserved for distal biliary filling defect on intraoperative cholangiogram during cholecystectomy. In the setting of hypertriglyceridemia, the goal of specific treatment is to bring down and maintain triglyceride level to less than 500 mg/dL. The options to achieve this goal include apheresis and insulin drip with or without glucose.
Local complications of pancreatitis include early (less than 4 weeks, peripancreatic fluid collection and pancreatitic/peripancreatic necrosis) and late (more than 4 weeks, pancreatic pseudocyst and walled-off necrosis). Acute peripancreatic fluid collection resolves spontaneously in most cases, and less than 10% result in pancreatic pseudocyst. Most of these pseudocysts resolve with observation alone with periodic follow-up using CT or MRI. Drainage is only recommended in symptomatic, infected or rapidly enlarging pseudocysts. The drainage modalities include endoscopic (transmural or transpapillary) or percutaneous, the endoscopic approach being the preferred modality.
Necrotic collection management remains challenging. The sterile collection is intervened if it caused symptoms such as persistent abdominal pain, nausea, vomiting, gastric outlet obstruction, bowel obstruction and disrupted pancreatic duct. One-third of this necrosis become infected. Infection results in clinical deterioration, lengthen the recovery, has high mortality. Antibiotics are initiated on earliest suspicion. The preferred antibiotic regimen includes a carbapenem alone, or combination of a quinolone, ceftazidime, or cefepime with metronidazole. Diagnosis of infected necrosis is established in the presence of gas bubbles in it on imaging and CT-guided percutaneous aspiration culture. Surgical necrosectomy is needed in patients continue to deteriorate clinically despite antibiotics. In stable patients, antibiotics are continued for 4 to 6 weeks and necrosectomy performed after the wall matures. The initial approach includes less invasive modalities which include endoscopic and percutaneous drainage and surgical debridement is reserved in unsuccessful cases.
The differentials for acute pancreatitis include the overall differential for abdominal pain and can often be greatly narrowed with a good history and physical as described above. Differential diagnoses include but is not limited to the following:
In many of these cases, an elevated lipase level 3 times the upper limit of normal will allow for determination of pancreatitis as the source of abdominal pain due to its high specificity. Abdominal ultrasound will help to differentiate cholecystitis whereas CT angiogram can be used when mesenteric ischemia is high on the differential. In high-risk patients, the cardiac source should be concurrently ruled out as pain can present atypically as epigastric. Progressing aortic dissection should be considered due to its particularly urgent nature, though the pain is often more severe and tearing than for those with acute pancreatitis.
Overall mortality of acute pancreatitis is approximately 1% to 2%; however, severe acute pancreatitis carries a much higher but undetermined mortality rate.
Severity assessment and prognostication is important to determine the level of care. Multiple clinical prediction scales have been developed and validated. Most are cumbersome to calculate and need 48-hour data. The Bedside Index for Severity in Acute Pancreatitis (BISAP) is a relatively recent addition to this list. This index has good predictive performance for both severe acute pancreatitis and mortality and has been validated prospectively, is simple and easy to calculate from initial presentation data. Use of the CT Severity Index (CTSI) can also aid in predicting mortality with the detection of any necrosis on CT imaging being a predictor of high mortality.
Critical care specialist
Acute pancreatitis is a serious disorder and the most effective way to manage the disorder is with a team of healthcare professionals that includes a surgeon, radiologist, endocrinologist, pulmonologist, intensivist, gastroenterologist, pharmacist, nurse, and addiction specialist. The three major causes of acute pancreatitis are gallstones, alcohol, and medications. The emphasis today is on prevention. The nurse and pharmacist are in the prime position to educate the patient on lowering their risks of acute pancreatitis by abstaining from alcohol, losing weight, eating a low-fat diet and lowering their lipid profile. In addition, the pharmacist can re-evaluate all the medications and recommend discontinuation of those associated with pancreatitis. (Level V)
Acute pancreatitis is a serious disorder which still carries a mortality of 5-15%, depending on the cause, patient age and comorbidity. In general patients with gallstone pancreatitis tend to have higher mortality than patients with alcoholic pancreatitis. In addition, the presence of type 2 diabetes significantly increases the risk of complications and death. In patients with multiorgan involvement, the mortality can be as high as 20%. Most deaths are due to multiorgan failure and hypotensive shock. Various classifications have been developed to assess the prognosis of patients with acute pancreatitis, but most are cumbersome for practical use. (Level V)
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