急性胰腺炎的臨床處理(美國胃腸病學(xué),2013.5)分析課件

1、華西醫(yī)院中西醫(yī)結(jié)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,凱薩醫(yī)療機構(gòu)） ; and

2、2 Center for Pancreatic Disease, Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Womens Hospital, Harvard Medical School, Boston, Massachusetts（波士頓，哈佛醫(yī)學(xué)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. 高發(fā)病率；平均住院時間：5天；治療費用高昂 Mortality ranges from 3% for patients with in

4、terstitial (edematous) pancreatitis to 15% for patients who develop necrosis. 死亡率：3%（間質(zhì)水腫性AP）-15%(壞死性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. 急性胰腺炎診治指南需進一步規(guī)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. 最新修訂版的亞特蘭大分類標(biāo)準(zhǔn)提供

9、了一個更加詳細的分類標(biāo)準(zhǔn)，它著重于疾病的嚴(yán)重程度，及包括胰腺和胰周液體聚集的綜合定義，而有更加完整的局部及系統(tǒng)性并發(fā)癥的定義。 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 局部并發(fā)癥的定義 Denition of Systemic Complications and Organ Failure 全身并發(fā)癥及器官衰竭的定義Denition of Severity嚴(yán)重程度分類4Roles of Advanced Imaging Techniques 影像學(xué)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. 間質(zhì)水腫性胰腺炎涉及急性胰周液體積聚和胰腺假性囊腫的形成 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). 急性胰周液體積聚（APFC）發(fā)生胰腺炎病程早期，滲出液均勻地而邊界模糊地分布于胰周，通常是無菌的，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). 如果一旦胰周積液不能自行吸收，它將可能發(fā)展為有完整炎癥性包膜容納少量滲出液及極少量壞死組織的假性囊腫(發(fā)生AP后4周)間質(zhì)水腫性胰腺炎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.急性胰周液體積聚（APFC）胰腺假性囊腫 Necrotizing pancreatitis involves acute collection of necrosis and walled-off necrosis. 壞死性胰腺炎包括急性壞死物積聚（A

15、NC）及包裹性壞死（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. 急性壞死物積聚（ANC）指的是胰腺實質(zhì)及胰周組織的壞死（如表格2），壞死物的積聚可是無菌性和感染性

16、，其中感染性的又叫感染壞死。 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，急性壞死物的

17、積聚逐漸變小，但很少有被完全吸收，通常發(fā)展為有炎癥性包膜容納混合大量滲出液及少量壞死物碎片的包裹性壞死（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.壞死性胰腺炎急性壞死物積聚（ANC）包裹性壞死（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. 在修訂版的亞特蘭大分類標(biāo)準(zhǔn)，全身并發(fā)癥被定義為，先前存在的疾病諸如慢性肺部疾病、慢性肝病、充血性心力衰竭等的突然惡化，這些被認為是呼吸系統(tǒng)、心血管系統(tǒng)、腎臟功能系統(tǒng)的損害加重而衰竭。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. 改良的馬歇爾評分系統(tǒng)用于器官衰竭的評分，該評分系統(tǒng)將急性胰腺炎的嚴(yán)重程度分為04級，以至于更能清晰及特征性地對器官功能障礙發(fā)展進行綜合評價。在該評分系統(tǒng)中，器官衰竭定義為有任何1個及多個器官功能評分 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 . 輕型急性胰腺炎患者無需影像學(xué)檢查，住院時間通常為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. 中度重癥急性胰腺炎需延長住院時間，但病死率低于重癥急性胰腺炎 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. 重癥急性胰腺炎有高達30%的病死率，當(dāng)出現(xiàn)持續(xù)性器官功能衰竭和感染壞死時，住院期間死亡的風(fēng)險成倍增加。 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的作用是用于評價急性胰腺炎發(fā)病及治療各階段的變化 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. 在發(fā)病的前幾天，不能通過CT檢查判斷出胰腺壞死的存在及其范圍，這可能是由于胰腺內(nèi)液體滲出導(dǎo)致了CT的不均勻增強。 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. 胰腺積液被重吸收后，后來的CT檢查才能夠區(qū)分液體積聚或胰腺壞死范圍。 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對膽管結(jié)石敏感，能夠減少因懷疑為膽源性胰腺炎而行ERCP檢查。 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能用于鑒別是包裹性壞死（WON）或是胰腺假性囊腫，因為T2加權(quán)像能很直觀地看出含有大量滲液體及固體壞死物的包裹性壞死。 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. 超聲內(nèi)鏡對膽石病高度敏感，可以代替對細小結(jié)石或淤泥樣膽汁不敏感的MRCP檢查。123Prognostic Factors預(yù)后因素Risk and Prognostic Factors Clinical scoring systems 臨床系統(tǒng)性評分Risk factors危險因素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. 發(fā)病第12-24h是臨床處理非常重要，器官功能障礙多發(fā)生于這個時段。 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 評分系統(tǒng)、ImrieGlasgow評分系統(tǒng)對疾病的危險分層評分滯后， 最新的AP嚴(yán)重程度床旁指數(shù)（BISAP） 可在發(fā)病24h內(nèi)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嚴(yán)重程度床旁指數(shù)BUN25 mg/dl(8.9mmol/L)Impaired mental status精神狀態(tài)受損SIRSage 60 years or olderpleural effusion胸腔積液 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. 發(fā)病24小時內(nèi)分數(shù)2分，發(fā)生器官衰竭的

36、風(fēng)險增加7倍，死亡的風(fēng)險增加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%). 輕癥急性胰腺炎評分（HAPS）則注重于在入院時不會發(fā)生與急性胰腺炎相關(guān)并發(fā)癥的病人的評分，特別是Hct、Cre正常，無反跳痛體征的病人，將不再發(fā)展為重癥急性胰腺炎（陽性率高達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. 最受到廣泛認同的評分系統(tǒng)為急性生理功能和慢性健康狀況評分系統(tǒng) (APACHE II)， 這些評分系統(tǒng)具有相當(dāng)?shù)乃降恼w精度。 全身炎癥反應(yīng)綜合征(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增加持續(xù)性器官衰竭、胰腺壞死、病死率（11-25%）的風(fēng)險。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，在發(fā)病的最初的24小時內(nèi)血肌酐1.8 mg/dL，發(fā)展為胰腺壞死的風(fēng)險增加35倍 紅細胞壓積持續(xù)44%也同

41、樣增加了胰腺壞死及器官衰竭的風(fēng)險。 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（肺隔離癥 ）. 積極的容量復(fù)蘇已經(jīng)成為治療的里程碑，疾病早期液體復(fù)蘇的容量不足會增加胰腺壞死及死亡的風(fēng)險，相反，如過度補液可能導(dǎo)致諸如肺隔離癥的并發(fā)癥，制定最優(yōu)化液體復(fù)蘇方案很重要。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，在急診科按20 mL/kg進行開始補液，隨后按 3mLkg-1 h-1的速度進行持續(xù)補液，每間隔6-8小時進行病情評估（包括生命體征、血氧飽和度、身體狀況）：如果BUN水平?jīng)]有下降，需反復(fù)地補液；相反，如果BUN水平下降了，則補液速度減少至1.5 mLkg-1 h-1 ，最后證明此治療方案在急診治療中是安全可行的。 In general, patients undergoing volume resuscitation should have the head of the

48、 bed elevated, undergo continuous pulse oximetry, and receive supplemental oxygen. 患者進行液體復(fù)蘇時，需抬高床頭，持續(xù)的血氧飽和度監(jiān)測及吸氧。 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. 與用生理鹽水復(fù)蘇相比，乳酸林格氏液能減少80%的SIRS發(fā)生，乳酸林格氏液對維持酸堿平衡有積極的影響，更加適用于早期的液體復(fù)蘇， 高鈣血癥患者慎用。 Volume expansion w

50、ith colloid has not been shown to be more effective than with crystalloids in critically ill patients. 對于危重病人，使用膠體液擴容的益處并不多于使用晶體液。NO.2 Indications for Intensive Care 重癥監(jiān)護的適應(yīng)癥 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）. 呼吸衰竭是最常見的器官功能障礙，病人因為沒有進行早期的液體復(fù)蘇，而出現(xiàn)了呼吸衰竭或低血壓的跡象，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. 存在多器官功能障礙是最重要的死亡因素，必須成立多由學(xué)科治療團隊組成的特別治療組進行臨床管理及診治。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，對有持續(xù)性SIRS、BUN水平升高、HCT升高或潛在的心肺疾病的病人，需在有監(jiān)控設(shè)置下進行管理及治療。NO.3 Indications for Transfer 轉(zhuǎn)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. 來自全國住院病人的大樣本數(shù)據(jù)表明，急性胰腺炎病人在年收治量高的醫(yī)療中心（118例/年）的死亡相對風(fēng)險，較年收治量低的醫(yī)療中心低25%。 因此，沒有進行早期液體復(fù)蘇，有持續(xù)器官衰竭、廣泛性局部并發(fā)癥的病人，必須轉(zhuǎn)院至擁有多學(xué)科治療手段，包括內(nèi)鏡治療、介入治療、外科手術(shù)治療的綜合性胰腺炎治療中心。NO.4 Analgesia 鎮(zhèn)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優(yōu)先給予有效地鎮(zhèn)痛 ， 盡管重要，但對急性胰腺炎患者的鎮(zhèn)痛管理策略還在研究中。 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 . 推薦采用綜合的疼痛管理方法，包括病人教育、收集病人慢性疼痛病史、使用有效的鎮(zhèn)痛儀器，以評價疼痛緩解情況。 Patients who receive repeated administration of narcotic analgesics should have oxygen saturation monitored. 反復(fù)使用靜脈麻醉止痛劑時，必須監(jiān)測病人的血氧飽和度。 Initial Resuscitation and ManagementNO.5 Nutritional Support 營養(yǎng)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. 研究數(shù)據(jù)支持發(fā)病早期提供MAP病人低脂固體食物

59、，但有膽總管石病、長期禁食、過早普食可導(dǎo)致再發(fā)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、持續(xù)性疼痛的患者需要更長久的營養(yǎng)支持，腸內(nèi)營養(yǎng)優(yōu)于腸外營養(yǎng) 。 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. 數(shù)據(jù)表明，與場外營養(yǎng)相比，腸內(nèi)營養(yǎng)可以減少病死率、全身感染、多器官功能障礙的風(fēng)險。Management of Local Complications1.Prophylactic Antibiotics 預(yù)防性抗感染 Two high-quality, double-blind