急性胰腺炎的临床处理（美国胃肠病学20135）分析课件

华西医院中西医结合科 Clinical Management of Patients With Acute Pancreatitis GASTROENTEROLOGY MAY 2013;144:12721281 Company Logo 1Center for Pancreatic Care, Southern California Permanente Medical Group, Department of Gastroenterology, Kaiser Permanente Los Angeles Medical Center, Los Angeles, California （南加州,凯 萨医疗机构） ; and 2 Center for Pancreatic Disease, Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Womens Hospital, Harvard Medical School, Boston, Massachusetts（波士顿， 哈佛医学院) Keywords: Clinical Management; Fluid Resuscitation; Necrosis; Quality Improvement. Company Logo Abstract Acute pancreatitis is the leading cause of hospitalization for gastrointestinal disorders in the US, with more than 280,000 hospitalizations each year. The average length of stay at US hospitals in 2010 was estimated to be 5 days, at an aggregate cost of $2.9billion. 高发病率；平均住院时间：5天；治疗费用高昂 Mortality ranges from 3% for patients with interstitial (edematous) pancreatitis to 15% for patients who develop necrosis. 死亡率：3%（间质水肿性AP）-15%(坏死性AP) As the rate of hospitalization for acute pancreatitis continues to increase, so does the demand for effective management. This demand has resulted in publication of at least 14 clinical practice guidelines in the past decade. An update to the American Pancreas Association and International Association of Pancreatology guidelines is forthcoming. 急性胰腺炎诊治指南需进一步规范 1. Peery AF, Dellon ES, Lund J, et al. Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterology 2012;143:11791187. 2. Singh VK, Bollen TL, Wu BU, et al. An assessment of the severity of interstitial pancreatitis. Clin Gastroenterol Hepatol 2011;9:10981103. 3. van Santvoort HC, Bakker OJ, Bollen TL, et al. A conservative and minimally invasive approach to necrotizing pancreatitis improves outcome. Gastroenterology 2011;141:12541263 Company Logo Contents Diagnosis1 Risk and Prognostic Factors 2 Treatment3 Prevention4 Company Logo Diagnosis The diagnosis of acute pancreatitis requires at least 2 of the following: 1.typical upper abdominal pain 典型的上腹部疼痛 2.serum levels of amylase or lipase 3 times the upper limit of normal, 胰腺酶水平3倍正常值的上限 3.confi rmatory fi ndings from crosssectional imaging analysis. 影像学支持 Company Logo A recently completed revision of the Atlanta Classifi cation provides a more detailed system that emphasizes disease severity and includes comprehensive defi nitions of pancreatic and peripancreatic collections. There are also more complete defi nitions of local and systemic complications. Disease Defi nitions: The Revised Atlanta Classifi cation The Atlanta Classifi cation system was developed at a consensus conference in 1992 to establish standard defi nitions for classifi cation of acute pancreatitis. 最新修订版的亚特兰大分类标准提供了一个更加详细的分类标准，它着重于疾病的 严重程度，及包括胰腺和胰周液体聚集的综合定义，而有更加完整的局部及系统性并发 症的定义。 12. Banks PA, Bollen TL, Dervenis C, et al. Classifi cation of acute pancreatitis2012: revision of the Atlanta classifi cation and defi nitions by international consensus. Gut 2013;62:102111. 13. Marshall JC, Cook DJ, Christou NV, et al. Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome.Crit Care Med 1995;23:16381652. Company Logo 1 2 3 Defi nition of Local Complications 局部并发症的定义 Defi nition of Systemic Complications and Organ Failure 全身并发症及器官衰竭的定义 Defi nition of Severity 严重程度分类 4 Roles of Advanced Imaging Techniques 影像学的作用 Diagnosis Company Logo 间质水肿性 胰腺炎 Defi nition of Local Complications 急性胰腺炎 急性胰周液体积聚（APFC） 胰腺假性囊肿 坏死性胰腺炎 急性坏死物积聚（ANC） 包裹性坏死（WON） Company Logo A variety of local complications have been delineated. Interstitial pancreatitis involves acute collection of peripancreatic fl uid（ACPF） and formation of pancreatic pseudocysts. 间质水肿性胰腺炎涉及急性胰周液体积聚和胰腺假性囊肿的形成 APFC develop during the early phase早期 of interstitial pancreatitis. They are homogeneous in appearance without a well-defi ned wall, usually remain sterile, and frequently resolve spontaneously (Figure A). 急性胰周液体积聚（APFC）发生胰腺炎病程早期，渗出液均匀地而边界模糊地分布于 胰周，通常是无菌的，可以自行吸收 If an acute peripancreatic fl uid collection does not resolve spontaneously, it could develop into a pseudocyst with a welldefi ned infl ammatory wall that contains fl uid with very little, if any, solid material (Figure B). 如果一旦胰周积液不能自行吸收，它将可能发展为有完整炎症性包膜容纳少量渗出液及 极少量坏死组织的假性囊肿(发生AP后4周) Company Logo 间质水肿性胰腺炎 Figure (A) Interstitial pancreatitis with acute peripancreatic fl uid collection. Peripancreatic fl uid collection (arrows) is poorly defi ned with homogeneous fl uid density. Figure(B) Resolving interstitial pancreatitis with pseudocyst. A pseudocyst (arrow) is typically a round or oval encapsulated collection with homogeneous fl uid density. 急性胰周液体积聚（APFC） 胰腺假性囊肿 Company Logo Necrotizing pancreatitis involves acute collection of necrosis and walled-off necrosis. 坏死性胰腺炎包括急性坏死物积聚（ANC）及包裹性坏死（WON）。 An acute necrotic collection refers to the presence of necrotic tissue involving pancreatic parenchyma and peripancreatic tissues (Figure 2). These collections can be sterile or infected. If infected,they are called infected necrosis. 急性坏死物积聚（ANC）指的是胰腺实质及胰周组织的坏死（如表格2），坏死物的积 聚可是无菌性和感染性，其中感染性的又叫感染坏死。 After 4 or more weeks, an acute necrotic collection can become smaller but rarely disappears completely and usually evolves into walled-off necrosis. Walled-off necrosis has a well-defi ned infl ammatory wall that contains varying amounts of fl uid and necrotic debris (Figure 3). 在4周及之后，急性坏死物的积聚逐渐变小，但很少有被完全吸收，通常发展为有炎症性 包膜容纳混合大量渗出液及少量坏死物碎片的包裹性坏死（WON）（如表格3）。 Company Logo Figure 2. Pancreatic and peripancreatic necrosis. This image shows an acute necrotic collection involving both the pancreas (large arrow) and peripancreatic tissue. Figure 3. Walled-off pancreatic necrosis is an encapsulated collection of necrosis. This type of collection typically forms 4 to 6 weeks after disease onset. This image shows pancreatic and peripancreatic necrosis. 坏死性胰腺炎 急性坏死物积聚（ANC）包裹性坏死（WON） Company Logo Defi nition of Systemic Complications and Organ Failure In the revised Atlanta Classifi cation, systemic complications are defi ned as exacerbations of preexisting comorbidities such as chronic lung disease, chronic liver disease, or congestive heart failure, recognizing the failure of respiratory, cardiovascular, and renal organ systems. 在修订版的亚特兰大分类标准，全身并发症被定义为，先前存在的疾病诸如慢性 肺部疾病、慢性肝病、充血性心力衰竭等的突然恶化，这些被认为是呼吸系统、心血 管系统、肾脏功能系统的损害加重而衰竭。 Company Logo Defi nition of Systemic Complications and Organ Failure The scoring system that has been chosen to characterize organ failure is the modifi ed Marshall scoring system . The modifi ed Marshall system classifi es disease severity on a scale from 0 to 4, so that the overall evaluation of organ dysfunction can be more completely delineated and characterized over time. In this system, organ failure is defi ned by a score of 2 for one or more of these organ systems. 改良的马歇尔评分系统用于器官衰竭的评分，该评分系统将急性胰腺炎的严重程度分 为04级，以至于更能清晰及特征性地对器官功能障碍发展进行综合评价。在该评分系统 中，器官衰竭定义为有任何1个及多个器官功能评分 2分。 13. Marshall JC, Cook DJ, Christou NV, et al. Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome.Crit Care Med 1995;23:16381652. Company Logo Defi nition of Severity MAPMAP Mild disease is defi ned as acute pancreatitis not associated with organ failure, local or systemic complications. 无器官衰竭、无局部或全身并发症 MSAPMSAP presence of transient organ failure (present for 48 hours). Most patients with persistent organ failure have pancreatic necrosis. 持续性器官衰竭（ 48 h）,多伴有胰腺坏死 Company Logo Most patients with mild acute pancreatitis do not require pancreatic imaging analysis and are usually discharged within 3 to 5 days of onset of illness . 轻型急性胰腺炎患者无需影像学检查，住院时间通常为3-5天 Patients with moderately severe acute pancreatitis frequently require extended hospitalization but have lower mortality rates than patients with severe acute pancreatitis. 中度重症急性胰腺炎需延长住院时间，但病死率低于重症急性胰腺炎 A meta-analysis found patients with severe acute pancreatitis with persistent organ failure have a 30% mortality rate; the risk of in- hospital death doubles when they have persistent organ failure and infected necrosis. 重症急性胰腺炎有高达30%的病死率，当出现持续性器官功能衰竭和感染坏 死时，住院期间死亡的风险成倍增加。 15. Petrov MS, Shanbhag S, Chakraborty M, et al. Organ failure and infection of pancreatic necrosis as determinants of mortality in patients with acute pancreatitis. Gastroenterology 2010;139:813820. Company Logo Roles of Advanced Imaging Techniques The role of CT in assessing patients with acute pancreatitis has changed with time. CT的作用是用于评价急性胰腺炎发病及治疗各阶段的变化 A contrast-enhanced CT scan obtained within the fi rst several days of illness cannot be used to determine whether a patient has necrotizing or severe interstitial pancreatitis. This might be because intrapancreatic fl uid causes heterogeneous enhancement, which can indicate necrosis. 在发病的前几天，不能通过CT检查判断出胰腺坏死的存在及其范围，这可能是由于 胰腺内液体渗出导致了CT的不均匀增强。 Over a period of several days, the fl uid can be reabsorbed such that a subsequent CT scan clearly shows the absence of necrosis. As such, patients should not be evaluated by CT within a few days after the onset of disease to establish the presence or extent of pancreatic necrosis. 胰腺积液被重吸收后，后来的CT检查才能够区分液体积聚或胰腺坏死范围。 Company Logo The best use of an early-stage CT scan is to confi rm a diagnosis of acute pancreatitis when the clinical situation is unclear. 发病早期行CT检查仅能用于诊断不明时，以确诊急性胰腺炎。 The best use of a CT scan after the fi rst 5 to 7 days is to evaluate the presence of local complications in patients with moderately severe or severe pancreatitis to guide ongoing care. 发病的第一个5-7天后行CT检查最大好处，用以评价中度重症急性胰腺炎或重 症急性胰腺炎病人的局部并发症，并指导治疗。 Company Logo MRCP has become a useful procedure for identifying retained common bile duct stones. Selective use of MRCP can reduce the need for ERCP for patients with suspected gallstone pancreatitis. MRCP对胆管结石敏感，能够减少因怀疑为胆源性胰腺炎而行ERCP检查。 MRI is helpful in distinguishing walled-off necrosis from a pseudocyst. For example, in walled-off necrosis, there are variable amounts of fl uid and solid debris that can be visualized using T2-weighted imaging. MRI能用于鉴别是包裹性坏死（WON）或是胰腺假性囊肿，因为T2加权像能很直观 地看出含有大量渗液体及固体坏死物的包裹性坏死。 Endoscopic ultrasonography is a highly sensitive test for detecting cholelithiasis and choledocholithiasis.19 It could be an alternative to MRCP, which has limited accuracy for detecting smaller gallstones or sludge. 超声内镜对胆石病高度敏感，可以代替对细小结石或淤泥样胆汁不敏感的MRCP检查 。 Company Logo 1 2 3 Prognostic Factors 预后因素 Risk and Prognostic Factors Clinical scoring systems 临床系统性评分 Risk factors 危险因素 Company Logo Risk factors Age Obesity Risk factors AP ？ Comorbid illnesses Alcohol 60 years of age or older cancer, heart failure, and chronic kidney and liver disease BMI30 kg/m2 chronic alcohol consumption increases the risk of severe pancreatitis 3-fold and mortality 2-fold Company Logo Clinical scoring systems The initial 12 to 24 hours of hospitalization is critical during patient management, because the highest incidence of organ dysfunction occurs during this period. 发病第12-24h是临床处理非常重要，器官功能障碍多发生于这个时段。 A number of clinical scoring systems and biomarkers have been developed to facilitate risk stratifi cation during this phase. Whereas previous scoring systems such as the Ranson or ImrieGlasgow scores required 48 hours to complete, 2 scoring systems were recently developed and involve a simplifi ed approach that can be performed during the fi rst 24 hours of hospitalizationThe Bedside Index of Severity in Acute Pancreatitis . Ranson 评分系统、ImrieGlasgow评分系统对疾病的危险分层评分滞后， 最新的AP 严重程度床旁指数（BISAP） 可在发病24h内完成。 26. Harrison DA, DAmico G, Singer M. Case mix, outcome, and activity for admissions to UK critical care units with severe acute pancreatitis: a secondary analysis of the ICNARC Case Mix Programme Database. Crit Care 2007;11(Suppl 1):S1. 27. Wu BU, Conwell DL. Update in acute pancreatitis. Curr Gastroenterol Rep 2010;12:8390. Company Logo Clinical scoring systems AP严重程度床旁指数 BUN25 mg/dl(8.9mmol/L) Impaired mental status 精神状态受损 SIRS age 60 years or older pleural effusion 胸腔积液 Score 2 within 24 hours is associated with a 7-fold increase in risk of organ failure and 10-fold increase in risk of mortality. 发病24小时内分数2分，发生器官衰竭的风险增加7倍，死亡的风险增加10倍。 Company Logo Another scoring system, the Harmless Acute Pancreatitis Score, uses a different approach to risk stratifi cation, identifying patients at the time of admission who are unlikely to experience complications related to acute pancreatitis. Specifi cally, patients with a normal hematocrit and normal serum level of creatinine without rebound tenderness or guarding, are unlikely to develop severe pancreatitis (positive predictive value of 98%). 轻症急性胰腺炎评分（HAPS）则注重于在入院时不会发生与急性胰腺炎相关 并发症的病人的评分，特别是Hct、Cre正常，无反跳痛体征的病人，将不再发展为 重症急性胰腺炎（阳性率高达98%）。 With respect to scoring systems, the most widely validated remains the Acute Physiology and Chronic Health Examination II score. These scoring systems have comparable levels of overall accuracy. 最受到广泛认同的评分系统为急性生理功能和慢性健康状况评分系统 (APACHE II)， 这些评分系统具有相当的水平的整体精度。 Company Logo Prognostic Factors Additional approaches have been developed to monitor disease progression. Parameters that are easy to determine and have been validated for their ability to determine disease activity include the presence of SIRS, level of BUN or Cr, and hematocrit. SIRS、尿素氮水平、肌酐水平、红细胞压积的参数，用于监测疾病的进展。 Prospective studies have shown that the level of BUN at admission and during the initial 24 hours of hospitalization is a strong prognostic factor. For example, patients with a level of BUN at admission 20 mg/dL that increased during the initial 24 hours have 9% to 20% mortality. By contrast, patients with an increased level of BUN at admission that decreased at least 5 mg/dL within 24 hours have 0% to 3% mortality. 入院时及入院后24小时内BUN水平的高低是一个非常重要的预后因素。例如，入院时 患者BUN20 mg/dL（7.14mmol/L），在发病最初24小时内可增加9%- 20%的病死率 ，相反，高BUN水平在入院后24小时内至少下降5 mg/dL(1.8mmol/L)则有0% - 3% 病 死率。 38. Wu BU, Bakker OJ, Papachristou GI, et al. Blood urea nitrogen in the early assessment of acute pancreatitis: an international validation study. Arch Intern Med 2011;171:669676. 39. Wu BU, Johannes RS, Sun X, et al. Early changes in blood urea nitrogen predict mortality in acute pancreatitis. Gastroenterology 2009;137:129 135. Company Logo 全身炎症反应综合征全身炎症反应综合征(SIRS)(SIRS) An increasing number of SIRS criteria during the initial 24 hours of hospitalization increases the risk of persistent organ failure and necrosis as well as mortality. Patients with persistent SIRS (beyond 48 hours) have 11% to 25% mortality. SIRS增加持续性器官衰竭、胰腺坏死、病死率（11-25%）的风险。 2 or more of the following criteria T38.3C 或90次/分 WBC12109/L 或 10% 呼吸20次/分 Company Logo A serum level of Cr 1.8 mg/dL（159umol/L） within the fi rst 24 hours of hospitalization is associated with a 35-fold increased risk of development of pancreatic necrosis. A persistent increase in HCT 44% has also been shown to increase the risk of necrosis and organ failure. 研究表明，在发病的最初的24小时内血肌酐1.8 mg/dL，发展为胰腺坏死的风险增 加35倍 红细胞压积持续44%也同样增加了胰腺坏死及器官衰竭的风险。 33. Muddana V, Whitcomb DC, Khalid A, et al. Elevated serum creatinine as a marker of pancreatic necrosis in acute pancreatitis.Am J Gastroenterol 2009;104:164170. 34. Brown A, Orav J, Banks PA. Hemoconcentration is an early marker for organ failure and necrotizing pancreatitis. Pancreas 2000;20:367372. Company Logo Treatment 1 2 3 Initial Resuscitation and Management 早期治疗 Management of Local Complications 局部并发症的治疗 Management of Extrapancreatic Complications 胰腺外并发症的治疗 4 Special Considerations Based on Etiology 对因治疗 Company Logo Initial Resuscitation and Management Aggressive volume resuscitation has been a cornerstone of therapy, based on studies in animal models and observational data from clinical studies . However, approaches to fl uid resuscitation require optimization. Under-resuscitation during the early phase of acute pancreatitis has been associated with increased risk of necrosis and mortality. In contrast, over- resuscitation can lead to complications such as pulmonary sequestration（肺 隔离症 ）. 积极的容量复苏已经成为治疗的里程碑，疾病早期液体复苏的容量不足会增加胰腺坏 死及死亡的风险，相反，如过度补液可能导致诸如肺隔离症的并发症，制定最优化液体复 苏方案很重要。 44. de-Madaria E, Soler-Sala G, Sanchez-Paya J, et al. Infl uence of fl uid therapy on the prognosis of acute pancreatitis: a prospective cohort study. Am J Gastroenterol 2011;106:18431850. 45. Mao EQ, Fei J, Peng YB, et al. Rapid hemodilution is associated with increased sepsis and mortality among patients with severe acute pancreatitis. Chin Med J 2010;123:16391644. NO.1 Initial Resuscitation Company Logo Initial Resuscitation and Management A prospective, randomized, controlled trial assessed the effects of bolus infusion of 20 mL/kg in the emergency department, followed by continuous infusion of 3 mLkg-1 h-1, with interval assessment every 6 to 8 hours (comprising vital sign monitoring, pulse oximetry, and physical examination). Repeat volume challenge was administered if the level of BUN did not decrease. Alternatively, if the BUN level decreased, the rate of the infusion was reduced to 1.5 mL kg-1 h-1. This approach was found to be safe and feasible in an acute care setting. 研究表明， 在急诊科按20 mL/kg进行开始补液，随后按 3mLkg-1 h-1的速度进行持续补液， 每间隔6-8小时进行病情评估（包括生命体征、血氧饱和度、身体状况）： 如果BUN水平没有下降，需反复地补液； 相反，如果BUN水平下降了，则补液速度减少至1.5 mLkg-1 h-1 ， 最后证明此治疗方案在急诊治疗中是安全可行的。 Company Logo In general, patients undergoing volume resuscitation should have the head of the bed elevated, undergo continuous pulse oximetry, and receive supplemental oxygen. 患者进行液体复苏时，需抬高床头，持续的血氧饱和度监测及吸氧。 Lactated Ringers solution reduces the incidence of SIRS by 80% compared with saline. Nevertheless, LRs solution is a reasonable choice for initial resuscitation, based on its positive effects on acid-base homeostasis, compared with large-volume saline resuscitation. Because lactated Ringers solution contains calcium, it should not be administered in quantity to patients with hypercalcemia. 与用生理盐水复苏相比，乳酸林格氏液能减少80%的SIRS发生，乳酸林格氏液对 维持酸碱平衡有积极的影响，更加适用于早期的液体复苏， 高钙血症患者慎用。 Volume expansion with colloid has not been shown to be more effective than