Acute Pancreatitis

ACUTE PANCREATITIS

Introduction

Acute pancreatitis can be a difficult diagnosis to make, as the condition is often not specifically considered.

A serum lipase should always be considered in any patient with epigastric pain, especially if they have well recognized risk factors for the condition such as gall stones or alcohol abuse.

Symptoms can precede significant rises in lipase levels and so when clinical suspicion is high or the presentation uncertain, a timed repeat level should be considered.

Once diagnosed then severity should be assessed.

Severe cases should have a CT scan performed.

It is important to diagnose severe cases, as these patients will require aggressive management in an ICU to prevent/ reverse multiorgan failure.

Pathophysiology

The pathogenesis of acute pancreatitis relates to the inappropriate activation of trypsinogen to trypsin, which in turn leads to local release of digestive enzymes with local tissue inflammation/ destruction and systemic effects in severe cases.

Causes

The commonest causes include:

1. Gallstones:

● The most common cause of acute pancreatitis is gallstones passing into the bile duct and temporarily lodging at the sphincter of Oddi.

2. Alcohol abuse

● This is the second most common cause.

3. Post-ERCP.

4. Idiopathic:

● Traditionally no clear cause was found in up to 30 % of cases

Occult microlithiasis (or “biliary sludge”) now appears to be responsible for many cases of “idiopathic” acute pancreatitis.

Other causes are much less common but can include: 5. Sphincter of Oddi dysfunction.

6. Trauma.

7. Drugs:

● Many have been implicated.

Rare causes include:

8. Toxins/ envenomations:

● The stings of some scorpion and spider species have been implicated.

9. Metabolic:

● Hypercalcemia from any cause can lead to acute pancreatitis

● Hypertriglyceridaemia

10. Anatomical abnormalities:

● Pancreatic cancers

● Pancreatic divisum

11. Infection:

● Several infectious diseases (mostly viral) may cause pancreatitis that usually is mild.

Those implicated have included:

♥ HIV, Coxsackie, Mumps, parasitic, ascariasis.

12. Auto-immune (vasculitis) conditions.

Complications

In severe cases release of digestive enzymes leads to severe inflammation which can result in SIRS (systemic inflammatory response syndrome) which may lead to MODS (multiorgan dysfunction syndrome) - and ultimately death.

Acute complications may include:

1. Hypovolemic shock:

● Due to fluid loss and / or hemorrhaging.

2. Electrolyte disturbances including: ● Hyperglycemia

● Hypocalcemia.

● Hypokalemia, in cases of persistent vomiting.

3. Septicaemia:

● From translocation of gut bacteria.

● Particularly in association with pancreatic necrosis.

● Septic shock

4. Multiorgan failure:

● Acute renal failure.

● Pulmonary:

♥ ARDS.

● Haematological:

♥ DIC

● CVS collapse.

5. Occasionally splenic vein thrombosis can occur.

Longer term complications may include:

1. Phlegmon:

● This is essentially an inflammatory mass.

2. Abscess:

● Abscess formation may occur within 2-3 weeks.

3. Pseudocyst

● This may form within 2-3 weeks.

● It is fluid sequestration into the lesser sac.

● It may cause compression of adjacent tissues, hypovolemia, infection, rupture (with consequent hemorrhage) or fistula formation. 4. Chronic pancreatitis:

● This can may occur with the attendant problems of malabsorption and diabetes.

Clinical assessment

Most cases are mild with recovery in 5-7 days.

Around 20 % develop severe pancreatitis.

Half of deaths that occur will be within the first week from multiorgan system failure.

Death after one week is usually due to infective complications.

Important Points of History:

1. Abdominal pain:

● The cardinal symptom of acute pancreatitis is epigastirc pain.

♥ Typically pain is acute in onset in cases of gallstone induced pancreatitis.

♥ In cases of other causes, in particular alcohol, the onset of pain is typically more insidious.

● The pain may be perceived more on the left or right side, depending on which portion of the pancreas is involved.

● The pain radiates to the back in approximately one half of the cases.

● The pain may be aggravated by meals or by lying supine and may be somewhat relieved by sitting up and leaning forward.

● The duration of pain is variable but typically longer than a day.

● Persistence of pain may indicate local complications.

2. Associated symptoms:

● Anorexia, nausea and vomiting are common associations.

3. Assess for risk factors:

In particular:

● Alcohol

● Biliary tract disease ● Recent ERCP

● Drugs

Important Points of Examination:

1. Assess any immediate ABC issues.

● Check for signs of circulatory shock and /or septicemia.

2. Abdominal findings:

These can be surprisingly few, given the degree of pain experienced, but may include:

● Tenderness, (mild to severe).

● Guarding.

● Distension, (due to ileus).

● Bowel sounds may be reduced or absent.

A few uncommon physical findings are associated with severe necrotizing pancreatitis and may occur 36-72 hours after the onset of pain:

They result from hemoperitoneum from retroperitoneal blood dissecting along tissue planes and include:

● Cullen’s sign:

♥ This is ecchymosis around the umbilicus,

● Grey-Turner’s sign:

♥ This is ecchymosis along the flanks resulting

● Fox’s sign:

♥ This is ecchymosis along the inguinal ligament.

3. Clinical features suggesting more severe disease include:

● Agitation/ confusion

● Abnormal vital signs:

♥ Hypoxemia (reduced SaO2 on pulse oximetry).

♥ Fever ♥ Tachycardia - persisting despite analgesia.

♥ Hypotension

♥ Tachypnea may suggest the onset of the serious complication of ARDS.

♥♥ Hypoventilation may be due to the pain of the adjacent inflamed tissues

Diagnostic criteria:

Diagnosis is established by the presence of two of the three following criteria:

1. Acute upper abdominal pain

2. Serum amylase and/or lipase levels greater than three times the upper limit of normal

3. Characteristic findings from abdominal imaging:

● CT

● MRI

● Ultrasound.

Severity assessment:

The majority of cases of acute pancreatitis are relatively mild and self-limiting, (around 80%) however, a sizable proportion can become severe (around 20 %) - with a subsequent average mortality rate of about 20%.

Severe cases of pancreatitis should have a CT scan to assess the degree of necrosis and/or other complications.

It is important to diagnose severe cases, as these patients will require aggressive management in an ICU to prevent/ reverse multiorgan failure.

In general terms factors which predict severe pancreatitis (and hence the need for aggressive therapy) in the ED include the following: 1

1. Age > 65 years

2. Body mass index > 30 kg/m2

3. Pleural effusion on CXR

4. > 30 % necrosis on CT scan

5. APACHE II score > 8 6. Signs and symptoms of organ failure in general:

For example:

● Persisting tachycardia

● Hypotension/ impaired peripheral perfusion.

● Hypoxia

● Agitation/ confusion

● Reduced urine output

● Biochemical parameters:

♥ Acidosis/ elevated lactate

♥ Renal failure

♥ CRP > 150 mg/L

Prognosis Scoring:

There are several scoring systems available to predict which patients will develop severe disease, including:

● Ranson’s criteria

● The CT Severity Index/ Necrosis Score

There is however no evidence that a particular severity scoring system is more accurate than any other.

Severity Classification:

The Revised Atlanta Classification is one method of assessing actual severity

See appendix 1 below.

Investigations

Blood tests:

1. FBE

2. CRP

● Levels above 150 mg/L at 24 or 48 hours predicts severe pancreatitis. 3. U&Es and glucose

4. Calcium level.

5. LFTs, looking for possible biliary tract disease:

● Findings on liver function tests, particularly the level of alanine aminotransferase (ALT), can be used as a surrogate marker for gallstone pancreatitis. ALT levels greater than or equal to 150 IU/L have a positive predictive value of 95% in diagnosing gallstone pancreatitis.

It is not a sensitive indicator however.

6. Serum triglycerides

7. Pancreatic enzymes:

The diagnosis is made on the amylase or more commonly the lipase levels.

Amylase: 3

● Serum amylase is readily available but not specific for pancreatitis, (as it may also be elevated in salivary gland disease, some cancers, and in chronic renal failure).

● A level of greater than 3 times normal however is highly suggestive.

● The serum half-life of amylase is short, and elevations generally occur within 2-3 hours then return to normal within a few days.

● A persistent elevation in amylase (greater than 10 days suggests a complication such as abscess or pseudocyst formation)

● Urinary amylase may be elevated for a period after serum amylase has returned to normal.

Lipase: 1, 3

● Lipase is both more sensitive and more specific than amylase for pancreatitis. 3 Unlike amylase, lipase is only produced in the pancreas.

In most institutions this test has replaced the older amylase test

● It rises in 4-8 hours:

Note that clinical symptoms can precede significant rises in lipase levels.

Non-elevated or mildly elevated levels should be considered against the timing of the test from symptom onset. ● Lipase also remains elevated in the serum for longer periods of time than amylase - up to 2 weeks.

● The level of serum amylase or lipase does not predict whether the disease is mild, moderate, or severe.

● A level of greater than 3 times normal is generally considered diagnostic of pancreatitis.

8. ABGs/ lactate:

● These should be done if there is respiratory distress or the patient is significantly unwell.

● Cardiac ischemia needs to be considered in the differential diagnoses in those patients who are high risk for ischemic cardiac events.

Plain Radiology:

● Especially if unwell or in respiratory distress, an ARDS may develop.

● The presence of a pleural effusion indicates more severe disease.

● This has a limited role in acute pancreatitis.

● It is primarily used to help rule out other causes of acute abdominal pain.

● In pancreatitis findings may include:

♥ “Sentinel” loops of bowel, indicating regions of local ileus.

♥ Calcifications may be seen in cases of chronic pancreatitis.

♥ Gallstones may occasionally be seen.

♥ Peripancreatic retroperitoneal gas suggests necrosis and infection of the pancreas.

Ultrasound:

This is the most useful initial test in determining the possible gallstone aetiology of acute pancreatitis.

All patients with acute pancreatitis should have an ultrasound to rule out gallstones and to assess the state of the bile ducts. Endoscopic ultrasound is better able to assess for the presence of gallstones in the distal common bile duct.

CT scan:

Routine CT with contrast scan is not generally indicated in mild cases of pancreatitis.

Indications include:

1. Where the diagnosis is uncertain:

● When the clinical presentation or biochemical tests are equivocal contrast-enhanced CT becomes the investigation of choice.

There may be a normal level of lipase and/or amylase because of a delayed presentation.

2. Excluding alternative diagnoses.

3. Assessing the severity of cases (degree of pancreatic necrosis) in unwell patients:

● Most accurate > 48 hours

● CT is the imaging study of choice for assessing for complications such as necrosis, haemorrhage or abscess.

● > 30 % necrosis is diagnostic of severe disease.

● Retroperitoneal gas on CT is an indicator of infected and necrotic pancreas.

4. The patient’s condition fails to improve clinically after 3 - 5 days.

MRI/ MRCP:

Magnetic resonance cholangiopancreatography (MRCP) is as good as contrast CT in diagnosing acute pancreatitis, and is an option for those patients with IV contrast allergy.

It is also a non-invasive technique for evaluating the intrahepatic and extrahepatic bile ducts and the pancreatic duct.

It is especially useful for detecting distal stones within the bile duct. MRCP has largely replaced ERCP as the gold standard for diagnosis of choledocholithiasis - a major reversible pathology for acute pancreatitis.

Patients with idiopathic pancreatitis should have endoscopic ultrasound ± magnetic resonance cholangiopancreatography to assess for microlithiasis, neoplasms and chronic pancreatitis. ERCP:

ERCP (Endoscopic Retrograde Cholangiopancreatography) indications include: 5

● Severe pancreatitis of proven or suspected choledocholithiasis aetiology

● Presence of cholangitis.

● Presence of jaundice.

It has the advantage over MRCP in that is can also be interventional, but the disadvantage of being invasive and requiring an anesthetic.

Management

1. Immediate attention to any ABC issues as required.

2. IV fluid resuscitation as clinically indicated.

● Significant third space losses can occur.

There should be early aggressive intravenous hydration with isotonic crystalloid solution within the first 12 - 24 hours.

Early aggressive fluid resuscitation reduces the risk and the extent of pancreatic necrosis, leading to improved clinical outcomes. The success of this therapy is thought to be related to improved pancreatic perfusion.

Large amounts of fluids may be necessary.

3. Monitoring:

● Establish monitoring according to how unwell the patient is with IDC, CVC, arterial line, pulse oximetry, continuous ECG.

4. Keep the patient nil orally:

● Patients should initially be kept nil by mouth.

Oral feeding can be recommenced in mild pancreatitis once pain and nausea and vomiting have resolved.

5. Nasogastric tube:

● This is not routinely required in milder disease but may be useful for protracted vomiting or in the presence of an ileus.

6. Analgesia:

● Parenteral opioids are usually necessary. ● IV Morphine titrated to clinical effect should be used.

There is no evidence to support the widespread belief that morphine exacerbates pancreatitis by stimulating the sphincter of Oddi.

● Pain can be severe and intractable, in these cases further options include:

♥ Morphine infusion via PCA (patient controlled analgesia) devices.

♥ Adjunctive (to morphine or fentanyl) low dose ketamine infusions (according to local hospital guidelines) can also be very beneficial in cases of intractable pain.

7. Antibiotics:

● These are not routinely required.

Antibiotics are given for extrapancreatic infection (e.g. cholangitis) or to patients with infected necrotizing pancreatic necrosis.

For empiric treatment:

♥ Tazocin.

♥ Metronidazole and Ceftriaxone.

8. Nutritional support:

● Enteral feeding is indicated in patients with predicted severe acute pancreatitis and should be commenced early, ideally after 48 hours of fasting, (despite historical concerns that this could exacerbate the condition).

Early nutritional support with nasoenteric or nasogastric feeding has been shown to improve clinical outcomes in patients with severe pancreatitis, resulting in reduced infective complications, a reduced length of stay and a tendency toward improved mortality.

Parenteral nutrition should be avoided if possible because of the increased risk of infectious complications.

9. ERCP:

● If the imaging and laboratory studies are consistent with severe acute gallstone pancreatitis or ascending cholangitis, early (within 24 hours) ERCP with sphincterotomy and stone extraction is indicated. 5 10. Surgery:

Cholecystectomy:

● Patients with gallstones should undergo cholycystectomy.

Failure to definitively clear gallstones results in unacceptable rates or readmission to hospital with recurrent pancreatitis.

Patients with mild biliary pancreatitis should have a laparoscopic cholecystectomy during their index admission. 5

Those unfit for this operation may have endoscopic sphincterotomy.

Pancreatic surgery:

● Necrotic and infected pancreatitis is an indication for surgical resection.

Disposition

All cases of acute pancreatitis require admission.

Patients are generally admitted under a Surgical unit.

If the patient is significantly unwell HDU / ICU admission will be required.

● All patients with organ failure or severe pancreatitis as defined by the revised version of the Atlanta classification should be managed in an intensive care setting.

Appendix 1

Prognostic Features / Severity Assessment Scores:

Ranson’s Criteria

Prognosis can be related to Ranson’s criteria: 1 Initial: Within 48 hours:

Age over 55 years HCT fall > 10%

WCC > 16000 / mm3 Urea rise > 1.8 mmol/L rise

Glucose > 10 mmol/L Ca < 2.0 mmol/L

LDH > 350 IU/L PaO2 < 60 mmHg

AST > 250 IU/L Base Deficit > 4 m Eq/L

Estimated fluid sequestration > 6 L.

1 point is given for each positive factor

A score of > 3 indicates severe pancreatitis.

Note however that the Ranson Score, can only be completed at 48 hours and so has limited utility within the ED.

The CT Severity Index and Necrosis Score

CT findings and grading of acute pancreatitis (CT severity index)

Grading based upon findings on unenhanced CT

Grade Findings Score A Normal pancreas - normal size, sharply defined, smooth contour, 0 homogeneous enhancement, retroperitoneal peripancreatic fat without enhancement

B Focal or diffuse enlargement of the pancreas, contour may show 1 irregularity, enhancement may be inhomogeneous but there is on peripancreatic inflammation

C Peripancreatic inflammation with intrinsic pancreatic abnormalities 2

D Intrapancreatic or extrapancreatic fluid collections 3

E Two or more large collections of gas in the pancreas or 4 retroperitoneum

Necrosis score based upon contrast enhanced CT

Necrosis, percent Score

33-50 4

≥50 6

CT severity index equals unenhanced CT score plus necrosis score: maximum = 10, ≥6 = severe disease.

Adapted from Balthazar, EJ, Robinson, DL, Megibow, AJ, Ranson, JH, Radiology 1990; 174:331.

The Revised Atlanta Classification:

Severity is an important indicator of mortality and facilitates management decisions about the need for a critical care bed and nutritional support.

The revised Atlanta classification is used to define severity of pancreatitis as follows:

Mild acute pancreatitis: ● No organ failure or local or systemic complications.

Most episodes of pancreatitis are mild and self-limiting, lasting less than 7 days.

Moderately severe acute pancreatitis:

● Transient organ failure of less than 48 hours or local complications (peripancreatic fluid collection, pancreatic necrosis) or systemic complications (exacerbation of pre-existing disease).

Severe acute pancreatitis:

● Persistent organ failure of greater than 48 hours.

High mortality rate of 20 - 30 %.

Appendix 2 Arterial phase computed tomography (CT) images (Day 0, Day 4 and Day 7) of a 65 year-old man with severe idiopathic pancreatitis who developed pancreatic necrosis.

A CT was performed on presentation to the emergency department for diagnostic purposes showing pancreatitis with significant peripancreatic stranding and free fluid.

A progress CT performed on Day 4 after presentation was done because of ongoing systemic inflammatory response syndrome and respiratory failure; this shows no significant change and did not aid the management.

Another progress CT, performed on Day 7 after presentation because of worsening sepsis; this shows pancreatic necrosis.

Arrows indicate the pancreas in each image.

References:

1. Heng K and Seow E, Pancreatitis in Textbook of Adult Emergency Medicine, Cameron et al 4th ed 2015.

2. Smith R. et al. Should Serum Pancreatic Lipase Replace Serum Amylase as a Biomarker of Acute Pancreatitis? ANZ J Surg 2005; 75: p.399- 404.

3. Manual of Use and Interpretation of Pathology Tests. The Royal college of Pathologists of Australasia. 2nd Ed 1997 p. 157 and 231

4. eTG - July 2016.

● Therapeutic Gastroenterology Guidelines March 2016

5. M. Nesvaderani et al. Acute pancreatitis: Update on Management. MJA 202 (8) 4 May 2015.