Acute pancreatitis

condition mostly caused by gall stone or alcohol.
common presentation is central upper abdominal pain .

1. Acute pancreatitis Dr Bhupendra shah Senior resident BP koirala institute of health sciences Dharan

2. Outline Introduction Epidemiology Pathophysiology Etiology Clinical Presentation Workup Severity Scoring System Treatment Prognosis Complications

3. PANCREATITIS Inflammation in pancreas associated with injury to exocrine parenchyma PANCREAS  Greek word with literal meaning ‘pan’ (all/whole) , ‘ creas ’ (flesh): sweatbread

4. DEFINITION Atlanta Symposium definition of acute pancreatitis : An acute inflammatory process of the pancreas with variable involvement of other regional tissues or remote organ systems.

5. CLASSIFICATION OF ACUTE PANCREATITIS Atlanta* criteria ( 1992) Mild acute pancreatitis (80% cases) (Acute Interstitial/edematous pancreatitis) Acute Absence of organ failure Absence of local complications Severe acute pancreatitis(20 % cases) (Acute Hemorrhagic Necrotizing (fulminant) pancreatitis) Local complications +/- Organ failure defined as SBP < 90 mm Hg PaO 2 ≤ 60 mm Hg GI bleed ≥ 500 ml/24 hrs Cret ≥ 2 mg/ dL after rehydration Ranson score ≥ 3 or APACHE ≥ 8 Revised Atlanta criteria ( 2012) Mild acute pancreatitis Absence of organ failure Absence of local complications Moderately severe acute pancreatitis Local complications +/- Transient organ failure(<48 h ) Severe acute pancreatitis Persistent organ failure**(>48 h) and/or death *defined as a score of 2 or more for one of these(CVS, Renal, Resp ) organ systems using the modified Marshall scoring system

6. Epidemiology World wide incidence ranges between 5 and 80 per 100,000 population GEOGRAPHICAL Highest incidence(worldwide) recorded in the United States and Finland ( 73.4 cases per 100,000)

7. Epidemiology Gender Predilection Generally  M>F In males  more often related to alcohol In females  more often related to biliary tract disease Idiopathic pancreatitis  no clear gender predilection AGE Young males and Old Females

8. Pathogenesis

9. Mechanisms against Auto-digestion of Pancreas Packing of enzyme in precursor form Synthesis of trypsin inhibitor Low calcium level inside acinar cell promote trypsin destruction

10. Gallstone pancreatitis   Two factors have been suggested: reflux of bile into the pancreatic duct due to transient obstruction of the ampulla during passage of gallstones obstruction at the ampulla secondary to stone(s) or edema resulting from the passage of a stone .

11. How Alcohol  Acute Pancreatitis?? Effects of diet Malnutrition Direct toxicity of alcohol Concomitant tobacco smoking Hypersecretion of gastric and pancreatic juices(rich in protein, low in bicarbonate/ trypsin inhibitor) protein plugsduct obstruction/reflux 6).Hyperlipidemia 7).Increased ductal permeability enzymes extrusion  damage 8).Release of free radicals- superoxide, hydroxyl 9).Spasm of sphincter of Oddi

12. Pathogenesis of Acute Pancreatitis

13. CLINICAL FEATURES Abdominal pain Other symptoms Physical examination

14. Other Manifestations Subcutaneous fat necrosis Small(<1 cm), red, tender nodules on extensor skin of legs Purtscher retinopathy(on fundoscopy )

15. 17 Grey Turner sign Cullen’s sign

16. DIFFERENTIAL DIAGNOSIS ABDOMINAL CONDITONS Perforated peptic ulcer/ gastroentritis Biliary colic/acute cholecystitis / Cholangitis Mesentric Ischemia Ruptured Aortic Anuerysm Intestinal Obstruction Gastric/colon/pancreatic CA Viral Hepatitis IBS SYSTEMIC CONDITIONS DKA THORAX CONDITIONS Pneumonia/ARDS Pleuritic pain MI GYNECOLOGICAL CONDITONS Ectopic pregnancy Salpingtis

17. DIAGNOSIS AP established by the presence of 2 of the 3 following criteria: ( i ) Abdominal pain consistent with the disease (ii) Serum amylase and / or lipase greater than three times the upper limit of normal (iii) Characteristic findings from abdominal imaging The American Journal of Gastroenterology , (30 July 2013) | doi:10.1038/ajg.2013.218 Guideline: Management of Acute Pancreatitis

18. HEMATOLOGICAL Pancreatic Enzymes’ Assays Serum Amylase: ONSET: almost immediately PEAK: within several hours 3-4 times upper limit of normal within 24 hrs (90%) RETURN to normal depends on severity(3-5 days ) normal at time of admission in 20% cases Compared with lipase, returns more quickly to values below the upper limit of normal. Serum Lipase: more sensitive/specific than amylase Remains elevated longer than amylase(12 days) Useful if late presentation

19. DIAGNOSIS Contrast-enhanced computed tomography (CECT) and / or magnetic resonance imaging (MRI) of the pancreas should be reserved for patients in whom (3- 5 days later ) The diagnosis is unclear Who fail to improve clinically within the first 48– 72 h after hospital admission Evaluate complications The American Journal of Gastroenterology , (30 July 2013) | doi:10.1038/ajg.2013.218 Guideline: Management of Acute Pancreatitis

20. DIAGNOSIS MRI is helpful in patients with : A contrast allergy Renal insufficiency where T2-weighted images without gadolinium contrast can diagnose pancreatic necrosis The American Journal of Gastroenterology , (30 July 2013) | doi:10.1038/ajg.2013.218 Guideline: Management of Acute Pancreatitis

21. ETIOLOGICAL INVESTIGATIONS Abdominal ultrasound US should be performed in all patients with AP In the absence of gallstones and / or history of significant history of alcohol use, serum triglyceride should be obtained and considered the etiology if >1000 mg/dl Alcohol-induced pancreatitis the diagnosis should not be entertained unless a person has a history of over 5 years of heavy alcohol consumption ( > 50 g per day, but is often much higher ) In a patient > 40 years old , a pancreatic tumor should be considered as a possible cause of AP The American Journal of Gastroenterology , (30 July 2013) | doi:10.1038/ajg.2013.218 Guideline: Management of Acute Pancreatitis

22. Genetic testing may be considered in young patients ( < 30 years old) if : No cause is evident & a family history of pancreatic disease is present The American Journal of Gastroenterology , (30 July 2013) | doi:10.1038/ajg.2013.218 Guideline: Management of Acute Pancreatitis

23. IDIOPATHIC AP IAP is defined as pancreatitis with no etiology established after initial laboratory (including lipid and calcium level) and imaging tests ( transabdominal ultrasound and CT in the appropriate patient) The American Journal of Gastroenterology , (30 July 2013) | doi:10.1038/ajg.2013.218 Guideline: Management of Acute Pancreatitis

24. SENTINEL LOOP SIGN

25. COLON CUT-OFF SIGN

26. SEVERITY SCORING SYSTEMS ACUTE PANCREATITIS SPECIFIC SCORING SYSTEMS Ranson score Glagsow score B edside I ndex for S everity in A cute P ancreatitis(BISAP) score H armless A cute P ancreatitis S core(HAPS) Hong Kong Criteria ACUTE PANCREATITIS NON-SPECIFIC SCORING SYSTEMS (ICU SCORING SYSTEMS) A cute P hysiology A nd C hronic H ealth E valuation(APACHE) II score S equential O rgan F ailure A ssessment(SOFA) score

27. Ranson Criteria Admission A ge > 55 (70 years) W BC > 16,000 (18000) G lucose > 200 (220) L DH > 350 (400) A ST > 250 wagla During first 48 hours H ematocrit drop > 10% Serum c alcium < 8 B ase deficit > 4.0 (6.0) Increase in B U N > 5 (2) F luid sequestration > 6L (4L) Arterial P O 2 < 60 hbo fuc 30 5% mortality risk with <2 signs 15-20% mortality risk with 3-4 signs 40% mortality risk with 5-6 signs 99% mortality risk with >7 signs

28. Glasgow- Imrie score ON ADMISSION Age > 55 yrs TLC > 15 x 10 9 l -1 BSR>180 mg/ dL ( 10 mmol l -1 ) (no H/O diabetes) BUN > 16 mmol l -1 (no response to IV fluids) Pa0 2 < 60 mmHg ( 8 KPa ) WITHIN 48 HOURS Serum Calcium < 2.0 mmol l -1 Serum albumin <32 g l -1 LDH > 600 units l -1 AST/ALT > 200 units l -1 NOTE: Disease classified as SEVERE when 3 or more factors are present

29. BISAP Score: ( B) Blood urea nitrogen (BUN) >22 mg% (I) Impaired mental status (S) SIRS: 2/4 present (A) Age >60 years (P) Pleural effusion BISAP Score Observed Mortality 0 0.1% 1 0.4% 2 1.6% 3 3.6% 4 7.4% 5 9.5 % Wu et al, Gut 2008

30. CT SEVERITY INDEX CT Grade (Balthazar grade) A : normal pancreas- 0 B : enlarged pancreas but without inflammation- 1 C : pancreatic or peripancreatic inflammation-2 D : single peripancreatic fluid collection-3 E :>= 2 peripancreatic fluid collections or gas in pancreas or retroperitoneum-4 Necrosis score None -0 <33% - 2 33-50% - 4 > 50% - 6 TOTAL SCORE = CT grade + Necrosis Sabistine S. Marc The massachusetts General hospital handbook of Internal Medicine. 3 rd edition Pg 3-12 33 0-3 = 3% mortality 4-6 = 6% mortality 7-10 = 17% mortality

31. Harmless Acute Pancreatitis Score Absence of rebound tenderness Absence of Guarding Normal Hct level Normal serum creatine level Accuracy of nonseverity is 98% Stephen et al.Current medical diagnosis and treatment:2012;692-693

32. A cute P hysiology A nd C hronic H ealth E valuation II score-1985 NOTE: Disease classified as SEVERE if clinical impression of very ill patient with APACHE II score above 8

33. Modified Marshall Scoring System for organ failure

34. Predicting Severe AP(ACG 2013) So rather than depending on a scoring system to predict severity of AP, one need to be aware of intrinsic patient-related risk factors , including laboratory and imaging risk factors , for the development of severe disease.

35. /////////////////////// Clinical findings associated with a severe course for initial risk assessment Patient characteristics Age > 55 years Obesity (BMI > 30 kg/m 2 ) Altered mental status Comorbid disease SIRS (> 2 of the following criteria) pulse > 90 bpm Resp rate > 20/min or PaCO 2 >4.3 KPa (32 mmHg) Temperature > 38 °C (100.4 o F)or < 36 °C(96.8 o F) TLC >12,000 or <4 ,000 cells/mm 3 or > 10% immature neutrophils (bands) Laboratory findings BUN > 20 mg/dl Rising BUN Hct > 44% Rising Hct Elevated creatinine Radiology findings Pleural effusions Pulmonary infiltrates Multiple or extensive extrapancreatic collections

36. TREATMENT GUIDELINES Supportive Transfer to intensive care Nutritional support Use of prophylactic antibiotics Treatment of infected necrosis Treatment of sterile necrosis Role of ERCP and biliary sphinchterotomy

37. INITIAL MANAGEMENT NPO Obtain vital signs at frequent intervals (such as every 4-6 h ) Supplemental oxygen be administered during the first 24–48 h , especially if narcotic agents are used to control pain ABG should be performed when oxygen saturation is ≤95% , hypoxemia or hypotension refractory to a bolus of IV fluids

38. PAIN MANAGEMENT   Parenteral analgesics usually needed. A number of parenteral narcotics are used In past, morphine avoided due to a concern it cause spasm of the SOD and worsens although no evidence in humans .   Meperidine with the accumulation of a neurotoxic metabolite ( normeperidine ) ,relatively short duration of action, and many hospitals have severely limited its use.. Hydromorphine may thus be preferred.

39. INITIAL MANAGEMENT ICU Transfer to ICU should be considered If there are : S igns that suggest that the pancreatitis is severe or is likely to be severe Need for very aggressive fluid resuscitation to overcome hemoconcentration, especially in an older person who may have underlying cardiovascular disease If a patient does not have hypoxemia but is showing signs of labored respiration , transfer should be considered to monitor pulmonary status carefully in anticipation

40. INITIAL MANAGEMENT Fluid therapy in acute pancreatitis: Adequate prompt fluid resuscitation Fluids are given intravenously Aim to maintain urine output > 0.5 ml/kg body weight Clinically relevant questions remain regarding the - Type of fluid ( crystalloid or colloid - Ringer’s lactate or normal saline ) !! - Rate of administration ( Fast or slow ) - Goal of FT ??

41. INITIAL MANAGEMENT Aggressive hydration , defined as 250-500ml per hour of isotonic crystalloid solution should be provided to all patients , unless cardiovascular, renal, or other related comorbid factors exist Early aggressive intravenous hydration is most beneficial during the first 12 – 24 hr , and may have little benefit beyond this time period In a patient with severe volume depletion , manifest as hypotension and tachycardia , more rapid repletion (bolus) may be needed

42. Lactated Ringer ’ s solution may be the preferred isotonic crystalloid replacement fluid Fewer patients developing SIRS as compared with patients receiving normal (0.9% ) saline Normal saline given in large volumes may lead to the development of a non-anion gap, hyperchloremic metabolic acidosis INITIAL MANAGEMENT The American Journal of Gastroenterology , (30 July 2013) | doi:10.1038/ajg.2013.218 Guideline: Management of Acute Pancreatitis

43. INITIAL MANAGEMENT Fluid requirements should be reassessed at frequent intervals within 6 hr of admission and for the next 24 – 48 hr The goal to decrease hematocrit (demonstrating hemodilution) and BUN (increasing renal perfusion) and maintain a normal creatinine during the first day of hospitalization The American Journal of Gastroenterology , (30 July 2013) | doi:10.1038/ajg.2013.218 Guideline: Management of Acute Pancreatitis

44. NUTRITION IN AP In mild AP , oral feedings can be started immediately if there is no nausea and vomiting, and the abdominal pain has resolved In mild AP , initiation of feeding with a low-fat solid diet appears as safe as a clear liquid diet The American Journal of Gastroenterology , (30 July 2013) | doi:10.1038/ajg.2013.218 Guideline: Management of Acute Pancreatitis

45. INITIAL MANAGEMENT Oral intake of limited amounts of calories is usually initiated when : Abdominal pain has subsided Parenteral narcotics are no longer required Abdominal tenderness has markedly decreased Nausea and vomiting have ceased Bowel sounds are present Overall assessment of the physician is that the patient has improved

46. NUTRITION IN AP In severe AP, enteral nutrition is recommended to prevent infectious complications. Parenteral nutrition should be avoided , unless the enteral route is - Not available - Not tolerated - Not meeting caloric requirements Nasogastric delivery and Nasojejunal delivery of enteral feeding appear comparable in efficacy and safety

47. NUTRITION IN AP Enteral Feeding Stabilizes gut barrier function , prevent systemic complications and improve morbidity and mortality Enteral feeding is safer and less expensive than TPN , but there is not major improvements in morbidity and mortality of acute pancreatitis

48. NUTRITION IN AP Nasogastric Feeding W as found to be comparable to nasojejunal feeding in terms of safety, morbidity , and mortality Whether pancreatic rest has a role to play in patients with severe AP is still uncertain !! Animal studies have shown that pancreatic exocrine secretion in experimental AP in response to CCK stimulation is suppressed Pancreas. 2012 Jan;41(1):153-9. doi : 10.1097/MPA. Evaluation of early enteral feeding through nasogastric and nasojejunal tube in severe acute pancreatitis: a noninferiority randomized controlled trial

49. NUTRITION IN AP Role of immediate oral feeding versus fasting in 60 patients with AP The orally fed group had a significant 2-day shorter length of hospital stay without differences in recurrent attacks of pancreatitis in a follow-up of 3 months. Pancreas. 2012 Jan;41(1):153-9. doi : 10.1097/MPA. Evaluation of early enteral feeding through nasogastric and nasojejunal tube in severe acute pancreatitis: a noninferiority randomized controlled trial

50. ROLE OF ANTIBIOTICS IN AP Routine use of prophylactic antibiotics in patients with severe AP is not recommended The use of antibiotics in patients with sterile necrosis to prevent the development of infected necrosis is not recommended Antibiotics should be given for an extra-pancreatic infection, such as cholangitis, catheter-acquired infections, bacteremia, urinary tract infections, pneumonia

51. ROLE OF ANTIBIOTICS IN AP Infected necrosis should be considered in patients with pancreatic or extrapancreatic necrosis who deteriorate or fail to improve after 7– 10 days of hospitalization Initial CT-guided (FNA) for Gram stain and culture to guide use of appropriate antibiotics or Empiric use of antibiotics after obtaining necessary cultures for infectious agents, without CT FNA , should be given The American Journal of Gastroenterology , (30 July 2013) | doi:10.1038/ajg.2013.218 Guideline: Management of Acute Pancreatitis

52. THE ROLE OF ANTIBIOTICS IN AP Once blood and other cultures are found to be negative and no source of infection is identified, antibiotics should be discontinued . In patients with infected necrosis, antibiotics known to penetrate pancreatic necrosis, such as carbapenems, quinolones, and metronidazole ( MCQ ) Routine administration of antifungal agents along with prophylactic or therapeutic antibiotics is not recommended

53. ERCP IN AP Patients with AP and concurrent acute cholangitis should undergo ERCP within 24 hr of admission ERCP is not needed early in most patients with gallstone pancreatitis who lack laboratory or clinical evidence of ongoing biliary obstruction The American Journal of Gastroenterology , (30 July 2013) | doi:10.1038/ajg.2013.218 Guideline: Management of Acute Pancreatitis

54. ERCP IN AP ERCP is indicated for clearance of bile duct stones in patients with : - Severe worsening biliary pancreatitis Cholangitis Poor candidates for cholecystectomy Post cholecystectomy Strong evidence of persistent biliary obstruction

55. TREATMENT OF INFECTED NECROSIS Treatment of choice in infected necrosis is surgical debridement (NOW minimal invasive procedure preferred ) 33% of patients with necrotizing pancreatitis develop infected necrosis, usually after 10 days of illness 48% of patients with infected necrosis have persistent organ failure , either documented initially at admission or sometime after admission Organ failure may occur in a substantial percentage of patients with both sterile 45 % & infected necrosis 62%

56. In stable patients with infected necrosis , surgical, radiologic, and/ or endoscopic drainage should be delayed by preferably 4 weeks to allow the development of a wall around the necrosis ( walled-off pancreatic necrosis ). The American Journal of Gastroenterology , (30 July 2013) | doi:10.1038/ajg.2013.218 Guideline: Management of Acute Pancreatitis

57. TREATMENT OF STERILE NECROSIS Sterile necrosis is best managed medically during the first 2–3 wk After this interval, if abdominal pain persists and prevents oral intake, debridement should be considered. This is usually accomplished surgically, but percutaneous or endoscopic debridement is a reasonable choice in selected circumstances with the appropriate expertise.

58. No or little role of……………….. Nasogastric suction and H 2 -blockers Secretion-inhibiting drugs Atropine, calcitonin, somatostatin and its analogue( Octreotide ) glucagon and fluorouracil Protease inhibiting drugs Aprotinin , gabexate mesylate , camostate , phospholipase A 2 inhibitors, FFP Indomethacin or PG inhibitors PAF antagonists PAF acetylhydrolase , Lexipafant

59. When to Discharge Pain is well controlled with oral analgesia Able to tolerate an oral diet that maintains their caloric needs, and all complications have been addressed adequately Follow up Routine clinical follow-up care (typically including physical examination and amylase and lipase assays) is needed to monitor for potential complications of the pancreatitis, especially pseudocysts . Within 7-10 days

60. Prognosis TYPE OF AP MORTALITY Overall 10-15 % (Biliary> alcholic ) Mild Acute Pancreatitis(80 % cases) 1 % Severe Acute Pancreatitis(20 % cases) Severe  20-50 % <1 week 1/3 cases MOF >1 week 2/3 cases Sepsis (+MOF)

61. REFERENCES: Harrison principal of internal medicine 18 th edition The American Journal of Gastroenterology , (30 July 2013) Guideline : Management of Acute Pancreatitis Robbins & Cotran Pathologic Basis of Disease - 8th Ed Bailey and Love’s short practice of surgery 25 th edition Washington Manual® of Medical Therapeutics, The, 33rd Edition Meta-analysis of parenteral nutrition versus enteral nutrition in patients with acute pancreatitis BMJ 2004; 328   Acute Pancreatitis.Frossard JL, Steer ML, Pastor CM. Lancet 2008; 371:14 Kun Jiang et al .world journal of Gastroenterology ‘present and future antibiotics for severe acute pancreatitis ,2012-1-21:279-286 Ryan Van Woerkom et al .Acute pancreatitis review and clinical update;2009-1 ;9-19