CRITICAL CARE MANAGEMENT OF ACUTE PANCREATITIS-AN UPDATE

of the pancreas that may extend to local and distant extrapancreatic tissues.1 The definitions of pancreatic inflammatory disease has been the subject of several international conferences in Marseilles 1963,2Cambridge 1983,3Marseilles 1984,4 and Atlanta 1992.1 The American College of Gastroenterology (ACG) practice guidelines provide acceptable terminology for the classification of acute pancreatitis and its complications.5

Inclusion criteria were English language literature from 1960 onwards, relating latest terminology allocated for acute pancreatitis and its complications, advancement of management with introduction of newer drugs and their clinical trial as well as some meta analysis, guidelines provided by British Gastroenterological society, American College of Physician with their update and recently recommended audit standard for management of acute pancreatitis.
Terminology 5 Mild acute pancreatitis is associated with minimal organ dysfunction and an uneventful recovery.The predominant pathological feature is interstitial oedema of the gland and it is also known as Interstitial pancreatitis.It implies preservation of pancreatic blood supply.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.However, organ failure present within the first week, which resolves within 48 hours should not be taken as marker for severity.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.necrosis suggests the disruption of pancreatic blood supply with resulting ischaemia.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.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.A pancreatic abscess is a circumscribed intraabdominal collection of pus, usually in proximity to the pancreas, containing little or no pancreatic necrosis, which arises as a consequence of acute pancreatitis.When acute pancreatitis occurs on two or more occasions (evidenced by elevation of the serum pancreatic enzymes), it is classified as acute recurrent pancreatitis.In some cases, acute recurrent pancreatitis progresses to chronic pancreatitis, implying the presence of parenchymal fibrosis and loss of glandular function.

Incidence
Acute pancreatitis accounts for 3% of all cases of abdominal pain admitted to hospital in the UK. 6 The yearly incidence of acute pancreatitis in the United States is approximately 17 new cases per 100,000 populations.Some epidemiological evidence suggests that the true incidence is probably increasing, 7 partly reflecting increased alcohol intake among the young 8,9 but also due to gallstones in some areas. 10
Pathophysiology 17 Pancreatitis results from an autodigestive process.Pancreatic digestive enzymes, vasoactive materials and other toxic materials extravasate out of the pancreas into the surrounding areas, leading to a widespread chemical irritation resulting in simple edema to severe hemorrhage and necrosis.Trypsin and chymotrypsin are the initiating enzymes; their release can in turn result in the release and activation of other proenzymes (including proelastase, procollagenase and phospholipases).Trypsin damages endothelial cells and mast cells, resulting in the release of histamine.This major inflammatory mediator enhances vascular permeability, leading to edema, hemorrhage and the activation of the kallikrein system, which in turn results in the production of vasoactive peptides or kinins.The latter are thought to cause pain and further aggravate the inflammatory response.In the case of gallstones, the major theories include (1) reflux of bile into the pancreatic duct; (2) reflux of duodenal content into the pancreatic duct; and (3) distal obstruction of the pancreatic duct, with continued pancreatic secretion leading to increased ductal pressure and resulting in pancreatitis.
Although alcohol has been implicated as a major cause of acute pancreatitis, there is no evidence that an occasional bout of excessive alcohol intake can lead to an acute attack.It is suggested that chronic ingestion may lead to chronic damage and sensitization, which may result in acute pain even with small amounts of alcohol.Alcohol can cause direct damage to acinar cells in a manner similar to that in which it damages liver cells.

Clinical features
Pain from acute pancreatitis is a knife-like, steady, sharp pain that starts suddenly and reaches its zenith rapidly.It is commonly localized to the epigastric area and may radiate directly to the back.It improves on leaning forward and is frequently associated with nausea or vomiting.Depending on the location of the inflammation, the pain may be referred to either the left upper quadrant or the right upper quadrant.Frequently the pain is dyspeptic in quality and aggravated by food.This is due partially to the fact that eating stimulates secretion.Classically the pain lasts between three and four days.When the pancreatitis is severe, it may result in shock and may lead to death.Recurrent nausea and vomiting may be due to a reflex mechanism secondary to pain and occurs in over 90% of the cases.Other causes include pseudo-obstruction secondary to ileus and distention or obstruction secondary to a pancreatic mass or pseudocyst.Jaundice may occur since the common bile duct traverses the pancreatic head before entering the duodenum, often transiently.
Between 50 and 90 percent of patients have signs of abdominal distension or muscle spasms with epigastric pain and left upper-quadrant tenderness. 18,19Other signs are fever, tachycardia and jaundice.Often the patient is restless and dehydrated on presentation. 18,20Depending on the severity of pancreatitis, the patient may appear in distress or be in shock.Bluish discoloration of the flanks (Grey Turner's sign) or of the periumbilical area (Cullen's sign) indicates that blood from hemorrhagic pancreatitis has entered the fascial planes.The signs are not specific and may occur in any condition that causes retroperitoneal hemorrhage.Tender red and painful nodules that mimic erythema nodosum may appear over the extremities.These are often due to circulating lipases.

Local complication
Local involvement of pancreatitis includes phlegmon (18%), pancreatic abscess (3%), pancreatic pseudocyst (10%) and thrombosis of the central portal system. 21hlegmon is an area of edema, inflammation and necrosis without a definite structure (unlike an abscess).A phlegmon results from acute intrapancreatic inflammation with fat necrosis and pancreatic parenchymal and peripancreatic necrosis.This arises from the ischaemic insult caused by decreased tissue perfusion and release of the digestive enzymes.The Atlanta Meeting 5 discouraged the term phlegmon and replaced it with pancreatic necrosis.When this damage is not cleared, further inflammation ensues, declaring itself by increased pain, fever and tenderness.In severe cases a secondary infection ensues, a process termed infected necrosis of the pancreas, which occurs within the first one to two weeks of the illness.Most clinical studies in adults cite pancreatic infection as the most common cause of death, accounting for 70-80% of deaths. 1,22In 3% of acute pancreatitis an abscess develops, usually several weeks into the illness.An abscess is a well-defined collection of pus occurring after the acute inflammation has subsided.A pseudocyst develops as a result of pancreatic necrosis and the escape of activated pancreatic secretions through pancreatic ducts.It contains blood and debris.This fluid coalesces and becomes encapsulated by an inflammatory reaction and fibrosis.These patients usually have pain and hyperamylasemia, but may be asymptomatic.They may present with an abdominal mass, causing compressive symptoms.

Diagnosis of Pancreatitis
According to the the American College Of Gastroenterology(ACG) guidelines, the diagnosis of Acute Pancreatis is supported by an elevation of the serum amylase and lipase in excess of three times the upper limit of normal.
The advantages of amylase testing are that it is quickly performed, easily obtained and inexpensive. 25Lipase measurements are better than those of amylase measurement, particularly in detecting alcoholic pancreatitis. 25The specificity of lipase measurement, as well as amylase measurement, may be improved by raising the threshold to at least three times the upper limit of the normal reference values. 26The severity of pancreatitis does not correlate well with the magnitude of elevation of serum amylase and lipase. 27There is no value in following daily trends of serum amylase and lipase as they do not correlate with recovery or prognosis.
Trypsin/Elastase.Based on median sensitivities and specificities, an elevated trypsin level has a better likelihood ratio for detecting pancreatitis than the amylase level and is probably the most accurate serum indicator for acute pancreatitis. 28The elastase level has not proved to be better than trypsin or lipase levels in assisting the diagnosis of acute pancreatitis.However, a serum trypsin assay is not widely available and therefore is not routinely used.
Hepatic Function Studies.Hepatic transaminase levels may be elevated in patients with pancreatitis caused by alcohol abuse or cholelithiasis with obstruction.Elevation of the serum alanine aminotransferase greater than 80 U/mL is highly specific but poorly sensitive for gallstone pancreatitis. 29perimental biochemical markers that may hold promise for assessing severity of disease include trypsinogen activation peptide, interleukin-6, interleukin-10, and C-reactive protein. 30

Radiologic Studies:
Abdominal radiograph shows Gas-filled duodenum (sentinel loop) secondary to obstruction is the most specific for pancreatitis. 20The abdominal radiograph is frequently normal, but an abdominal radiograph is helpful for excluding other causes of acute abdominal pain.Chest radiograph reveals pleural effusions (most commonly left-sided), atelectasis, infiltrates suggestive of ARDS.
Ultrasonography.The sensitivity of this study in detecting pancreatitis is 62 to 95 percent. 31,32wever, in 35 percent of cases, the pancreas is obscured secondary to bowel gas. 25It detects gallstones as a potential cause,it rules out and acute cholecystitis as a differential cause of pain and hyperamylasemia.It detects biliary dilatation suggestive of the need for early endoscopic retrograde cholangiopancreatography (ERCP).
Computed Tomography (CT).The American College of Gastroenterology (ACG) practice guidelines state that "a dynamic contrast-enhanced CT is recommended at some point beyond the first 3 days in severe acute pancreatitis (on the basis of a high APACHE score or organ failure) to distinguish interstitial from necrotizing pancreatitis." 22A CT should also be considered for those in whom a localized pancreatic complication is suspected (e.g., pseudocyst, splenic vein thrombosis, splenic artery aneurysm).CT evidence of necrosis correlates well with the risk of other local and systemic complications. 33The decision to perform CT will usually be taken after approximately one week of hospital admission with persisting organ failure, signs of sepsis, or deterioration in clinical status 6-10 days after admission. 347 This procedure is sometimes done to enable endoscopic sphincterotomy and remove impacted stones.
Blood glucose level to detect hyperglycaemia and hypocalcaemia should be identified at early diagnosis.
Investigations to diagnose etiology 34 • Fasting plasma lipids

Prediction of Severity
About 20 to 30 percent of patients with acute pancreatitis develop complications of necrosis, organ failure, or both 38-40.Unfortunately, the serum amylase level and the lipase level are not specific enough measures of disease activity to be used prognostically.
Clinical monitoring is inadequate for determining severity and predicting the course of pancreatitis because it only detects about 39 percent of severe cases. 41Several systems have been developed in an attempt to provide reliable prognostic classification for patients with acute pancreatitis.However, two systems, the APACHE II scale 42 and the multiple organ system failure (MOSF) scale 43 have some advantages over the Ranson criteria 5 and Glasgow criteria 34 .
World Health Association has provided a composite guideline. 44Features that may predict a severe attack present within 48 hours of admission to hospital.There is no evidence to support the use of repeated APACHE II scores for monitoring progress.

Oxygen
Saturation should be measured continuously and supplemental oxygen should be administered to maintain an arterial saturation greater than 95%. 34

Intravenous fluid
Early oxygen supplementation and fluid resuscitation may be associated with resolution of organ failure, 45 and early resolution of organ failure is associated with very low mortality, 46,47 It is wise to treat every patient aggressively until disease severity has been established. 36uids are given intravenously (crystalloid or colloid as required) to maintain urine output .0.5 ml/kg body weight. 34In addition to maintenance fluid requirements, the amount sequestered should be monitored and replaced with isotonic fluids such as normal saline, with a goal of evolution and hemodilution.Some patients may require as much as 250 to 350 mL/hr, particularly in the early phases of Acute Pancreatitis.Of course, the aggressiveness of fluid replacement must be tempered in the presence of underlying cardiac or renal disease.The rate of fluid replacement should be monitored by frequent measurement of central venous pressure in appropriate patients.

Analgesia
In addressing the patient's pain, analgesia with meperidine (Pethidine) along with an antiemetic is preferred over the use of morphine, because morphine may cause spasm of the sphincter of Oddi, which has the potential to worsen the condition. 2

NUTRITION
• Withholding oral intake in an attempt to reduce pancreatic stimulation by food, hydrochloric acid, cholecystokinin and secretin. 18Nasogastric tube may be used when the patient has protracted vomiting or if obstruction is seen on the abdominal radiograph. 18,21,23,48Nutrition support may be withheld in mild pancreatitis for several days.The ACG guidelines advise nutrition support if NPO status is maintained for longer than 5 to 7 days. 22In patients with severe disease, oral intake is inhibited by nausea; the acute inflammatory response is associated with impaired gut mucosal barrier function.It has been suggested that nutritional support may help to preserve mucosal function and limit the stimulus to the inflammatory response.In these circumstances enteral feeding seems to be safer than parenteral feeding, with fewer septic complications. 49,50The use of enteral feeding may be limited by ileus.If this persists for more than five days, parenteral nutrition will be required.

Prophylactic antibiotic
[53][54][55][56][57][58] There remains no consensus view on the value of antibiotic prophylaxis.If antibiotic prophylaxis is used, it seems sensible to limit the duration of prophylaxis to 7-14 days.Treatment should not be continued beyond that time without evidence of infection provided by bacterial growth on culture.When such evidence exists, appropriate antibiotic therapy should be guided by the results of sensitivity testing in accordance with critical care medicine guidelines.SPECIFIC DRUG THERAPY There is no proven therapy for the treatment of acute pancreatitis. 36,591][62] Anticholinergics have been used in an attempt to decrease gastric secretions and increase pH.As with the use of nasogastric tubes, anticholinergics do not decrease hospital stay or pain.

GALL STONE PANCREATITIS AND TREATMENT OF GALL STONES
• ERCP with papillotomy and stone extraction in the setting of stone impaction and cholangitis. 63Severe gallstone pancreatitis in the presence of increasingly deranged liver function tests and signs of cholangitis (fever, rigors, and positive blood cultures) require an immediate and therapeutic ERCP." 44 SURGICAL TREATMENT FOR ACUTE PANCREATITIS AND PANCREATIC NECROSIS • Patients with persistent symptoms for more than seven days, and greater than 30% pancreatic necrosis, and those with smaller areas of necrosis and clinical suspicion of sepsis should undergo image guided fine needle aspiration (FNA) to obtain material for culture.64 • All patients with infected necrosis require intervention by radiological or surgical drainage.36,59,64 • Local complications of pancreatic necrosis, such as pseudocyst and pancreatic abscess, often require surgical, endoscopic, or radiological intervention.Reported results of surgical and endoscopic drainage are similar.36,59 Outcome: Overall outcome is variable.Incase of Interstitial Acute Pancreatitis it is <1%, incase of Sterile it is 10% and incase of Infected one 30%.
bile for crystals-bile and pancreatic cytology • ERCP-bile and pancreatic cytology • Sphincter of Oddi manometry • Pancreatic function tests to exclude chronic pancreatitis Genetic analysis is only indicated in the presence of a family history of one or more of the following: acute pancreatitis, recurrent undiagnosed abdominal pain, pancreatic carcinoma, or type 1 diabetes mellitus.