急性胰腺炎的临床处理(美国胃肠病学,2013.5)分析课件

1、华西医院中西医结合科 Clinical Management of Patients With Acute PancreatitisGASTROENTEROLOGY MAY 2013;144:127212811Center 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、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.Abstract Acute pancreatitis is the leading c

3、ause 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 in

4、terstitial (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

5、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;14

6、3:11791187.2. 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. Gastr

7、oenterology 2011;141:12541263 ContentsDiagnosis1Risk and Prognostic Factors 2Treatment3Prevention4 A recently completed revision of the Atlanta Classication provides a more detailed system that emphasizes disease severity and includes comprehensive denitions of pancreatic and peripancreatic collecti

8、ons. There are also more complete denitions of local and systemic complications.Disease Denitions: The Revised Atlanta Classication The Atlanta Classication system was developed at a consensus conference in 1992 to establish standard denitions for classication of acute pancreatitis. 最新修订版的亚特兰大分类标准提供

9、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. Classication of acute pancreatitis2012: revision of the Atlanta classication and denitions by international consensus. Gut 2013;62:102111.13. Marshall JC, Cook DJ, Christou NV, et al. Multiple

10、 organ dysfunction score: a reliable descriptor of a complex clinical outcome.Crit Care Med 1995;23:16381652.123Denition of Local Complications 局部并发症的定义 Denition of Systemic Complications and Organ Failure 全身并发症及器官衰竭的定义Denition of Severity严重程度分类4Roles of Advanced Imaging Techniques 影像学的作用 Diagnosis

11、A variety of local complications have been delineated. Interstitial pancreatitis involves acute collection of peripancreatic 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 app

12、earance without a well-dened 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 uid collection does not resolve spontaneously, it could develop into a pseudocyst with a welldened inammatory

13、 wall that contains 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)间质水肿性胰腺炎Figure (A) Interstitial pancreatitis with acute peripancreatic uid collection. Peripancreatic uid collection (arrows) is poorly dened with homogeneous uid d

14、ensity. Figure(B) Resolving interstitial pancreatitis with pseudocyst. A pseudocyst (arrow) is typically a round or oval encapsulated collection with homogeneous uid density.急性胰周液体积聚（APFC）胰腺假性囊肿 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（A

15、NC）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

16、，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-dened inammatory wall that contains varying amounts of uid and necrotic debris (Figure 3). 在4周及之后，急性坏死物的

17、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）。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 o

18、f 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）Denition of Systemic Complications and Organ Failure In the revised Atlanta Classication, systemic complications are dened as exac

19、erbations 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。Denitio

20、n of Systemic Complications and Organ Failure The scoring system that has been chosen to characterize organ failure is the modied Marshall scoring system . The modied Marshall system classies disease severity on a scale from 0 to 4, so that the overall evaluation of organ dysfunction can be more com

21、pletely delineated and characterized over time. In this system, organ failure is dened 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. Multipl

22、e organ dysfunction score: a reliable descriptor of a complex clinical outcome.Crit Care Med 1995;23:16381652. 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 Patien

23、ts 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%

24、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

25、 patients with acute pancreatitis. Gastroenterology 2010;139:813820. 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 rst several days of illness cannot

26、be used to determine whether a patient has necrotizing or severe interstitial pancreatitis. This might be because intrapancreatic 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 uid can be

27、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。 MRCP has become a useful proced

28、ure 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

29、, there are variable amounts of 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 alternati

30、ve 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。123Prognostic 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Risk factors AgeObesity Risk factorsAP？Comorbid illnessesAlcohol60 years of a

31、ge or oldercancer, heart failure, and chronic kidney and liver diseaseBMI30 kg/m2chronic alcohol consumption increases the risk of severe pancreatitis 3-fold and mortality 2-fold Clinical scoring systems The initial 12 to 24 hours of hospitalization is critical during patient management, because the

32、 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 stratication during this phase. Whereas previous scoring systems such as the Ranson or ImrieGlasgow scores

33、required 48 hours to complete, 2 scoring systems were recently developed and involve a simplied approach that can be performed during the 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.

34、 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 Gastroent

35、erol Rep 2010;12:8390.Clinical scoring systemsAP严重程度床旁指数BUN25 mg/dl(8.9mmol/L)Impaired mental status精神状态受损SIRSage 60 years or olderpleural 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

36、风险增加7倍，死亡的风险增加10倍。 Another scoring system, the Harmless Acute Pancreatitis Score, uses a different approach to risk stratication, identifying patients at the time of admission who are unlikely to experience complications related to acute pancreatitis. Specically, patients with a normal hematocrit an

37、d 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 val

38、idated 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。 全身炎症反应综合征(SIRS) An increasing number of SIRS criteria during the initial 24 hours of hospital

39、ization 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 criteriaT38.3C 或90次/分WBC12109/L或 10%呼吸20次/分 A serum level of Cr 1.8 mg/dL（

40、159umol/L） within the 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

41、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. Pan

42、creas 2000;20:367372.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 uid resuscitation require optimization. Under-resuscitation during the

43、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,

44、Soler-Sala G, Sanchez-Paya J, et al. Inuence of 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 acut

45、e pancreatitis. Chin Med J 2010;123:16391644.NO.1 Initial ResuscitationInitial 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 asses

46、sment 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

47、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。 In general, patients undergoing volume resuscitation should have the head of the

48、 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 ef

49、fects 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 w

50、ith colloid has not been shown to be more effective than with crystalloids in critically ill patients. 对于危重病人，使用胶体液扩容的益处并不多于使用晶体液。NO.2 Indications for Intensive Care 重症监护的适应症 Respiratory failure is the most common form of organ dysfunction. Patients with signs of respiratory failure or hypotension t

51、hat fail to respond to initial resuscitation should be considered for direct admission to an intensive care unit（ICU）. 呼吸衰竭是最常见的器官功能障碍，病人因为没有进行早期的液体复苏，而出现了呼吸衰竭或低血压的迹象，可以直接送至 ICU。 Patients with multiorgan dysfunction are at the greatest risk for death and should be managed in a critical care setting

52、with a multidisciplinary care team. 存在多器官功能障碍是最重要的死亡因素，必须成立多由学科治疗团队组成的特别治疗组进行临床管理及诊治。In addition, patients with persistent SIRS, increased levels of BUN or creatinine, increased hematocrit, or underlying cardiac or pulmonary illness should strongly be considered for management in a monitored setting

53、. 另外，对有持续性SIRS、BUN水平升高、HCT升高或潜在的心肺疾病的病人，需在有监控设置下进行管理及治疗。NO.3 Indications for Transfer 转院指征Data from the Nationwide Inpatient Sample indicate that patients with acute pancreatitis treated at high-volume centers (118 admissions/y) have a 25% lower relative risk of death than patients treated at low-vo

54、lume centers. Thus, patients who do not respond to initial resuscitation, with persistent organ failure or extensive local complications, should be considered for transfer to a comprehensive pancreatitis center with multidisciplinary expertise that includes therapeutic endoscopy, interventional radi

55、ology, and surgery. 来自全国住院病人的大样本数据表明，急性胰腺炎病人在年收治量高的医疗中心（118例/年）的死亡相对风险，较年收治量低的医疗中心低25%。 因此，没有进行早期液体复苏，有持续器官衰竭、广泛性局部并发症的病人，必须转院至拥有多学科治疗手段，包括内镜治疗、介入治疗、外科手术治疗的综合性胰腺炎治疗中心。NO.4 Analgesia 镇痛 Effective analgesia should be a priority in caring for patients with acute pancreatitis. Despite its importance, st

56、rategies to manage pain in patients with acute pancreatitis are under studied. 急性胰腺炎病人需要优先给予有效地镇痛 ， 尽管重要，但对急性胰腺炎患者的镇痛管理策略还在研究中。 We recommend a comprehensive pain management approach that includes patient education, collecting patients histories of chronic pain, and using validated pain instruments t

57、o assess pain relief . 推荐采用综合的疼痛管理方法，包括病人教育、收集病人慢性疼痛病史、使用有效的镇痛仪器，以评价疼痛缓解情况。 Patients who receive repeated administration of narcotic analgesics should have oxygen saturation monitored. 反复使用静脉麻醉止痛剂时，必须监测病人的血氧饱和度。 Initial Resuscitation and ManagementNO.5 Nutritional Support 营养支持 Data from 2 randomized

58、 controlled trials support early-stage introduction of low-fat solid food as the initial meal for patients who have developed mild pancreatitis; choledocholithiasis, duration of fasting, and quickly placing patients on a full diet have been associated with recurrence of pain. 研究数据支持发病早期提供MAP病人低脂固体食物

59、，但有胆总管石病、长期禁食、过早普食可导致再发腹痛。 For patients with more severe forms of illness or persistent abdominal pain who require further nutritional support, enteral nutrition has clear advantages over total parenteral nutrition. 病情更重、持续性疼痛的患者需要更长久的营养支持，肠内营养优于肠外营养 。 A Cochrane meta-analysisof 8 randomized control

60、led trials found a reduction in mortality, systemic infection, and multiorgan dysfunction among patients who received enteral as opposed to parenteral nutrition. 数据表明，与场外营养相比，肠内营养可以减少病死率、全身感染、多器官功能障碍的风险。Management of Local Complications1.Prophylactic Antibiotics 预防性抗感染 Two high-quality, double-blind