II. Definitions

  1. Ascending Cholangitis
    1. Acute, life threatening infection of the biliary tree by Bacteria ascending from the Small Intestine (duodenum)
    2. Associated with bile duct obstruction (e.g. Common Bile Duct Stone) resulting in hepatic intraductal pressure increase

III. Epidemiology

  1. Incidence rare under age 40 years
    1. However can occur in children with risk factors

IV. Risk Factors

  1. Choledocolithiasis
  2. Biliary atresia or Biliary tract stricture
  3. Surgical anastomotic stricture
  4. Extrinsic compression from malignancy
  5. Liver Transplant history
  6. Roux-en-Y Bypass Surgery

V. Pathophysiology

  1. Complete biliary duct obstruction (e.g. Choledocolithiasis) results in increased hepatic intraductal pressures
  2. Intestinal Bacteria (Gram Negative Bacteria, Anaerobic Bacteria) pass through sphincter of odi from duodenum
    1. E. coli (25-50%)
    2. Klebsiella (15-20%)
    3. Enterobacter (5-10%)
    4. Enterococcus (10-20%)
    5. Bacteroides
    6. Clostridium
    7. Pseudomonas
  3. Reflux of Bacteria into the Lymphatics, hepatitic veins
    1. Results in systemic spread and rapid progression to Sepsis

VII. Signs

  1. Presentations may be cryptic
    1. Altered Mental Status
    2. Sepsis with unknown source
  2. Charcot's Triad (Test Sensitivity 25%, Test Specificity 85%)
    1. Fever
    2. Jaundice
    3. Right Upper Quadrant Abdominal Pain
  3. Reynold's Pentad (7 to14% of patients)
    1. Charcot's Triad and
    2. Hypotension (Shock) and
    3. Altered Mental Status
  4. Other findings
    1. Fever (>40% of patients)
    2. Abdominal Pain (>60% of patients)
    3. Jaundice (60 to 70% of patients)
    4. Toxic appearance
    5. Hepatomegaly (with tender liver edge)
    6. Splenomegaly

VIII. Labs

  1. Complete Blood Count
    1. Leukocytosis (>80% of patients)
      1. Leukopenia (<4000/mm3) may be present instead
    2. Neutrophil to Lymphocyte ratio (NLR) >5.3
  2. Liver Function Tests abnormal
    1. Total Bilirubin elevated in urine and plasma (40% of patients)
      1. Greater Specificity for Cholangitis when Total Bilirubin >4 mg/dl
    2. Serum alkaline phsophatase elevated (>90% of patients)
    3. Gamma glutamyl transferase elevated (>90% of patients)
    4. Transaminases (AST, ALT) may also be increased
  3. Blood Cultures (positive in 50 to 70% of patients)
    1. Gram Negative bacteremia

IX. Imaging

  1. RUQ Ultrasound
    1. Dilated common bile duct (>7 mm, or post-Cholecystectomy >10 mm)
    2. Dilated intrahepatic ducts
    3. Test Sensitivity 25-60% for Common Bile Duct Stones
    4. Do not rely on RUQ Ultrasound to exclude Ascending Cholangitis when suspicion is high
      1. Consider serial Ultrasounds and advanced imaging
  2. CT Abdomen and Pelvis with IV Contrast
    1. Dilated and obstructed common bile ducts and intrahepatic ducts (including external compression forces)
    2. Preferred study in evaluating cause and complications from Cholangitis
  3. MRI Abdomen with MRCP
    1. Indicated when CT and Ultrasound are non-diagnostic

X. Differential Diagnosis

  1. See Sepsis
  2. Acute Cholecystitis
  3. Post-op status (esp. Laparoscopic Cholecystectomy) Bile Duct Injury with Biliary Leak
  4. Acute Pancreatitis
  5. Liver Abscess

XI. Grading (Tokyo Guidelines 13)

  1. Severe (1 or more criteria)
    1. Hypotension requiring Vasopressors
    2. Altered Mental Status
    3. PaO2/FIO2 <300
    4. Oliguria
    5. Serum Creatinine >2 mg/dl
    6. INR >1.5
    7. Platelet Count <100,000/mm3
  2. Moderate (2 or more criteria)
    1. White Blood Cell Count >12,000 or <4000/mm3
    2. Fever >=39 C (102.2 F)
    3. Age >= 75 years old
    4. Total Bilirubin >= 5 mg/dl
    5. Albumin <70% of lower limit of normal
  3. Mild
    1. Criteria not sufficient for moderate or severe Cholangitis

XII. Management

  1. See Acute Cholecystitis
  2. See Cholecystectomy
  3. Broad spectrum Parenteral antibiotics (Gram Negatives, enteric Streptococcus, Anaerobes)
    1. Initial antibiotic regimen for life threatening infection
      1. Piperacillin-Tazobactam 4.5 g IV q8 hours OR
      2. Ertapenem 1 g IV every 24 hours OR
      3. Other Carbapenems
        1. Imipenem 0.5 g IV every 6 hours OR
        2. Meropenem 1 g IV every 8 hours OR
        3. Doripenem 500 mg IV every 8 hours
      4. Alternative antibiotic regimen (2 drug regimen)
        1. Metronidazole 1 g IV load, then 500 mg IV every 6 hours AND
        2. Cefepime or Ceftazidime
    2. Initial antibiotic regimen for mild to moderate community acquired infection
      1. Metronidazole 500 mg IV every 6 hours AND
      2. One of the following
        1. Cephalosporin (Cefazolin, Cefuroxime, Ceftriaxone, Cefotaxime) OR
        2. Fluoroquinolone (Moxifloxacin 400 IV q24h or Ciprofloxacin 400 mg IV q12 h)
          1. Risk of Fluoroquinolone resistance
    3. Additional antibiotics if indicated
      1. Vancomycin
        1. May be added to regimen if Healthcare Associated Infection
    4. References
      1. (2019) Acute Cholangitis, Sanford Guide, accessed 3/29/2019
      2. (2019) Acute Cholangitis, UpToDate, accessed 3/29/2019
  4. Sepsis and symptomatic management
    1. See Septic Shock
    2. Volume Resuscitation with IV fluids
    3. Vasopressor support as needed
    4. Opioid Analgesics
    5. Endotracheal Intubation is often required in severe cases
  5. Rapid decompression of biliary tree
    1. Endoscopy with ERCP and sphincterotomy
      1. Preferred as initial intervention (90% success rate)
      2. Emergent ERCP decompression in severe cases
      3. Mild to moderate Cholangitis responds well to antibiotics in 70-80% of patients
        1. ERCP decompression may be delayed 24-48 hours in these cases
        2. Urgent ERCP decompression is indicated if poor response to antibiotics in first 24 hours
      4. Delayed ERCP >48 hours when medical management has failed is associated with worse outcomes
        1. Prolonged hospitalization, ICU stay, Ventilator support, Vasopressor support and organ failure
        2. Increased mortality as high as 80%
    2. Percutaneous drainage of biliary tree
      1. Consider when ERCP not possible (e.g. Roux-en-Y Bypass, whipple resection, duodenal stenosis)
    3. Open common bile duct exploration
      1. High mortality and morbidity
      2. Consider in cases refractory to other measures

XIII. Prognosis

  1. Mortality approaches 100% if untreated
    1. High mortality (up to 30%) even with optimal care

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