AUTHOR INFORMATION

Section 1 of 10

Authored by Ghattas Khoury, MD, President, Lebanese Order of Physicians, Clinical Professor, Department of Surgery, American University of Beirut

Coauthored by Samer S Deeba, MD, Fellow, Department of Surgery, St Mary's Hospital, Imperial College, London

Edited by Jerome FX Naradzay, MD, FACEP, Emergency Services Medical Director, Department of Emergency Medicine, Maria Parham Medical Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Eugene Hardin, MD, FACEP, FAAEM, Chair and Associate Professor, Department of Emergency Medicine, Charles R Drew University of Medicine and Science; Chair, Department of Emergency Medicine, Martin Luther King, Jr/Drew Medical Center; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Jonathan Adler, MD, Attending Physician, Department of Emergency Medicine, Massachusetts General Hospital; Division of Emergency Medicine, Harvard Medical School

Author's Email:	Ghattas Khoury, MD
Editor's Email:	Jerome FX Naradzay, MD, FACEP

eMedicine Journal, December 6 2006, VOLUME 7, Number 12

INTRODUCTION

Section 2 of 10

Background: Pancreatitis is an inflammatory process in which pancreatic enzymes autodigest the gland.

The gland can sometimes heal without any impairment of function or any morphologic changes. This process is known as acute pancreatitis. It can recur intermittently, contributing to the functional and morphologic loss of the gland. Recurrent attacks are referred to as chronic pancreatitis. Both forms of pancreatitis are present in the ED with acute clinical findings.

Pathophysiology: Because the pancreas is located in the retroperitoneal space with no capsule, inflammation can spread easily. In acute pancreatitis, parenchymal edema and peripancreatic fat necrosis occur first. This process is known as acute edematous pancreatitis.

When necrosis involves the parenchyma, accompanied by hemorrhage and dysfunction of the gland, the inflammation evolves into hemorrhagic or necrotizing pancreatitis.

Pseudocysts and pancreatic abscesses can result from necrotizing pancreatitis because of enzymes being walled off by granulation tissue (ie, pseudocyst formation) or bacterial seeding of pancreatic or peripancreatic tissue (ie, pancreatic abscess formation). An ultrasound or, preferably, a CT scan can be used detect both.

The inflammatory process can cause systemic effects because of the presence of cytokines, such as bradykinins and phospholipase A. These cytokines may cause vasodilation, increase in vascular permeability, pain, and leukocyte accumulation in the vessel walls. Fat necrosis may cause hypocalcemia. Pancreatic B cell injury may lead to hyperglycemia.

Frequency:

• In the US: Annual incidence of acute pancreatitis is 19.5 per 100,000 population and chronic pancreatitis is 8.3 per 100,000 population per year.

Mortality/Morbidity:

• Although acute pancreatitis should be noted, chronic pancreatitis has a more severe presentation as episodes recur.

• Acute respiratory distress syndrome (ARDS), acute renal failure, cardiac depression, hemorrhage, and hypotensive shock all may be systemic manifestations of acute pancreatitis in its most severe form.

Race: Annual incidence of acute pancreatitis in Native American persons is 4 per 100,000 population, in white persons is 5.7 per 100,000 population, and in black persons is 20.7 per 100,000 population.

Sex: No predilection exists.

Age: The risk for African American persons aged 35-64 years is 10 times higher than for any other group. African American persons are at higher risk than white persons in that same age group.

CLINICAL

Section 3 of 10

History:

• The main presentation of acute pancreatitis is epigastric pain or right upper quadrant pain radiating to the back

• Nausea and/or vomiting

• Fever

• Query the patient about recent surgeries and invasive procedures (ie, endoscopic retrograde cholangiopancreatography) or family history of hypertriglyceridemia.

• Patients frequently have a history of previous biliary colic and binge alcohol consumption, the major causes of acute pancreatitis.

Physical:

• Tachycardia

• Tachypnea

• Hypotension

• Fever

• Abdominal tenderness, distension, guarding, and rigidity

• Mild jaundice

• Diminished or absent bowel sounds

• Because of contiguous spread of inflammation (effusion) from the pancreas, lung auscultation may reveal basilar rales, especially in the left lung.

• Occasionally, in the extremities, muscular spasm may be noted secondary to hypocalcemia.

• Severe cases may have a Grey Turner sign (ie, bluish discoloration of the flanks) and Cullen sign (ie, bluish discoloration of the periumbilical area) caused by the retroperitoneal leak of blood from the pancreas in hemorrhagic pancreatitis.

Causes:

• The major causes are long-standing alcohol consumption and biliary stone disease.

• In developed countries, the most common cause of acute pancreatitis is alcohol abuse.
  • On the cellular level, ethanol leads to intracellular accumulation of digestive enzymes and their premature activation and release.

  • On the ductal level, ethanol increases the permeability of ductules, which allow enzymes to reach the parenchyma, resulting in pancreatic damage.

  • Ethanol increases the protein content of the pancreatic juice and decreases bicarbonate levels and trypsin inhibitor concentrations. This leads to the formation of protein plugs that block the pancreatic outflow and obstruction.

• Another major cause of acute pancreatitis is biliary stone disease (eg, cholelithiasis, choledocholithiasis). A biliary stone may lodge in the pancreatic duct or ampulla of Vater and obstruct the pancreatic duct, leading to extravasation of enzymes into the parenchyma.

• Minor causes of acute pancreatitis

• Medications, including azathioprine, corticosteroids, sulfonamides, thiazides, furosemides, NSAIDs, mercaptopurine, methyldopa, and tetracyclines

• Endoscopic retrograde cholangiopancreatography (ERCP)

• Hypertriglyceridemia (When the triglyceride (TG) level exceeds 1000 mg/U, an episode of pancreatitis is more likely.)

• Peptic ulcer disease

• Abdominal or cardiopulmonary bypass surgery, which may insult the gland by ischemia

• Trauma to the abdomen or back, resulting in sudden compression of the gland against the spine posteriorly

• Carcinoma of the pancreas, which may lead to pancreatic outflow obstruction

• Viral infections, including mumps, Coxsackievirus, cytomegalovirus (CMV), hepatitis virus, Epstein-Barr virus (EBV), and rubella

• Bacterial infections, such as mycoplasma

• Intestinal parasites, such as ascaris, which can block the pancreatic outflow

• Pancreas divisum

• Scorpion and snake bites

• Vascular factors, such as ischemia or vasculitis

DIFFERENTIALS

Section 4 of 10

Aneurysm, Abdominal
Cholangitis
Cholecystitis and Biliary Colic
Cholelithiasis
Gastroenteritis
Hepatitis
Mesenteric Ischemia
Obstruction, Large Bowel
Obstruction, Small Bowel

Other Problems to be Considered:

Perforated viscus
Acute peritonitis
Choledocholithiasis
Macroamylasemia
Macrolipasemia
Intestinal obstruction
Pancreatic cancer
Malabsorption syndromes/processes

WORKUP

Section 5 of 10

Lab Studies:

• A complete blood count (CBC) demonstrates leukocytosis (WBC >12000) with the differential being shifted towards the segmented polymorphs.

• If blood transfusion is necessary, as in cases of hemorrhagic pancreatitis, obtain type and crossmatch.

• Measure blood glucose level because it may be elevated from B cell injury in the pancreas.

• Obtain measurements for BUN, creatine (Cr), and electrolytes (Na, K, Cl, CO₂, P, Mg); a great disturbance in the electrolyte balance is usually found, secondary to third spacing of fluids.

• Measure amylase levels, preferably the Amylase P, which is more specific to pancreatic pathology. Levels more than 3 times higher than normal strongly suggest the diagnosis of acute pancreatitis

• Lipase levels also are elevated and remain high for 12 days. In patients with chronic pancreatitis (usually caused by alcohol abuse), lipase may be elevated in the presence of a normal serum amylase level

• Perform liver function tests (eg, alkaline phosphatase, serum glutamic-pyruvic transaminase [SGPT], serum glutamic-oxaloacetic transaminase [SGOT], G-GT) and bilirubin, particularly with biliary origin pancreatitis.

Imaging Studies:

• Perform a plain KUB (Kidneys, ureters, bladder) with the patient in the upright position to exclude viscus perforation (ie, air under the diaphragm). In cases with a recurrent episode of chronic pancreatitis, peripancreatic calcifications may be noted.

• Ultrasound can be used as a screening test. If overlying gas shadows secondary to bowel distention are present, it may not be specific.

• CT scan is the most reliable imaging modality in the diagnosis of acute pancreatitis. The criteria for diagnosis are divided by Balthazar and colleagues into 5 grades, as follows:

• Grade A - Normal pancreas

• Grade B - Focal or diffuse gland enlargement

• Grade C - Intrinsic gland abnormality recognized by haziness on the scan

• Grade D - Single ill-defined collection or phlegmon

• Grade E - Two or more ill-defined collections or the presence of gas in or nearby the pancreas

• The use of contrast material intravenously is yet to be proved detrimental on the microcirculation of the pancreas in cases of severe necrotizing pancreatitis.

Other Tests:

• Para-aminobenzoic acid test (ie, bentiromide [Chymex] test) for chronic pancreatitis

TREATMENT

Section 6 of 10

Emergency Department Care: Most of the cases presenting to the ED are treated conservatively, and approximately 80% respond to such treatment.

• Fluid resuscitation

• Monitor accurate intake/output and electrolyte balance of the patient.

• Crystalloids are used, but other infusions, such as packed red blood cells (PRBCs), are occasionally administered, particularly in the case of hemorrhagic pancreatitis.

• Central lines and Swan-Ganz catheters are used in patients with severe fluid loss and very low blood pressure.

• Patients should have nothing by mouth, and a nasogastric tube should be inserted to assure an empty stomach and to keep the GI system at rest.

• Begin parenteral nutrition if the prognosis is poor and if the patient is going to be kept in the hospital for more than 4 days.

• Analgesics are used to relieve pain. Meperidine is preferred over morphine because of the greater spastic effect of the latter on the sphincter of Oddi.

• Antibiotics are used in severe cases associated with septic shock or when the CT scan indicates that a phlegmon of the pancreas has evolved.

• Other conditions, such as biliary pancreatitis associated with cholangitis, also need antibiotic coverage. The preferred antibiotics are the ones secreted by the biliary system, such as ampicillin and third generation cephalosporins.

• Continuous oxygen saturation should be monitored by pulse oximetry and acidosis should be corrected. When tachypnea and pending respiratory failure develops, intubation should be performed.

• Perform CT-guided aspiration of necrotic areas, if necessary.

• An ERCP may be indicated for common duct stone removal.

Consultations: Consult a general surgeon in the following cases:

• For phlegmon of the pancreas, surgery can achieve drainage of any abscess or scooping of necrotic pancreatic tissue. It should be followed by postoperative lavage of the pancreatic bed.

• In patients with hemorrhagic pancreatitis, surgery is indicated to achieve hemostasis, particularly because major vessels may be eroded in acute pancreatitis.

• Patients who fail to improve despite optimal medical treatment or patients who push the Ranson score even further are taken to the operating room. Surgery in these cases may lead to a better outcome or confirm a different diagnosis.

• In biliary pancreatitis, a sphincterotomy (ie, surgical emptying of the common bile duct) can relieve the obstruction. A cholecystectomy may be performed to clear the system from any source of biliary stones.

MEDICATION

Section 7 of 10

The goal of pharmacotherapy is to relieve pain and minimize complications.

Drug Category: Antibiotics -- Used to cover the microorganisms that may grow in biliary pancreatitis and acute necrotizing pancreatitis. The empiric antibiotic regimen usually is based on the premise that enteric anaerobic and aerobic gram-bacilli microorganisms are often the cause of pancreatic infections. Once culture sensitivities are made, adjustments in the antibiotic regimen can be done.

Drug Name	Ceftriaxone (Rocephin) -- Third-generation cephalosporin with broad-spectrum gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin binding proteins.
Adult Dose	1-2 g IM/IV once or divided bid
Pediatric Dose	50-75 mg/kg/d IM/IV divided q12h
Contraindications	Documented hypersensitivity
Interactions	Probenecid may increase levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal impairment; caution in breastfeeding women and allergy to penicillin

Drug Name	Ampicillin (Marcillin, Omnipen) -- Bactericidal activity against susceptible organisms. Alternative to amoxicillin when unable to take medication orally.
Adult Dose	250-500 IM/IV mg q6h
Pediatric Dose	25-50 mg/kg/d IM/IV divided q6-8h
Contraindications	Documented hypersensitivity; viral mononucleosis
Interactions	Probenecid and disulfiram elevate levels; allopurinol decreases effects and has additive effects on ampicillin rash; may decrease effects of oral contraceptives
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reaction

Drug Category: Analgesics -- Pain control is essential to quality patient care. It ensures patient comfort, promotes pulmonary toilet, and has sedating properties, which are beneficial for patients who have sustained trauma or have painful lesions.

Drug Name	Meperidine (Demerol) -- Analgesic with multiple actions similar to those of morphine. May produce less constipation, smooth muscle spasm, and depression of cough reflex than similar analgesic doses of morphine.
Adult Dose	15-35 mg/h IV; 50-150 mg IM q3-4h
Pediatric Dose	1.1-1.8 mg/kg IM q3-4h
Contraindications	Documented hypersensitivity; MAOIs; upper airway obstruction or significant respiratory depression; during labor when delivery of premature infant is anticipated
Interactions	Monitor for increased respiratory and CNS depression with coadministration of cimetidine; hydantoins may decrease effects; avoid with protease inhibitors
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in head injuries because may increase respiratory depression and CSF pressure (use only if absolutely necessary); caution when using postoperatively and with history of pulmonary disease (suppresses cough reflex; substantially increased dose levels may aggravate or cause seizures because of tolerance, even if no prior history of convulsive disorders; monitor closely for morphine-induced seizure activity if seizure history exists

FOLLOW-UP

Section 8 of 10

Further Inpatient Care:

• Transfer patients with Ranson scores of 0-2 to a hospital floor.

• Transfer patients with Ranson scores 3-5 to an intensive care unit.

• Transfer patients with Ranson scores higher than 5 to an intensive care unit with emergency surgery as a possibility.

• Two other systems, the Acute Physiology and Chronic Health Evaluation (APACHE) and the Multiple Organ System Score (MOSS), have been used recently, but these are used more in an ICU setting.

Further Outpatient Care:

• The patient should be followed routinely with physical examination and amylase and lipase assays.

Complications:

• Infected pancreatic necrosis may result from seeding of bacteria into the inflammation.

• An acute pseudocyst is an effusion of pancreatic juice that is walled off by granulation tissue after an episode of acute pancreatitis.

• Hemorrhage into the GI tract retroperitoneum or the peritoneal cavity is possible because of erosion of large vessels.

• Intestinal obstruction or necrosis may occur.

• Common bile duct obstruction may be caused by a pancreatic abscess, pseudocyst, or biliary stone that caused the pancreatitis.

• An internal pancreatic fistula from pancreatic duct disruption or a leaking pancreatic pseudocyst may occur.

Prognosis:

• Ranson developed a series of different criteria for the severity of acute pancreatitis.

• Present on admission
  • Older than 55 years

  • WBC higher than 16,000 per mcL

  • Blood glucose higher than 200 mg/dL

  • Serum lactate dehydrogenase (LDH) more than 350 IU/L

  • SGOT (ie, aspartate aminotransferase [AST]) greater than 250 IU/L

• Developing during the first 48 hours
  • Hematocrit fall more than 10%

  • BUN increase more than 8 mg/dL

  • Serum calcium less than 8 mg/dL

  • Arterial oxygen saturation less than 60 mm Hg

  • Base deficit higher than 4 mEq/L

  • Estimated fluid sequestration higher than 600 mL

• A Ranson score of 0-2 has a minimal mortality rate.

• A Ranson score of 3-5 has a 10%-20% mortality rate.

• A Ranson score higher than 5 has a mortality rate of more than 50% and is associated with more systemic complications.

Patient Education:

• Educate patients about the disease and advise then to avoid alcohol in binge amounts and to discontinue any risk factor, such as fatty meals and abdominal trauma.

• For excellent patient education resources, visit eMedicine's Liver, Gallbladder, and Pancreas Center. Also, see eMedicine's patient education article, Pancreatitis.

TEST QUESTIONS

Section 9 of 10

CME Question 1: Which of the following signs is not seen on ultrasonography?

A: Cullen sign
B: Biliary obstruction
C: Pancreatic pseudocyst
D: Pancreatic abscess
E: Pancreatic calcifications

The correct answer is A: The Cullen sign is bluish discoloration of the periumbilical area observed on physical examination, not on ultrasonography.

CME Question 2: Which of the following findings is not useful in determining the prognosis in acute pancreatitis?

A: A white blood cell count higher than 20,000
B: A serum calcium level less than 8 mg/dL
C: A patient older than 55 years
D: A serum amylase level more than 1000 Somogyi units
E: Hypoxia

The correct answer is D: The amylase level is not included in Ranson criteria.

Pearl Question 1 (T/F): Pancreatitis is most common among Native American persons.

The correct answer is False: Annual incidence of acute pancreatitis in Native American persons is 4 per 100,000 population, in white persons is 5.7 per 100,000 population, and in black persons is 20.7 per 100,000 population.

Pearl Question 2 (T/F): Pancreatitis most common in African Americans.

The correct answer is True: Annual incidence of acute pancreatitis in Native American persons is 4 per 100,000 population, in white persons is 5.7 per 100,000 population, and in black persons is 20.7 per 100,000 population. The risk for African American persons aged 35-64 years is 10 times higher than for any other group. African American persons are at higher risk than white persons in that same age group.

Pearl Question 3 (T/F): A Ranson score of 0-2 results in a 10-20% mortality rate.

The correct answer is False: Upon presentation, if the patient is younger than 55 years, the WBC count should be more than 16,000 and the blood glucose should be higher than 10 mmol/L. After 48 hours, a decrease of more than 10 in the patient`s hematocrit level, a BUN rise higher than 5 mg/dL, Ca ions less than 8 mg/dL, arterial oxygen saturation of less than 60 mmHg, a base deficit of more than 4 mmol/L, and fluid sequestration more than 6 L. After obtaining the Ranson score by adding the positive tests, the following scenarios are possible:

• A Ranson score of 0-2 has a minimal mortality rate.
• A Ranson score of 3-5 has a 10-20% mortality rate
• A Ranson score higher than 5 has mortality rate higher than 50% and is associated with more systemic complications.

Pearl Question 4 (T/F): Alcohol consumption is the most common cause of pancreatitis in the US.

The correct answer is True: In developed countries, the most common cause of acute pancreatitis is alcohol abuse.

BIBLIOGRAPHY

Section 10 of 10

• Calleja GA, Barkin JS: Acute pancreatitis. Med Clin North Am 1993 Sep; 77(5): 1037-56[Medline].
• Moscati RM: Cholelithiasis, cholecystitis, and pancreatitis. Emerg Med Clin North Am 1996 Nov; 14(4): 719-37[Medline].
• Plock JA, Schmidt J, Anderson SE, et al: Contrast-enhanced computed tomography in acute pancreatitis: does contrast medium worsen its course due to impaired microcirculation?. Langenbecks Arch Surg 2005 Feb 12;[Medline].
• Schwartz Gr, et al: Acute pancreatitis. In: Principles and Practice of Emergency Medicine. Vol 2. 1992: 1782-6.
• Steer ML: Classification and pathogenesis of pancreatitis. Surg Clin North Am 1989 Jun; 69(3): 467-80[Medline].
• Taylor SL, Morgan DL, Denson KD, et al: A comparison of the Ranson, Glasgow, and APACHE II scoring systems to a multiple organ system score in predicting patient outcome in pancreatitis. Am J Surg 2005 Feb; 189(2): 219-22[Medline].
• Trede M, Carter DC: Acute pancreatitis. In: Surgery of the Pancreas. 1993: 161-259.
• Werner J, Feuerbach S, Uhl W, Buchler MW: Management of acute pancreatitis: from surgery to interventional intensive care. Gut 2005 Mar; 54(3): 426-36[Medline].

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Author Information | Introduction | Clinical | Differentials | Workup | Treatment | Medication | Follow-up | Test Questions | Bibliography