Ministry of Health of the Republic of Moldova   State University of Medicine and Pharmacy "Nicolae Testemiţanu" ACUTE PANCREATITIS Severity Classification, Complications and Outcome Mahamied Manar Gr.1638

Physiology In response to a meal, the pancreas secretes digestive enzymes in an alkaline (pH 8.4) bicarbonate-rich fluid. The proteolytic enzymes are secreated in an inactive form, the maintenance of this is important in preventing pancreatitis. Spontaneous secretion is minimal; the hormone secretin, which is released from the duodenal mucosa, evokes a bicarbonate-rich fluid. Cholecystokinin (CCK) (synonym: pancreozymin) is released from the duodenal mucosa in response to food. CCK is responsible for enzyme release. Vagal stimulation increases the volume of secretion.

Pathophysiology Due to many causes, pancreatic pro-enzymes will be activated, and not released to the duodenum, so they will return back to the pancreas in the active form and cause autodigestion of the pancreas, which in turn will lead to an acute inflammatory reaction.

Incidence Acute pancreatitis accounts for 3% of all cases of abdominal pain. The disease may occur at any age, with a peak in young men and older women.

Etiological Factors 1 Biliary tract disease 7 Scorpion venom 2 Alcohol 8 Drugs 3 Ischemia (hypotension, cardio-pulmonary by-pass, atheroembolism, vasculitis) 9 Pancreatic duct obstruction (tumor, pancreatic divisum, ampullary stenosis, ascaris infestiopn) 4 Duodenal obstruction 10 Metabolic (hypercalcemia, hyperthyroidism, Hyperlipidemia) 5 Trauma (external, operative, ERCP) 11 Viral infection (mumps, coxsaki B4) 6 Familial 12 Idiopathic

Clinical features (Symptoms) Pain (sudden,intense,continuous, upper abdomen back, bizarre position) Nausea and Vomiting

Clinical features (Signs) General Local Shock Peritonitis Fever Paralytic ileus Jaundice Abdominal mass Left pleural effusion Cullen’s sign. Grey Turner sign Acute pulmonary failure Subcutaneous necrosis Cerebral abnormalities

Severity Classification Pancreatitis severity ranges from mild to MOF with sepsis and necrotizing or hemorrhagic forms Overall mortality: 10-15% Biphasic time to death

Prognostic scoring systems Atlanta classification Ranson Score Glasgow Score Modified Glascow

Atlanta Classification ACUTE PANCREATITIS Acute pancreatitis is an acute inflammatory process of the pancreas, with variable involvement of other regional tissues or remote organ systems. SEVERE ACUTE PANCREATITIS Severe acute pancreatitis is associated with organ failure and/or local complications such as necrosis (with infection), pseudocyst or abscess. Most often this is an expression of the development of pancreatic necrosis, although patients with oedematous pancreatitis may manifest clinical features of a severe attack. MILD ACUTE PANCREATITIS Mild acute pancreatitis is associated with minimal organ dysfunction and an uneventful recovery. The predominant pathological feature is interstitial oedema of the gland. ACUTE FLUID COLLECTIONS Acute fluid collections occur early in the course of acute pancreatitis, are located in or near the pancreas, and always lack a wall of granulation of fibrous tissue. PANCREATIC NECROSIS AND INFECTED NECROSIS Pancreatic necrosis is a diffuse or focal area(s) of non-viable pancreatic parenchyma, which is typically associated with peripancreatic fat necrosis. The onset of infection results in infected necrosis, which is associated with a trebling of the mortality risk. ACUTE PSEUDOCYST An acute pseudocyst is a collection of pancreatic juice enclosed in a wall of fibrous or granulation tissue that arises following an attack of acute pancreatitis. Formation of a pseudocyst requires four or more weeks from the onset of acute pancreatitis. PANCREATIC ABSCESS A pancreatic abscess is a circumscribed intra-abdominal collection of pus, usually in proximity to the pancreas, containing little or no pancreatic necrosis, which arises as a consequence of acute pancreatitis. SPECIALIST UNIT A specialist unit is one in which multidisciplinary expertise is available on-site. Full intensive care facilities are mandatory, together with recourse to ERCP at any stage on an emergency basis. Expert radiological input for dynamic scanning, percutaneous procedures and angiography is essential. A surgeon with pancreatico-biliary expertise should supervise management.

Glasgow Scoring system for the initial prediction of severity in acute pancreatitis Age >55 years White blood cell count >15 × 109/L Glucose >10 mmol/l Urea >16 mmol/l PaO2 <60 mm Hg Calcium <2 mmol/l Albumin <3.2 g/l Lactate dehydrogenase >600 units/L Asparate/alanine aminotransferase >100 units/L

Modified Glasgow Score Age >55 years PaO2 <60mmHg WCC >15x109/litre Ca2+ <2.0 mmol/L LDH >600 IU glucose >10 mmol/L urea >16 mmol/L albumin <3.2g/L Minimum score: 0 Maximum score: 8 If score<3: severe pancreatitis unlikely If score>=3:severe pancreatitis likely

Ranson’s Criteria Ranson's Criteria on Admission : age greater than 55 years a white blood cell count of > 16,000/µL blood glucose > 11 mmol/L (>200 mg/dL) serum LDH > 350 IU/L serum AST >250 IU/L Ranson's Criteria after 48 hours of admission : fall in hematocrit by more than 10 percent fluid sequestration of > 6 L hypocalcemia (serum calcium < 2.0 mmol/L (<8.0 mg/dL)) hypoxemia (PO2 < 60 mmHg) increase in BUN to >1.98 mmol/L (>5 mg/dL) after IV fluid hydration base deficit of >4 mmol/L Score 0-2: 2% mortality Score 3-4: 15% mortality Score 5-6: 40% mortality Score 7-8: 100% mortality

Differential diagnosis Acute cholecystitis. Perforated peptic ulcer. Inferior wall MI. Intestinal obstruction. Mesenteric ischemia. Ruptured abdominal aortic aneurysm.

Management of severe acute pancreatitis Rest the patient (Relief pain): Pethidine 1mg/kg + antispasmodic. Rest the pancreas: NPO(nil per os). Rest the bowel: nothing by the mouth. Resuscitation: IV fluid, electrolytes replacement. Resist enzymatic activity: Protease inhibitors. Resist infection: Antibiotics. Repeated examination. Repeated serum estimations:Ca+2, Mg+2. Respiratory support.

Management Urgent ERCP and biliary sphincterotomy within 72 hours improves outcome of severe gallstone pancreatitis. Surgery in case of: Uncertain diagnosis. Infected pancreatic necrosis. Complicated pancreatitis.

Causes of death: Hypovolemic shock. Electrolyte disturbances. Sepsis. Renal failure. Respiratory failure.

Complications Systemic Local (More common in the first week) (Usually develop after the first week) Cardiovascular Shock Arrhythmias Pulmonary ARDS Renal failure Haematological DIC Metabolic Hypocalcaemia Hyperglycaemia Hyperlipidaemia Gastrointestinal Ileus Neurological Visual disturbances Confusion, irritability Encephalopathy Miscellaneous Subcutaneous fat necrosis Arthralgia Acute fluid collection Hemorrhagic pancreatitis Sterile pancreatic necrosis Infected pancreatic necrosis Pancreatic abscess Pseudocyst Pancreatic ascites Pleural effusion Portal/splenic vein thrombosis Pseudoaneurysm Chronic pancreatitis

Hemorrhagic pancreatitis Definition: Bleeding into the parenchyma and retroperitoneal structures with extensive pancreatic necrosis. Signs: Abdominal pain Shock Cullen’s sign, Grey turner’s sign & Fox’s sign

Grey Turner’s sign Cullen’s sign Cullen’s sign Fox’s sign

Acute fluid collection Located in or near the pancreas The fluid is sterile, and most such collections resolve. No intervention is necessary unless a large collection causes symptoms or pressure effects.

Sterile and infected pancreatic necrosis Refers to a diffuse or focal area of non-viable parenchyma that is typically associated with peripancreatic fat necrosis. Necrotic areas can be identified by an absence of contrast enhancement on CT. These are sterile to begin with, but can become subsequently infected, probably due to translocation of gut bacteria. Necrotizing pancreatitis accounts for 10% of all pancreatitis but is lethal disease. Sterile necrotic material should not be drained or interfered with.

Pancreatic necrosictomy Peritoneal lavage Management Laparostomy Pancreatic necrosictomy Peritoneal lavage If the sepsis worsens despite this, then a pancreatic necrosectomy should be considered. This is a challenging operation that carries a high morbidity and mortality, and is best carried out in a specialist unit. The overwhelming majority of patients with peripancreatic sepsis can be successfully treated by conservative means, and necrosectomy should be necessary in a very small proportion of patients. The surgical approach may be through a midline laparotomy, especially if the area involved is around the head of the gland. The duodenocolic and gastrocolic ligaments should be divided and the lesser sac opened. Thorough debridement of the dead tissue around the pancreas should be carried out. If the body and tail of the gland are primarily involved (Fig. 64.25), a retroperitoneal approach though a left flank incision may be more appropriate. The tissues are inevitably friable, and one should be careful not to precipitate excessive bleeding or inadvertently breach the bowel wall. Blunt dissection is preferable to sharp dissection. A feeding jejunostomy may be a useful adjunct to the procedure. If gallstones are the precipitating factor of the pancreatitis, a cholecystectomy should be included. Some prefer a minimally invasive approach to a formal laparotomy. A rigid laparoscope is inserted into the peripancreatic area through a retroperitoneal approach, and vigorous irrigation and suction is combined with a gradual nibbling away of the necrotic debris. Once a necrosectomy has been completed, further necrotic tissue may form. There are several possible ways of dealing with this (listed below), none of which has been proved to be more effective than the others. The last two approaches make greater logistic demands as one is committed to a re-exploration every 48–72 hours. • Closed continuous lavage: Tube drains are left in and the raw area flushed (Beger) (Fig. 64.26). • Closed drainage: The incision is closed, but the cavity is packed with gauze-filled Penrose drains and closed suction drains. The Penrose drains are brought out through the flank and slowly pulled out and removed after 7 days Open packing: The incision is left open, and the cavity is packed with the intention of returning to the operating room at regular intervals and repacking until there is a clean granulating cavity. • Closure and relaparotomy: The incision is closed with drains with the intention of performing a series of planned relaparotomies every 48–72 hours until the raw area granulates (Bradley).

Pancreatic abscess Definition: is a circumscribed collection of pus intra-abdominal resulting from tissue necrosis, liquefaction, and infection. It may be an acute fluid collection or a pseudocyst that has become infected Presentation: Fever Unresolving pancreatitis Epigastric mass

is a late complication of acute necrotizing pancreatitis. It is estimated that approximately 3% of the patients suffering from acute pancreatitis will develop an abscess. Abdominal CT scans with needle aspiration to send for culture & Gram stain should be performed. Organisms found Gram –ve (most common) E.coli, pseudomonas, klebsiella Gram +ve Staphylococcus aureas, candida

Tx: Antibiotics and percutanous drain placement OR Operative debridement and drain placement. An unremoved infected abscess may lead to sepsis, fistula formation and recurrent pancreatitis.

Pseudo cyst Definition: Encapsulated collection of pancreatic fluid by inflammatory fibrosis NOT epithelial cell lining, that's why called “pseudo"cyst. Its incidince is approximately 1 in 10 after alcoholic pancreatitis. Presentation: Epigastric pain Vomiting Mild fever Weight loss Signs Palpable epigastric mass, Tender epigastrium, Ileus

Investigations: CBC >> leuckocytosis Amylase >> high Bilirubin>> high if there is obstruction US >> fluid filled mass CT >> fluid filled mass, Multiple cysts ERCP : radiopaque contrast material fills the cyst if there is a communicating pseudocyst

Cystadenocarcinoma,cystadenoma Complications : DDx : Cystadenocarcinoma,cystadenoma Complications : Infection Bleeding into the cyst Fistula Pancreatic ascitis Gastric outlet obstruction Biliary obstruction SOB

Treatment : drainage of the cyst or observation 50% will resolve spontaneously within 6 weeks infection: Percutaneous external drainage & IV antibiotics bleeding: angiogram and embolization

Cysts larger than 5cm have a small chance of resolving & a higher chance of complications(bleeding, Infection, rupture). Treatment options are percutanous CT guided aspiration or operative drainage (cystogastrostomy, cystoduodenostomy). A biopsy should be taken during surgical drainage to rule out cystic carcinoma.

Case history A 53-year-old man presents to the emergency department complaining of severe mid- epigastric abdominal pain that radiates to the back. The pain improves when the patient leans forwards or assumes the fetal position and worsens with deep inspiration and movement. He also complains of nausea, vomiting, and anorexia, and gives a history of heavy alcoholic intake this past week. He is tachycardic, tachypnoeic, and febrile with hypotension. He is slightly agitated and confused. He is diaphoretic with decreased breath sounds over the base of the left lung.

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