Acute Pancretaitis

SEMINAR

1. ACUTE PANCREATITIS R.Anusha PharmD 5 th Year Roll No:07 1

2. ACUTE PANCREATITIS 2 Acute pancreatitis (AP) is an inflammatory disorder of the pancreas characterized by severe pain in the upper abdomen and increased serum concentrations of pancreatic lipase and amylase. In the majority of patients, acute pancreatitis is a self-limiting disease that resolves spontaneously without complications. The risk for progression to chronic pancreatitis after an initial episode of acute pancreatitis is related to the etiology.

3. ETIOLOGY 3 Common (90%) Gall stones Alcohol Idiopathic Rare Metabolic: hypercalcemia, hypertriglyceridemia Drugs: thiazide, azathioprine, sodium valproate, pentamidine Infection: mumps, coxsackie virus Post ERCP (due to back pressure of contrast into ductal system) Trauma Organ transplantation Post GI surgery

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5. PATHOPHYSIOLOGY 5 The pathophysiology of acute pancreatitis is based on events that initiate injury and secondary events that establish and perpetuate the injury. Gallstones, alcohol abuse, and other causes of pancreatitis produce different initial insults to the pancreas. However, the resulting pathophysiologic process may be similar and include a combination of autodigestion and inflammatory response. The pancreas secretes the digestive enzymes as pro enzymes which are activated in the intestinal lumen. Acute pancreatitis may result when activation occurs in pancreatic duct system or acinar cells.

6. P r o e n z y m e s Activated p r o t eoly t i c enzymes Defective intracellular transport and secretion of pancreatic zymogens Pancreatic duct obstruction (common bile duct stones, tumors) Acute pancreatitis Hyperstimulation of pancreas (alcohol, triglycerides) Reflux of infected bile or duodenal contents into pancreatic duct (sphincter of Oddi dysfunction) P ancr e a t i c secretory trypsin inhibitors + + + + -

7. 7 The premature activation of trypsinogen to trypsin within the pancreas leads to activation of other digestive enzymes and autodigestion of the gland. In addition to activation of digestive enzymes within the pancrease , enzymes are also released into surrounding fat, vascular endothelium and other surrounding tissues and structures causing further damage and necrosis. Lipase damages fat cells, producing noxious substances that cause further pancreatic and peripancreatic injury. There may be an independent response from intra-acinar activation of inflammatory factors. The release of cytokines by acinar cells directly causes their injury and enhances the inflammatory response.

8. 8 Injured acinar cells liberate chemo-attractants that recruit neutrophils, macrophages, and other cells to the area of inflammation. These immune responses cause a systemic inflammatory response syndrome (SIRS). Vascular damage and ischemia causes the release of kinins, which makes capillary walls permeable and promotes tissue edema. The release of damaging oxygen-free radicals appears to correlate with the severity of pancreatic injury. Finally, pancreatic infection may result from increased intestinal permeability and translocation of colonic bacteria.

9. CLINICAL PRESENTATION 9 Upper abdominal pain that radiates into the back; it may be aggravated by eating, especially foods high in fat. Swollen and tender abdomen Nausea and vomiting Fever Increased heart rate Respiratory distress Severe advanced cases may develop bruising and discoloration in the left flank ( Grey Turner’s sign due to tissue catabolism of Hb) and around the umbilicus ( Cullen’s sign due to hemoperitoneum). These are the rare and late signs of extensive pancreatic destruction

10. Cullen’s sign Grey Turner’s sign

11. 11 Diagnosis The diagnosis of acute pancreatitis requires two of the following three: upper abdominal pain, a serum lipase or amylase concentration at least three times greater than the upper limit of normal, or characteristic findings on imaging studies. Lipase is more sensitive and specific than amylase and is the preferred laboratory test. Imaging studies are not necessary for diagnosis if the other two findings are positive.

12. 12 Clinical Course and Prognosis The clinical course of acute pancreatitis varies from a mild transitory disorder to a severe necrotizing disease. Mild acute pancreatitis is self-limiting and subsides spontaneously within 3 to 5 days. Mortality is influenced by etiology, as idiopathic and postoperative acute pancreatitis have higher rates than gallstone- or alcohol-related disease. First and second occurrences also carry a higher mortality than subsequent episodes.

13. 13 Complications Early complications are a result of SIRS and organ failure. The most common systemic complication of acute pancreatitis is respiratory failure. In addition, patients may experience systemic complications due to exacerbation of pre-existing renal, lung or heart disease. A second phase occurs in patients with moderately severe or severe disease.These patients have persistent organ failure and may have local complication including fluid collections that may become necrotic.

14. 14 Long-term complications include glucose intolerance and recurrence of acute pancreatitis. There are also local complications that may occur, including interstitial pancreatitis (acute peripancreatic fluid collection and pancreatic pseudocysts) and collection of necrosis. These develop approximately 3 to 4 weeks after the initial attack. Pancreatic infections occur in 15% to 30% of those with pancreatic necrosis and are usually secondary infections of necrotic tissue.

15. TREATMENT 15 Desired Outcomes Treatment of acute pancreatitis is aimed at relieving abdominal pain and nausea, replacing fluids, correcting electrolyte, glucose, and lipid abnormalities, minimizing systemic complications, and managing pancreatic necrosis and infection. Management varies depending on the severity of the attack. Patients with mild acute pancreatitis respond very well to the initiation of supportive care. Patients with severe acute pancreatitis should be treated aggressively and monitored closely.

16. 16 General Approach to Treatment All patients with acute pancreatitis should receive supportive care, including IV fluid resuscitation, adequate nutrition, and effective relief of pain and nausea. Patients should be evaluated for admission to the intensive care unit. Patients predicted to follow a severe course may require treatment of systemic complications. Fluid therapy is recommended and may help prevent organ failure.

17. 17 Patients with pancreatitis and SIRS should be treated according to SIRS guidelines. IV potassium, calcium, and magnesium are used to correct electrolyte deficiency states. Insulin is used to treat hyperglycemia. Local complications resolve as the inflammatory process subsides. However, patients with necrotizing pancreatitis may require antibiotics and procedural intervention.

18. 18 Non pharmacologic Therapy Nonpharmacologic therapy includes ERCP(endoscopic retrograde cholangio pancreatography) for removal of any underlying biliary tract stones, procedural interventions, and nutritional support. Advances in minimally invasive surgical techniques are changing practice with respect to timing and approach to managing infected necrotizing pancreatitis, and may help lower the risk of mortality in the most critical patients.

19. 19 Nutrition Nutritional support plays an important role in the management of patients with mild or severe disease as acute pancreatitis creates a catabolic state that promotes nutritional depletion. This can impair recovery, increase the risk of complications, and prolong hospitalization. Patients with mild acute pancreatitis can begin oral feeding when pain is decreasing and inflammatory markers are improving. It is not necessary to withhold oral nutrition until lipase normalizes.

20. 20 In severe or complicated disease, nutritional deficits develop rapidly and are complicated by tissue necrosis, organ failure, and surgery. If enteral feeding is not possible or if the patient is unable to obtain sufficient nutrients, total parenteral nutrition should be implemented before protein and calorie depletion become advanced. ASPEN guidelines state that IV lipids are considered safe unless the serum triglyceride concentration is greater than 400 mg/dL (4.52 mmol/L) and the patient has a history of hyperlipidemia .

21. 21 Pharmacologic Therapy Patients with acute pancreatitis often require IV antiemetics for nausea. Those requiring ICU admission should be treated with antisecretory agents (such as famotidine or pantoprazole) if they are at risk of stress-related mucosal bleeding. Patients also require appropriate fluid resuscitation and pain management.

22. 22 Fluid Resuscitation Vasodilation from the inflammatory response, vomiting, and nasogastric suction contributes to hypovolemia and fluid and electrolyte abnormalities, thus necessitating replacement. Patients with acute pancreatitis should receive aggressive fluid replacement to reduce the risks of persistent SIRS and organ failure. The IAP/APA guidelines recommend goal directed intravenous fluid with lactated Ringer’s at an initial rate of 5 to 10 mL/kg/h while the ACG guidelines recommend 250 to 500 mL/h with crystalloids.

23. 23 Goals for fluid therapy are one or more of the following: Heart rate less than 120/min Mean arterial pressure 65 to 85 mm Hg, Urinary output greater than 0.5 to 1 mL/kg/h, Invasive measures of stroke volume or intrathoracic blood volume, or Hematocrit 35% to 44% (0.35-0.44) with transfusion of blood. Patients with SIRS or sepsis should be resuscitated according to sepsis guidelines

24. 24 Relief of Abdominal Pain Parenteral opioid analgesics are used to control abdominal pain associated with acute pancreatitis despite a lack of high quality evidence to support the practice. A Cochrane review found a lack of studies to support any specific agent or class of agents for pain management in acute pancreatitis. Parenteral morphine is often recommended for pain control because it provides a longer duration of pain relief than other opioids. Although morphine increases biliary pressure, there is no evidence to indicate that it is contraindicated for use in acute pancreatitis.

25. 25 Antimicrobial use in Acute Pancreatitis Use of prophylactic antibiotics is not recommended in patients with acute pancreatitis without signs or symptoms of infection, including those with necrosis. However, empiric antimicrobial therapy may be considered in patients with necrosis who deteriorate or fail to improve with in 7 to 10 days. Because the source of bacterial contamination is most likely the colon, the antibiotic regimen for patients with known or suspected infected pancreatitis should be broad-spectrum, covering the range of enteric aerobic gram-negative bacilli and anaerobic microorganisms.

26. 26 Antibiotics of choice are CARBAPENAMS. IMIPENAM 500 mg 8th hourly given. Patients with infected necrotic pancreatitis are generally treated with a combination of invasive interventions and antibiotics. Antibiotics alone may be sufficient in some cases or at least delay the need for an invasive procedure long enough for the necrotic areas to be walled off.

27. 27 REFERENCES Pharmacotherapy-A Pathophysiologic Approach,10 th edition Davidson’s principles and practice of medicine 22nd edition.