Acute Cholangitis

Reviewed and revised 11 August 2014

OVERVIEW

Acute or ascending cholangitis is a potentially life-threatening systemic infection resulting from inflammation and infection of the biliary tree due to bacterial growth in the bile, usually in the context of biliary obstruction

• Definitive diagnosis involves (1) a history of biliary disease, (2) the clinical manifestations, (3) laboratory data that indicate the presence of inflammation and biliary obstruction, and (4) imaging findings that indicate biliary obstruction
• Severity can be graded as follows:
  • mild (grade I) – responsive to treatment, no organ dysfunction
  • moderate (grade II) – unresponsive to treatment, no organ dysfunction
  • severe (grade III) – presence of organ dysfunction

CAUSE

Causative organisms

• E. coli (up to 50%)
• Klebsiella spp
• Enterococcus spp
• Streptococcus spp
• Enterobacter spp
• Pseudomonas aeruginosa
• rarely due to tropical parasites (e.g. Clonorchis sinensis and Opisthorchis spp )

Pathogenesis

• cholangiovenous and cholangiolymphatic reflux due to increased intra-biliary pressures as a result of obstruction
• translocation of pathogenic micro-organisms from the duodenum up the biliary tree and into the bloodstream
• infection overcomes normal barriers: mucosal barriers, continuous biliary flushing, IgA, Kupffer cells

Underlying cause

• choledocholithiasis
• benign stenoses (eg, in primary sclerosing cholangitis, as seen in Figure 1)
• malignant stenoses
• biliary stent obstruction
• strictured bilioenteric anastomoses
• parasitic colonization of the bile duct
• procedures (e.g. surgery, ERCP, PTC, biliary sphincterotomy, stent placement, surgical sphincteroplasty, bilioenteric anastomosis)

Predisposing factors

• gallstones
• previous cholecystectomy
• ERCP or cholangiogram
• previous cholangitis
• immunocompromise
• malignancy

CLINICAL FEATURES

History

• fever (>80%)
• abdominal pain (especially RUQ) (>80%)
• nausea and vomiting, malaise
• predisposing factors and history of an underlying cause

Examination

• tachycardia, hypotension, shock
• altered mental state
• jaundice (60-70%)

Eponymous findings

• Charcot triad (50-75% of cases): fever, RUQ pain and jaundice
• Reynold’s pentad (~5% of cases): Charcot triad plus altered mental state and shock

INVESTIGATIONS

Bedside

• blood gas including glucose (liver failure, HAGMA, lactate)
• ECG (myocardial ischaemia)

Laboratory

• FBC (neutrophilia)
• UEC (renal failure due to MODS)
• LFTs (hyperbilirubinaemia is almost always present; hepatitic picture (raised AST, ALT) in addition to obstruction (raised ALP))
• lipase (co-existent pancreatitis)
• Coagulation profile (e.g. liver impairment or DIC from overwhelming sepsis)
• septic screen (take blood cultures before giving antibiotics)

Imaging

• abdominal ultrasound (evidence of biliary obstruction: CBD dilation is >90%, although the diameter of the CBD becomes a less useful parameter in patients who have previously undergone cholecystectomy, as physiological dilation of the CBD can occur in this setting. Transabdominal ultrasound has a poor sensitivity for detecting mid to distal CBD stones.)
• CXR (pneumonia, GI perforation)
• Abdominal CT (if unclear diagnosis)
• MRCP (if unclear diagnosis)

DIFFERENTIAL DIAGNOSIS

• biliary leak
• cholecystitis
• hepatic abscess
• Mirizzi syndrome
• pancreatitis
• right lower lobe pneumonia
• infected choledochal cyst
• recurrent pyogenic cholangitis
• biliary malignancy

MANAGEMENT

Resuscitation

• as appropriate using ABC approach
• treat septic shock

Early antibiotics (<1h of presentation)

• amoxcillin 1 g IV q6h (child 25 mg/kg up to 1g), AND
  gentamicin 4 to 6 mg/kg  IV, for 1 dose  (<10y: 7.5 mg/kg; >10y: 6 mg/kg) and 1 or 2 further doses at intervals based on renal function
• If susceptibility results are not available by 72h:
  • change gentamicin to piperacillin/tazobactam or ticarcillin/clavulanate
• If gentamicin is contraindicated or penicillin sensitivity:
  • ceftriaxone 1 g IV q24h (child: 25 mg/kg up to 1 g) OR 2 cefotaxime 1 g IV q8h (child: 25 mg/kg up to 1 g)
• If immediate penicillin hypersensitivity seek expert advice.
• If history of previous biliary tract surgery or known biliary obstruction, need to treat anaerobes:
  • add metronidazole 500 mg IV q12h (child: 12.5 mg/kg up to 500 mg).
• If unresponsive to initial therapy:
  • piperacillin/tazobactam 4+0.5 g IV q8h (child: 100+12.5 mg/kg up to 4+0.5 g) OR
    ticarcillin/clavulanate 3+0.1 g IV q6h (child: 50+1.7 mg/kg up to 3+0.1 g)
• After clinical improvement, change to oral therapy.
  • If susceptibility results are not available, use amoxycillin+clavulanate 875+125 mg q12h po (child: 22.5+3.2 mg/kg up to 875+125 mg)
  • For uncomplicated disease, the total course duration is up to 7 days.

Urgent relief of biliary obstruction

• endoscopic retrograde cholangiopancreatography [ERCP] witihn 24-48h
• sphincterotomy +/- biliary stone removal
• PTC (percutaneous transhepatic cholangiography)
• Ultrasound-guided drainage
• lithotripsy if stone >2cm
• open surgical decompression

Definitive treatment of the underlying cause

• e.g. cholecystectomy, biliary stent

Supportive care and monitoring

• e.g. FAST HUGS IN BED Please

Seek and treat complications

• Biliary obstruction (e.g. serum bilirubin >85 umol/L) may potentiate aminoglycoside nephrotoxicity
• complications of septic shock
• complications of procedures (e.g. pancreatitis, haemorrhage)

References and Links

Journal articles

• Lee JG. Diagnosis and management of acute cholangitis. Nat Rev Gastroenterol Hepatol. 2009 Sep;6(9):533-41. PMID: 19652653.
• Mosler P. Management of acute cholangitis. Gastroenterol Hepatol (N Y). 2011 Feb;7(2):121-3. PMC3061017.
• Wada K, et al. Diagnostic criteria and severity assessment of acute cholangitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg. 2007;14(1):52-8. PMC2784515.