Acute Pancreatitis (According to American College of Gastroenterology 2013 guidelines)

This Presentation focuses on definition, new classification, different scoring systems for severity, rationale for radiological signs and new management recommendations as per 2013 American College of Gastroenterology guidelines

1. Acute Pancreatitis [Acute inflammation of abdominal tiger] (According to American College of Gastroenterology 2013 guidelines) Jibran Mohsin Resident, Surgical Unit I SIMS/Services Hospital Lahore

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. CLINICAL CLASSIFICATION *Considered a phase of chronic pancreatitis ** resulting from fibrosis within pancreas

5. ACUTE PANCREATITIS CLINICAL DEFINITION An acute condition presenting with abdominal pain-usually associated with raised blood/urine pancreatic enzymes as a result of pancreatic inflammation PATHOLOGICAL DEFINITION Reversible* pancreatic parenchymal injury associated with inflammation ___________________________________________________________ *if underlying cause of pancreatitis is removed, heal without any impairment of function or morphologic loss of gland *Recurrent attacks with irreversible parenchymal injury leading to impairment of function and morphologic loss is chronic pancreatitis

6. 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

7. Modified Marshall Scoring System for organ failure

8. Two Distinct phases of Acute Pancreatitis Early Phase(within 1 week) Characterized by SIRS +/- organ failure Severity assessed by functional /clinical Severity Scoring System ( Ranson / Galsgow etc ) Late Phase (>1 week) Characterized by local complication Severity assessed by morphological scoring system(Balthazar Scoring) __________________________________________________________________________*Early clinical and the later morphologic classifications do not necessarily overlap and do not necessarily correlate with one another

9. 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)

10. Epidemiology Median ages of onset for various etiologies Etiology Median Ages of onset Alcohol-related 39 years Biliary tract–related 69 years Trauma-related 66 years Drug-induced etiology 42 years ERCP-related 58 years AIDS-related 31 years Vasculitis -related 36 years

11. 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

12. Epidemiology RACE H ospitalization rates  3 times higher for blacks than whites (racial differences more pronounced for males than females) Risk for African Americans aged 35-64 years  10 times higher than for any other group

13. PATHOPHYSIOLOGY Autodigestion of pancreatic substance by inappropriately activated pancreatic enzymes (especially trypsinogen )

14. PATHOPHYSIOLOGY TRYPSINOGEN  TRYPSIN (hydrolysis of N-terminus hexapeptide by brush border enterokinase ) Activation of prekallikrein Activation of kinin system Activation of Hageman factor-XII Activation of clotting and complement systems  thrombosis and inflammation Activation of Phospholipase Activation of Prostaglandins and Bradykinins Lipase activation  Triglycerides  Glycerol + Fatty acids Fatty acids+ calcium  saponified fat H ypocalcemia Elastase activation  Digestion of elastic fibers  Capillary leak/rupture/ Pseudoaneurysm 3 rd space Sequestration of blood/fluid  Hemorrhage+ Hypovolemic shock Activation of Lysolecithinase (derived from bile) Membrane damage  Necrosis Release of inflammatory mediators into circulation systemic complications

15. MICROBIOLOGY-in infected necrosis Commonly polymicrobial infection-60% Source: gall bladder, colon, small bowel( Transmural ) or hematogenous spread INCIDENCE: 24%(1 week) and 70 %( 3 weeks) ORGANISMS: E.Coli (35%), klebsiella ( 25%), Enterococcus (25%) Others….. Staphlyococci , pseudomonas, proteus , enterobacter , anaerobes, candida(10%)

16. Etiology Mechanical causes Metabolic causes Infective causes Genetic causes Vascular causes Idiopathic AP

17. MECHANICAL CAUSES OF ACUTE PANCREATITIS Gall stones  Choledocholithiasis ( 4 0-70 %) Most common biliary tract disease leading to AP MOA: Ductal obstruction causing ductal hypertension and acinar cell injury “Common channel hypothesis”-Opie in 1901(bile /activated enzymes reflux)- CONTROVERSIAL Risk factors: inverse relation to size , wide cystic duct 5 % of gall stones causes pancreatitis M:F=1:3 Ampullary tumor sphincter of Oddi dysfunction Pancreatic CA(1-2 % ) 5 % present as AP Choledochoceles , biliary sludge Abdominal trauma(1.5 %cases) 17 % cases have high enzymes and 5 % have clinical AP Penetrating>Blunt Iatrogenic Injury Operative injury - Endoscopic procedures with dye injection

18. METABOLIC CAUSES OF ACUTE PANCREATITIS Alcoholism ( 25-35 %) M:F=6:1 Hyperlipoproteinemia (1-4 %) Type I and V hyperlipidemia >1000 mg/ dL (diagnostic criteria) More severe than alcohol/gallstone Malnutrition Diabetes, Azotemia Porphyria Hypercalcemia /hyperparathyroidism Hyper secretion and formation of calcified stones intraductally Acinar injury Drugs (2 % cases)(usually mild) Definite association ( azathioprine, sulfonamaides , sulindac , tetracycline, valproic acid , Didanosine , Methyldopa,estrogens , furosemide, 6-Mercaptopurine, pentamidine , 5-ASA , steriods , octreotide ) Probable association ( thiazides , Flagyl , Methandienone , Nitrofurantoin , phenformin, piroxicam, procainamide , Colaspase , chlorthalidone , asparagine, cimetidine, cisplatin , cytosine arabinoside , diphenoxylate , ethacrynic acid)

19. INFECTIVE CAUSES OF ACUTE PANCREATITIS Viruses M M R, Dengue virus(complication of dengue hemorrhagic fever MOA: Capillary leak 3 rd space loss ) , Coxsackie B , Hepatitis virus, CMV , EBV, Echovirus, VZV, HSV Bacteria M. tuberculosis , M. avium complex, Mycoplasma , Legionella, Leptospira , Salmonella, Campylobacter, Yersinia, Brucella , Nocarbia Fungi Aspergillus Parasites Clonorchis sinensis , Toxoplasma, Cryptosporidium, Ascaris , Echinococcus granulosus , Fasciola Hepatica, Opistorhcis sp and Dicrocoelium dendriticym Scorpion and snake bite Trinidalian scorpion* ( Tityus trinitatis ) MOA: Neurotransmitter discharge from cholinergic nerve terminals, leading to massive production of pancreatic juice(same MOA in antiacetylcholinesterase /OPC insecticide) *Most common cause of AP in Republic of Trinidad and Tobago , a twin island country off the northern edge of South America

20. GENETIC CAUSES OF AUTE PANCREATITIS Pancreas divisum ( unfused ducts of Wirsung and Santorini ) Seen in 20-45 % cases MOA(controversial): stenotic minor papillae and atretic duct of santorini Anomalous union of pancreaticobiliary duct(annular pancreas) Autoimmune pancreatitis-associated with IBD Hereditary pancreatitis- Autosomal dominant, gain of function, m utations in cationic trypsinogen (PRSS1)with 80 % penetrance  premature activation of trypsinogen Mutation in trypsin inhibitor (SPINK1) genes  blockade of active binding of trypsin  rendering it inactive Acute pancreatitis in teens Chronic in next 2 decades 40 % risk of pancreatic cancer by 70 year Celiac disease Cystic fibrosis-CFTR mutation  abnormality of ductal secretion

21. VASCULAR CAUSES OF ACUTE PANCREATITIS Shock Hypothermia Atheroembolism Vasculitis ( Polyarteritis nodosa , SLE)

22. 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 Hyperlipidemia Increased ductal permeability  enzymes extrusion damage Release of free radicals- superoxide, hydroxyl Spasm of sphincter of Oddi

23. Alcohol-induced Pancreatitis M anifests as a spectrum, ranging from discrete episodes of AP to chronic irreversible silent changes. D iagnosis should not be entertained unless a person has a history of over 5-(15) years of heavy(>50 g per day, types less significant) alcohol consumption. Clinically evident AP occurs in <5 % of heavy drinkers; thus, there are likely other factors that sensitize individuals to the effects of alcohol, such as genetic factors and tobacco use. 1 st attack is considered alcohol induced AP Although it may be 1 st manifestation of (acute on) chronic pancreatitis

24. Idiopathic Acute Pancreatitis Defined as pancreatitis with no etiology established after initial laboratory (including lipid and calcium level,autoimmune markers, viral titers) and imaging tests (USG and CT in the appropriate patient ) In some patients an etiology may eventually be found(70 % of IAP due to microlithiasis ), yet in others no definite cause is ever established. Patients with IAP should be evaluated at centers of excellence focusing on pancreatic disease, providing advanced endoscopy services and a combined multidisciplinary approach. ________________________________________________________ Careful search for the etiology must be made in all cases, and no more than 20 % of cases should fall into the idiopathic category

25. Hyperlipidemia induced AP In the absence of gallstones and/or history of significant history of alcohol use, a serum triglyceride should be obtained and considered the etiology if > 1,000 mg /d l L actescent (milky) serum has been observed in as many as 20 % of patients with AP T herefore a fasting triglyceride level should be re-evaluated 1 month after discharge when hypertriglyceridemia is suspected MOA : Lipase liberate large amounts of toxic fatty acids into pancreatic microcirculation Leading to endothelial injury, sludging of blood cells, and consequent ischemic states

26. Iatrogenic-Operative Pancreatitis Surgeries performed on/close to pancreas Pancreatic biopsy B iliary duct exploration Distal or Billroth II gastrectomy Jejunostomy Splenectomy Surgeries that use low systemic perfusion Cardiopulmonary bypass (also due to hypothermia, atheromatous emboli) Cardiac transplantation

27. Post-ERCP Pancreatitis 3 rd Most common cause of AP(after gallstone and alcohol) i.e. 4% Most common complication of ERCP INCIDENCE 2-4 % (Historically, 5-10%) patients undergoing ERCP develop acute pancreatitis Risk of severe AP < 1/500. CAUSE Duct disruption , enzyme extravasation PREDISPOSING FACTORS Sphincter of Oddi dysfunction(risk increases to 30 %) H/O recurrent pancreatitis Sphincterotomy Balloon dilation of sphincter Inexperienced endoscopist

28. CLINICAL MANIFESTATION

29. ABDOMEN PAIN- Cardinal Symptom SITE : usually experienced first in the epigastrium but may be localized to either upper quadrant or felt diffusely throughout the abdomen or lower chest ONSET : characteristically develops quickly, generally following substantial meal and precedes NV SEVERITY : frequently severe, reaching max. intensity within minutes rather than hours NATURE : “boring through”, “knifing” (illimitable agony) DURATION : hours-days COURSE : constant (refractory to usual doses of analgesics, not relieved by vomiting) RADIATION : directly to back(50%), chest or flanks RELEIVING FACTOR : sitting or leaning/stooping forward (MUHAMMEDAN PRAYER SIGN) due to shifting forward of abdominal contents and taking pressure off from inflamed pancreas AGGRAVATING FACTOR : food/alcohol intake, walking, lying supine _______________________________________________________________________________ Pain described as dull, colicky, or located in the lower abdominal region is not consistent with AP and suggests an alternative etiology

30. OTHER MANIFESTATIONS Nausea, frequent and effortless vomiting, anorexia,diarrhea Due to reflex pylorospasm More intense in necrotizing than in edematous pancreatitis Persistent retching despite empty stomach Hiccups Due to gastric distension/diaphragmatic irritation Fever Low grade, seen in infective pancreatitis Weakness, Anxiety, Sweating Indicates severe attack Polyarthritis

31. General Physical Examination Appearance: well  gravely ill with profound shock, toxicity and confusion Vitals: Tachypnea(and dyspnea-10%), Tachycardia(65%), Hypotension, temp  high(76%)/normal/low (acute swinging pyrexia in cholangitis) Icterus(28%) gallstone pancreatitis or due to edema of pancreatic head Cyanosis Improper lung perfusion Pallor, cold clammy skin,diaphoretic

32. ABDOMEN EXAMINATION Tenderness + Rebound tenderness: epigastrium/upper abdomen Distension: Ileus(BS decreased or absent) ascites with shifting dullness Mass in epigastrium(usually absent) due to inflammation Guarding(also called “ defense musculaire ” )-upper abdomen tensing of the abdominal wall muscles to guard inflamed organs within the abdomen from the pain of pressure upon them(i.e. during palpation) Rigidity(involuntary stiffness)-unusual Tensing of the abdominal wall muscles to guard inflamed organs even if patient not touched

33. Cutaneous Ecchymosis(1 % cases) * *Neither sign is pathognomonic of acute pancreatitis *takes 24-48 hours to develop with 10-40 % mortality **More commonly, ruddy erythema in flanks due to extravasated pancreatic exudate

34. Differential Diagnosis GREY TURNER/CULLEN/FOX SIGNs Acute Pancreatitis Pancreatic Hemorrhage Ruptured AAA Blunt abdominal trauma Ruptured ectopic pregnancy Retroperitoneal hemorrhage Coagulopathy Above: George Grey Turner Above: Thomas Stephen Cullen

35. GREY TURNER 1 SIGN CULLEN 2 SIGN FOX 3 SIGN Named after British surgeon George Grey Turner(1877-1951) 2. Named for Thomas Stephen Cullen (1869-1953), Canadian gynecologist who first described the sign in ruptured ectopic pregnancy in 1916 3.Named after George Henry Fox(1846-1937), American dermatologist

36. RESPIRATORY EXAMINATION Left sided* Pleural effusion(10-20%) + pulmonary edema+ pneumonitis Reduced chest movements+ decreased vocal fremitus/resonance + stony dull percussion note+ decreased air entry basally bilaterally + basal fine mid/end-inspiratory crepitation's- don’t change with cough *Due to close approximation of body and tail of pancreas to the left sided diaphragm

37. Neurological Examination

38. Other Manifestations Subcutaneous fat necrosis Small(<1 cm), red, tender nodules on extensor skin of legs Purtscher retinopathy(on fundoscopy ) Activation of complement and agglutination of blood cells within retinal vessels causing Ischemic injury of retina May cause temporary or permanent blindness

39. MANIFESTAIONS OF COMPLICATIONS Hypocalcaemia circumoral numbness or paresthesia (1 st symtpom to develop) / tingling of distal extremities carpopedal spasm (=main d'accoucheur - French " hand of the obstetrician ”) Flexion of wrist and MCP joints with extension of IP joints laryngospasm generalized seizures Chvostek *(-Weiss) sign Depending on calcium level, graded response occur: twitching first at angle of mouth, then by nose, the eye and the facial muscles Positive in 10 % population in absence of hypocalcaemia Trousseau** sign of latent tetany BP cuff around arm and inflating to 20 mmHg above SBP for 3-5 minutes Carpal spasm observed More specific and sensitive than chvostek sign( postive even before tetany / hyperreflxia ) * František Chvostek ( German: Franz Chvostek ) Czech-Austrian military physician (1835 – 1884 ), described this sign in 1876. ** Armand Trousseau, French physican (1801-1867) described this phenomenon in 1861

40. MANIFESTAIONS OF COMPLICATIONS

41. 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

42. Diagnostic criteria M ost often established by the presence of two of the three following criteria : (i) abdominal pain consistent with the disease, ( ii) serum amylase and/or lipase greater than three times the upper limit of normal, and/or ( iii) characteristic findings from abdominal imaging. _________________________________________________________ CT and/or MRI of the pancreas should be reserved for patients in whom the diagnosis is unclear(typical pain with normal enzymes) who fail to improve clinically within the first 48–72 h after hospital admission (e.g., persistent pain, fever, nausea, unable to begin oral feeding ) to evaluate complications

43. WORKUP HEMATOLOGICAL investigations RADIOLOGICAL investigations Miscellaneous investigations

44. HEMATOLOGICAL BASELINES CBC: Low Hb : prolonged hemetemesis /melena, internal hemorrhage Leucocytosis (10,000-30,000/ mcL )-infection, non infectious inflammation Low platelets-DIC Hct –raised in hemoconcentration LFT’s: raised bilirubin, AST/ALT/LDH, ALP, GGTP- gall stone pancreatitis RFT’s: raised BUN/ cretainine - ATN  ARF Coagulation profile: increased INR-DIC BSR: > 180 mg/dl-diabetes as a sequelae or cause Serum electrolytes: Low sodium/potassium: persistent vomiting Hypocalcemia - saponification/fat necrosis Serum Protein: low protein/ albumin Diabetes Mellitus AP

45. HEMATOLOGICAL ABG’s Etiology specific investigations Serum fasting lipid profile Viral titers Serum Calcium ( Hypercalcemia APHypocalcemia ) Autoimmune markers increased serum levels of IgG4 serum autoantibodies such as anti-nuclear antibody (ANA), anti- lactoferrin antibody, anti-carbonic anhydrase II antibody, and rheumatoid factor (RF), Acid-Base Disturbance Etiology Metabolic (Lactic) acidosis with high anion gap Hypovolemic shock Cholride -responsive Hypokalemic Hypochloremic metabolic alkalosis (Urine chloride < 20 mEq /L) persistent vomiting Respiratory acidosis ARDS/ resp failure

46. 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

47. Pancreatic Enzymes’ Assays Urine Amylase More sensitive than serum levels Remain elevated for several days after serum levels returned to normal Pancreatic-specific amylase(p-amylase) Measuring p-amylase instead to total amylase(also includes salivary amylase) makes diagnosis more specific(88-93%)

48. CONDITIONS ASSOCIATED WITH RAISED SERUM AMYLASE ABDOMEN Small bowel obstruction strangulation ileus mesenteric ischemia Acute appendicitis Cholecystitis Perforated Duodenal Ulcer Gastroenteritis Biliary peritonitis Spasm of sphincter of Oddi GYNE Ruptured Ectopic pregnancy T orsion of an ovarian cyst OTHERS Parotitis (Mumps) Macroamylasaemia Opioids administration Low GFR Brain injury(CVA)- hyperstimulation of pancreas

49. Plain CXR-PA view Left sided Pleural effusion : blunting of costophrenic and cardiophrenic angles + haziness in lower zones Elevated diaphragm on left side Linear focal atelactasis of lower lobe of lungs ARDS: diffuse alveolar interstitial shadowing Pulmonary edema : prominent vascular markings _________________________________________________________ Not diagnostic of Acute Pancreatitis; useful in differential diagnosis

50. Plain X-ray abdomen erect AP view Sentinel* loop sign Localized isolated Distended gut loop (Ileus) seen near the site of injured viscus or inflamed organ RATIONALE : body's effort to localize the traumatic or inflamed lesions ETIOLOGY : Localized paralysis followed by accumulation of gas SITE : Acute Pancreatitis  Left hypochondrium (PROXIMAL JEJUNUM) Acute Appendicitis Right iliac fossa Acute Cholecystitis  Right Hypochondrium Diverticulitis Left iliac fossa *SENTINEL: A soldier stationed as a guard to challenge all comers and prevent a surprise attack _______________________________________________________________ Not diagnostic of Acute Pancreatitis; useful in differential diagnosis

51. SENTINEL LOOP SIGN

52. Plain X-ray abdomen erect AP view Colon cut-off sign Gas filled (Distended) segment of proximal(mainly transverse) colon associated  with narrowing of the splenic flexure abruptly ending at the area of pancreatic inflammation with collapse of descending colon RANTIONALE : Extension of inflammatory process from the pancreas into the phrenicocolic ligament  via the transverse mesocolon r esulting in functional spasm and/or mechanical narrowing of the splenic flexure at the level where the colon returns to the retroperitoneum . Differential DIAGNOSIS : IBD Carcinoma of colon Mesenteric Ischemia ____________________________________________________________________________________ Not diagnostic of Acute Pancreatitis; useful in differential diagnosis

53. COLON CUT-OFF SIGN

54. Plain X-ray abdomen erect AP view Renal halo sign RATIONALE: peripancreatic inflammatory reaction extension into pararenal space ETIOLOGY : water-density (radiolucent-halo)of inflammation in anterior pararenal space contrasts with perirenal fat; more common on left side OTHERS _______________________________________________________________ Not diagnostic of Acute Pancreatitis; useful in differential diagnosis Air in the duodenal C-loop increased gastrocolic separation G astric curvature distortion To rule out perforated DU(gas under diaphragm) Obliteration of psoas shadow Localized ground glass appearance ( localized increased high soft tissue density) Calcified gall stones Pancreatic calcification(chronic pancreatitis)

55. Renal Halo Sign NORMAL RENAL HALO SIGN

56. Transcutaneous Abdominal Ultrasonography Not diagnostic Should be performed within 24 hours in all patients to detect gall stones* as a potential cause Rule out acute cholecystits as differential diagnosis Detect dilated CBD sensitivity-(70-80%) DEMERIT: overlying gas shadows 2ndary to bowel distension THERAPEUTIC: USG-guided aspiration for gram staining and culture USG-guided pig tail catheter insertion ______________________________________________________________________________ * Identification of gallstones as the etiology should prompt referral for cholecystectomy to prevent recurrent attacks and potential biliary sepsis. Gallstone pancreatitis is usually an acute event and resolves when the stone is removed or passes spontaneously.

57. IV Contrast enhanced Computed Tomography Scan Provides over 90 % sensitivity and specificity for the diagnosis of AP….. BUT Routine use in patients with AP is unwarranted, as the diagnosis is apparent in many patients and most have a mild, uncomplicated course .

58. IV Contrast enhanced Computed Tomography Scan* INDICATIONS-DIAGNOSTIC Diagnostic uncertainty (differentiating pancreatitis from other possible intra-abdominal catastrophes) Severe acute pancreatitis- distinguish interstitial from necrotizing pancreatitis Necrosis( non enhancement area > 30 % or 3 cm) done at 72 hrs * Systemic complications: Progressive deterioration, MOF, sepsis Localized complications: Altered fat and fascial planes, Fluid collection, pseudocyst , psduoaneurysm , Bowel distension, mesenteric edema, hemorrhage _____________________________________________________________ *INVESTIGATION OF CHOICE **Seldom needed within first 72 hrs after symptom onset unless the diagnosis is uncertain, because inflammatory changes are often not radiological present until this time

59. IV Contrast* enhanced Computed Tomography Scan INDICATIONS-DIAGNOSTIC Initial assessment of prognosis(CT severity index) Perfusion CT at 3 rd day  area of ischemia predict pancreatic necrosis INDICATIONS-THERAPEUTIC: CT-guided aspiration of fluid collection/necrotic tissue for gram staining and culture(sterile vs infected necrosis) specimen should be delivered to the laboratory within an hour and interpreted promptly CT-guided pig tail catheter insertion ______________________________________________________________ *Use of IV contrast may increase risk of complications of pancreatitis and AKI *Avoided if serum creatinine >1.5 mg/ dL *MRI suitable alternative

60. BALTHAZAR CT severity index(CTSI)-1994 ___________________________________________________________________ Mild (0-3) moderate (4-6) severe (7-10) CT Severity Index Inflammation score + Necrosis score

61. M agnetic R esonant I maging Suitable alternative to CT in patients with a contrast allergy and renal insufficiency where T2-weighted images without gadolinium contrast can diagnose pancreatic necrosis

62. M agnetic R esonant C holangio p ancreatography INDICATION: diagnosis of suspected biliary and pancreatic duct obstruction in the setting of pancreatitis . Repeated attacks of idiopathic acute pancreatitis Merit used if choledocholithiasis is suspected but there is concern that pancreatitis might worsen is ERCP is performed Provide non-invasive/fast/safe high-quality (Heavily T2–weighted) imaging for diagnostic and/or severity purposes

63. E ndoscopic U ltra S onography INDICATIONS Repeated idiopathic acute pancreatitis* occult biliary disease- small stones/sludge secretin-stimulated EUS study may reveal resistance to ductal outflow at the level of the papilla, as evidenced by dilatation of the pancreatic duct to a greater extent and longer duration than in a healthy population Age >40 to exclude malignancy especially those with prolong or recurrent course RATIONALE: 5 % CA pancreas present as AP _________________________________________ *Endoscopic investigation in patients with acute idiopathic pancreatitis should be limited, as the risks and benefits of investigation in these patients are unclear and should be referred to centers of expertise.

64. E ndoscopic R etrograde C holangio p ancreatography INDICATION Severe gallstone AP or AP with concurrent acute cholangitis/biliary obstruction/ biliary sepsis/jaundice (due to persistent stone) E RCP within 24(-72) h of admission Sphincterotomy /stent and bile duct clearance reduces infective complications/mortality NOT INDICATED N ot needed early in most patients with gallstone pancreatitis who lack laboratory or clinical evidence of ongoing biliary obstruction As most of gallstones causing AP readily pass to duodenum and are lost in stool MRCP or EUS recommended if CBD stone still suspected as risk of post-ERCP pancreatitis is greater with normal calibre bile duct and normal bilirubin MRCP /EUS as accurate as diagnostic ERCP

65. MISCELLANEOUS Peritoneal(sensitivity 54%,specificity 93%)/Pleural fluid tap High amylase/lipase/protein Urine Complete Examination Proteinuria, granular cast, glycosuria Electrocardiography ST-T wave changes Bile Aspiration Crystal analysis, if suspicion of microlithiasis Manometry Sphincterof Oddi dysfunction as a cause Genetic testing may be considered in young(<30 yrs ) patients if no cause is evident and a family history (especially if >1 family member)of pancreatic disease is present

66. 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

67. Each system has merits and demerits, and none is currently recognized as a criterion standard ______________________________________

68. Although amylase/lipase are used in diagnosing pancreatitis, they are NOT use for predicting severity of disease _____________________________________ i.e. patient with normal amylase(raised in 90 % cases) levels may still have severe acute pancreatitis

69. RANSON SCORE-1974 (for alcohol pancreatitis) ON ADMISSION Age > 55 yrs TLC > 16,000/mm3 BSR> 200 mg/ dL AST > 250 IU/L LDH > 350 IU/L WITHIN 48 HOURS BUN rise >5 mg/ dL Pa0 2 < 60 mmHg ( 8 KPa ) Serum Calcium < 8 mg/ dL Base deficit > 4 meq /L Fluid Sequestration > 6000 mL Hct fall > 10 % NOTE: Disease classified as SEVERE when 3 or more factors are present

70. Revised RANSON SCORE-1979 (for Gallstone pancreatitis) ON ADMISSION Age > 70 years TLC > 18000/mm 3 BSR > 220 mg/ dL AST> 250 IU/L LDH >400 IU/L WITHIN 48 HOURS BUN rise >5 mg/ dL Pa0 2 < 60 mmHg ( 8 KPa ) Serum Calcium < 8 mg/ dL Base deficit > 5 meq /L Fluid Sequestration > 4 litres Hct fall > 10 % NOTE : Disease classified as SEVERE when 3 or more factors are present

71. RANSON SCORE Ranson score Mortality rate SEVERITY Interpretation 0-2 ≈ 0-2 % i.e. minimal mortality Mild AP Admit in regular ward 3-5 10-20 % Severe AP Admit in ICU/HDU 6-7 40 % Associated with more systemic complications >7 >50 % Same as above SCORING SYSTEM SENSITIVITY SPECIFICITY Ranson Criteria 73% 77% APACHE II 77% 84% CRP 73% 71%

72. RANSON SCORE……. DRAWBACKS One has to measure all 11 signs to achieve the best predictability of prognosis 2 full days are needed to complete the profile . A delay of 48 hours after admission merely for assessment may squander a valuable opportunity to prevent a complication during this time . Best used within the initial 48 hours of hospitalization and have not been validated for later time intervals . Threshold for abnormal valve depends on whether cause is gallstone or alcohol Only 73 % sensitive and 77 % specific in predicting mortality

73. 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

74. Modified Glasgow/PANCREAS score P aO2 < 8kPa (60mmhg) A ge > 55 years N eutrophils: WBC >15 x109/l C alcium < 2mmol/l R enal function: ( Urea > 16mmol/l) E nzymes: (AST/ALT > 200 iu /L or LDH > 600 iu /L) A lbumin < 32g/l S ugar: (Glucose >10mmol/L) * Applicable for both gallstone and alcohol induced pancreatitis within 48 hours of admission * Omission of age/serum transaminase increases the predictive valve of scoring system as serum transaminase did not differ significantly between mild and severe pancreatitis *Bold 4 factors are independently significant in predicting the severity

75. 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

76. APACHE Scoring System MERIT Immediate assessment of the severity of pancreatitis possible Can be used even after 48 hours Unlike ALL pancreatic specific scoring systems, APACHE (and SOFA) also includes clinical features of patient besides laboratory values (Clinical findings are more important than lab findings in predicting SIRS,sepsis and other complications) Best validated( medscape )

77. DEMERITS OF AP-specific scoring systems(ACG 2013) Uniformly cumbersome, typically requiring 48 h to become accurate when the score demonstrates severe disease, the patient’s condition is obvious regardless of the score. H ave a limited value, as they provide little additional information to the clinician in the evaluation of patients and may delay appropriate management. No laboratory test is practically available or consistently accurate to predict severity in patients with AP. Even the acute-phase reactant CRP , the most widely studied inflammatory marker in AP, is not practical as it takes 72 h to become acc urate. CT and/or MRI imaging also cannot reliably determine severity early in the course of AP, as necrosis usually is not present on admission and may develop after 24 – 48 h. _________________________________________________________________ Thus , in the absence of any available test to determine severity, close examination to assess early fluid losses, hypovolemic shock, and symptoms suggestive of organ dysfunction is crucial.

78. 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.

79. 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

80. MANAGEMENT Mild acute pancreatitis Conservative Approach Admit in general ward Non invasive monitoring (Moderate)Severe acute pancreatitis Aggressive Approach Admit in HDU/ICU Invasive monitoring __________________________________________ Recognizing patients with severe acute pancreatitis ASAP is critical for achieving optimal outcomes

81. Mild Acute Pancreatitis mild and self-limiting, needing only brief hospitalization . Rehydration by IV fluids Frequent non-invasive observation/monitoring( atleast 8 hrly ) Brief period of fasting till pain/vomiting settles Little physiological justification for prolonged NPO No medication required other than analgesics(important) and anti-emetics Antibiotics not indicated in absence of signs or documented sources of infection Pain results in ongoing cholinergic discharge, stimulating gastric and pancreatic secretions Analgesics: WHO analgesic ladder-1986 Avoid Morphine-cause sphincter of Oddi spasm Metabolic support Correction of electrolyte imbalance

82. Modified WHO analgesic Ladder

83. 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

84. Severe Acute Pancreatitis P: Pain relief Proton pump inhibitors-omeprazole Peritoneal lavage A Admit in HDU/ICU Antibiotics N Nasogastric intubation(if vomiting) Nasal oxygen Nutrition support C Calcium gluconate CVP line Catherisation - Foley R Rehydration by IV fluids,plasma,blood Ranitidine(for stress ulcer) Radiology: CT scan, USG Resuscitation when required E Endotracheal intubation Electrolytes management ERCP A Antacids S Swan- Ganz catheter for CVP and TPN Suction-in case of aspiration Steroids in case of ARDS Supportive therapy for organ failure Inotropes Hemofiltration Ventilator(PEEP)

85. Monitoring CLINICAL Vitals UOP CV pressure INVESTIGATIONS Baselines Serial ABGs Serial BSR Serum calcium/magnesium

86. ACG 2013 Recommendations Despite dozens of randomized trials, no medication has been shown to be effective in treating AP. However , an effective intervention has been well described: EARLY AGRESSIVE IV hydration .

87. Rationale for EARLY AGRESSIVE IV hydration F requent hypovolemia due to vomiting , reduced oral intake, third spacing of fluids(increased vascular permeability) increased respiratory losses, and diaphoresis . Combination of microangiopathic effects and edema of the inflamed pancreas decreases blood flow , leading to increased cellular death, necrosis , and ongoing release of pancreatic enzymes activating numerous cascades. _________________________________________________________ *provides micro- and macrocirculatory support to prevent serious complications such as pancreatic necrosis

88. EARLY AGRESSIVE IV hydration Kon sa ? Lactated Ringer ’s solution may be the preferred isotonic crystalloid replacement fluid Ringer lactate is better electrolyte balance and more pH-balanced Normal saline given in large volumes may lead to the development of a non-anion gap, hyperchloremic metabolic acidosis and increased chances of SIRS Low pH activates the trypsinogen , makes the acinar cells more susceptible to injury and increases the severity of established AP Kab ? Early aggressive IV hydration is most beneficial during the first 12 – 24 h , and may have little benefit beyond this time period Kitna ? Aggressive hydration, defined as 250 – 500 ml per hour of isotonic crystalloid solution should be provided to all patients, unless cardiovascular, renal, or other related comorbid factors exist. In a patient with severe volume depletion, manifest as hypotension and tachycardia, more rapid repletion (bolus) may be needed Fluid requirements should be reassessed at frequent intervals within 6 h of admission and for the next 24 – 48 h.

89. EARLY AGRESSIVE IV hydration Hematocrit and BUN has been widely recommended as surrogate markers for successful hydration No absolute numbers recommended Goal to decrease Hct and BUN and maintain normal cret In elderly and cardiac/renal comorbidities hydration is monitored by Central venous pressure via CV line or Intrathoracic blood volume index Better/more accurate correlate with cardiac index than CVP

90. Antibiotics Routine use* NOT recommended(ACG 2013) as Prophylaxis in severe AP Preventive measure in sterile necrosis to prevent development of infected necrosis Indicated in Established infected pancreatic necrosis or Extraperitoneal infections Cholangitis, catheter-acquired infections, bacteremia, UTIs, pneumonia ______________________________________________ *Routine use of antifungal agents along with prophylactic or therapeutic antibiotics NOT recommended(ACG 2013)

91. Antibiotics As SIRS may be indistinguishable from sepsis syndrome, so if infection is suspected, antibiotics should be given while source of infection is being investigated Once blood and other cultures are found negative, antibiotics should be discontinued Few antibiotics penetrate due to consistency of pancreatic necrosis cefuroxime, or imipenem , or ciprofloxacin plus metronidazole

92. Antibiotics Use of probiotics is associated with increased mortality in severe AP Selective decontamination of bowel, targeting both bacteria and fungi, in order to prevent infected necrosis Controversial R elatively stable patients with infected necrosis can be managed conservatively on antibiotics without needing surgery( necrosectomy ) or intervention (percutaneous or endoscopic drainage) Surgical debridement recommended if no response to conservative treatment or deteriorates clinically

93. ……………………………………………………. Rather than preventing infection, the role of antibiotics in patients with necrotizing AP is NOW to treat established infected necrosis

94. Nutrition In mild AP oral feedings can be started immediately if there is no nausea/vomiting, and the abdominal pain/tenderness/Ileus has resolved(amylase return to normal, patient feel hunger) Initiation of feeding with a small and slowly increasing low-fat (low-protein) soft diet appears as safe as a clear liquid diet, providing more calories Stepwise manner increase from clear liquids to soft diet NOT necessary In severe AP Enteral route is recommended to prevent infectious complications Parenteral nutrition should be avoided, unless enteral route is not available, not tolerated, or not meeting caloric requirements

95. RATIONALE OF EARLY ENTERAL NUTRITION The need to place pancreas at rest until complete resolution of AP no longer seem imperative Bowel rest associated with intestinal mucosal atrophy and bacterial translocation from gut and increased infectious complications Early enteral feeding maintains the gut mucosal barrier, prevents disruption, and prevents translocation of bacteria that seed pancreatic necrosis Decrease in infectious complications, organ failure and mortality

96. ……………………………………………….. Rather than using antibiotics to prevent infected necrosis………….start early enteral feeding to prevent translocation of bacteria RATIONALE MANAGEMENT PREVENTION OF STERILE NECROSIS Early aggressive IV hydration PREVENTION OF INFECTED NECCROSIS Early enteral feeding( NOT antibiotics) TREATMENT OF INFECTED NECROSIS Antibiotics, drainage, necrosectomy

97. Route of enteral Nutrition Traditionally nasojejunal route has been preferred to avoid the gastric phase of stimulation BUT Nasogastric route appears comparable in efficacy and safety MERITS OF NASOGASTRIC ROUTE DEMERITS OF NASOGASTRIC ROUTE NG tube placement is far easier than nasojejunal tube placement( requiring interventional radiology or endoscopy, thus expensive) especially in HDU/ICU setting Slight increased risk of aspiration (Can be overcome by placing patient in upright position and be placed on aspiration precautions)

98. Role of Surgery in AP In case of mild gallstone AP, cholecystectomy should be performed before discharge to prevent a recurrence of AP Within 48-72 hour od admission or briefly delay intervention(after 72 hrs but during same admission Along with intraoperative cholangiography and any remaining CBD stones can be dealt with intra/post operative ERCP or Along with preoperative EUS or MRCP In case of necrotizing biliary AP, in order to prevent infection, cholecystectomy is to be deferred until active inflammation subsides and fluid collections resolve or stabilize Cholecysectomy done for recurrent AP (IAP) with no stones/sludge on USG and no significant elevation of LFTs is associated with >50 % recurrence of AP _________________________________________________________ If patient unfit for surgery(comorbid/elderly), biliary sphincherotomy alone may be effective to reduce further attacks of AP

99. Sterile necrosis infected necrosis Asymptomatic doesnot mandate intervention regardless of size, location and extension surgical, radiologic, and/or endoscopic drainage should be delayed preferably for more than 4 weeks to allow liquefaction of the contents and the development of a fibrous wall around the necrosis Initially treated with antibiotics Stable Symptomatic (associated with GOO or bile obstruction) minimally invasive methods of necrosectomy are preferred to open necrosectomy Urgent debridement unstable Minimally invasive approach: laparoscopic surgery(ant or retroperitoneal approach), percutaneous radiologic catheter drainage or debridement, video-assisted or small incision-based left retroperitoneal debridement, and endoscopy

100. 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

101. Recurrent AP

102. 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)

103. SYSTEMIC COMPLICATIONS CARDIOVASCULAR Shock- hypovolemic and septic Arrhythmias/pericardial effusion/sudden death ST-T nonspecific changes Pulmonary Respiratory failure/pneumonia/atelectasis/pleural effusion Acute Respiratory Distress Syndrome (ARDS) Renal Failure Oliguria Azotemia Renal artery/vein thrombosis Hematological Hemoconcentation Disseminated Intravascular Coagulopathy (DIC)

104. SYSTEMIC COMPLICATIONS Metabolic Hypocalcemia Hyperglycemia Hyperlipidemia Gastrointestinal Peptic Ulcer/Erosive gastritis Ileus Portal vein or splenic vein thrombosis with varices Neurological Visual disturbances-Sudden blindness( Purtscher’s retinopathy ) Confusion,irritability,psychosis Fat emboli Alcohol withdrawal syndrome Encephalopathy Miscellaneous Subcutaneous fat necrosis Intra-abdominal saponification Arthralgia

105. LOCAL COMPLICATIONS P eripancreatic fluid collections ( Peri ) P ancreatic necrosis( sterile + infected) P ancreatic abscess( Phlegmon ) P seudocyst P ancreatic ascites P seudoaneurysm Involvement of adjacent organs, with hemorrhage, thrombosis, bowel infraction, obstructive jaundice, fistula formation, or mechanical obstruction

106. THANK YOU……….