Acute Pancreatitis


Acute Pancreatitis

  1. Definition
    • nonbacterial inflammation of the pancreas caused by the activation and digestion of the gland by its own enzymes
    • may be divided into 2 broad categories:

    1. Interstitial Edematous Pancreatitis
      • acute inflammation of the pancreas and peripancreatic tissues
      • no tissue necrosis
      • 90% of cases
      • usually follows a benign, self-limited course

    2. Necrotizing Pancreatitis
      • 10% of cases
      • may progress to multiorgan failure and sepsis

  2. Etiology
    1. Gallstone Pancreatitis
      • gallstones are the most common cause of acute pancreatitis in the U.S.
      • women > men, with a peak incidence between 50 and 60 years
      • there are several theories, to explain the relationship between gallstones and pancreatitis

      1. Common Channel Theory
        • proposes that an obstructing stone creates a common channel between the bile duct and the pancreatic duct, allowing reflux of bile into the pancreatic duct
        • according to this theory, bile triggers pancreatitis either by activating pancreatic enzymes or by injuring pancreatic cells directly

      2. Pancreatic Duct Obstruction
        • this theory proposes that pancreatic duct obstruction leads to ductal hypertension, rupture of small ducts, and extravasation of pancreatic juice into the substance of the gland

    2. Alcohol Abuse
      • 2nd most common cause of acute pancreatitis
      • most cases occur in chronic alcoholics after an episode of binge drinking
      • alcohol is directly toxic to pancreatic acinar cells
      • alcohol also increases tone in the sphincter of Oddi, which may lead to obstruction of pancreatic flow, protein precipitation, and ductal hypertension

    3. Postprocedure Pancreatitis
      • post-ERCP pancreatitis develops in ~5% of cases
      • severe pancreatitis may follow cardiopulmonary bypass, possibly related to ischemia
      • pancreatitis has been described after common duct exploration, sphincteroplasty, distal gastrectomy, splenectomy

    4. Ductal Obstruction
      • pancreatic tumors and strictures can cause pancreatitis, presumably by interfering with drainage of secretions
      • other rare causes of pancreatic duct obstruction include duodenal diverticula, choledochal cysts, and possibly pancreas divisum

    5. Drugs
      • numerous drugs have been linked to acute pancreatitis
      • frequent offenders include azathioprine, 6-mercaptopurine, estrogens, thiazide diuretics, furosemide, antiretroviral drugs

    6. Hyperlipidemia
      • triglyceride levels > 1000 mg/dL increase the risk of pancreatitis
      • lipolysis of triglycerides may release toxic levels of free fatty acids which cause acinar cell injury

    7. Hypercalcemia
      • usually secondary to hyperparathyroidism

    8. Infection
      • viruses associated with acute pancreatitis include mumps, coxsackievirus, and cytomegalovirus
      • incidence of acute pancreatitis is substantially higher in patients with AIDS

    9. Trauma
      • blunt abdominal trauma may result in pancreatic contusions, lacerations, or transections
      • patients may develop a posttraumatic ductal stricture

    10. Idiopathic
      • ~ 10% of cases
      • many of these patients have small biliary stones or sludge (microlithiasis) and benefit from cholecystectomy or ERCP

  3. Pathophysiology
    1. Pancreatic Enzyme Activation
      • after pancreatic injury, zymogen granules and lysosomes colocalize inside the acinar cells
      • cathepsin B, a lysosomal enzyme, activates trypsin in these colocalization organelles
      • activated trypsin then activates the remaining pancreatic proteases, resulting in autodigestion of pancreatic parenchyma
      • damaged pancreatic tissue results in activation of the proinflammatory cytokine cascade (TNF-α and IL-1)
      • cytokines may further damage pancreatic tissue and amplify the inflammatory response
      • in most patients, the inflammatory cascade is self-limited
      • in a smaller group of patients, inflammatory mediators may be released systemically, causing SIRS and multi-organ failure

  4. Clinical Manifestations
    1. Symptoms
      • has a diverse presentation: from a mild, self-limited illness to a severe, toxic condition that may progress to multiorgan failure and death
      • predominant symptom is pain: midepigastric, constant, often severe, radiating through to the back
      • pain may develop shortly after ingesting a large meal (gallstone pancreatitis) or 12 to 48 hours after a drinking binge (alcoholic pancreatitis)
      • nausea and vomiting are common and may be severe and protracted

    2. Physical Findings
      • fever (100° to 101°), tachycardia, epigastric tenderness, and abdominal distention with absent bowel sounds are common findings
      • hypotension, hypovolemia, tachypnea and/or respiratory failure, and obtundation may be present in the most severe cases
      • patients with hemorrhagic pancreatitis may have a bluish discoloration of the umbilical region (Cullen’s sign) or of the flanks (Grey Turner’s sign) from retroperitoneal blood that has tracked along tissue planes to these areas
      • jaundice is an uncommon finding and may represent either an impacted gallstone or compression of the common bile duct by edema of the pancreatic head

  5. Diagnosis
    • requires that 2 out of 3 criteria are met: upper abdominal pain, threefold or higher elevations in serum amylase or lipase, or imaging evidence
    • must consider other causes of acute upper abdominal pain as well: perforated ulcer, cholecystitis, bowel obstruction

    1. Lab Tests
      1. Serum Amylase
        • since an elevated amylase may occur in many acute abdominal conditions, it is not specific for pancreatitis
        • in addition, there is a false-negative rate of ~ 10%
        • degree of hyperamylasemia is not a predictor of the severity of acute pancreatitis

      2. Serum Lipase
        • more accurate indicator of acute pancreatitis since it is produced only by the pancreas
        • has a longer half-life than amylase, making lipase levels particularly valuable in patients who present several days after the onset of pain

    2. Radiologic Tests
      1. Chest X-ray
        • obtained to rule out free air
        • findings supporting a diagnosis of acute pancreatitis include left lobe atelectasis, left pleural effusion, and elevation of the left hemidiaphragm

      2. Abdominal X-ray
        • usually obtained to rule out a bowel obstruction
        • many nonspecific findings are suggestive of acute pancreatitis:
          • air in the duodenal loop, representing a localized ileus
          • sentinel loop sign: dilated jejunal loop in the left upper quadrant
          • colon cutoff sign: colonic distention to the level of the mid transverse colon with no air distally
          • obliteration of the psoas muscle secondary to retroperitoneal edema
          • pancreatic calcifications are diagnostic of chronic pancreatitis but not acute pancreatitis

      3. Ultrasound
        • major role is in assessing the gallbladder for gallstones and the common bile duct for size in patients with suspected gallstone pancreatitis
        • the pancreas is often obscured by overlying bowel gas, but occasionally peripancreatic edema and acute fluid collections can be seen

      4. CT Scan
        • contrast-enhanced dynamic CT is the most accurate method for diagnosing acute pancreatitis, but is not necessary in uncomplicated cases
        • will rarely change management early in the disease process
        • major role is in defining the amount of pancreatic necrosis or infected necrosis present in patients who fail to progress or recover
        • findings specific for acute pancreatitis include: 1) diffuse or focal pancreatic enlargement, 2) parenchymal edema, 3) parenchymal necrosis, 4) blurring of tissue planes, and 5) the presence of fluid collections

        CT - Acute Edematous Pancreatitis
        Acute Edematous Pancreatitis

      5. MRCP
        • no role in the acute setting
        • most valuable in visualizing the entire biliary and pancreatic duct anatomy in patients with recurrent and unexplained pancreatitis

      6. ERCP
        • no role as a diagnostic tool in the acute setting
        • indicated when cholangitis complicates gallstone pancreatitis

  6. Classification of Disease Severity
    • used to predict the progression to severe pancreatitis and overall mortality
    • multiple clinical and imaging based scoring systems exist

    1. Ranson Criteria
      • based on 11 parameters obtained on admission and 48 hours later
      • severe pancreatitis is diagnosed if three or more Ranson’s criteria are present
      • main drawback to the system is that it takes 48 hours to acquire the required data, so that it does not predict disease severity on admission
      • has been modified for gallstone pancreatitis

      Ranson Criteria
    2. APACHE II
      • based on patient’s age, previous health status, and 12 routine physiologic measurements
      • main advantage is that it can be used on admission and repeated at any time
      • disadvantages include its complexity and that it is not specific for acute pancreatitis
      • APACHE II score >7 defines severe pancreatitis

    3. Atlanta Criteria – Revised
      • combines both early clinical findings and later image-based findings
      • has replaced Ranson criteria and APACHE II in many centers

      Revised Atlanta Criteria
  7. Initial Management
    1. Standard Supportive Measures
      1. Fluid Resuscitation
        • single most important therapeutic maneuver
        • enormous amounts of fluid can be sequestered within the bowel and retroperitoneum
        • under resuscitation leads to end-organ injury
        • over resuscitation leads to pulmonary failure and abdominal compartment syndrome
        • adequacy of resuscitation is guided by urine output, blood pressure, and hematocrit

      2. Pain Control
        • adequate pain control will require parenteral narcotics
        • some clinicians avoid morphine, since it may cause spasm of the sphincter of Oddi
        • Dilaudid or Fentanyl are effective choices

      3. Nutrition
        • patients are initially made NPO
        • patients with mild to moderate pancreatitis can resume oral intake when their pain, ileus, and hyperamylasemia have resolved
        • patients with severe pancreatitis benefit from early nutritional support (<48 hours)

        1. Enteral Nutrition
          • preferred over TPN
          • preserves gut integrity, prevent bacterial translocation, and decrease infectious complications
          • medium chain fatty acid formulations are preferred because they cause less stimulation of the pancreas
          • appears to be no difference in outcome between nasogastric and nasojejunal feedings

        2. Parenteral Nutrition (TPN)
          • not every patient will tolerate enteral feedings
          • complications include hyperglycemia and catheter-related infections
          • TPN may be combined with low-volume enteral feedings

      4. Antibiotics
        • use of prophylactic antibiotics in severe pancreatitis remains controversial
        • current evidence shows that routine prophylactic antibiotics do not reduce infectious complications or mortality
        • antibiotics should only be used in documented or suspected infections
        • imipenem has good penetration into pancreatic tissue

  8. Complications of Acute Pancreatitis
    1. Abdominal Compartment Syndrome
      • recognized by oliguria and high peak inspiratory pressures
      • bladder pressure > 20 is diagnostic
      • initial management is by reducing volume infusion if possible
      • percutaneous drainage of ascites is also valuable
      • ultimately, a decompressive laparotomy may be required

    2. Pseudoaneurysms
      • most commonly involved arteries are the splenic and gastroduodenal
      • often present with unexplained hypotension or bleeding from a drain
      • diagnosis is made by CTA
      • management is by angioembolization

      Acute Pancreatitis - Pseudoaneurysm
    3. Fistulas
      • most common organs involved are the colon and duodenum
      • caused by ischemia or direct erosion
      • most are successfully managed with drainage and nutritional support

    4. Acute Fluid Collections
      • occur in ~ 60% of cases
      • most will spontaneously resorb
      • if fever and elevated WBC persists, fluid may need to be aspirated and cultured
      • infected fluid will require percutaneous drainage and IV antibiotics

      Acute Pancreatitis Fluid Collection
    5. Sterile Necrosis
      • may be focal, or diffuse throughout the gland
      • diagnosed by contrast-enhanced CT
      • it can be challenging to determine whether sterile necrosis has become secondarily infected
      • CT-guided aspiration and culture may be required for patients with persistent fever and elevated WBC
      • operation is indicated for unresolving SIRS or persistent unwellness lasting 4 weeks
      • 50% of these patients will be found to have infected pancreatic necrosis

      Acute Pancreatitis Necrosis
    6. Infected Necrosis
      • complicates sterile necrosis
      • results from bacterial translocation from the nearby colon
      • diagnosed by CT findings (air bubbles in the lesser sac), cultures from CT-guided aspiration, or persistent unwellness

      Infected Pancreatitis Necrosis
  9. Management of Gallstone Pancreatitis
    1. Mild Gallstone Pancreatitis
      • in the majority of patients, the pancreatitis resolves within 2 to 3 days
      • laparoscopic cholecystectomy can safely and cost-effectively be performed at this time
      • an operative cholangiogram is mandatory
      • avoids the risk of recurrent gallstone pancreatitis that is associated with interval cholecystectomy

    2. Moderate-to-Severe Gallstone Pancreatitis
      • patients with a protracted clinical course and extensive pancreatic and peripancreatic edema and acute fluid collections on CT scan benefit from a delayed approach to cholecystectomy
      • operation should be delayed for at least 6 weeks to allow the inflammation to subside
      • repeat CT scan should be done before cholecystectomy to prove that the inflammation has resolved

    3. Clinical Deterioration
      • if the patient deteriorates within 24 to 48 hours of admission, one must rule out that the patient has an impacted common duct stone
      • early use of ERCP and sphincterotomy appears to result in fewer complications and deaths than does traditional supportive management
      • if endoscopy is unable to clear the common duct, then an operative common duct exploration is carried out, as well as a cholecystectomy or cholecystostomy tube

  10. Management of Infected Pancreatic Necrosis
    1. Timing of Surgical Intervention
      • early intervention is associated with a worse outcome
      • surgery should be delayed for at least 4 weeks from presentation
      • benefit of delayed operation is attributed to better demarcation between viable and non-viable tissue, less risk of hemorrhage, less injury to surrounding organs, and less removal of viable pancreatic tissue

    2. Drainage Procedures
      1. Percutaneous Drainage
        • may be used to stabilize patients while awaiting definitive surgery
        • drains may be exchanged and upsized as needed
        • goal is to reduce the source of infection rather than to evacuate all necrotic tissue
        • requires a skilled and dedicated IR team
        • some patients will avoid formal debridement

      2. Endoluminal Drainage
        • the necrosis cavity is entered with ultrasound guidance via an opening in the posterior stomach
        • the endoscope is positioned inside the cavity and forceps can be used to remove solid material
        • the cavity is copiously irrigated
        • double pigtail catheters can be left between the stomach and cavity for continued drainage
        • patients often require multiple treatments

        Endoluminal Debridement - Acute Pancreatitis
    3. Debridement Procedures
      • goal of all debridement procedures is to remove all necrotic tissue and to unroof any cavities in the retroperitoneal space

      1. Video-Assisted Retroperitoneal Debridement (VARD)
        • previously placed percutaneous drain serves as a guide
        • a small left flank incision is made along the drain tract
        • debridement is performed under direct vision using suction and grasping forceps
        • using a long laparoscopic port, the cavity can then be insufflated, and debridement performed under videoscopic guidance
        • large-bore drains are left in place, and the cavity is continuously lavaged

        Video-Assisted Retroperitoneal Debridement
      2. Laparoscopic Debridement
        • lesser sac is entered via the gastrocolic ligament or transverse mesocolon
        • hand-assist port may facilitate the debridement

      3. Open Debridement
        • blunt dissection is used to remove all necrotic tissue
        • multiple methods exist to provide drainage after necrosectomy
        • multiple drains are placed and brought out in as dependent position as possible and the abdomen is closed (closed packing)

        Open Pancreatic Debridement
    4. Step-Up Approach
      • early surgical intervention for necrotic pancreatitis has a high mortality rate
      • delaying definitive surgery for 4 weeks or more leads to better outcomes
      • during that 4-week window, a stepwise approach to these patients shows promising results
      • very resource-intensive approach that is only available in specialized centers

      1. Source Control
        • percutaneous or endoscopic drain placement
        • goal is to allow the inflammation to subside and the necrosis to become better demarcated
        • ~35% of patients will be available to avoid operative debridement

      2. Minimally Invasive Debridement
        • next step up in patients who have necrosis not amenable to complete removal with percutaneous or endoscopic drainage
        • can be approached retroperitoneally (VARD) or laparoscopically

      3. Open Debridement
        • used only as a last resort in patients who have not responded to less invasive interventions
        • remains a valid approach if the less invasive techniques are not available







References

  1. Sabiston, 20th ed., pgs 1524 - 1530
  2. Schwartz, 10th ed., pgs 1351 - 1361
  3. Cameron, 13th ed., pgs 501 – 510, 510 – 514, 522 – 525
  4. UpToDate. Management of Acute Pancreatitis. Santhi Swaroop Vege, MD. Mar 09, 2020. Pgs 1 – 38