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1、Acute Pancreatitis:Management Update,Jamie S.Barkin,M.D.,MACP,MACG,AGAF,FASGE Professor of MedicineUniversity of Miami,Miller School of MedicineChief,Division of GastroenterologyMount Sinai Medical Center,Overview of Acute Pancreatitis,85%of patients have interstitial pancreatitis;15(range 4 47%)hav
2、e necrotizing pancreatitisAmong patients with necrotizing pancreatitis,33%(range 16-47%)have infected necrosis Approximately 10%of patients with interstitial pancreatitis experience organ failure,but in the majority it is transientMortality in acute pancreatitis overall,is approximately 5%:3%in inte
3、rstitial pancreatitis,17%in necrotizing pancreatitisIn necrotizing pancreatitis,mortality 3-fold infected vs.sterile necrosisMortality increases with development of organ failure 3%(0-8%)and with multi-system organ failure 47%(range 28-69),ACG Practice Guidelines in Acute Pancreatitis Am J Gastroent
4、erol 2006;101:2379-2400,Acute Pancreatitis:Concepts 2009,1)Volume replacement is the foundation of therapy2)Establish severityUtilize initial laboratory datastandardized modalities i.e.Ranson criteria require 48 hrsCT abnormalities correlate with severity No need for early CT to establish severity3)
5、Establish etiologyImportance is to prevent recurrence4)Biliary Pancreatitis Utilize laboratory markers for diagnosis of retained CBD ERCP is only for treating patients with cholangitis,5)Do not use prophylactic antibiotics6)CT guided aspiration is the diagnostic test for pancreatic infection&allows
6、directed antibiotic therapy,Acute Pancreatitis:Concepts 2009,Acute Pancreatitis:Concepts 2009,(Cont)7)Surgical intervention in patients with infected pancreatic necrosis but rarely in sterile necrosis8)Early enteral feeding is safe,prevents leaky gut and is associated with less complications than TP
7、N,Definition of Severe Acute Pancreatitis(SAP),SAP is acute pancreatitis with local and/or systemic complicationsLocal complications are:necrotizing pancreatitisInfected necrosisPancreatic abscessPeripancreatic fluid collection and pseudocystic lesionsSystemic complications are:Pulmonary and renal f
8、ailureShockCardio-circulatory dysfunctions systemic sepsis coagulation disorderBradley EL,III.Arch Surg 1993;128:585-590,Acute Pancreatitis:Mechanisms of Intra and-Extrapancreatic Inflammation,Mediated by cytokines and other inflammatory mediators:Activation of inflammatory cellsChemo-attraction of
9、activated inflammatory cells to the microcirculationActivation of adhesion molecules allowing the binding of inflammatory cells to the endotheliumMigration of activated inflammatory cells into areas of inflammationACG Practice Guidelines in Acute Pancreatitis.Am J Gastroenterol 2006;101:2379-2400,Ac
10、ute Pancreatitis,Mechanism of organ dysfunctionVolume depletionVisceral hypofusion Capillary permeability bowel permeability(TNF,IL6,angioprotin adipokines)Bacterial translocationSIRSDavid Whitcomb,M.D.,Causes of mortality,Acute Pancreatitis,Systemic Inflammatory Response Syndrome(SIRS),ACG Practice
11、 Guidelines in Acute Pancreatitis Am J Gastroenterol 2006;101:2379-2400,Acute Pancreatitis,Prognosis in Acute Pancreatitis,Acute Pancreatitis,Early Indicators of Severity,Tachycardia,hypotensionTachypnea,hypoxemiaHemoconcentrationOliguriaEncephalopathy,Early Diagnostic Indicators in Acute Pancreatit
12、is,Acute Pancreatitis,Organ Dysfunction Affects Prognosis in Acute Pancreatitis,Organ Dysfunction Affects Prognosis,A Buter et al.,Brit.J.Surgery 2002;89:298,J Martinez et al.,Pancreas 1999;19:15,Effect may be greatest with a high waist/hip fat ratioPossible Mechanisms Free fatty acids Cytokines(TNF
13、aIL-6)Reduced diaphragmatic excursion,Body Mass Index(kg/m2),%Patients,0,20,40,60,25,25-29,29,Severe Pancreatitis,Systemic complications,Obesity Worsens Prognosis,Autoimmune Pancreatitis,Obesity Worsens the Prognosis in Acute Pancreatitis,Diagnostic Guideline I:Look for Risk Factors of Severity at A
14、dmission,Older age(55 yrs)Obesity BMI 30Organ failure at admissionPleural effusion and/or infiltratesWhen organ failure is corrected within 48 hours,mortality is close to 0When organ failure persists for more than 48 h,mortality is 36%Level of Evidence III,ACG Practice Guidelines in Acute Pancreatit
15、is Am J Gastroenterol 2006;101:2379-2400,APACHE II score=(acute physiology score),Rectal temperature(C)Mean arterial pressure(mmHg)Heart rate(bpm)Respiratory rate(bpm)Oxygen delivery(mL/min)PO2 mmHg)Arterial pHSerum sodium(mmol/LSerum potassium(mmol/L)Serum creatinine(mg/dL)Hematocrit(%)White cell c
16、ount(103/mL)History of severe organ insufficiency,ACG Practice Guidelines in Acute Pancreatitis.Am J Gastroenterol 2006;101:2379-2400,Diagnostic Guideline II:Determination of severity by Laboratory Tests at Admission or 48 Hours,Level of Evidence IIIHematocrit 44 at admission and failure of admissio
17、n hematocrit to decrease at 24 h are the best predictors of necrotizing pancreatitis Absence of hemoconcentration at admission or during the first 24 h is strongly suggestive of a benign clinical courseC-reactive protein greater than 150 mg/L within the first 72 h of disease correlate with the prese
18、nce of necrosis with a sensitivity and specificity that are both 80%The peak of c-reactive protein is generally 36 72 h after admission,therefore this test is not helpful at admission in assessing severityACG Practice Guidelines in Acute PancreatitisAm J Gastroenterol 2006;101:2379-2400,Hematocrit a
19、nd Severity,Acute Pancreatitis,Brown J,et al.,Pancreas 2000;20:367,Hematocrit and Severity of Acute Pancreatitis,Acute Pancreatitis,Indications for Computed Tomography(CT)in Acute Pancreatitis,Modified CT Severity Index,Summary:Significant correlation with severity and organ failure,Ref:Mortele K,et
20、 al.AJR 2004;183:1261-1265,Computed Tomography and Magnetic Resonance Imaging in the Assessment of Acute Pancreatitis,Aim:To compare the accuracy of magnetic resonance imaging with computed tomography in assessing acute pancreatitisMethod:MRI was performed with intravenous secretin and contrast medi
21、umResults39 patients were studiedAcute pancreatitis was assessed clinically as severe in 7 patientsConsidering the Ranson score,MRI detected severe AP with 83%(58-96,95%CI);sensitivity,91%(68-98)specificity vs.78%(52-93)and 86%(63-96)for CTMagnetic resonance showed pancreatic duct leakage in 3 patie
22、nts(8%)Arvanitakis M,et al.Gastroenterology 2004;126(3):715-23,MRI Provides Prognostic Information in Acute Pancreatitis,CT vs MRI Score,MR-SI,CT-SI,2,4,6,8,10,8,10,6,4,2,Arvanitakis,Gastro 2004,126,0,0,MRI Provides Prognostic Information in Acute Pancreatitis,Acute Pancreatits,Diagnostic Guideline
23、IIIDetermination of Severity During Hospitalization,Contrast-Enhanced CT ScanNot on admission if diagnosis is determined-A few days after admission to distinguish interstitial from necrotizing pancreatitis when there is clinical evidence of increased severity.Level of Evidence IIITo guide aspiration
24、 in patients with fluid collection to determine if infected,ACG Practice Guidelines in Acute PancreatitisAm J Gastroenterol 2006;101:2379-2400,Acute Pancreatitis,Etiologies of acute pancreatitis,Etiologies,Acute Idiopathic Pancreatitis:does it really exist or is it a myth?,Background:Gallstones and
25、alcohol abuse are the most frequent causes(75%of patients)of acute pancreatitisConsider hyperlipidemia,hypercalcemia and drugsIn 10%to 40%,no cause is identified Identifying a cause in these patients is important,since the recurrence rate is high,Van Brummelen SE,et al.Scand J Gastroenterol(Suppl)20
26、03;(239):117-22,Microlithiasis is the Most Common Cause Acute Idiopathic Pancreatitis,Results:Microlithiasis or biliary sludge is an important cause of acute idiopathic pancreatitis in up to 80%of patientsMicrolithiasis can be detected by trans-abdominal/endoscopic ultrasonography or polarizing ligh
27、t microscopy of bileAcute pancreatitis can be prevented by performing cholecystectomy and opening the sphincter of Oddi,Adapted from:Van Brummelen SE,et al.Scand J Gastroenterol(Suppl)2003;(239):117-22,Microlithiasis:Effect of Treatment,E Ros,Gastroenterology 1991;101:1701SP Lee,N Engl J Med 1992,32
28、6:589,Microlithiasis:Effect of Treatment,Acute Pancreatitis,Etiologies of acute pancreatitis expanded,Etiologies,Drug-Induced Pancreatitis,1.4%to 2.0%of patientsMechanism hypersensitivity-early vs.toxic metabolite(usually 12 weeks),Acute Pancreatitis,Drug induced pancreatitis sorted by incidence,Dru
29、g Induced Acute Pancreatitis 2009,IsoniazidPegylated interferon alfa-2bClarithromycinMetronidazoleTrimethoprim-sulfamethoxazole,Atorvastatin,Rosuvastatin,SimvastatinEstrogen/TamoxifenPropofol,Jawaid Q,et al.Dig Dis Sci 2002;47(3):614-17Tosun E,et al.Acta Cardiol 2004;59(5):571-572Chow KM,et al.Van Z
30、uiden Communications 2004;62(1)Cecchi E,et al.Emergency Medicine Australasia 2004;16:473-475Schouwenberg BJJW,Deinum J.van Zuiden Communication 2003;61(7)Singh S,et al.JOP J Pancreas 2004;5(6):502-504Perego E,et al.JOP J Pancreas 2004;5(5):353-356Nigwekar SU,Casey KJ.JOP J Pancreas 2004;5(6):516-519
31、Neth J med 2005;63:275,Acute Pancreatitis,Infections and pancreatitis,Infectious Causes of Acute Pancreatitis:2003-2009,MeaslesHerpes SimplexHepatitis A B,C EHIVTakebayashi K,et al.Trop Gastroenterol 2003Khanna S,Viji JC.Trop Gastroenterol 2003;24(1):25-6Makharia GK,et al Trop Gastroenterol 2003;24(
32、4):200-01Tyner R,Turett G.South Med J 2004;97(4):393-94Shintaku M,et al.Arch Pathol Lab Med 2003;127:231-234,Other Causes of Acute Pancreatitis,Inflammatory bowel disease Crohns(not 5 ASA)4-foldUlcerative colitis 1.5 foldIschemia systemic lupus sickle cell crisisPreeclampsia-eclampsiaToxins carbofur
33、an insecticidesOrganophosphates Fan HC,et al.J Microbial Immunol Infect 2003;36(3):212-4Ahmed S,et al.Am J Hematol 2003 73(3):190-3Parmar MS.JOP 2004;5(2):101-4Rizos E,et al.JOP 2004;5(1):44-7Munk AM J Gastro 2004,Acute Pancreatitis,Hypertriglyceridemia,Tumors as Causes of Acute Pancreatitis:,Primar
34、yPancreatic adenocarcinomaIDPMTAmpullary tumorsLymphomaAdult T-cell leukemia/lymphomaMetastasesLungSalva R,et al.Ann Surg 2004;239(5):678-85Adv Thr 2005;22:225Mori A,2003 DDS,Acute Biliary Pancreatitis,Goals are to identify:patients whose stones have not passedpatients with complications of stones c
35、holangitisERCP is done only if there is biliary obstruction with cholangitis,Biliary Pancreatitis:What happens to CBD stones?,Stone or concretion is found in CBDwithin 48 hours after admission in 62%75%After 48 hours post admission CBD stones are found in 3%33%The natural history of CBD stones is pa
36、ssage,The Value of Magnetic Resonance Cholangio-pancreatography in Predicting CBD Stones in Patients with Gallstone Disease,Results:CBD stones were demonstrated in 43(12%)of 366 patientsMRCP had an observed sensitivity of 95%specificity of 100%positive predictive value of 100%and negative predictive
37、 value of 98%,Topal B,et al.Br J Surg 2003;90:42-47,Treatment Guideline VIIIRole of ERCP and Biliary Sphincterotomy in Gallstone Pancreatitis,Indicated for clearance of bile duct stones in patients with severe pancreatitis,in those with cholangitisERCP should be performed primarily in patients with
38、high suspicion of bile duct stones when therapy is indicatedEUS or MRCP can be used to identify common bile duct stonesLevel of Evidence:I,ACG Practice Guidelines in Acute Pancreatitis.Am J Gastroenterol 2006;101:2379-2400,Acute Biliary Pancreatitis:First 24 to 48 hours,Jaundice with Bilirubin 1.35
39、24 hrs,ERCP,MRCP,Pos,Neg,Stone removal,Elective surgical cholecystectomy,CBD stones,Neg,Pos,Role of Surgery in Patients with Severe Acute Pancreatitis,Early versus Late Necrosectomy in Severe Necrotizing Pancreatitis,Patients were randomly allocated to two treatment arms as follows:Group A included
40、early necrosectomy(within 48 to 72 hours of onset)Group B included late necrosectomy(at least 12 days after onset)Results:Difference in the mortality rate(58%vs.27%)was not statistically significant,the odds ratio for mortality was much higher in the early operation groupEarly surgery in severe acut
41、e pancreatitis is only required in cases with proven early infection of the pancreatic necrosis(and not stable),Mier J,et al.Am J Surg 1997;173:71-7Buchler MW,et al Dig Dis 1992;10:354-62Mai G,et al Berlin,Blackwell Science 1999;475-85,ROLE OF PROPHYLACTIC ANTIBIOTICS IN PATIENTS WITH SEVERE ACUTE P
42、ANCREATITIS,Adapted from H.Beger et al.,Gastroenterology 1986;91:433,Acute Pancreatitis,The incidence of pancreatic infections increases with time,Local and Systemic Infections in Acute Pancreatitis,After week 1,the prognosis.is mainly determined by bacterial infection of pancreatic and peripancreat
43、ic necrosisMortality increases from 5%-25%in patients with sterile necrosis to 15%-28%in patients with infected necrosisRau B,et al.J Am Coll Surg 1995;181:279-288Rau B,et al.World j Surg 1997;21:155-161Isenmann R,et al.Br J Surg 1999;86:1020-1024Wilson PG,et al.J Antimicrob Chemother 1998;41(suppl
44、A):51-63Tenner S,et al.Gastroenterology 1997;113:899-903Buchler MW,et al.Ann Surg 2000;232:619-626,Preoperative morbidity in patients with infected and sterile necrosis,Cardiovascular complications(systemic Pa min 14 31.0 5 7.3 0.001*Pulmonary insufficiency(Pa02120 M)19 42.2 15 21.7 0.02Sepsis(recta
45、l temperature 38.5C;leukocytes 12,000/mm3;platelets-4 16 35.66 8.70.001*Gastrointestinal bleeding 8 17.84 5.8 0.05*P=0.05 by Holms rejective multiple test procedure,Ref:Beger,et al.Pancreatology 2005;5:10-19,Antibiotic Therapy for Prophylaxis Against Infection of Pancreatic Necrosis in Acute Pancrea
46、titis,Aim:to determine the effectiveness and safety of prophylactic antibiotic therapy in patients with severe acute pancreatitis who have developed pancreatic necrosisResultsA survival advantage for antibiotic therapy(Odds ratio 0.32,p=0.02)was demonstratedPancreatic sepsis showed an advantage for
47、therapy(Odds ratio 0.51,p=0.04)Extra-pancreatic infection could be evaluated in three studies,but showed no significant advantage for therapy(Odds ratio 0.47,p=0.05),Cochrane Database Syst Rev 2003;(4):CD002941,Antibiotic Therapy for Prophylaxis Against Infection of Pancreatic Necrosis in Acute Panc
48、reatitis,(Cont)Surgery rates were not significantly reduced(Odds ratio 0.55,p=0.08)Fungal infections showed no strongly increased preponderance with therapy(Odds ratio o.83,p=0.7)Reviewers ConclusionStrong evidence that intravenous antibiotic prophylactic therapy for 10 to 14 days decreased the risk
49、 of super-infection of necrotic tissue and mortality in patients with severe acute pancreatitis with proven pancreatic necrosis at CTCochrane Database Syst Rev 2003;(4):CD002941,Prophylactic Antibiotic Treatment in Patients with Predicted Severe Acute Pancreatitis:A placebo-controlled,double-blind t
50、rial,Method114 patients with acute pancreatitis in combination with a serum C-reactive protein exceeding 150 mg/L and/or necrosis on contrast-enhanced CT scan,were enrolledPatients received either intravenous CIP(2 x 400 mg/day)+MET(2 x 500 mg/day)or PLAStudy medication was discontinued and switched
