Acute Pancreatitis: Pathophysiology and Treatment PDF

58 58 Acute Pancreatitis Santhi Swaroop Vege CHAPTER OUTLINE INCIDENCE AND BURDEN OF DISEASE.............. 893 Chest Radiography...............................

58 58 Acute Pancreatitis Santhi Swaroop Vege CHAPTER OUTLINE INCIDENCE AND BURDEN OF DISEASE.............. 893 Chest Radiography............................ 907 DEFINITIONS.................................. 894 Abdominal US................................ 907 EUS and ERCP................................ 908 COURSE OF THE DISEASE........................ 895 CT......................................... 908 PATHOGENESIS AND PATHOPHYSIOLOGY............ 896 MRI........................................ 908 PREDISPOSING CONDITIONS...................... 897 DISTINGUISHING ALCOHOLIC FROM GALLSTONE Obstruction.................................. 898 PANCREATITIS................................. 908 Ethyl Alcohol and Other Toxins.................... 899 PREDICTORS OF DISEASE SEVERITY................ 909 Drugs...................................... 899 Scoring Systems.............................. 910 Metabolic Disorders........................... 900 CT......................................... 910 Infections................................... 901 Chest Radiography............................ 910 Vascular Disease.............................. 901 Trauma..................................... 901 TREATMENT................................... 910 Post-ERCP................................... 902 Initial Management During the First Week........... 910 Postoperative State............................ 903 Intravenous Fluid and Electrolyte Resuscitation....... 912 Hereditary and Genetic Disorders................. 903 Respiratory Care.............................. 912 Miscellaneous Causes.......................... 903 Cardiovascular Care........................... 912 Controversial Causes........................... 904 Metabolic Complications........................ 912 Antibiotics................................... 912 CLINICAL FEATURES............................ 904 Urgent ERCP................................. 913 History..................................... 904 Nutrition.................................... 913 Physical Examination........................... 905 Other Non-Interventional Treatments............... 914 DIFFERENTIAL DIAGNOSIS....................... 906 Interventional Treatments....................... 914 LABORATORY DIAGNOSIS........................ 906 Other Complications........................... 915 Pancreatic Enzymes........................... 906 Long-Term Sequelae of Acute Pancreatitis........... 916 Standard Blood Tests........................... 907 Abdominal Compartment Syndrome............... 916 DIAGNOSTIC IMAGING........................... 907 Miscellaneous Complications.................... 916 Abdominal Plain Film........................... 907 INCIDENCE AND BURDEN OF DISEASE of incidence are inaccurate because the diagnosis of mild disease The human and financial burden of acute pancreatitis (AP) con- may be missed and death may occur before diagnosis in 10% of tinues to grow, and it is now one of the most common reason for patients with severe disease.6 Conversely, many patients with hospitalization with a GI condition.1 Many studies demonstrate a abdominal pain from other sources who present with a slight ele- variable yet consistent increasing worldwide incidence, generally vation in the serum amylase and/or lipase are falsely diagnosed in the range of 20 to 40 per 100,000 population.2 Studies from as having AP. Europe suggest an increase overall, with differences in underlying The rising incidence of AP has likewise been associated with etiology based upon the region studied. For example, gallstones increasing costs.7 In 2014 the United States, AP was one of the are the dominant etiology in Southern Europe and alcohol in top 3 leading hospital discharge diagnoses, along with GI bleed- Eastern Europe, with intermediate gallstone-to-alcohol ratios in ing and gallstone disease. There were 279,145 annual admissions, Northern and Western Europe.2 Studies from EDs likewise have with a 30-day readmission rate of 14.3% and 0.7% mortality. The shown a rise in visits for AP, with a 12% rise in a 6-year period in health care cost was 2.6 billion dollars. In the same year, there one study; a 15% increase in hospital admissions; and that AP was were 2834 deaths directly related to AP and 5392 deaths contrib- the 12th most common GI condition seen in the ED in 2012.3 uted to by AP in the USA, making it the 14th most common cause This continued escalation in ED visits and associated costs appear of death due to GI diseases. Although the length of hospital stay to be driven by younger patients with alcohol-associated and and mortality have decreased from 1997 to 2012 in the USA, the acute on chronic pancreatitis. Based on population-based cohort mean hospital costs have increased by 120% to nearly $34,000.8 studies, globally, AP is the most common pancreatic disease, The overall mortality rate from AP has substantially dropped whereas pancreatic cancer is the most lethal.4 A large increase from >10% several years ago to less than 2% in recent years.1,7,9 in pediatric cases also accounts for the rising increase in the inci- The following sections are written with the main focus on clinical dence of AP.5 This increase is presumably—as in adults—due to management based on recent evidence-based literature and are the rise in obesity-associated cholelithiasis. However, estimates not meant to be an encyclopedic description of the topic. 893 894 PART VII Pancreas BOX 58.1 2012 Atlanta Classification Revision of Acute Pancreatitis12 MILD ACUTE PANCREATITIS No organ failure No local or systemic complications MODERATELY SEVERE ACUTE PANCREATITIS Transient organ failure (48 hr)___single organ or multiorgan    *Local complications are peripancreatic fluid collections, pancreatic necrosis and peripancreatic necrosis (sterile or infected), pseudocyst, and walled- off necrosis (sterile or infected). DEFINITIONS The 1992 Atlanta Symposium10 served physicians involved in car- ing for patients with AP well for nearly 2 decades, but subsequent advancements about various aspects of the disease necessitated the recent consensus revision.11 Whereas AP is best defined physiologi- cally as an acute inflammatory process of the pancreas with variable Fig. 58.1 CT showing acute interstitial pancreatitis with diffuse swelling involvement of other regional tissues or remote organ systems, AP of the pancreas (P) and peripancreatic inflammatory changes (arrows). is now defined by a patient meeting 2 of the following 3 criteria11: The pancreas was well perfused without evidence of necrosis. (1) symptoms (e.g., acute onset epigastric and/or left upper quad- G, gallbladder. rant pain, often radiating to the back) consistent with pancreatitis, (2) a serum amylase or lipase level greater than 3 times the upper limit of the laboratory’s reference range, and (3) radiologic imaging consistent with pancreatitis, usually using CT or MRI. Pancreatitis is classified as acute unless there are findings on CT, MRI, EUS, or ERCP suggestive of chronic pancreatitis. If such findings are present, pancreatitis is classified as chronic pan- creatitis, and any further episode of AP is considered an exacer- bation of chronic pancreatitis (see Chapter 59). Patients, though, G can present with an attack of acute on chronic pancreatitis, using all 3 criteria as well. Once the diagnosis of AP is established, patients are then clas- sified based on disease severity. The Atlanta Criteria revision of 201211 (Box 58.1) classified severity as mild, moderately severe, or severe. Mild AP, the most common form, has no associated organ failure, no local or systemic complications, and usually resolves in the first week. Moderately severe AP12 is defined by the presence of transient organ failure (lasting 48 hours). Local complications include acute peripancreatic fluid col- lections, acute necrotic collections (pancreatic and peripancreatic necrosis, sterile or infected), pseudocyst, and walled-off necrosis Fig. 58.2 CT showing acute pancreatic necrosis with focal areas of (WON; sterile or infected; Figs. 58.1 and 58.2). Other acceptable decreased perfusion in the pancreatic parenchyma (arrows) and sur- markers of severe pancreatitis include 3 or more of Ranson’s 11 rounding peripancreatic inflammation. The necrosis was estimated to criteria for nongallstone pancreatitis13 and an Acute Physiology involve less than 30% of the pancreas. G, gallbladder. and Chronic Health Evaluation (APACHE-II) score above 8.14 Even in the original Atlanta classification,10 certain confusing terms like phlegmon (which means different things to different a mild course. Necrotizing pancreatitis according to the revised specialists) and hemorrhagic pancreatitis were omitted. The term Atlanta classification includes both pancreatic and/or peripan- hemorrhagic pancreatitis is not a synonym for necrotizing pancre- creatic necrosis. Approximately 45% of all cases of necrotizing atitis. When occurring early in the course, bleeding may be due pancreatitis involve both pancreatic and peripancreatic tissues, to venous bleeding from the severe inflammatory process. Later with another 45% of cases being isolated peripancreatic necrosis. and when severe, hemorrhage is more commonly associated with Pure pancreatic necrosis is seen only in about 5% of the cases.15 pseudoaneurysm formation leading to hemorrhagic collections Pancreatic necrosis is diagnosed on CT scan when ≥30% of the or hemoperitoneum. Interstitial pancreatitis accounts for nearly pancreatic parenchyma is low-attenuating or nonenhancing. 75% to 80% of the cases and, on contrast-enhanced CT scan in Acute peripancreatic fluid collections are seen as low attenua- such patients, the pancreas is perfused well, without any non- tion areas around the pancreas. If these collections cross the fas- perfused, low attenuation areas. The terms mild and interstitial cial planes like Gerota fascia, then one should consider them as pancreatitis are used interchangeably, as both are associated with acute peripancreatic necrotic collections rather than simple fluid  CHAPTER 58 Acute Pancreatitis 895 collections. Approximately 30% to 50% of cases of AP, mainly BOX 58.2 Factors Associated With Severe Acute 58 the interstitial type, have peripancreatic fluid collections, which typically resolve. After a period of approximately 4 weeks, if the Pancreatitis acute peripancreatic fluid collections persist and develop a wall, then they are called a “pseudocyst.” Because most of these col- PATIENT CHARACTERISTICS lections resolve, true pseudocysts are uncommon, although most Age >55 yr11,13,210,327 of the persistent fluid collections are loosely described as “pseu- Obesity (BMI >30 kg/m2)313 docyst.” Pseudocysts are located adjacent to or off the body of Altered mental status223,224 the pancreas. At times, these enzyme-rich fluid-filled sacs can Comorbid disease11 be found distantly in the pelvis or chest. When a pseudocyst is Systemic inflammatory response syndrome (SIRS)11,20,217,223,224 located within the body of the pancreas, the cyst may contain Two or more of the following (SIRS criteria) necrotic pancreatic debris on MRI and EUS, even when the Pulse >90/min pseudocyst is fluid appearing with low attenuation on CT. Such Respirations >20/min or PaCO2 38°C or 12,000 or 10% band forms a wall after 4 weeks and are then referred to as WON. The term LABORATORY FINDINGS pancreatic abscess, defined in the original Atlanta classification, was BUN >20 mg/dL or rising BUN level225 omitted because this is usually the end result of infected necrosis Elevated serum creatinine level314 and is also rare. Similarly the term infected pseudocyst is also dis- Hematocrit >44% or rising hematocrit231 couraged as spontaneous infection without intervention is rare. Of all these terms, the most important distinction is that IMAGING FINDINGS between pancreatic necrosis and pseudocyst. WON is pancreatic Pleural effusion(s)195 necrosis that has liquefied after 5 to 6 weeks.16 Similar to a pseudo- Pulmonary infiltrate(s)11 cyst, a wall develops. However, whereas a pseudocyst always con- Multiple or extensive extrapancreatic fluid collections203 tains fluid, pancreatic necrosis, even if walled off early, contains a significant amount of debris that only becomes liquefied after 5 to BUN, Blood urea nitrogen level. 6 weeks. Draining WON too early (before 4 weeks) is discouraged because the debris is typically thick, often with the consistency of rubber, early in the course of the disease. After 4 weeks, WON can be treated similarly to a pseudocyst and drained surgically, endo- cytokine-mediated SIRS; if organ failure is persistent, then AP scopically, or percutaneously (see Chapter 61). is considered severe. The first phase of AP usually lasts 1 week. During this phase, the disease severity is directly related to extrapancreatic organ COURSE OF THE DISEASE failure from the patient’s SIRS elicited by acinar cell injury. Mul- AP appears to have 2 distinct phases. The first phase usually lasts tiple cytokines are involved, including platelet activating factor a week and is characterized by systemic symptoms that may result (PAF), TNF-α, nuclear factor κB (NF-κB), and numerous inter- in organ failure. The pancreatic inflammation may lead to the leukins (ILs; see Chapter 2). During this first week, the initial systemic inflammatory response syndrome (SIRS). Infectious state of inflammation evolves dynamically, with variable degrees complications are uncommon in this phase.17 Fever, tachycardia, of pancreatic and peripancreatic ischemia or edema toward either hypotension, respiratory distress, and leukocytosis are typically resolution, irreversible necrosis and liquefaction, or the develop- related to SIRS (Box 58.2). Failure of the respiratory, circulatory ment of fluid collections in and around the pancreas. The extent and renal systems are usually associated with persistent SIRS. GI of the pancreatic and peripancreatic changes is usually propor- bleeding, liver failure, and coagulation disturbances have been tional to the severity of extrapancreatic organ failure. However, included in some older studies, but the revised Atlanta classifica- organ failure may develop independent of pancreatic necrosis.16 tion11 removed them because they are rare and data regarding Conversely, patients with pancreatic necrosis may have no evi- these complications is sparse. Most organ failure observed in the dence of organ failure. The development of organ failure appears first week is also present on day 1, and at that time, one should to correlate with the persistence of the systemic inflammatory consider (and treat) the patient as having severe AP. If the organ response cascade (discussed later). failure persists beyond 48 hours, severe AP is confirmed. If organ Approximately 75% to 80%, of patients with AP have a reso- failure resolves within 48 hours and local complications evolve, lution of the disease process (interstitial pancreatitis) and do not the case would be classified as moderately severe AP. If no local enter a second phase. However, in ∼20% of patients, a more pro- complications are seen, the revised Atlanta classification still clas- tracted course develops, typically related to the necrotizing pro- sifies the patient as moderately severe pancreatitis; however, the cess (necrotizing pancreatitis) lasting weeks to months. Mortality original description of moderately severe AP described patients in this second phase is related to a combination of factors, includ- with local complications but without organ failure.12 Future clas- ing organ failure secondary to sterile necrosis, infected necrosis, sifications may address patients with simple fluid collections, local complications from the severe necrotic process, or compli- transient organ failure alone and exacerbation of preexisting cations from surgical/minimally invasive intervention.18-20 medical comorbidities differently than as moderately severe AP. There are 2 time peaks for mortality in AP. Most studies in the The second phase usually starts after 7 days and is mainly USA and Europe reveal that about half the deaths occur within characterized by the local complications and ensuing infec- the first week or 2, usually from multiorgan failure.18-20 Death tion of such local complications. The organ failure seen in the can be very rapid. For example, in Scotland about one quarter of first phase may continue and contribute to late morbidity and all deaths occurred within 24 hours of admission, and one third mortality, usually with infected necrosis. Hence, by definition, within 48 hours.20 After the second week of illness, patients suc- mild AP is not associated with the second phase, except rare cumb to pancreatic infection associated with multiorgan failure. patients who continue to have pain without any organ failure Some studies in Europe report a very high late mortality rate or local complications. Organ failure occurs in ∼5% of intersti- from infection.21 It is unclear if this is related to endogenous tial pancreatitis (often synonymous with mild severity) due to infection of the pancreatic necrosis or to surgical interventions