FRONTIERS IN ENDOSCOPY, SERIES #47 FRONTIERS IN ENDOSCOPY, SERIES #47 Douglas G. Adler MD, FACG, AGAF, FASGE, Series Editor Current Management of Ascending Cholangitis Dan McEntire Douglas G. Adler Ascending cholangitis is an infectious syndrome of the biliary tree that can pose significant morbidity to affected patients if not recognized and treated appropriately. Accurate diagnosis and assessment of disease severity is essential to guide selection of antimicrobials, timing of biliary decompression, and selection of a decompression technique. This article reviews the current literature related to ascending cholangitis management, in conjunction with current international guidelines. INTRODUCTION scending cholangitis (AC) is an infection of polymicrobial.2 The most frequently isolated Gram- the biliary tract. The normal biliary tree is negative organisms are E. coli and K. pneumoniae, near-sterile secondary to constant drainage, with Enterococcus species being the most common A 3,4 bacteriostatic bile salts, and mucosal immune Gram-positive organism. Anaerobes, primarily mechanisms. Biliary obstruction disrupts these Bacteroides and Clostridium, are relatively processes and causes elevated intraductal pressure infrequently isolated.3,4 with increased bile duct permeability, which Accurate diagnosis and assessment of permits endotoxin and bacterial translocation severity are fundamental to guide appropriate into lymphatic and portosystemic circulation.1 therapy. In additional to clinical support and Biliary obstruction is most frequently caused resuscitation, antibiotic administration and biliary by biliary stones, though there are many causes decompression represent the central components including mass effect of malignancy, benign and of AC management. This article presents current malignant strictures, parasites (e.g., Ascaris), and data pertinent to these areas. iatrogenic causes (e.g., biliary stenting, surgery).1 (Figures 1 and 2) Diagnosis of Ascending Cholangitis The organisms implicated in AC originate The classic clinical characteristics of AC are fever, from enteric flora, and cultures are usually right-upper-quadrant (RUQ) abdominal pain, and jaundice (Charcot’s triad). More severe cases may Dan McEntire MD, Douglas G. Adler MD, University present with hypotension and altered mental status of Utah School of Medicine, Gastroenterology (Reynold’s pentad). However, because few cases and Hepatology, Salt Lake City, UT present with all of these features, standardized 28 PRACTICAL GASTROENTEROLOGY • NOVEMBER 2018 Current Management of Ascending Cholangitis FRONTIERS IN ENDOSCOPY, SERIES #47 FRONTIERS IN ENDOSCOPY, SERIES #47 criteria were recently developed.5,6 dysfunction. Organ dysfunction is defined as the The current Tokyo Guidelines 2018 (TG18) presence of cardiovascular dysfunction requiring diagnostic criteria for AC are based on evidence intravenous dopamine >5µg/kg/min or any of systemic inflammation, cholestasis, and dose of norepinephrine, neurologic dysfunction biliary obstruction. The presence of systemic (i.e., disturbance of consciousness), respiratory inflammation is defined as fever >38°C, shaking dysfunction (PaO2/FiO2 <300), renal dysfunction chills, leukocyte count <4,000/µL or >10,000/µL, (oliguria or serum creatinine >2mg/dL), or C-reactive protein (CRP) ≥1 mg/dL. Cholestasis hepatic dysfunction (INR >1.5), or hematologic is defined as clinical jaundice, total bilirubin dysfunction (platelet count <100,000/µL). Grade ≥2 mg/dL, or alkaline phosphatase, aspartate II (moderate) cholangitis is defined by the presence aminotransferase, alanine aminotransferase, or of high fever (>39°C), leukocyte count <4,000/ gamma-glutamyltransferase >1.5 times the upper µL or >12,000/µL, advanced age (>75 years), or limit of normal. The presence of biliary dilatation, hypoalbuminemia (<70% lower limit of normal). or evidence of the etiology (e.g., stone, stricture), Grade I (mild) cholangitis lacks the aforementioned indicates obstruction. A definitive diagnosis is criteria. A large study that stratified patients by made when at least one criterion is met in each severity grade found 5.1%, 2.6%, and 1.2% 30- of the three categories. A suspected diagnosis is day mortality in patients with Grade III, II, and I made when one criterion is met in the systemic disease, respectively.7 inflammation category, plus one item in either the cholestasis or imaging categories. One study found Antibiotics that the diagnostic criteria successfully identified Initiation of antibiotics should occur within one 90% (73.1% definitive, 16.9% suspected) of cases.7 hour in cases of sepsis, or within six hours for The remaining undiagnosed 10% were mild cases all other cases.4,8 Prescribing adequate empiric that lacked systemic inflammation. This suggests coverage is becoming increasingly difficult due reasonable performance of criteria, especially for to antibiotic resistance patterns.2,9 Appropriate moderate to severe disease. selection of empiric coverage is also made with Imaging is necessary to make a definitive consideration given to comorbidity, allergy, or diagnosis of cholangitis (though clinical suspicion other factors. may be high in known cases of preexisting General recommendations for empiric pancreaticobiliary disease). Abdominal ultrasound coverage include intravenous treatment with a (US) is the suggested first step due to its wide third-generation cephalosporin or a penicillin availability, noninvasive nature, and low cost. US derivative/beta-lactamase inhibitor combination.4 is well suited to visualize the proximal common TG18 and the Surgical Infection Society/Infectious bile duct (CBD) and common hepatic duct, Disease Society of America (SIS/IDSA) guidelines but visualization of the distal CBD is typically recommend to consult local antibiograms and limited. Computed tomography (CT) and administer alternative medications if community magnetic resonance imaging/magnetic resonance pathogen resistance exceeds 10-20%.4,10 cholangiopancreatography (MRI/MRCP) can be Ampicillin-sulbactam and fluoroquinolones are not performed. MRI/MRCP is favored given the high- recommended for empiric use due to widespread resolution imaging of the common bile duct that E. coli resistance, but are frequently used in is possible. Invasive endoscopic or percutaneous clinical practice.2,4,9,10 Antipseudomonal agents imaging options, discussed below, can be both can be reserved for severe cases and healthcare- diagnostic and therapeutic. associated infection.3,4 Coverage of Enterococcus species with vancomycin is recommended in Severity Grading of Ascending Cholangitis severe or healthcare-associated disease, or in TG18 includes a severity grading system that immunocompromised patients.4,10 Anaerobic has prognostic value and may help to guide coverage with metronidazole is recommended in appropriate intervention timing.5 Grade III (severe) patients with a surgical history of biliary enteric cholangitis is manifested by evidence of organ (continued on page 34) PRACTICAL GASTROENTEROLOGY • NOVEMBER 2018 29 Current Management of Ascending Cholangitis FRONTIERSNUTRITION ISSUES IN ENDOSCOPY, IN GASTROENTEROLOGY, SERIES #47 SERIES #174 (continued from page 29) Figure 1. Ascending Cholangitis Treated via ERCP Figure 1a. Ampulla with purulent material visible at orifice Figure 1b. Cannulation of the bile duct with a sphincterotome Figure 1c. After cannulation, copious pus starts to drain Figure 1d. After sphincterotomy a large stone is extracted spontaneously from the duct with a balloon catheter. Figure 1e. A biliary stent is placed to further promote Figure 2. Placement of a metal stent via ERCP in a patient drainage of purulent contents. This stent was removed 2 with pancreatic cancer who developed cholangitis. Note weeks later. purulent drainage. (continued on page 36) 34 PRACTICAL GASTROENTEROLOGY • NOVEMBER 2018 Current Management of Ascending Cholangitis FRONTIERSNUTRITION ISSUES IN ENDOSCOPY, IN GASTROENTEROLOGY, SERIES #47 SERIES #174 FRONTIERS IN ENDOSCOPY, SERIES #47 (continued from page 34) Endoscopic Biliary Drainage anastomosis or for general prophylaxis.4,10 This is ERCP biliary decompression by direct cannulation due to a relative scarcity of anaerobe isolation in of the major duodenal papilla is the gold standard AC, and reports that anaerobic coverage for other for acute cholangitis.25,26 This is due to high success indications does not improve outcomes.2,3,11,12,13 rates, minimally invasive nature, and fewer adverse Antibiotic treatment can be adjusted based events compared to percutaneous or surgical on patient response and pathogen susceptibility procedures.26,27,28,29 Disadvantages, however, include data. TG18 and SIS/IDSA guidelines recommend need for sedation.30 Endoscopic duct clearance a total of 4-7 days of therapy after source control by sphincterotomy, balloon extraction, and/or is obtained, obstruction removed, and assuming endoscopic stenting for strictures is performed absence of local complications (e.g., liver as needed. Patients in whom stone extraction abscess).4,10 In the presence of Gram-positive cannot be performed can simply undergo stent bacteremia, 2 weeks of therapy is recommended.4 placement. An additional adjunctive technique is direct cholangioscopy with lithotripsy. Nasobiliary Timing of Biliary Decompression drains are rarely used in modern practice.26,27,31 Several studies, mostly related to ERCP, have Balloon-assisted enteroscopy ERCP (BE-ERCP) assessed clinical outcomes in AC patients with is recommended