Acute Pancreatitis Dr Shah Vishal Maheshkumar FCCM Part

Acute Pancreatitis Dr Shah Vishal Maheshkumar FCCM Part 2 Nov 2016 Sterling Hospital, Vadodara

Introduction • Acute pancreatitis is a rapidly-onset inflammation of pancreas. • In majority of cases it runs benign course. • In 20% of cases the disease , it is severe and may be associated with mortality up to 20%.

Definitions • Acute pancreatitis -Acute inflammation of pancreas. • Mild acute pancreatitis -Minimal organ dysfunction responsive to fluid administration. • Severe acute pancreatitis -One of the following -Local complication -Pancreatic necrosis -Pancreatic pseudocyst. -Pancreatic abscess.

Organ failure -More than 3 ranson criteria. -More than 8 Apache-2 score.

• Acute fluid collection -Fluid collection in or near pancreas. - Occurs early in course. -Lacks defined wall. • Pancreatic necrosis -Non viable pancreatic necrosis diagnosed by iv contrast enhanced CT scan.

• Acute pseudocyst -Fluid collection containing pancreatic secretion. Defined wall. • Pancreatic abscess -Collection of pus, usually in or near pancreas.

Causes of pancreatitis. • • Gall stone. (Most common cause) Alcohol(2 nd most common cause) Idiopathic. Trauma. Steroids. Mumps & other viruses(Epstein- Barr, CMV) Auto-immune-disease(Polyarteritis nodosa, SLE) Hypercalcemia, hyperlipidemia/hypertriglyceride mia, hypothermia.

• ERCP • Drugs. Steroids, Sulfonamides, Azathioprine, NSAI DS, diuretics, such as frusemide and thiazide. • Duodenal ulcer.

Less common causes. • • • Pancreas divisum Long common bile duct. Carcinoma of head of pancreas. Ascarias blocking pancreatic outflow. Chinise liver fluke. Ischaemia from bypass surgery. Fatty necrosis. Pregnancy. Infection other than mumps including varicilla zoster. Repeated marathon running. Cystic fibrosis.

Causes by demographic • Western countries-chronic alcoholism and gall-stones accounting for 85% of all cases. • Eastern countries-Gall stones. • Children-trauma. • Adolescents and young adults-mumps

Clinical presentation • Abdominal pain. -Acute onset upper abdominal pain usually located in the epigastrium. -Moderate to severe in nature. -It increases in severity for initial few hours, then plateaus, and lasts for several hours to days. -It may radiate to back and sometime also to flanks, chest, shoulder and lower-abdomen. -Character of pain is steady and boring, not colicky.

• In some patient, pain becomes less on bending forward or drawing the knee upwards. • Pain may be there later on in disease due to acute fluid collection or pseudocyst.

Painless pancreatitis • Peritoneal dialysis • Post-operative-esp. -renal transplantation. • Legionnaire’s disease.

Other symptoms • Nausea, vomiting. • Vomiting may persist even after the stomach has been emptied. • Paralytic ileus which may cause abdominal -distension and vomiting.

Fever • Fever is present in the beginning of the disease. • May go upto 102 degree F and may lasts for few days. • Fever in 1 st week is usually due to acute inflammation and mediated by inflammatory cytokines. • Fever in 2 nd or 3 rd week in patient of ANP is due to infection of necrotic tissue. • It carries high mortality and warrants surgical intervention.

Physical examination • Appears in obvious distress. • Tachycardia, tachypnoea, hypotension. • Shock is not unusual and cause is - Hypovolemia secondary to exudation of blood & plasma-proteins into retroperitoneal-space. -Increase formation & release of kinin peptides which causes vasodilation and increase vascular permeability. -Systemic effects of proteolytic & lipolytic enzymes released into the circulation.

Respiratory system • Atelectasis. • Basal crepitations. • Presence of pleural-effusion, particularly on left side. • Patient may go into respiratory-failure.

Abdominal signs • Less marked as compared with severity of pain • Mild tenderness. • Signs of peritonitis may be present in severe pancreatitis. • Bowel sounds are generally absent or sluggish. • Ascites may be there because of chemical peritonitis and exudation of fluids from inflammed pancreatic bed.

• Grey-Turner’s sign -it is the blue-gray discoloration of flanks due to exudation of blood stained fluid into subcutaneous-tissues, usually after 72 hrs of illness. • Cullen’s sign -A bluish discoloration in periumbilical area due to retroperitoneal haematoma. • A palpable lump in the epigastrium may be due to pseudocyst. • Jaundice may be due to compression of intrapancreatic portion of CBD due to edematous head of pancreas.

Renal manifestation • Oliguria • ARF • Fluid overload, acidosis, electrolyte imbalance.

Neurological signs • Most of the patient have clear sensorium, but may have altered sensorium, because of, -Hypoxia -Electrolyte imbalance -Hypotension -Alcohol withdrawal or toxaemia.

Skin manifestation • Areas of tender subcutaneous induration and erythema that resembles erythema nodosum may be found because of fat digestion by circulating pancreatic lipase.

Laboratory data-Routine blood test • Depleted intravascular volume due to -Anorexia, Nausea, Vomiting. -Collection of large amount of fluid in retroperitoneum due to pancreatic inflammation. -Capillary leak results in additional loss. • All these leads to rise in Hb, Hct, BUN, Cr. • Leucocytosis. • Thrombocytopaenia, DIC in severe pancreatitis.

• Hyperglycemia due to -decrease insulin release. -elevated circulating catacholamines. -increase glucagon release. • Hypoalbuminaemia may be present in 10% of cases, which is associated with severe pancreatitis and with higher mortality.

• Hypocalcemia-Found in 25% of the patient. • Marked hypocalcemia is a sign of poor prognosis. • Cause is not known exactly. • Intraperitoneal saponification of calcium by fatty acid in the areas of fat necrosis may occur with large amount suspended in ascitic fluid.

LFT • Hyperbilirubinaemia, transient most of the times, returns to normal in 4 -7 days. • Alkpo 4 and SGOT level may go up. • Marked rise in LDH level (>500) is associated with poor prognosis. • Hypertriglyceridemia may be found, which may be associated with spuriously normal Amylase.

Pancreatic enzymes • Rise in Amylase level. • Does not co-relate with severity. • Starts rising in 2 -12 hrs after the onset and usually starts declining on 3 rd day and becomes normal within 6 day. • In 10% cases , it may be normal.

Causes of Hyperamylasaemia • Pancreatic - Pancreatitis, pseudocyst, ascities. - Pancreatic cancer. - Pancreatic duct obsruction. - Pancreatic trauma. • Nonpancreatic intra-abdominal -Perforated hollow viscus. -Bowel obstruction. -Cholengitis, cholecystitis. -Mesenteric infarction. -Ovarian cyst -Renal failure. -Ruptured ectopic pregnancy.

• Extra-abdominal -Salivary gland tumor, trauma, infection, obstruction. -Lung tumors. -Burns. -Diabetic acidosis. -Pneumonia.

Other enzyme assay. • Urine amylase level may remain elevated for sevral days after serum amylase comes down to normal level. • Serum lipase level is also remained high after amylase comes to normal value. • Markedly increased levels of peritoneal or pleural fluid (>5000) is also helpful, if present, establishing the diagnosis. • If lipase level is about 2. 5 -3. 0 times than that of Amylase, it is an indication of pancreatitis due to alcohol.

• It is usually not necessary to measure both serum amylase and lipase. Serum lipase may be preferable because it remain normal in some nonpancreatic condition that increase serum amylase including macroamylaesemia, parotitis and some carcinomas. In general serum lipase is thought to be more sensitive and specific than serum amylase in diagnosis of acute pancreatitis. • Although amylase is widely available and provides acceptable accuracy for diagnosis, where lipase is available, it is preferred for diagnosis of acute pancreatitis. (Recommandation grade A).

Radiological Investigation • Routine chest and abdominal x-ray findings are non-specific. • Generally, it is done to rule out other causes of acute abdomen like, perforated viscus, bowel-obstruction.

USG • Usually limited by presence of intestinal gas in the upper abdomen during early stage of the disease. • Detects GB stones/bile duct dilatation. • USG may be very useful in detecting and monitoring pancreatic inflammatory masses and pseudocyst.

CT scan • Regarding the need of CT, practice guidelines state: -2006 -Many patient with acute pancreatitis may not require CT scan on admission or at any time during hospitalization. For example a CT scan is usually not essential in patient with recurrent mild pancreatitis caused by alcohol. A reasonable indication for a CT scan at admission (not necessarily with contrast) is to distinguish acute pancreatitis from another serious intraabdominal condition such as perforated ulcer. -2005 -Patient with persisting organ failure, signs of sepsis, or deterioration in clinical status, 6 -10 days after admission will require CT. (Recommandation grade-B)

• CT abdomen should not be performed before the 1 st 48 hours of onset of symptoms as early CT(<48 hours) may result in equivocal or normal findings. • CT scan with contrast has three major roles in evaluation of patient with known or suspected pancreatitis. -Diagnosis -Staging of the severity of the inflammatory process. -Detection of complications, particularly the identification & quantification of parenchymal and peripancreatic necrosis.

Balthazar scoring • Balthazar scoring for the grading of acute pancreatitis • The CT severity score is the sum of CT grade and necrosis grade score.

CT grade score CT grade Grade A Grade B Grade C Grade D Grade E Appearance on CT Normal CT Focal or diffuse enlargement of pancreas. Pancreatic gland abnormalities and peripancreatic inflamation Fluid collection in single location. CT grade points 0 points 1 point 2 points 3 points Two or more fluid collection and/or 4 points. gas bubbles in or adjacent to pancreas.

Necrosis score Necrosis percentage Points No necrosis 0 points 0 -30 % 2 points 30 -50% 4 points Over 50% 6 points

CT grade(0 -4) + = total 0 -10 0 -2 Necrosis score(0 -6) Negligible mortality 3 -6 Low mortality 7 -10 17% mortality

Differential diagnosis • • • Perforated viscera Acute cholecystitis and biliary-colic Acute intestinal obstruction. Mesenteric vascular occlusion. Renal colic. Myocardial-infarction. Dissecting aortic aneurysm Connective tissue disorder with vasculitis. Pneumonia. Diabetic ketoacidosis.

Course of the disease • About 20% of patient belongs to category of severe pancreatitis. • Out of which, about 20%patient dies.

Prognostic indices • • Ranson’s criteria. Imrie’s prognostic signs. APACHE 2 score. Most but not all studies report that APACHE score may be more accurate. • Practice guidelines states: 2006: The two tests that are most helpful at admission in distinguishing mild from severe acute pancreatitis are APACHE-2 score and serum hamatocrit. It is recommended that APACHE 2 scores generated during the 1 st days of hospitalization and thereafter as needed to help in this distinction. It is also recommended that serum haematocrit be obtain at admission, 12 hours after admission and 24 hours after admission to help gauge adequacy fluid resuscitation.

• 2005: Immidiate assessment should include clinical evaluation, particularly of any cardiovascular, respiratory and renal compromise, body mass index, chest x ray, and APACHE 2 sore.

Ranson’s prognostic sign • On admission -Age >55 -WBC >16, 000/mm 3 -RBS > 200 mg% -LDH > 350 IU/L. -SGOT>250

• During initial 48 hours -Haematocrit decreases more than 10 %. -BUN rises more than 5 mg%. -Serum Ca below 8 mg%. -Base deficit over 4 m. Eq/L. -Fluid sequestration > 6 L.

• Ranson’s criteria -< 3 -Associated with mild pancreatitis, little morbidity, mortality< 1%. ->3 -Associated with severe pancreatitis with 34% incidence of septic complicaton. -7 -8 , mortality may reach upto 90%.

Imrie’s prognostic signs • • • Age >55 yrs. WBC>15, 000/mm 3 RBS>10 mmol/L. Serum urea >16 mmol/L. Pao 2 <60. S. Ca <2 mmol/. LDH>600 mcg/L SGOT>100 S. Albumin<3. 2 mg%.

• >3 imrie criteria are associated with severe pancreatitis. • <3 are associated with mild pancreatitis.

• APACHE>8 predicts 11 -18% mortality.

Glassgow scoring system • • Arterial Pa. O 2 S. Albumin S. Ca WBC SGOT LDH Blood Glucose Blood urea -<60. -<3. 2. -< 2 mmol/L. ->15, 000. - >200. ->600. - >10 mmol/L. - >16 mmol/L.

Risk factors that adversely affect survival in acute pancreatitis • Organ failure -CVS-Hypotension-SBP<90 or tachycardia>130 beats/min. -Pulmonary-Pa. O 2 <60. -Renal-Oliguria-<50 ml/hour or increasing BUN or Cr. -GI bleed.

• • • Pancreatic necrosis. Obesity-BMI >29. Age >70. Haemoconcentration(Haematocrit>44%) CRP>150 mg%. Trypsinogen activatio peptide a. >3 Ranson criteria b. APACHE 2 score >8.

Management • Initial management includes: -Pain control. -IV fluids & colloids to maintain intravascular volume. -No oral alimentation. -Nasogastric suction.

• Goals of initial management includes: -Fluid replacement. -Electrolyte balance. -Caloric support. -Prevention of local & systemic complication.

Pain management • Opioids are drug of choice. • Morphine-Studies has not demonstrated adverse effect of morphine by contracting sphincter of oddi. • PCA by epidural analgesia is very useful.

Fluid management. • Massive amount of fluid loss is there because of vomiting, decrease fluid intake, fluid loss into inflamed peritoneum. • Fluids should be replaced accordingly. • UOP should be monitored with indwelling catheter. • If required, central line should be put and fluids should be given accordingly. • ABG, haematocrit, electrolyte should be monitored.

Bowel rest • Food in stomach stimulate pancreatic secretion and pain. • Hence, patient should be kept NBM. • Approximately, 75% of relapses occurs within 48 hours of oral feedings. • Post pyloric feeding may reduces such relapses.

Nutritional support • Why nutrition is required? - Hypercatabolic-state. -Hence, there is rapid loss of body-weight, fat and protein. • Nutritional support is the integral part of patient care and is started early. • Mild to moderate disease do not require nutritional support, because most of the patient are started orally within 4 days of presentation.

• Severe pancreatitis patient are started enteral/parentral nutrition. • Enteral is preferred because it is more physiological, prevents gut mucosal atrophy, and is free from side effects of TPN. • Enteral nutrition is given post pyloric(nasoenteric).

Advantage of naso-enteric feed. • It does not have any effect on pancreatic exocrine secretion. • Reduces the risk of aspiration.

Antibiotics • Controversial. • Six randomized trial have demonstrated a reduction in infected necrosis, surgery, morbidity and in one study mortality in patient with severe pancreatitis. • The current recommendation is the use of systemic antibiotic such as Imipenam-Cilastin 500 mg 8 hourly for 2 weeks in patient with documented pancreatic necrosis. • Prophylactic antibiotics cannot reduce infected pancreatic necrosis and mortality in ANP. (American journal of gastro-enterologist, Jan-2008) (Study by Dept. of Gastro-enterology, Shangai, China. )

Antiproteases • Gabexate Mesilate -Prophylactic use can prevent the complication in AP after ERCP. -Two meta –analysis suggested significant reduction in systemic complication and need for surgery without contemporaneous reduction in mortality.

Anti-secretive • Somatostatins and ocreotide. • Clinical studies have conflicting results. • Generally, they are not recommended.

Platelet activating factor antagonist • Lexipafant. • One multicenter, prospective, controlled, double blind, randomized trial demonstrated a significant difference in mortality among treated patient. • Unfortunately, larger study did not confirm any advantage in terms of mortality rate, thus, routine use is not recommanded.