ACUTE ASCENDING CHOLANGITIS Introduction Acute cholangitis (or ascending cholangitis) is a clinical syndrome that is classically characterized by the triad of: ● Fever ● Abdominal pain ● Jaundice The condition occurs as a result of obstruction/ stasis and subsequent infection within the biliary tract. In the absence of appropriate treatment the condition has significant potential for mortality and morbidity. It is a medical emergency that requires prompt antibiotic treatment and urgent relief of biliary obstruction (usually by endoscopic retrograde cholangiopancreatography ERCP). History Jean M. Charcot was the first to describe this illness in 1877. He described a triad of fever, jaundice, and right upper quadrant pain. Epidemiology Acute cholangitis is predominantly seen in adults, most commonly around 40-70 years of age. Physiology Normal barrier mechanisms to cholangitis infection include ● The sphincter of Oddi, which normally forms an effective mechanical barrier to duodenal reflux and ascending bacterial infection. ● Continuous flushing action of bile plus the bacteriostatic activity of bile salts which help maintain bile sterility. ● Secretory IgA and biliary mucous probably also function as anti-adherence factors, preventing bacterial colonization Pathology Organisms: Ascending cholangitis is usually associated with Gram-negative or anaerobic sepsis. ● Aerobic organisms include Escherichia coli and Klebsiella and Enterococcus species. ● The most common anaerobic organism is Bacteroides fragilis. Clostridia may also cause serious infection. Causes: Ascending cholangitis essentially occurs as consequence of obstruction of the biliary tract. Stasis leads to secondary bacterial infection; the organisms typically ascending from the duodenum. Biliary obstruction raises intrabiliary pressure and leads to increased permeability of bile ductules, permitting translocation of bacteria and toxins from the portal circulation into the biliary tract. Elevated pressures also favour migration of bacteria from bile into the systemic circulation, increasing the risk of septicaemia. Hematogenous spread from the portal vein may also occur but this is much less common. The causes of biliary tract obstruction include: ● Choledocholithiasis ● Biliary tract manipulations/interventions and stents, (usually for malignant obstructions). ● Hepatobiliary malignancies ● Benign stenosis, (previous scarring). ● Primary sclerosing cholangitis Complications; These include: ● Rupture and peritonitis ● Septicemia and septic shock ● Acute renal failure Cholecystitis ● Pyogenic liver abscess Clinical features Important points of history: Important points to o note on history will include: ● Past history of gallstones ● Recent history of biliary tract manipulations/ stents ● Any past history of biliary tract disease in general. ● Known Hepatobiliary tract malignancy Important points of examination: The “classic” presentation is of “Charcot’s triad”, consisting of: ● Fever ● Abdominal pain, (right upper quadrant). ● Jaundice Only 50 - 75% of patients however will present with all three features, most commonly of the group that do not, will have abdominal pain and fever (but not jaundice). Patients with more severe illness - suppurative cholangitis - may show additional confusion/ altered conscious state and hypotension - so called “Reynolds’s pentad”, which is associated with significant morbidity and mortality Ultimately septic shock and multiorgan failure can lead to death. Differential diagnoses: There are many, but the principle ones will include: ● Cholecystitis ● Biliary leaks, (following laparoscopic cholecystectomy). ● Right lower lobe pneumonias ● Pancreatitis ● Diverticulitis ● Hepatitis ● Liver abscess Investigations Blood tests: 1. FBE ● Elevated WCC and neutrophilia 2. CRP: ● This will be elevated. 3. U&Es/ glucose 4. LFTs: ● Elevated bilirubin and liver enzymes: ♥ This will be a cholestatic pattern with elevations in the serum alkaline phosphatase, gamma-glutamyl transpeptidase (GGT), and bilirubin (predominantly conjugated). ♥ In severe illness however an acute hepatocyte necrosis pattern can be can be seen with aminotransferase levels as high as 2000 IU/L 5. Lipase: ● There may be an associated obstructive pancreatitis. 5. Coagulation profile 6. Blood cultures: ● Cultures should also be obtained from bile or stents removed at endoscopic retrograde cholangiopancreatography (ERCP). Ultrasound An ultrasound examination to confirm ● Biliary tract obstruction ● Gallstones: ♥ The highest risk for severe sepsis will come from impacted stones. ● Associated pathology: cholecystitis, liver abscess. If the patient is at high risk for complications from ERCP endoscopic ultrasound is a further option to look for evidence of bile duct stones or obstruction, MRCP If the transabdominal ultrasound is normal, magnetic resonance cholangio- pancreatography (MRCP) can be utilized. This is to look for bile duct stones or alternative diagnoses that may have been missed on transabdominal ultrasound. ERCP Endoscopic retrograde cholangio-pancreatography (ERCP) is both diagnostic and therapeutic. It is the best imaging first up in unwell patients, (especially if abnormal LFTs) because of its ability to therapeutically intervene. Management The prognosis is variable depending on the degree of illness, the co-morbidities and the underlying cause of the obstruction. The best chance of a good outcome, other factors being equal will depend on early antibiotic treatment and appropriate drainage and decompression of biliary tract. 1. Analgesia: ● Pain is usually significant and titrated IV opioids will be necessary. 2. Nil by mouth 3. Fluid resuscitation: ● IV fluid resuscitation will often be required. 4. Antibiotics: Some patients with acute cholangitis will respond to conservative management with antibiotic therapy. Biliary drainage can then be performed on a semi-elective basis (within 24 to 48 hours) Options include: ● Tazocin and metronidazole If sensitive to penicillin, (but not life-threatening) ● Ceftriaxone and metronidazole If life-threatening penicillin reaction: ● Ciprofloxacin and metronidazole If the patient does not improve over the first 24 hours with conservative management, urgent biliary decompression is required. See latest Antibiotic Guidelines for full prescribing details. 5. Endoscopic drainage: ● If the ultrasound shows ductal dilation or stones, it should be followed promptly (within 24 hours, but earlier if the patient is particularly unwell) by ERCP to provide biliary drainage. ● Endoscopic drainage has largely replaced emergency surgical common duct exploration and T-tube drainage as standard treatment. ● Endoscopic sphincterotomy with stone extraction and/or stent insertion (depending on the cause of the obstruction) is the treatment of choice for establishing biliary drainage in acute cholangitis Patients who require urgent drainage are those with signs of acute suppurative cholangitis, including: ● Persistent / intractable abdominal pain ● High fever (> 38.5) ● Hypotension despite adequate resuscitation ● Mental confusion (a predictor of poor outcome) 6. Percutaneous transhepatic cholangiography: ● Occasionally ERCP is not technically feasible or fails to establish biliary drainage. In such cases, biliary drainage can often be achieved by percutaneous transhepatic cholangiography. 7. Open surgical decompression: ● Surgical decompression is done for patients in whom endoscopic drainage is unsuccessful or unavailable. 8. Supportive: ● Supportive treatments are provided as required. Hypoxemia and hypotension as well as renal support may need to addressed References 1. Antibiotic Therapeutic Guidelines, 14th ed 2010. 2. Nezam H Afdhal et al. Acute cholangitis in Up to Date Website October 2013. Dr J.Hayes October 2013. .