Cholangitis

Dr. Hendra Cipta

I. Introduction

Acute cholangitis is inflammation of the biliary system caused by an infection and

bile flow obstruction.9,12Epidemiologically, this disease shows
different incidences around the world. In the United States, cholangitis is relatively
rarely, and the occurrences are often related to the causes of obstruction and bactibilia
that is in the ERCP procedure (1-3%) which often occurs due to the injection of contrast agents.
retrograde. Meanwhile, in other countries, Oriental cholangio-hepatitis is very
endemic in Southeast Asia, China, and Taiwan. In this form, it often arises
recurrent pyogenic cholangitis with intra & extrahepatic stones in 70-80%
patients and cholelithiasis in 50-70% of patients. There is no difference in gender.
in the incidence of this disease. The majority of patients are in their forties.
five, and at an older age will be more accompanied by comorbid diseases
the others and their mortality rate is also higher.12)

There are racial differences in the incidence of cholangitis. However, this turns out to be more

due to different dietary patterns. In the northern European nations,

Hispanics, Americans, and Pima Indians who have the habit of
consuming a high-fat diet, then Cholangitis occurs related to
cholelithiasis caused by cholesterol stones. On the contrary, among nations
those who consume a lot of high-fiber foods like in Asia, then the cause
The most common cholangitis is the primary stone in the common bile duct caused by
due to infection, bile stasis, strictures, and parasites ('recurrent pyogenic cholangitis').
Meanwhile, in Africa: there is something unique related to patients who
suffering from sickle cell anemia.12,15)

The mortality of this disease was very high, at 100%, especially if accompanied by
accompanying diseases. Currently, the mortality rate has significantly decreased to around 7
- 40%. If emergency surgery is performed, the mortality rate will increase.
that is 17 - 40 %. However, if a definitive surgical therapy is performed
elective, the mortality rate will decrease to only 3%.12,14)

This paper will briefly discuss several aspects of this disease.

The therapy and surgical management will also be discussed in more detail.

II. Etiology

Cholangitis can be caused by various pathological conditions that will all

ends with a stasis of bile fluid flow and ultimately leads to infection by bacteria
due to the increased multiplication in the biliary system. Various types of etiology
can be seen in the following table:

Table 1: Etiology of Cholangitis

Choledocholithiasis
Biliary system stricture
Neoplasm in the biliary system
Iatrogenic complications due to manipulation of the 'CBD' (Common Bile Duct)

Parasite: Ascaris worm, Clonorchis sinensis

Chronic pancreatitis
Pseudocyst or pancreatic tumor
Ampullary stenosis
Congenital choledochal cyst or Caroli's disease
Mirizzi Syndrome or Mirizzi Syndrome Variant
Duodenal diverticulum

Bile duct stones are the most common cause (nearly 90%), followed by
followed by biliary system strictures and tumors in the biliary system. In Asian countries
Southeast Asia and China worms are often found as the cause, although the type
The worms found are various.1,4,5,10,12,15)

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III. Pathophysiology

In normal conditions, the biliary system is sterile and the flow of bile does not experience
obstruction so that there is no backflow to the biliary system. Cholangitis occurs
due to stasis or obstruction in the biliary system accompanied by bacteria that
experiencing multiplication. Obstruction mainly caused by 'CBD' stones, strictures,
stenosis, or tumor, as well as endoscopic manipulation 'CBD'. Thus, the passage
bile becomes sluggish so that bacteria can multiply after experiencing
migration to the biliary system via the portal vein, the portal lymphatic system, or directly
from the duodenum. Therefore, there will be an ascending infection towards the duct.
hepatitic, which will eventually cause high intrabiliary pressure
and exceeded the limit of 250 mmH20. Therefore, there will be a back flow of bile.
which results in infections in the biliary canaliculi, hepatic veins, and lymphatics
perihepatic, which in turn will lead to bacteremia that can continue.
becomes sepsis (25-40%). If in that state accompanied by
the formation of pus leads to suppurative cholangitis.9,10,12)

There are various pathological and clinical forms of cholangitis, namely:5,9)

1. Cholangitis with cholecystitis: In this condition, no obstruction is found.

in the biliary system, as well as the dilation of both intrahepatic and extrahepatic ducts.

This condition is often caused by small "CBD" stones, compression by the vesica.
bile / lymph nodes / pancreatitis, edema/spasms of the Oddi sphincter,
mucosal edema 'CBD', or hepatitis. (see image 1.)

2. "Acute Non Suppurative Cholangitis": There is biliary bacteria without pus in the system
biliary which is usually caused by partial obstruction. (Figure 2.)

CBD contains pus and there are bacteria, but

there is no total obstruction so the patient is not in a state of sepsis. (See
Image 3.)

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 Figure 3: Cholangitis accompanied by pus and partial obstruction

4. "Obstructive Acute Suppurative Cholangitis": Here there is a total obstruction of the system
biliary pressure exceeding the normal pressure in the biliary system, which is above 250
mm H20 resulting in bacteremia due to reflux of bile fluid accompanied by
with the influx of bacteria into the lymphatic system and hepatic vein. (See Figure)
5. If bacteremia continues, various complications will arise, namely sepsis.
sepsis, septic shock, multiple organ failure which is usually preceded by renal failure
caused by hepatorenal syndrome, pyogenic liver abscess (often multiple)
and even peritonitis. If there are already complications, then the prognosis
get worse. Some conditions that worsen the prognosis are
as follows (table 2.).

Table 2: Factors that increase mortality

Age
Fever
Leukocytosis
Septic Shock
Blood culture (+)
Disruption of the phagocytosis system

Immunosuppression
The presence of liver neoplasm

Multiple intrahepatic obstruction

chronic liver disease
Liver abscess

IV. Bacteriology

The presence of bacterial infection is important in the pathogenesis of Cholangitis.

According to the previously outlined infection route, the type of bacteria that

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should be found in bile liquid culture as well as in blood is the most numerous
consecutively, namely gram-negative bacteria, anaerobic and gram-positive that are primarily
originating from the small intestine. Table 2. Shows various types of bacteria that can
found in both bile and blood.14)

Table 3: Bacteriology of Acute Cholangitis

EMPEDU

Cholecystitis Cholangitis Both Blood

Escherichia coli 31% 26% 44% 26%

Enterococcus 18% 11% 13% 9%
Klebsiella species 15% 12% 11% 14%
Pseudomonas spp 6% 5% 5% 9%
Enterobacter spp 2% 5% 4% 1%
Staphylococcus 0.3% 3% 3% 9%
Bacteroides spp 3% 4% 4% 2%
Clostridium spp 2% 4% 3% 0.3%

Toloza EM & Wilson SF. In: Fry DE (ed). Surgical Infections 1995

There are various factors that can be used as predictors of the occurrence of bactibilia.

as stated in table 3.14)

Table 4: Predictor factors for the occurrence of bactibilia.

Age > 60 years

Fever > 37.30C
Total Bilirubin > 8.6 μmol/L
Leukocytosis > 14,000/mm3

Acute cholecystitis episode or recent cholangitis

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 Biliary cannulation or bypass procedure
Diabetes mellitus
Hyperamylasemia
Obesity

Toloza EM & Wilson SF. In: Fry DE (ed). Surgical Infections 1995

Diagnosis

Acute cholangitis diagnosis can be established clinically, namely by

the discovery of 'Charcot's Triad' which consists of pain in the right upper quadrant, jaundice
and fever that occurs with/without shivering. However, less than 50% of cases
all three were found simultaneously. The frequency of symptoms and signs is
the signs that can be found are : (14)

Fever > 38 C 87 - 90 %
Abdominal pain 40%
Jaundice 65%

The absence of all three signs simultaneously is primarily caused by

incomplete obstruction of the bile duct. If the condition worsens,
if accompanied by sepsis or shock, 'Reynold's Pentad' will be found
marked by Charcot's triad plus 'Mental confusion / Lethargy'
and shock. This condition occurs in 10 - 23 % of patients. The changes are caused by
due to total obstruction of the bile duct causing increased pressure that leads to
bile flow reflux allows bacteria to reach the systemic blood vessel system
and sepsis occurs. Therefore, in this situation, drainage must be performed immediately.
to carry out decompression and control of the source of infection.

The examination of assistive devices is especially useful for finding possible etiology.

Cholangitis is crucial in determining the type of therapy that must be undertaken as treatment.

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definitive surgery as well as for temporary decompression purposes. Examination that
what is done is:1,6,10,12,14)

USG of the hepatobiliary system and pancreas:

There must be a dilated 'CBD' found.

Possibly accompanied by "CBD" stone.
CT.Scan is more sensitive and specific than ultrasound and provides an image:
Stone "CBD".
Biliary or pancreatic tumor
Stones in the intrahepatic biliary system

The presence of atrophy in the liver

Abscess in the liver (usually multiple if caused by stones)

MR Cholangiography: This examination is very sensitive and specific, as well as accurate.
namely each 91.6%: 100%, and 96.8%. The advantage of this tool is non
invasive, can be done at almost any age and can differentiate between types of stones

cholesterol from other types clearly.

Cholangiography: Causes morbidity of 1-7% and mortality of 0.25%, by

therefore it is advisable to avoid it, unless accompanied by decompression actions that
performed together. It can be done through ERCP (Endoscopic Retrograde)
Cholangio Pancreatography or PTC (Percutaneous Transhepatic)
Cholangiography.

Cholescintigraphy with HIDA:

Showing liver uptake
There is no visualization of the gallbladder, CBD, or small intestine by
due to total obstruction.

The laboratory shows the following changes:

Leukocytosis > 10,000 / mm333-80%
2-10 mg/dl : 68-76 %
Alkaline phosphatase 2-3 times normal in 90%

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 C-reactive protein: Usually found to be increased

VI. Management:

Considering the high mortality if surgical therapy is performed during an emergency,

the initial steps for the treatment of acute cholangitis are as follows:
(3,5,10,12,14)

Improvement of the general condition :

The patient is fasting.

Decompression with NGT ("Naso Gastric Tube")

Infusion installation and rehydration performed

Correction of electrolyte abnormalities is performed.

Administration of parenteral antibiotics

By taking that action, 80-85% of patients will experience improvement.

so that in the next period (within 48 - 72 hours) an examination can be carried out
further to ensure the diagnosis of the cause and determine the type of surgery
definitively.

However, if the patient comes for the first time with shock and
severe tissue hypoperfusion requires:

Invasive monitoring
Non-narcotic analgesics, however, if there is a diagnostic confirmation, Meperidine.
or Fentanyl can be administered.

In 15% of cases, medication therapy does not improve the general condition.
the patient, so emergency decompression action is needed and can be performed
in the way:

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 Open surgery
Endoscopic drainage
Percutaneous biliary drainage system

After medication therapy and other supportive measures successfully improved the condition

in general, surgical action for decompression can be performed electively and

generally what is done is:

Cholecystectomy + Exploration of 'CBD' +/- T-tube drainage, +/- choledoch-

enterostomy

Mortality in various procedures, both surgical and non-surgical, is as follows

the following:

Conservative therapy without drainage results in a mortality rate between 40-100.

%.
Surgical decompression actions as a whole will show figures
mortality between 2 - 13% and morbidity is 12 - 21%.
Endoscopic drainage will be accompanied by a mortality rate of 1 - 13.
%, and morbidity 4 – 24 %.

Minimal invasive therapy with the technique 'Percutaneous Transhepatic'

Cholangiography Drainage (PTCD) shows a low mortality rate
0.05 – 7.00 %, but its morbidity varies greatly from 4 – 80 %.
If the cause is a primary malignant neoplasm then:

The mortality rate of surgical procedures is up to 40%, however

if there is extensive metastasis, it will increase to
59 %.

Endoscopic drainage will provide a mortality rate of up to 46.

%.

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Parenteral antibiotic therapy is also important, so
the selection of the appropriate empirical antibiotic type is as follows:14)

Table 5. Types of empirically chosen parenteral antibiotics.

. Acute Cholecystitis
- Aminoglycoside - penicillin
Penicillin broad spectrum
Third generation cephalosporin

. Acute Cholangitis
Penicillin broad spectrum
Aminoglycoside - penicillin
Third generation cephalosporin
Imipenem-cilastatin
Second generation cephalosporin
. Prophylaxis:
Second generation cephalosporin
Broad spectrum penicillin

The presence of third-generation cephalosporins is a step forward in therapy.

bacterial infection, however its use must be correct. This type has
strong antibacterial spectrum against Escherichia coli, Klebsiella, enterococci and
anaerobic bacteria such as Bacteroides which are the most common bacteria
found in bile fluid and causes increased stone formation
in the bile duct system. Those included in this group are
Cefotaxime, Ceftriaxone, and Ceftizoxime because they have clinical indications and
spectrum of the same antibiotics.15)

Of the three cephalosporins mentioned above, it seems that Ceftriaxone is the choice.
the best considering the following advantages: (14)
24-hour network penetration and a sufficiently high bile concentration.

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24-hour protection with a dosage of 1 gram once a day.
3. 'Dual Excretion' refers to the kidneys and liver, enhancing safety.
4. The bactericidal activity is quite broad.
5. Economic advantages of pharmacoeconomics in terms of overall costs and staff workload.

hospital.
6. Low side effects.
A dose once a day has been clinically proven to be effective.

In cases accompanied by an increase in bilirubin exceeding 5.0 mg/dl,

The use of Aminoglycosides should be avoided due to the increasing risk of nephrotoxicity.
increased. This is due to renal sensitization caused by renal perfusion that
reduced, increased bilirubin and other bile salts, and the presence of endotoxemia
gram-negative bacteria.

Baktibilia can continue to persist even though the obstruction has been successfully resolved. This condition

can be caused by anaerobic bacteria, bacteria that are resistant to

antibiotics, gram-negative bacteria, and fungi.

As previously explained, the most common cause is

choledocholithiasis, and therefore its management will be discussed further
as deep as stated in the image 5 below.

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 No jaundice

Suspicion of CBD stones

Routine pre-op selective per-operative cholangiogram pre-op ERCP

cholangiogram

CBD stones No stones CBD stones

open laparosc laparosc laparoscopy endoscopic sphincter

expl chickpeas expl BCD cholecystectomy and duct clearance

failure failure success failure

post-op open laparoscopy

ERCP expl CBD expl CBD
failure
Algorithm showing available strategies for CBD stone.
Hepatobil Pancreatic Surgery 1999
Image 5:
Algorithm as a strategy in handling 'CBD' stones.

Thus, in accordance with the above scheme, the choices within

There are two types of actions in its management, namely 'One Step Approach' and 'Two Step'
Approach (see Image 6. And 7.) The chosen action must be
based on the consideration of the availability of existing facilities, the skills of the surgeon

who handles it and of course the costs that must be incurred for
its management. There are advantages and disadvantages to both techniques. (See
table 6.

Table 6: Comparison of advantages and disadvantages between two techniques.

One-step approach Two-step approach

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LC+LTCDCBDE LC + pre/post-op ERS

Advantages Advantages
Lower costs Shorter operating time
Shorter hospital stay Less technically
demanding
Potentially decreased morbidity Requires less equipment
Disadvantages Disadvantages
More technically demanding Longer hospital stay
Requires expensive equipment Increased total costs
Longer operative time Potentially increased
morbidity
Increased operating room cost Two separate procedures

Rosenthal RJ et al. World J Surg 1998; 22: 1125-1132

Detailed management steps for each type of stage can be seen

in images 6. and 7.

Onestepapproachtosuspected
choledocholithiasis
Patient with suspected choledocholithiasis

Intraoperative cholangiography

No CBD stone CBD stone

Laparoscopic Stone < 0.9 mm Stone > 0.9 mm

cholecystectomy

LC + Lap transcystic Laparoscopic Open CBD

CBD exploration choledochotomy exploration

Successful Retained stones

Rosenthal RJ et al. World J Surg 1998; 22: 1125-1132

Figure 6.
Single-stage CBD stone management technique

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In single-stage management technique, after experiencing improvements in general conditions

the patient underwent laparoscopic cholecystectomy and cholangiography

intraoperative. If CBD stones or obstruction in the flow of contrast material are not found
into the duodenum then cholecystectomy alone is sufficient. However, if it is found
the CBD stone then the next action depends on the size of the stone found.
If a stone is found to be small, that is < 0.9 mm, then exploration can be carried out.
Cystic bile duct laparoscopically if facilities and expertise are available.
If the stone is larger than 0.9 mm, then a laparoscopic choledochotomy is performed.
or open exploration of the bile ducts. The advantage of this method is the duration
short treatment, low cost, and lower morbidity, however
requires high laparoscopic skills and complete equipment and
expensive, as well as longer operating hours.

Two-stepapproachtopatientwith
suspectedchoe
l dochotilha
i ss
i

Patient with suspected choledocholithiasis

Nonresolving pancreatitis, Jaundice, Cholangitis, Poor operative risk

Yes No
ERCP / ERS Laparoscopic intraoperative
Stone Extraction cholangiography

Retained stones Laparoscopic cholecystectomy

Postoperative Yes
Stones cleared Retained stones
ERCP / ERS /
stone extraction No
Laparoscopic Open CBDE / percutaneous Done
cholecystectomy stone extraction
Rosenthal RJ et al. World J Surg 1998; 22: 1125-1132

Figure 7: Two-stage Management Technique

Patients with cholangitis caused by choledocholithiasis are not uncommon.

having a high surgical risk, so often the two-stage technique is more appropriate
done because initial actions can involve minimally invasive surgical therapy and
does not require a long operation time. If after invasive action minimal
like ERCP/ERS, the stone causing the obstruction can be removed, then the action

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Cholecystectomy can be performed after the patient's general condition improves.
Furthermore, if there are still stones after extraction through ERCP technique,
then an open exploration of the bile duct is carried out simultaneously
Cholecystectomy was performed and the remaining gallstones were removed. Option
Another action will be performed first, laparoscopic cholecystectomy.
if there are no high operational risks, then ERCP is performed to
removing the retained bile duct stones. The advantage of this approach is
relatively shorter operating time, does not require equipment and expertise
which is too high, but there is a disadvantage that it requires a maintenance time that
longer and higher morbidity.

The choice of approach selected certainly depends mainly on the means.

and the available skills, as well as intensive care that involves various
disciplines related such as surgery, internal medicine, radiology, and
anesthesiology.

VII. Cases of Cholangitis in Bandung:

To give an idea of the extent of experience in handling cases

cholangitis, the author presents cases encountered in the city of Bandung in
the period from 1983 to 1998. The cases involved are those that were committed
the management by the author at major hospitals, namely RSUP Dr. Hasan
Sadikin, St. Borromeus Hospital, Advent Hospital, Immanuel Hospital, and Kebonjati Hospital. From

A total of 1574 cases of surgery on the bile ducts were found as follows:

Table 7: Summary of cholangitis cases in Bandung:

The number of cases of bile duct surgery 1574

Number of cholangitis cases 308 (19.56%)
Jumlah penderita
Man 162 people
Woman 146 people
Average age (years): 50.09 + 15.8
Morbidity: surgical complications 5 cases (1.62%)

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Mortality 3 cases (0.97%)

Table 8.: Types of cholangitis causes found in 308 cases:

Etiology Number Percentage

case
Cholecystitis + Cholelithiasis 103 33.44%
Choledocholithiasis + Cholecystitis + Cholelithiasis 171 55.51%
Hepatolithiasis 9 2.92 %
Sclerosing cholangitis 3 0.97 %
Worm 3 0.97 %
Stricture 4 1.29%
Choledochal Cyst 4 1.29%
Pancreatic tumor 2 0.64%
Ca Empedu 5 1.62 %
Post ERCP 3 0.97 %
Pancreatic stone 1 0.32 %
Total 308

The handling carried out in those cases is in accordance with the protocol.
which has been described in this paper is the non-performance of surgical action
emergency, but first provided with conservative therapy to improve
general condition and then further examination was carried out to determine
the cause of the diagnosis. After sufficient preparation for the operation, which is the patient's condition that

Once repairs and the correct diagnosis have been established, surgery is performed.
definitive electively. With the management pattern as described above, the level
its mortality rate is very low at 0.97 %.

VIII. Conclusion:
1. Acute cholangitis, especially when accompanied by sepsis and shock, must receive
immediate handling because it is a hepatobiliary emergency.

Immediate operational actions are needed to address the causes, but they must
postponed until hemodynamics stabilize to reduce the numbers
mortality, in addition, the cause must be known during the perioperative period
cholangitis.

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3. New developments have been found in means to accelerate diagnosis,
emergency measures for pus drainage or temporarily reducing obstruction, as well as
endoscopic intervention.

The type of surgical therapy chosen is adjusted according to the available facilities and
his surgical skills, but the most important thing is since the patient entered
treatment must involve intensive multidisciplinary care, which is collaboration.
between surgery specialists, internal medicine, anesthesiology, and radiology.

IX. References:

1. Benjamin I.S., Benign and Malignant Lesions of the Biliary Tract, in Garden O.J.
(Ed), Hepatobiliary and Pancreatic Surgery, W.B. Saunders Company Ltd.1999 :
201 - 219.

2. Csendes A., Burdiles P., Diaz J.C., Present Role of Classic Open
Choledochostomy in the Surgical Management of Patients with Common Bile
Duct Stones, World Journal of Surgery 1998; 22: 1167 - 1170.

3. Karnadihardja W., Acute Cholangitis as a Complication of Biliary Obstruction

Bile, PIT IKABI IX, Semarang, 1994.

4. Liu C.L., Fan S.T., Wong J., Primary Biliary Stones: Diagnosis and Management,
World Journal of Surgery 1998; 22 : 1162 - 1166.

5. Lipsett P.A., Pitt H.A., Acute Cholangitis, in The Surgical Clinics of North
America, December 1990: 1297 - 1312.

6. Moston R.W., Menzies D., Gallstones in Garden O.J. (Ed), Hepatobiliary and
Pancreatic Surgery, W.B. Saunders Company Ltd. 1999: 175-197.

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7. Microbiology and Pharmacokinetics of Parenteral Cephalosporins, Roche
Products 1985 – 621 – 93472 (Sydney).

8. Navarrete C.G., Castillo C.T., Castillo P.Y., Choledocholithiasis: Percutaneous

Treatment, World Journal of Surgery 1998; 22: 1151 - 1154.

9. Pitt H.A., Longmire W.P., Suppurative Cholangitis, in Hardy J.D. (Ed), Critical
Surgical Illness, Second Edition, W.B. Saunders Company, 1980 : 380 - 408.

10. Raraty M.G.T., Finch M., Neoptolemos J.P., Acute Cholangitis and Pancreatitis
Secondary to Common Bile Duct Stones: Management Update, World J Surg
1998; 22: 1151 - 1161.

11. Rosenthal R.J., Rossi R.L., Martin R.F., Options and Strategies for Management
of Choledocholithiasis, World J Surg 1998; 22: 1125-1132.

12. Sally Santen, Cholangitis in Emergency Medicine, 11/09/1999 at

www.emedicine.com.

13. Seitz U, Bapaye A, Bochnaker S., et al., Advances in Therapeutic Endoscopic

Treatment of Common Bile Duct Stones, World J Surg 1998; 22 : 1133.

14. Toloza EM & Wilson SF. Cholecystitis and Cholangitis, In: Fry DE (ed). Surgical
Infections, 1995: 251 - 260.

15. Thistle J.L., Pathophysiology of Bile Duct Stones, World Journal of Surgery 1998;
22 : 1114 - 1118.

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