Pyogenic cholangitis

How can I be sure that the patient has pyogenic cholangitis?

The classical presentation for patients with cholangitis includes jaundice, fever, and right upper quadrant (RUQ) abdominal pain. Because, by far, most episodes of cholangitis are due to gallstones, the majority of patients will have known or suspected gall bladder calculi or will have had prior episodes of RUQ abdominal pain. As with most classical presentations, there is a broad overlap with other conditions, including viral hepatitis, alcoholic hepatitis, cirrhosis, and hepatic abscesses. In addition, many – typically elderly – patients may have little or no abdominal pain associated with biliary suppuration. On occasion, patients will have such systemic compromise from suppurative cholangitis that the condition is associated with frank sepsis, altered mental status, renal failure, or cardiovascular collapse.

A tabular or chart listing of features and signs and symptoms

Clinical presentation features of cholangitis

Following is a list of features of cholangitis (adapted from Englisbe MJ and Dawes LG. HPB 2005).

Age 69 +/- 2 years

Fever >102 F 77%

Abdominal pain 70%

Jaundice 69%

WBC 17.2 +/- 1.9

Bilirubin 5.8 +/- 0.7 mg/dL

Alkaline. Phosphatase 421 +/- 45 IU/dL

AST 165 +/- 26 IU/dL

Notes:

Elevated white blood cell count (WBC): 95% of patients

Bilirubin (direct or conjugated fraction) more than 2 mg/dL: 95% of patients

Serum alkaline phosphatase more than 2 times upper limit of normal: 75% of patients

Elevated serum transaminase levels, usually elevated above normal: occasionally as high as 10 times above normal levels.

(The elevated transaminases lead to cholangitis being confused with hepatitis on occasion, but this elevation is quite commonly seen in cholangitis.)

Elevated serum lipase: 50% to 60% of patients. On occasion, the elevation is dramatic and drops precipitously as debris or stones disimpact the distal duct.

How can I confirm the diagnosis?

In patients with no prior biliary surgery, an ultrasound of the right upper quadrant would be an important first step.

If the transabdominal ultrasound is normal but the concern for cholangitis persists, further evaluation can be performed with a magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound (EUS) to identify the presence of stones in the biliary tract. If there is felt to be a high likelihood of intraductal stones, or if choledocholithiasis or cholangitis are diagnosed by clinical and radiographical evidence, ERCP may be indicated.

Routine findings for pyogenic cholangitis

Patient profile

Low-grade fever to high, spiking fevers
Occasionally, septic patients are hypothermic.
BP and pulse: usually normal except for modest tachycardia – with sepsis, hypotension, and tachycardia
Jaundice: usually noted but not always
Pain: usually RUQ but may be epigastric (Remember, the bile duct is midline epigastric!)
In some: confusion, agitation.
If sepsis presents: occasionally, multiorgan failure is noted.

Laboratory

Usually elevated white cell count
Modest (not extreme) elevation of bilirubin: almost always direct or conjugated predominant
Transaminases usually elevated; may be dramatic if there is sudden impaction of stones.
Alkaline phosphatase: elevated to 2 to 4 times upper limits of normal. Rarely above 10 mg/dL

What other diseases, conditions, or complications should I look for in patients with pyogenic cholangitis?

Biochemical profiles of biliary tract disease mimicking cholangitis are shown in Table I.

Laboratory tests	Post-traumatic cholestasis	Cholangitis	Malignancy	Benign CBD stricture
Bilirubin	Up to 30 mg/dL	<10 mg dL	Up to 30 mg/dL	Up to 30 mg/dL
ALT	Normal	Up to 300 IU/L	Normal	Normal
AST	Normal	Up to 300 IU/L	Normal	Normal
Alk p’tase	Normal	Up to 400 IU/L	Up to 2000 IU/L	Up to 2000 IU/L
Bacteremia	None	Usual	Rare to never	Rare to never

Complications of untreated cholangitis

Sepsis. Hypotension, multiorgan failure, death: 20%

Hepatic abscesses. Usual with no treatment: 50%

Bacteremia. Persistent if no or incorrect antibiotics: 90%

Recurrent cholangitis. Usual

Biliary cirrhosis. With long-term obstruction: inevitable

What is the right therapy for the patient with pyogenic cholangitis?

Cholangitis is invariably the result of biliary obstruction with infected bile proximal to the obstruction.

A single Gram-negative organism is most commonly noted.
Bile in patients without stones or stricture is invariably sterile.
Bile in patients with stones: overall, more than 75% have bacterial isolates, more likely with pigment than cholesterol stones
Usual organisms: E. coli, 55%; P. aeruginosa, 25%; Enterococcus spp., 15%; Klebsiella spp., 5%

Primary therapy

Primary therapy is decompression of the bile duct.

General suggestions for decompression

All decompression must await stabilization with fluids and antibiotics. An emergency procedure done in haste often becomes a tragic disaster.

Endoscopic retrograde cholangiopancreatography (ERCP). Performed by the right personnel, is the most efficient at decompression.

Decompression by ERCP usually necessitates sphincterotomy. Decompression is essential; stenting is preferred after sphincterotomy rather than tedious and time-consuming stone extractions. Temporary plastic stents are mostly used with elective stone removal planned over several weeks’ time.

NOTE: Given the severity of illness, most patients should be endoscoped with anesthesia assistance.

Transhepatic cholangiographic decompression.Usually performed in Interventional radiology – also should have anesthesia assistance. Once again, decompression, not stone removal is the premier goal, that is, to decompress the obstruction by stenting.

Surgical decompression. Occasionally, it is the only available resource; it may be done laparoscopically.

When minimally invasive treatments fail or are not available, laparotomy should be done to decompress the obstructed biliary tree. Ordinarily, a CT scan should be done first to localize the etiology and site of biliary obstruction.

Emergency decompression. The mainstay of decompression, it is best done emergently with a T tube with external drainage.

What is the most effective initial therapy?

Initial therapy includes the following antibiotics in patients with community-acquired biliary infections: all usually in combination with metronidazole 500 mg every 8 hours.

Imipenem-cilastatin (Primaxin): 500 mg q 6 hrs
Piperacillin-tazobactam (Zosyn): 3.375 g q 6hrs
Ertapenem (Ivanz): 1 g q 24 hrs
Meropenem: 1 g q 8 hrs
Doripenem (Doribax): 500 mg q 8 hrs
Ciprofloxacin (Cipro): 400 mg q 12 hrs
Levofloxacin (Levaquin): 750 mg q 24 hrsV
Cefepime (Mefoxin): 2 g q 6 hrs

In complicated infections, particularly with prior hospital interventions, adding vancomycin 15 to 20 mg/kg every 8 to 12 hours should be considered.

Listing of usual initial therapeutic options, including guidelines for use, along with expected result of therapy.

Initial treatments must be aimed at patient stabilization. Routine guidelines for patient care must be followed. The initial therapy cannot be to “page” the GI fellow or consultant on call.

The following personnel must be consulted urgently; the clinician should not wait for complications to occur.

Surgeon
Interventional radiologist
Gastroenterologist
Intensivist, if patient is unstable

A listing of a subset of second-line therapies, including guidelines for choosing and using these salvage therapies

Salvage therapies should always include surgical consultation and exploratory laparotomy.

Especially in patients with prior biliary tract disease, abdominal surgery, morbid obesity, hemodynamic instability, extensive consultations should be sought. The patient should not be worked up until consultants are brought into the picture. Unstable elderly, complex patients, especially, cannot wait for elective consultation.

Antibiotic treatment alone is grossly insufficient. The primary disease is an abscess or pus under pressure. Remember that antibiotics are supplementary to adequate decompression.

Listing of these, including any guidelines for monitoring side effects.

Patients, post treatment (surgical, radiological, or endoscopic) must be monitored in an intensive care unit or step-down unit for a sufficient period to ensure stabilization.

How should I monitor the patient with pyogenic cholangitis?

Stabilization of the patient after successful decompression and initiation of antibiotic therapy is assured by maintenance of appropriate vital signs, mentation, and adequate urine output.

Often, with adequate early decompression, patients report feeling better very quickly.

Routine tests such as WBC, liver function tests, and electrolyte panels should be ordered daily until the trend of improvement is documented. Blood and other specimen culture results should be reviewed frequently.

In the vast majority of cases, cholangitis is associated with bacteremia of a single Gram-negative organism. Be certain to check the culture results and the sensitivities to antibiotics, especially for patient with prior interventions or a prior bilioenteric anastomosis. Rare, but more frequently in patients previously in hospitals, unusual organisms and/or resistance to antibiotics may be noted.

In follow up, patient should be seen by consultants soon after discharge. For patients who have undergone definitive surgery, routine surgical follow up can be arranged.

Most important, remember that decompression of the bile duct with an intact gallbladder remaining is not adequate definitive therapy for cholelithiasis. The remaining gallbladder following ERCP sphincterotomy/stent placement will neither fill nor empty adequately.

Necrosis of the gallbladder, gallbladder abscesses with or without sepsis, can occur by leaving an intact gallbladder in place after sphincterotomy. The gallbladder must be resected.

Additionally, all stents, except metal mesh stents left in the biliary tree need to be removed and/or replaced. The stents will gradually occlude with biofilm and microcalculi. Small stents (5 or 7 French size) should be removed by 6 weeks. Larger stents (10 French size) may be left for 2 or even 3 months but will eventually occlude.

The change of stents or their removal should be scheduled before initial patient discharge and the schedule (also documented in the chart) adequately communicated to the patient.

What's the evidence?

Englesbe, MJ, Dawes, LG. “Resistant pathogens in biliary obstruction: importance of cultures to guide antibiotic therapy”. HPB (Oxford). vol. 7. 2005. pp. 144-8.

Kochlef, A, Gargouri, D, Kilani, A. “Retained common bile duct stones after endoscopic sphincterotomy: temporary and long-term treatment with biliary stenting”. Tunis Med. vol. 89. 2011. pp. 342-6.

Kow, AW, Wang, B, Wong, D. “Using percutaneous transhepatic cholangioscopic lithotripsy for intrahepatic calculus in hostile abdomen”. Surgeon. vol. 9. 2011. pp. 88-94.

Mosler, P. “Diagnosis and management of acute cholangitis”. Curr Gastroenterol Rep. vol. 13. 2011. pp. 166-72.

Rimon, U, Kleinmann, N, Bensaid, P. “Percutaneous transhepatic endoscopic holmium laser lithotripsy for intrahepatic and choledochal biliary stones”. Cardiovasc Intervent Radiol. 2010 Dec 16.

Itoi, T, Sofuni, A, Itokawa, F. “Transnasal endoscopic biliary drainage as a rescue management for the treatment of acute cholangitis”. World J Gastrointest Endosc. vol. 2. 2010. pp. 50-3.

Castaing, D, Vibert, E, Bhangui, P. ” Results of percutaneous manoeuvres in biliary disease: the Paul Brousse experience”. Surg Endosc. 2010 Dec 7.

Brand, M, Bizos, D, O’Farrell, P. “Antibiotic prophylaxis for patients undergoing elective endoscopic retrograde cholangiopancreatography”. Cochrane Database Syst Rev. 2010. pp. CD007345

Doganay, M, Yuksek, YN, Daglar, G. “Clinical determinants of suppurative cholangitis in malignant biliary tract obstruction”. Bratisl Lek Listy. vol. 111. 2010. pp. 336-9.

Guaglianone, E, Cardines, R, Vuotto, C. “Microbial biofilms associated with biliary stent clogging”. FEMS Immunol Med Microbiol. vol. 59. 2010. pp. 410-20.

Horiuchi, A, Nakayama, Y, Kajiyama, M. “Biliary stenting in the management of large or multiple common bile duct stones”. Gastrointest Endosc. vol. 71. 2010. pp. 1200-3.

Catalano, OA, Sahani, DV, Forcione, DG. “Biliary infections: spectrum of imaging findings and management”. Radiographics. vol. 29. 2009. pp. 2059-80.

Parra-Membrives, P, DÃaz-GÃ³mez, D, Vilegas-Portero, R. “Appropriate management of common bile duct stones: a RAND Corporation/UCLA appropriateness method statistical analysis”. Surg Endosc. vol. 24. 2010. pp. 1187-94.

Li, KW, Zhang, XW, Ding, J. “A prospective study of the efficacy of endoscopic biliary stenting on common bile duct stones”. J Dig Dis. vol. 10. 2009. pp. 328-31.

Lee, JK, Lee, SH, Kang, BK. “Is it necessary to insert a nasobiliary drainage tube routinely after endoscopic clearance of the common bile duct in patients with choledocholithiasis-induced cholangitis? A prospective, randomized trial”. Gastrointest Endosc. vol. 71. 2010. pp. 105-10.

**The original author for this chapter was John Cello. The chapter was revised by Dr. Bruce R. Bacon.

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