ACUTE PANCREATITIS Dr Prajwala Reddy Definition Acute Pancreatitis

ACUTE PANCREATITIS Dr. Prajwala Reddy

Definition � Acute Pancreatitis is an inflammatory process of Pancreas that may be associated with varying degrees of auto digestion, edema, necrosis & hemorrhage of pancreatic tissue. Function: � 1. Exocrine -Insulin production. � 2. Endocrine-Manufacturing and secretion of � digestive enzymes.

Pathophysiology v AP occurs as a consequence of premature activation of Zymogen granules & due to injury to Acinar cells releasing protease which digest the pancreas &the surrounding tissue. v It may occur when factors involved in maintaining cellular homeostasis are out of balance. v The initiating event may be any thing that injures the acinar cells& impairs them(eg : alcohol , gall stones , Drugs , etc. , )

v It is unclear exactly what pathophysiologic event triggers the onset. v Its believed that both extracellular factors& intracellular factors play a role. v In addition AP can develop when ductal cell injury leads to delayed or absent enzymatic secretions , as seen in pts with CRTF gene mutation.

• Cellular injury • Fusion of lysosomal & zymogen granule compartments • Activation of trypsinogen to trypsin • Triggers the entire zymogen activation cascade • Extrution of secretory vesicles across the basolateral membranes in to the interstitium • Inflammatory cells

• Activated neutrophils • Release of superoxide or proteolytic enzymes(Catheprins. B, D&G, collagenase and elastase • Release of cytokines by Macrophages that further mediate local inflammatory response.

In severe cases these mediators of inflammation Increased pancreatic vascular permeability Hemorrhage , Edema Pancreatic necrosis

When these mediators are exerted in to the circulatory system , complications arise. ØARDS ØPleural Effusion ØGI Hemorrhage ØRenal Failure ØSIRS Systemic Shock ØHemodynamic instability& Death.

Epidemiology v Highest incidence : US & Finland. (alcoholic Pancreatits is MC). Europe& other developed countries, Honkong(Gall stone Pancreatitis is MC). v More among males. v Males: MC due to Alcohol. v Females: MC due to Biliary tract disease. v Ideopatic has no relation to sex. v Risk of incidence in African Americans aged 3565 is times higher than any other group.

Etiology v Common: Gal stone Pancreatitis & Alcohol (70%) v Uncommon: Pancreatic divisum Autoimmune Pancreatitis Hypertriglyceridemia Drugs(Azotioprine , Thiazide Diuretics, Sulphonamides , Sodium Valporate , Tetracylines , etc. , ) Post ERCP Sphincter of oddi dysfunction Idiopathic

v Rare : Malignancy Heriditary Vascular(eg: ischemia) Abdominal trauma Toxins Hypercalcemia Infections(Mumps, CMV, EBV, VZV, Rubella , Mycoplasma pneumonia, Measels, Salmonella, Mycobacterim tuberculosis) Parasites (Ascaris & Clonorchis)

History v Alcohol v Gal stone disease v Drugs v Hypertriglyceridemia v Malignancy

Signs & symptoms: v Abdominal pain v Nausea, Vomiting, Anorexia Physical findings: v Fever v Tachycardia v Hypotension v Abdominal tenderness , guarding, distension, deminished or absent bowel sounds(ileus) v Jaundice v Dyspnoea, tachypnea, Pleural effusion. v In severe cases: Hemodynamic instability, Hematemesis or melena , pale, diaphoretic & listless appearance,

Extremity muscle spasm secondary to hypocalcemia. v Uncommon Findings ass with severe Necrotizing Pancreatitis-Cullens Sign Grey Turner Sign Erythematous skin nodules.

Investigations Complete Hemogram Sr. Amylase& Sr. Lipase Sr. Calcium ABG, Electrolytes, Blood Glucose , Sr. Triglycerides RFT LFT CRP Blood c/s LDH Radiological : Chest & abdominal X-Rays , CT, MRI, MRCP, EUS.

Diagnosis As per the Atlanta Symposium, any 2 of the following: v Abdominal pain. v Amylase/lipase elevated>3 times upper limit of normal. v Pancreatic inflammation in cross sectional imaging

Classification v Mild v Severe: 1. Evidence of organ failure(BP: systolic <90 mm. Hg, Pa. O 2</=60 mm. Hg, Sr. Creatinine>/=2 mg/dl). 2. GI Bleeding>/=500 ml /24 hrs. 3. Local complications(eg: necrosis, abscess, pseudocyst) 4. Ransons score of 3/higher or APACHE score of 8/higher.

RANSONS CRITERIA Age WBC Blood Glucose LDH Asparate aminotransferase Hematocrit BUN Sr. Ca Pa. O 2 Base deficit Fluid sequestration v v At 0 hrs At 48 hrs >55 yrs >16, 000/mm 3 >200 mg/dl >350 U/L >250 U/L Fall by >/=10% Increased by>5 mg/dl(despite of fluids) <8 mg/dl <60 mm. Hg >4 m. Eq/L >6000 ml It’s a method for severity of AP 1 -3 is –Mild. >/=3 with in first 48 hrs is- Severe. Mortality rate rises significantly with a score of 4 or more

BISAPS score (For early mortality prediction in first 24 hrs) v BUN >25 mg/dl v Impaired mental status v SIRS 2 or more v Age >60 yrs v Pleural effusion Ø Mortality increases from 1 to 5. Ø A score of >3 predicts persistent organ failure& necrosis.

BALTHZAR GRADING SYSTEM (CT Grading for severity of AP) v A. Normal appearing pancreas. v B. Focal or diffuse enlargement of pancreas. v C. Pancreatic gland abnormalities ass with mild peripancreatic inflammatory changes(strandings). v D. Fluid collection in single location , normally with in anterior pararenal space. v E. Two or more fluid collections near the pancreas&/or presence of gas in or adjacent to pancreas

CT Grade Score CT grade Score Necrosis(nee Score A 0 None 0 B 1 <33% 2 C 2 33%-50% 4 D 3 >/=50% 6 E 4 v CT ds iv) grade( 0 -4)+necrosis grade(0 -6)= Total score

Management v All pts who have severe pain, vomitings, dehydration& raised amylase should be hospitalized. v Pts who is hemodynamically unstable& has tachycardia, hypoixia, decreased UOP indicates severe course and needs ICU admission. v General supportive care is the main stay of treatment. v Initial maintenace of ABC.

1. Fluids: v v v v These pts have huge fluid loss in to the third space , that increases the hemo-concentration & relative pancreatic bed ischemia, which increases the necrosis. Hence large amounts of fluids are required. Rapid restoration of fluids , Mc crystalloids. ~500 -1000 ml of fluid should be installed till organ hypo perfusion subsides. At very best at least 250 -350 ml/hr to maintain UOP@0. 5 ml/kg/hr. Vasopressors after adequate intravenous volume is achieved. Invasive hemodynamic monitoring(esply in poor Cardiac function, Chronic Renal failure, hemodynami unstability)to maintain UOP>0. 5 ml/kg/hr, hematocrit<30%& CVP@6 -8 cm. H 2 o

2. Pain: v v v Conventional analgesics by Iv route. Transdermal Fentanyl patch of 25 -50 mcg. Avoid NSAIDs 3. Nutrition: AP is a hypercatabolic state& can lead lo severe nutritional deficiencies. v Enteral /oral feeds should be started as early as possible. v Traditionally the only way of treating pancreatitis was to give rest to pancreas by not feeding& by NG tube aspiration. v Now NG tube aspiration is indicated only if pts has gastric ileus & repeated vomitings. v

v In mild uncomplicated AP, energy calories cam be received with IV Dextrose. v Enteral nutrition with NJ tube should be started as early as with in 48 hrs. v It helps in nutrition as well as prevention of sepsis. v Some recent studies show that NG feeding in pts who cannot tolerate oral feeds is as good as NJ feeds, but it still remains controversial. v Give enteral feeds as continuous 24 hrs infusion. v Start with 500 ml/day& increase gradually@250500 ml/day un till the targeted caloric needs are met. v If targets cannot be met after 5 -7 days trail with enteral route then consider TPN+EN. v Draw backs of only TPN usage : expensive , increase risk of line sepsis, fasting promotes gut atrophy with decreased mucosal lymphocytes & Ig. A, that predisposes bacterial translocation.

v Avoid over feeding& improve glucose tolerance by supplying some calories as lipids and maintain the triglyceride levels, 400 mg. v When pt can resume orally, should be initially fed with low calorie & low fat diet , which should gradually be increased. v This can be continued till pts start taking adequately orally(may b after 2 -3 wks). 4. Insilin: Monitor Sr. Glucose levels & iv insulin can be given if indicated.

5. Antibiotics: v Its use is quite controversial. v Initial phase clinical features are primarily of inflammation (SIRS)& do not require antibiotics. v Only definitive indication of therapeutic antibiotics is Cholangitis due to CBD Gram–ve pathogens such as E. coli &anaerobes are typical pathogens. Third generation Cephalosporins , Fluoroquinolones are good initial choice. v The other rationale is for prophylactic use to prevent infection of Pancreatic necrosis. v Imipenem class is used for Pancreatitis complicated by infected pancreatic necrosis. v Current guide lines do not recommend the use of prophylactic antibiotics.

v In practice , lot of pts with severe AP will be in ICU with CVC, urinary catheters, some on MV or Dialysis, thus they are prone to hospital acquired infections. v Antibiotics of choice for these pts depends on local epidemiology of infection in ICU with the sensitivities of these organisms. 6. IV calcium : v Only in pts with Hypocalcemia who have Tetany. 7. Somatostatin & octreotide: v There role is very small and there is insufficient evidences to support there use , there fore its effect is unlikely to have a significant effect in management of ANP

8. Protease inhibitors: v There use showed no significant reduction in mortality , length of stay or the need for surgery. Probably due to the time lag between the onset of pancreatitis and the administration. v Additionally derangement to the microvascular control of pancreas combined with increased vascular parmiability may contribute. v Continuos regional artery infusion or intraperitoneal administration may be more advantageous. v At present there is insufficient evidence to recommend them in ANP

9. Anti-inflammatory therapy: Pts with ANP exhibit a generalized uncontrolled inflammatory response. v Potentially there is a therapeutic window between the onset of symptoms and the development of organ failure , during which the anti-inflammatory therapy may be successful. v But currently there are not published trails of corticosterod therapy in ANP. v 10. Antifungal therapy: Antibiotic administration has been claimed to promote fungal infections ; how ever up to 25%of pts who do not receive antibiotics also develop fungal infections with an associated mortality up to 84%. One small randomized trail suggests that Fluconazole reduced the rate of fungal infection but had no effect on mortality.

CT: v. A CECT of abdomen is the first modality available to morphologically diagnose& quantify necrosis. v CT scan should be postponed till 72 hrs or more. v The only indication of early CT scan is when one I not clear about diagnosis , follow up CT scan if development of complications are suspected. 11. Early ERCP: (48 -72 hrs) v In Acute Biliary Pancreatitis with evidence of Cholangitis. v If in doubt EUS/MRCP can be done to decide if the stone is still in CBD

12. Management of complications Pseudocyst: v It’s a collection of pancreatic juice, which is enclosed by granulation tissue. v Takes at least 4 wks to form. v Drainage by percutaneous ultrasound guided, endoscopic or surgical is required in those with large&/or symptomatic pseudocyst. v MC complications include compression of adjacent structures , rupture, infection& bleeding(5%). v CT guided drainage of infected collection(multiple drains may be required)

13. Surgery: Indications: v In pts with Infected Pancreatic Necrosis not doing well. v When other techniques of draining in infected pancreatic necrosis is not possible. v Abdominal compartment syndrome in which percutaneous/other drainage techniques are not successful. v Surgery should be delayed to the 4 th wk as results before this are not good. v Local complications. v Bowel Infarction. v Pancreatic necrosis with pseudo-aneurism & massive intra-abdominal hemorrhage is best managed by Angiographic Embolization.

v Removal of GB: scheduled as early as possible to avoid the recurrence of biliary pancreatitis(30%). In severe attacks its recommended to wait up to 46 wks. Laparoscopic approach is feasible & safe even in cases where surgical debridement is required. Controversial indications: v Extensive(30%) sterile necrosis with persisting multi organ failure despite of intensive care therapy. v Most surgeons avoid surgery for this as the mortality rate is very high.

Prognosis v 10 -15% mortality. v About 80% of all cases are mild with a mortality of<5%. v 98% of deaths occur in the 20% of severe cases. v 1/3 rd occurs in first wk usually from multi organ failure. v After this the majority from sepsis, especially that complicate infected necrosis.

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