| Acute pancreatitis | |
| Synonyms: | Acute pancreatic necrosis[1] |
| Field: | Gastroenterology, general surgery |
Acute pancreatitis (AP) is a sudden inflammation of the pancreas. Causes, in order of frequency, include: a gallstone impacted in the common bile duct beyond the point where the pancreatic duct joins it; heavy alcohol use; systemic disease; trauma; and, in children, mumps. Acute pancreatitis may be a single event; it may be recurrent; or it may progress to chronic pancreatitis and/or pancreatic failure (the term pancreatic dysfunction includes cases of acute or chronic pancreatitis where the pancreas is measurably damaged, even if it has not failed).
Mild cases are usually successfully treated with conservative measures: hospitalization, pain control, nothing by mouth, intravenous (IV) nutritional support, and intravenous fluid rehydration. Severe cases often require admission to an intensive care unit to monitor and manage complications of the disease. Complications are associated with a high mortality, even with optimal management. For people with this condition, the pancreas will begin to secrete active enzymes such as trypsin, chymotrypsin and carboxypeptidase, instead of their inactive forms. Damage to the pancreatic ducts can occur as a result of this. Damage to the liver, gallbladder, and spleen can result in severe cases of pancreatitis.
Although these are common symptoms, frequently they are not all present; and epigastric pain may be the only symptom.[3]
The following are associated with severe disease:
Locoregional complications include pancreatic pseudocyst (most common, occurring in up to 25% of all cases, typically after 4–6 weeks) and phlegmon/abscess formation, splenic artery pseudoaneurysms, hemorrhage from erosions into splenic artery and vein, thrombosis of the splenic vein, superior mesenteric vein and portal veins (in descending order of frequency), duodenal obstruction, common bile duct obstruction, progression to chronic pancreatitis, pancreatic ascites, pleural effusion, sterile/infected pancreatic necrosis.[5]
Systemic complications include acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome, disseminated intravascular coagulation (DIC), hypocalcemia (from fat saponification), hyperglycemia and insulin dependent diabetes mellitus (from pancreatic insulin-producing beta cell damage), malabsorption due to exocrine failure
Acute pancreatitis occurs when there is abnormal activation of digestive enzymes within the pancreas. This occurs through inappropriate activation of inactive enzyme precursors called zymogens (or proenzymes) inside the pancreas, most notably trypsinogen. Normally, trypsinogen is converted to its active form (trypsin) in the first part of the small intestine (duodenum), where the enzyme assists in the digestion of proteins. During an episode of acute pancreatitis, trypsinogen comes into contact with lysosomal enzymes (specifically cathepsin), which activate trypsinogen to trypsin. The active form trypsin then leads to further activation of other molecules of trypsinogen. The activation of these digestive enzymes lead to inflammation, edema, vascular injury, and even cellular death. The death of pancreatic cells occurs via two main mechanisms: apoptosis, which is physiologically controlled, and necrosis, which is less organized and more damaging. The balance between these two mechanisms of cellular death is mediated by caspases which regulate apoptosis and have important anti-necrosis functions during pancreatitis: preventing trypsinogen activation, preventing ATP depletion through inhibiting polyADP-ribose polymerase, and by inhibiting the inhibitors of apoptosis (IAPs). If, however, the caspases are depleted due to either chronic ethanol exposure or through a severe insult then necrosis can predominate.
The two types of acute pancreatitis are mild and severe, which are defined based on whether the predominant response to cell injury is inflammation (mild) or necrosis (severe). In mild pancreatitis, there is inflammation and edema of the pancreas. In severe pancreatitis, there is necrosis of the pancreas, and nearby organs may become injured.
As part of the initial injury there is an extensive inflammatory response due to pancreatic cells synthesizing and secreting inflammatory mediators: primarily TNF-alpha and IL-1. A hallmark of acute pancreatitis is a manifestation of the inflammatory response, namely the recruitment of neutrophils to the pancreas. The inflammatory response leads to the secondary manifestations of pancreatitis: hypovolemia from capillary permeability, acute respiratory distress syndrome, disseminated intravascular coagulations, renal failure, cardiovascular failure, and gastrointestinal hemorrhage.
The acute pancreatitis (acute hemorrhagic pancreatic necrosis) is characterized by acute inflammation and necrosis of pancreas parenchyma, focal enzymic necrosis of pancreatic fat and vessel necrosis (hemorrhage). These are produced by intrapancreatic activation of pancreatic enzymes. Lipase activation produces the necrosis of fat tissue in pancreatic interstitium and peripancreatic spaces as well as vessel damage. Necrotic fat cells appear as shadows, contours of cells, lacking the nucleus, pink, finely granular cytoplasm. It is possible to find calcium precipitates . Digestion of vascular walls results in thrombosis and hemorrhage. Inflammatory infiltrate is rich in neutrophils. Due to the pancreas lacking a capsule, the inflammation and necrosis can extend to include fascial layers in the immediate vicinity of the pancreas.
Acute pancreatitis is diagnosed using clinical history and physical examination, based on the presence of at least 2 of 3 criteria: abdominal pain, elevated serum lipase or amylase, and abdominal imaging findings consistent with acute pancreatitis.[11] Additional blood studies are used to identify organ failure, offer prognostic information, and determine if fluid resuscitation is adequate and whether endoscopic retrograde cholangiopancreatography is necessary.
The differential diagnosis includes:[12]
Regarding selection on these tests, two practice guidelines state:
"It is usually not necessary to measure both serum amylase and lipase. Serum lipase may be preferable because it remains normal in some nonpancreatic conditions that increase serum amylase including macroamylasemia, parotitis, and some carcinomas. In general, serum lipase is thought to be more sensitive and specific than serum amylase in the diagnosis of acute pancreatitis"[14]
"Although amylase is widely available and provides acceptable accuracy of diagnosis, where lipase is available it is preferred for the diagnosis of acute pancreatitis (recommendation grade A)"[15]
Most, but not all individual studies support the superiority of the lipase.[16] In one large study, there were no patients with pancreatitis who had an elevated amylase with a normal lipase.[17] Another study found that the amylase could add diagnostic value to the lipase, but only if the results of the two tests were combined with a discriminant function equation.[18]
While often quoted lipase levels of 3 or more times the upper-limit of normal is diagnostic of pancreatitis, there are also other differential diagnosis to be considered relating to this rise.[19]
Regarding the need for computed tomography, practice guidelines state:
CT is an important common initial assessment tool for acute pancreatitis. Imaging is indicated during the initial presentation if:
CT is recommended as a delayed assessment tool in the following situations:
Abdominal CT should not be performed before the first 12 hours of onset of symptoms as early CT (<12 hours) may result in equivocal or normal findings.
CT findings can be classified into the following categories for easy recall:
The principal value of CT imaging to the treating clinician is the capacity to identify devitalised areas of the pancreas which have become necrotic due to ischaemia. Pancreatic necrosis can be reliably identified by intravenous contrast-enhanced CT imaging,[20] and is of value if infection occurs and surgical or percutaneous debridement is indicated.
While computed tomography is considered the gold standard in diagnostic imaging for acute pancreatitis,[21] magnetic resonance imaging (MRI) has become increasingly valuable as a tool for the visualization of the pancreas, particularly of pancreatic fluid collections and necrotized debris.[22] Additional utility of MRI includes its indication for imaging of patients with an allergy to CT's contrast material, and an overall greater sensitivity to hemorrhage, vascular complications, pseudoaneurysms, and venous thrombosis.[23]
Another advantage of MRI is its utilization of magnetic resonance cholangiopancreatography (MRCP) sequences. MRCP provides useful information regarding the etiology of acute pancreatitis, i.e., the presence of tiny biliary stones (choledocholithiasis or cholelithiasis) and duct anomalies. Clinical trials indicate that MRCP can be as effective a diagnostic tool for acute pancreatitis with biliary etiology as endoscopic retrograde cholangiopancreatography, but with the benefits of being less invasive and causing fewer complications.[24] [25]
On abdominal ultrasonography, the finding of a hypoechoic and bulky pancreas is regarded as diagnostic of acute pancreatitis.
Initial management of a patient with acute pancreatitis consists of supportive care with fluid resuscitation, pain control, nothing by mouth, and nutritional support.
Currently, following the findings of the WATERFALL clinical trial[26], moderate hydration at a rate of 1.5 ml/kg per hour of isotonic crystalloid solution (e.g. normal saline or lactated Ringer's solution), preceded by one or more boluses of 10 mL/kg in case of hypovolaemia, is recommended in acute pancreatitis [27] .
Fluid requirements should be reassessed at frequent intervals in the first six hours of admission and for the next 24 to 48 hours. The rate of fluid resuscitation should be adjusted based on clinical assessment, hematocrit and blood urea nitrogen (BUN) values.
In the initial stages (within the first 12 to 24 hours) of acute pancreatitis, fluid replacement has been associated with a reduction in morbidity and mortality.[28] [29] [30] [31]
Abdominal pain is often the predominant symptom in patients with acute pancreatitis and should be treated with analgesics.
Opioids are safe and effective at providing pain control in patients with acute pancreatitis.[32] Adequate pain control requires the use of intravenous opiates, usually in the form of a patient-controlled analgesia pump. Hydromorphone or fentanyl (intravenous) may be used for pain relief in acute pancreatitis. Fentanyl is being increasingly used due to its better safety profile, especially in renal impairment. As with other opiates, fentanyl can depress respiratory function. It can be given both as a bolus as well as constant infusion.Meperidine has been historically favored over morphine because of the belief that morphine caused an increase in sphincter of Oddi pressure. However, no clinical studies suggest that morphine can aggravate or cause pancreatitis or cholecystitis.[33] In addition, meperidine has a short half-life and repeated doses can lead to accumulation of the metabolite normeperidine, which causes neuromuscular side effects and, rarely, seizures.
In the management of acute pancreatitis, the treatment is to stop feeding the patient, giving them nothing by mouth, giving intravenous fluids to prevent dehydration, and sufficient pain control. As the pancreas is stimulated to secrete enzymes by the presence of food in the stomach, having no food pass through the system allows the pancreas to rest. Approximately 20% of patients have a relapse of pain during acute pancreatitis.[34] Approximately 75% of relapses occur within 48 hours of oral refeeding.
The incidence of relapse after oral refeeding may be reduced by post-pyloric enteral rather than parenteral feeding prior to oral refeeding. IMRIE scoring is also useful.
Recently, there has been a shift in the management paradigm from total parenteral nutrition (TPN) to early, post-pyloric enteral feeding (in which a feeding tube is endoscopically or radiographically introduced to the third portion of the duodenum). The advantage of enteral feeding is that it is more physiological, prevents gut mucosal atrophy, and is free from the side effects of TPN (such as fungemia). The additional advantages of post-pyloric feeding are the inverse relationship of pancreatic exocrine secretions and distance of nutrient delivery from the pylorus, as well as reduced risk of aspiration.
Disadvantages of a naso-enteric feeding tube include increased risk of sinusitis (especially if the tube remains in place greater than two weeks) and a still-present risk of accidentally intubating the trachea even in intubated patients (contrary to popular belief, the endotracheal tube cuff alone is not always sufficient to prevent NG tube entry into the trachea).
Oxygen may be provided in some patients (about 30%) if Pao2 levels fall below 70mm of Hg.
Up to 20 percent of people with acute pancreatitis develop an infection outside the pancreas such as bloodstream infections, pneumonia, or urinary tract infections.[35] These infections are associated with an increase in mortality.[36] When an infection is suspected, antibiotics should be started while the source of the infection is being determined. However, if cultures are negative and no source of infection is identified, antibiotics should be discontinued.
Preventative antibiotics are not recommended in people with acute pancreatitis, regardless of the type (interstitial or necrotizing) or disease severity (mild, moderately severe, or severe)[11] [37]
In 30% of those with acute pancreatitis, no cause is identified. Endoscopic retrograde cholangiopancreatography (ERCP) with empirical biliary sphincterotomy has an equal chance of causing complications and treating the underlying cause, therefore, is not recommended for treating acute pancreatitis.[38] If a gallstone is detected, ERCP, performed within 24 to 72 hours of presentation with successful removal of the stone, is known to reduce morbidity and mortality.[39] The indications for early ERCP are:
The risks of ERCP are that it may worsen pancreatitis, it may introduce an infection to otherwise sterile pancreatitis, and bleeding.
Surgery is indicated for (i) infected pancreatic necrosis and (ii) diagnostic uncertainty and (iii) complications. The most common cause of death in acute pancreatitis is secondary infection. Infection is diagnosed based on 2 criteria
Surgical options for infected necrosis include:
Acute pancreatitis patients recover in majority of cases. Some may develop abscess, pseudocyst or duodenal obstruction. In 5 percent cases, it may result in acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation DIC. Acute pancreatitis can be further divided into mild and severe pancreatitis.
Mostly the Ranson Criteria are used to determine severity of acute pancreatitis. In severe pancreatitis serious amounts of necrosis determine the further clinical outcome. About 20% of the acute pancreatitis are severe with a mortality of about 20%. This is an important classification as severe pancreatitis will need intensive care therapy whereas mild pancreatitis can be treated on the common ward.
Necrosis will be followed by a systemic inflammatory response syndrome (SIRS) and will determine the immediate clinical course. The further clinical course is then determined by bacterial infection. SIRS is the cause of bacterial (Gram negative) translocation from the patients colon.
There are several ways to help distinguish between these two forms. One is the above-mentioned Ranson Score.
In predicting the prognosis, there are several scoring indices that have been used as predictors of survival. Two such scoring systems are the Ranson criteria and APACHE II (Acute Physiology and Chronic Health Evaluation) indices. Most,[42] [43] but not all[44] studies report that the Apache score may be more accurate. In the negative study of the APACHE-II, the APACHE-II 24-hour score was used rather than the 48-hour score. In addition, all patients in the study received an ultrasound twice which may have influenced allocation of co-interventions. Regardless, only the APACHE-II can be fully calculated upon admission. As the APACHE-II is more cumbersome to calculate, presumably patients whose only laboratory abnormality is an elevated lipase or amylase do not need assessment with the APACHE-II; however, this approach is not studied. The APACHE-II score can be calculated at www.sfar.org.
Practice guidelines state:
2006: "The two tests that are most helpful at admission in distinguishing mild from severe acute pancreatitis are APACHE-II score and serum hematocrit. It is recommended that APACHE-II scores be generated during the first 3 days of hospitalization and thereafter as needed to help in this distinction. It is also recommended that serum hematocrit be obtained at admission, 12 h after admission, and 24 h after admission to help gauge adequacy of fluid resuscitation."
2005: "Immediate assessment should include clinical evaluation, particularly of any cardiovascular, respiratory, and renal compromise, body mass index, chest x ray, and APACHE II score"[15]
See main article: Ranson criteria. The Ranson score is used to predict the severity of acute pancreatitis. They were introduced in 1974.
The criteria for point assignment is that a certain breakpoint be met at any time during that 48 hour period, so that in some situations it can be calculated shortly after admission. It is applicable to both gallstone and alcoholic pancreatitis.
Alternatively, pancreatitis can be diagnosed by meeting any of the following:[2]
Ranson's score of ≥ 8Organ failureSubstantial pancreatic necrosis (at least 30% glandular necrosis according to contrast-enhanced CT)
InterpretationIf the score ≥ 3, severe pancreatitis likely.If the score < 3, severe pancreatitis is unlikelyOr
Score 0 to 2 : 2% mortalityScore 3 to 4 : 15% mortalityScore 5 to 6 : 40% mortalityScore 7 to 8 : 100% mortality
See main article: APACHE II. "Acute Physiology And Chronic Health Evaluation" (APACHE II) score > 8 points predicts 11% to 18% mortality
Developed in the early 1990s by Emil J. Balthazar et al.,[45] the Computed Tomography Severity Index (CTSI) is a grading system used to determine the severity of acute pancreatitis. The numerical CTSI has a maximum of ten points, and is the sum of the Balthazar grade points and pancreatic necrosis grade points:
Balthazar grade
| Balthazar grade | Appearance on CT | CT grade points | |
|---|---|---|---|
| Grade A | Normal CT | 0 points | |
| Grade B | Focal or diffuse enlargement of the pancreas | 1 point | |
| Grade C | Pancreatic gland abnormalities and peripancreatic inflammation | 2 points | |
| Grade D | Fluid collection in a single location | 3 points | |
| Grade E | Two or more fluid collections and / or gas bubbles in or adjacent to pancreas | 4 points |
Necrosis score
| Necrosis percentage | Points | |
|---|---|---|
| No necrosis | 0 points | |
| 0 to 30% necrosis | 2 points | |
| 30 to 50% necrosis | 4 points | |
| Over 50% necrosis | 6 points |
CTSI's staging of acute pancreatitis severity has been shown by a number of studies to provide more accurate assessment than APACHE II, Ranson, and C-reactive protein (CRP) level.[46] [47] [48] However, a few studies indicate that CTSI is not significantly associated with the prognosis of hospitalization in patients with pancreatic necrosis, nor is it an accurate predictor of AP severity.[49] [50]
The Glasgow score is valid for both gallstone and alcohol induced pancreatitis, whereas the Ranson score is only for alcohol induced pancreatitis. If a patient scores 3 or more it indicates severe pancreatitis and the patient should be considered for transfer to ITU. It is scored through the mnemonic, PANCREAS:
Predicts mortality risk in pancreatitis with fewer variables than Ranson's criteria. Data should be taken from the first 24 hours of the patient's evaluation.
Patients with a score of zero had a mortality of less than one percent, whereas patients with a score of five had a mortality rate of 22 percent. In the validation cohort, the BISAP score had similar test performance characteristics for predicting mortality as the APACHE II score.[51] As is a problem with many of the other scoring systems, the BISAP has not been validated for predicting outcomes such as length of hospital stay, need for ICU care, or need for intervention.
In the United States, the annual incidence is 18 cases of acute pancreatitis per 100,000 population, and it accounts for 220,000 hospitalizations in the US.[52] In a European cross-sectional study, incidence of acute pancreatitis increased from 12.4 to 15.9 per 100,000 annually from 1985 to 1995; however, mortality remained stable as a result of better outcomes.[53] Another study showed a lower incidence of 9.8 per 100,000 but a similar worsening trend (increasing from 4.9 in 1963–74) over time.[54]
In Western countries, the most common cause is alcohol, accounting for 65 percent of acute pancreatitis cases in the US, 20 percent of cases in Sweden, and 5 percent of those in the United Kingdom. In Eastern countries, gallstones are the most common cause of acute pancreatitis. The causes of acute pancreatitis also varies across age groups, with trauma and systemic disease (such as infection) being more common in children. Mumps is a more common cause in adolescents and young adults than in other age groups.
Without support for the superiority of the lipase: