CHOLANGITIS [S+DT]

TG18/TG13 diagnostic criteria for acute cholangitis

A. Systemic inflammation
A-1. Fever and/or shaking chills
A-2. Laboratory data: evidence of inflammatory response
B. Cholestasis
B-1. Jaundice
B-2. Laboratory data: abnormal liver function tests
C. Imaging
C-1. Biliary dilatation
C-2. Evidence of the etiology on imaging (stricture, stone, stent, etc)
Suspected diagnosis: one item in A + one item in either B or C
Definite diagnosis: one item in A, one item in B and one item in C
A-2: Abnormal white blood cell counts, increase of serum C-reactive protein levels, and other changes indicating inflammation
B-2: Increased serum ALP, r-GTP (GGT), AST, and ALT levels

Thresholds
A-1	Fever		BT >38°C
A-2	Evidence of inflammatory response	WBC (×1,000/μl)	<4 or >10
		CRP (mg/dl)	≥1
B-1	Jaundice		T-Bil ≥2 (mg/dl)
B-2	Abnormal liver function tests	ALP (IU)	>1.5 × STD
		γGTP (IU)	>1.5 × STD
		AST (IU)	>1.5 × STD
		ALT (IU)	>1.5 × STD

TG18/TG13 severity assessment criteria for acute cholangitis

Grade III (severe) acute cholangitis
“Grade III” acute cholangitis is defined as acute cholangitis that is associated with the onset of dysfunction at least in any one of the following organs/systems:
1. Cardiovascular dysfunction: hypotension requiring dopamine ≥5 μg/kg per min, or any dose of norepinephrine
2. Neurological dysfunction: disturbance of consciousness
3. Respiratory dysfunction: PaO2/FiO2 ratio <300
4. Renal dysfunction: oliguria, serum creatinine >2.0 mg/dl
5. Hepatic dysfunction:PT-INR >1.5
6. Hematological dysfunction: platelet count <100,000/mm3
Grade II (moderate) acute cholangitis
“Grade II” acute cholangitis is associated with any two of the following conditions:
1. Abnormal WBC count (>12,000/mm3, <4,000/mm3)
2. High fever (≥39°C)
3. Age (≥75 years)
4. Hyperbilirubinemia (total bilirubin ≥5 mg/dl)
5. Hypoalbuminemia (<STD × 0.7)
Grade I (mild) acute cholangitis
“Grade I” acute cholangitis does not meet the criteria of “Grade III (severe)” or “Grade II (moderate)” acute cholangitis at initial diagnosis

Management Of Acute Cholangitis:

*Blood culture should be taken into consideration before antibiotics are started. Bile samples should be taken during biliary drainage and cultured. †Principles of treatment for acute cholangitis consist of antimicrobial administration, biliary drainage, and treatment of the etiology. For patients with mild or moderate choledocholithiasis, if possible the etiology should be treated at the same time as biliary drainage is performed

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CHOLANGITIS [DT]

Detailed Overview of Cholangitis

Pathogenesis

Cholangitis is an infection of the biliary tract that occurs due to a combination of biliary obstruction, bacterial colonization, and subsequent systemic infection. The process involves several key steps:

1. Obstruction of Bile Flow:
   • Obstruction can occur due to stones, strictures, tumors, or external compression, which leads to stasis of bile.
2. Elevation of Intra-Ductal Biliary Pressure:
   • Obstruction increases pressure within the biliary ducts, which promotes bacterial translocation into the bloodstream and lymphatic system.

3. Bacterial Colonization:

   • Bile stasis allows bacteria to colonize the biliary system. The most common organisms include gram-negative bacteria such as Escherichia coli, Klebsiella spp., and Enterobacter spp.. Anaerobes and gram-positive organisms may also be involved.

   Microorganisms in Cholangitis

   • Common Microorganisms:
     • Gram-negative bacteria:
       • Klebsiella spp.
       • Escherichia coli (E. coli)
     • Gram-positive bacteria:
       • Enterococcus spp.
     • Anaerobes: More common in patients with bilioenteric anastomoses.
     • Candida spp.: Seen in immunosuppressed patients or those with liver transplantation.
     • Pseudomonas spp.: Rare but associated with high mortality.
   • Systemic Inflammatory Response:
   • Bacteria and their endotoxins enter the systemic circulation, triggering an inflammatory response that can progress to severe sepsis or septic shock if not promptly treated.

Clinical Presentation

• Charcot’s Triad:
  • Classic presentation includes fever, right upper quadrant pain, and jaundice.
  • This triad is highly specific but lacks sensitivity, as not all patients with cholangitis will present with all three symptoms.
• Reynaud’s Pentad:
  • Includes the elements of Charcot’s triad plus hypotension and altered mental status.
  • This indicates a more severe form of the disease, often associated with septic shock and multiorgan dysfunction.
• Symptoms:
  • Patients may present with fever, chills (rigors), abdominal pain (often localized to the right upper quadrant), jaundice, nausea, vomiting, and possibly altered mental status.
  • The onset can be acute, with rapid progression to systemic illness, especially in severe cases.

Diagnostic Evaluation

• History and Physical Examination:
  • Detailed history including prior episodes of biliary disease, gallstones, malignancies, or biliary interventions.
  • Physical examination should focus on assessing the severity of illness, including signs of sepsis, jaundice, abdominal tenderness, and any signs of peritonitis.
• Laboratory Testing:
  • CBC with Differential: May reveal leukocytosis with a left shift, indicating infection.
  • Liver Function Tests: Elevated bilirubin, alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) suggest biliary obstruction.
  • Blood Cultures: Should be obtained before starting antibiotics, especially if there is evidence of systemic infection.
  • Arterial Blood Gas: Important in assessing patients with respiratory distress, hemodynamic instability, or altered mental status.
• Imaging:
  • Ultrasound: First-line imaging modality for detecting biliary obstruction; however, sensitivity for detecting CBD stones varies widely.
  • CT Scan: Useful in identifying complications such as abscesses, perforations, or other causes of biliary obstruction.
  • MRCP: High specificity (93%) but not 100% sensitive, particularly for small stones or those impacted in the ampulla.
  • Endoscopic Ultrasound (EUS): Offers high sensitivity and specificity for detecting bile duct stones, especially in difficult cases.

Severity Grading

• Tokyo Guidelines (TG18):
  • TG18 provides a standardized diagnostic and severity grading system for cholangitis based on clinical, laboratory, and imaging findings.
  • Grade I (Mild): Low mortality, usually manageable with antibiotics and supportive care.
  • Grade II (Moderate): Higher mortality, benefits significantly from early biliary decompression.
  • Grade III (Severe): Highest mortality, requires urgent biliary decompression and intensive care management.

Management

• Supportive Care:
  • Initial management includes intravenous fluids, broad-spectrum antibiotics, and close monitoring in an intensive care setting for severe cases.
• Biliary Decompression:
  • Indications: Any patient who does not respond to initial medical therapy, or those with moderate to severe disease (Grade II or III).
  • Methods:
    • Endoscopic Retrograde Cholangiopancreatography (ERCP): The preferred method for biliary drainage.
    • Percutaneous Transhepatic Cholangiography (PTC): Used when ERCP is not feasible.
    • Surgical Decompression: Reserved for cases where endoscopic or percutaneous methods are unsuccessful or unavailable.
• Follow-Up and Prognosis:
  • Early recognition and treatment are critical to improving outcomes in cholangitis.
  • Severe cases (Grade III) have the highest mortality, but early intervention with biliary decompression can reduce mortality and improve outcomes.

Additional Considerations

• Differential Diagnosis:
  • Acute cholecystitis, acute hepatitis, and other causes of fever and jaundice should be considered in the differential diagnosis.
  • In patients with a history of biliary instrumentation, the risk of cholangitis is higher.
• Complications:
  • Recurrent cholangitis can lead to secondary biliary cirrhosis, hepatic abscesses, and further deterioration in liver function.

MCQ

Answer: d) Anaerobes

Explanation: The most common microorganisms involved in cholangitis are Escherichia coli, Klebsiella spp., and Enterococcus spp. Anaerobes are more commonly seen in patients with bilioenteric anastomoses and are not the most common pathogens in typical cases of cholangitis.

Summary Key Points on Microorganisms in Cholangitis

• Most Common Microorganisms:
  • Klebsiella spp., Escherichia coli, and Enterococcus spp.
• Specific Scenarios:
  • Anaerobes: Common in patients with bilioenteric anastomoses.
  • Candida spp.: Seen in immunosuppressed individuals or after liver transplantation.
  • Pseudomonas spp.: Rare but associated with high mortality.

Imaging Studies for Cholangitis

Noninvasive Imaging Modalities

• Transabdominal Ultrasound:
  • Preferred first-line imaging for suspected cholangitis.
  • Advantages:
    • Low cost, widely available, no ionizing radiation.
    • Sensitivity of 85%-95% for detecting intrahepatic and extrahepatic biliary dilation.
  • Limitations:
    • Limited sensitivity (20%-75%) for detecting choledocholithiasis, especially small stones or those in the distal CBD obscured by bowel gas.
• Computed Tomography (CT):
  • Advantages:
    • Overcomes ultrasound limitations.
    • Accurately detects biliary obstruction and characterizes the cause of biliary stenosis.
    • Can detect complications such as hepatic abscess and pylephlebitis.
  • Limitations:
    • Sensitivity for detecting CBD stones varies (25%-90%) due to similar density between stones and bile.
    • Risk of nephrotoxicity from contrast material, especially in hemodynamically unstable patients.
• Magnetic Resonance Cholangiopancreatography (MRCP):
  • Advantages:
    • Provides 3D imaging of the biliary tree.
    • High sensitivity (93%) and specificity (96%) for detecting choledocholithiasis.
  • Limitations:
    • Cannot differentiate stones from air bubbles, sludge, or blood clots.
    • Cannot detect stones <3 mm or impacted stones in the ampulla.
    • Limited accessibility, high cost, and contraindications in cases of morbid obesity or metallic foreign bodies.

Invasive Imaging Modalities

• Endoscopic Ultrasound (EUS):
  • Advantages:
    • High-resolution imaging (<1 mm) for accurate detection of small gallstones and other obstructions.
    • Sensitivity approaching 100%, specificity >90%, overall accuracy 96% for bile duct stones.
    • Can be combined with fine-needle aspiration or ERCP during the same session.
  • Limitations:
    • Not suitable for patients with altered anatomy (e.g., post-gastrectomy or gastric bypass) or significant calcified pancreas/hilar biliary pathology.
• Intraductal Ultrasonography (IDUS):
  • Advantages:
    • High-resolution imaging (0.07–0.018 mm) for detailed visualization of biliary and pancreatic ducts.
    • Can identify lesions missed by traditional imaging, useful adjunct to ERCP.
  • Limitations:
    • Requires specialized equipment and operator expertise.
    • Limited depth of penetration (2–3 cm), high cost.
• Direct Cholangiography:
  • Current Use:
    • Largely limited to the initial step of a therapeutic procedure rather than purely diagnostic purposes.
  • Complications:
    • Biliary infection, pancreatitis, hemorrhage.

Summary Key Points on Imaging Studies for Cholangitis

• Transabdominal Ultrasound: First-line imaging, highly sensitive for biliary dilation, but limited for small stones.
• CT: Useful for detecting obstruction and complications; sensitivity varies for stones.
• MRCP: High sensitivity and specificity, but not 100% accurate, especially for small or impacted stones.
• EUS: Nearly 100% sensitive, excellent for detecting small obstructions.
• IDUS: High-resolution, specialized use in combination with ERCP.
• Direct Cholangiography: Now primarily a therapeutic tool.

In case of Suspected Cholangitis:

Management of Cholangitis:

1. Initial Management:
   • Supportive Care:
     • Aggressive fluid resuscitation.
     • Correction of electrolyte imbalances.
     • IV antibiotic administration.
     • Close monitoring of heart rate, blood pressure, mental status, and urine output.
     • Patients should be fasted in anticipation of possible procedural intervention.
   • Severity Assessment:
     • Utilize the Tokyo Guidelines 2018 (TG18) severity grading to assess the severity of cholangitis. This should be repeated if clinical status changes or new data become available.
2. Antimicrobial Therapy:
   • Empiric Antimicrobial Therapy:
     • Target a broad spectrum of organisms, including gram-negative aerobes like E. coli and Klebsiella spp., and gram-positive Enterococcus spp.
     • Consider anaerobes in cases of biliary-enteric anastomosis and fungal infections (e.g., Candida spp.) in liver transplant or immunosuppressed patients.
     • Adjust antibiotics based on culture results to ensure appropriate coverage and minimize the development of antibiotic resistance.
   • Healthcare-Associated Infections:
     • Be aware of multidrug-resistant organisms such as ESBL, carbapenemase-producing Enterobacteriaceae, and vancomycin-resistant enterococci.
     • Use local antibiograms to guide empiric therapy decisions.
   • Duration of Therapy:
     • Continue until biliary obstruction is relieved and the patient is afebrile for at least 48 hours.
     • A typical course lasts 4 to 7 days post-source control, but longer durations may be required for specific situations (e.g., gram-positive bacteremia, recurrent cholangitis, or liver abscess).
3. Definitive Management:
   • Once the infection is controlled, address the underlying cause of cholangitis. The treatment approach will vary depending on the specific cause and patient factors.
   • Procedural Modalities (as outlined in the flowchart provided):
     • Biliary Lithiasis:
       • Choledocholithiasis: Endoscopic techniques like ENBD or EBS, followed by surgery if unsuccessful.
       • Intrahepatic Stones: Options include surgery, cholangioscopic drainage, and lithotripsy, depending on disease extent and patient tolerance.
       • Recurrent Pyogenic Cholangitis: Infection eradication followed by possible surgical intervention.
     • Nonlithiasis Obstruction:
       • Management strategies are determined based on specific causes like AIDS cholangiopathy, biliary strictures, primary sclerosing cholangitis, and IgG4 sclerosing cholangitis.

Procedures for Biliary Decompression in Cholangitis

Overview: The management of acute cholangitis requires prompt biliary decompression and drainage to relieve the obstruction and prevent the progression of sepsis. Several techniques are available, and the choice depends on factors such as the patient's clinical status, the cause of obstruction, the location of the obstruction, the availability of specific techniques, and the expertise of the medical team.

1. Endoscopic Transpapillary Biliary Drainage (ETBD):

• Gold Standard: This is the preferred method for biliary drainage in cholangitis, particularly when the cause is benign or malignant.
• Procedure: A side-viewing endoscope is used to visualize and cannulate the ampulla of Vater. Contrast is injected to visualize the obstruction under fluoroscopy, and a guidewire is passed across the obstruction.
• Techniques:
  • Endoscopic Nasobiliary Drainage (ENBD): A drainage tube is placed over the guidewire to provide external drainage. Advantages include the ability to monitor bile and collect cultures, though patient discomfort and risk of dislodgement are disadvantages.
  • Endoscopic Biliary Stenting (EBS): A plastic stent is inserted into the bile duct for internal drainage, avoiding the discomfort associated with external tubes but carrying a slightly higher risk of stent occlusion.
• Considerations: If the patient is unstable, the focus should be on decompression rather than complete stone removal. ENBD and EBS have similar success rates, and the choice depends on specific patient factors.

2. Endoscopic Sphincterotomy and Balloon Dilation:

• Endoscopic Sphincterotomy (EST): Involves making an incision in the duodenal papilla to facilitate bile drainage and stone extraction. It is typically performed in a single session, although it carries risks such as hemorrhage and pancreatitis.
• Endoscopic Papillary Balloon Dilation (EPBD): Uses a balloon to dilate the duodenal papilla, preserving the sphincter of Oddi. EPBD is less successful for stone removal compared to EST but has a lower risk of bleeding, making it an alternative when the bleeding risk is high.

3. Single-Balloon and Double-Balloon Endoscopy:

• Applications: Used to access the duodenal papilla in patients with surgically altered anatomy, such as after Roux-en-Y gastric bypass.
• Success Rates: High success rates have been reported, but these techniques require specialized training and equipment. Procedure times are generally longer compared to other methods.

4. Percutaneous Transhepatic Cholangial Drainage (PTCD):

• Indications: PTCD is a second-line therapy, typically reserved for cases where endoscopic access is not possible, such as in patients with altered anatomy or proximal obstructions.
• Procedure: A peripheral bile duct is catheterized under ultrasonographic guidance, and a guidewire is advanced across the obstruction. A catheter is placed to decompress the biliary system. PTCD is associated with a higher risk of complications, such as bleeding and bile peritonitis, compared to endoscopic techniques.

5. Endoscopic Ultrasound–Guided Bile Duct Drainage (EUS-BD):

• Emerging Technique: EUS-BD is used as a second-line option after failed endoscopic transpapillary drainage.
• Approaches:
  • Intrahepatic drainage via the transgastric or transjejunal route.
  • Extrahepatic drainage by a transduodenal or transgastric approach.
  • Antegrade stenting.
• Advantages: EUS-BD allows access to the bile duct in patients with abnormal anatomy and provides internal drainage without external catheters. It requires highly skilled practitioners and specialized equipment.

6. Surgical Common Bile Duct Exploration:

• Last Resort: Surgical drainage is considered when non-invasive procedures fail or are not possible. It carries the highest mortality rate among the options.
• Procedure: Involves decompression of the biliary system, often with the placement of a T-tube. This tube helps maintain patency and allows for postoperative cholangiography.

Summary of Procedures:

• Endoscopic Transpapillary Biliary Drainage (ETBD): Gold standard, ENBD and EBS options based on patient condition.
• Endoscopic Sphincterotomy (EST): Preferred for stone removal but carries bleeding risk.
• Percutaneous Transhepatic Cholangial Drainage (PTCD): Second-line therapy, higher complication rates.
• Endoscopic Ultrasound–Guided Bile Duct Drainage (EUS-BD): Second-line after failed ETBD, requires specialized expertise.
• Surgical Exploration: Last resort, used when other methods fail or are unavailable.

Answer: b

Antibiotic Duration in Cholangitis

Key Points:

• Antibiotic Therapy: The duration of antibiotic therapy in cholangitis is crucial for preventing complications and ensuring proper resolution of the infection. TG18 guidelines provide a framework for determining the appropriate duration of therapy based on the clinical scenario.
  • Minimum Duration: Antibiotic therapy should continue until the patient is afebrile and biochemical liver function tests have normalized for at least 48 hours.
  • Persistent Infection: For persistent partial obstruction or abscesses, antibiotic therapy may need to be extended until the underlying cause is fully treated.
  • Gram-Positive Bacteremia: In cases of gram-positive bacteremia, a minimum of 2 weeks of antibiotic therapy is recommended.
  • Source Control: The importance of effective source control cannot be understated. However, the option to stop antibiotics 3 days after effective source control is not a standard recommendation and is, therefore, the incorrect option in this context.

EUS-BD Approaches

Three different EUS-BD approaches:

1. Intrahepatic biliary drainage via the transgastric or transjejunal route.
2. Extrahepatic biliary drainage by a transduodenal or transgastric approach.
3. Antegrade stenting.

Different Lithotripsy Techniques

Lithotripsy techniques used in the management of biliary stones:

• Mechanical Lithotripsy: Utilizes mechanical force to crush the stone within the bile duct.
• Electrohydraulic Lithotripsy (EHL): A technique with an 88% successful clearance rate, it uses an electric spark to create a shock wave that fragments the stones.
• Laser Lithotripsy: Known for its high success rate of 95%, it uses laser energy to fragment stones.
• Extracorporeal Shock Wave Lithotripsy (ESWL): This method uses shock waves generated outside the body to break down stones and has an 84% success rate.