CHOLANGITIS (Part Two)

Acute Cholangitis (Cont.)

RADIOGRAPHIC DIAGNOSTIC MEASURES

Plain radiographs of the abdomen are usually not helpful unless the patient has radiopaque gallstones, which are present in only 20% of cases.

• Nonspecific findings, such as ileus, may be noted.
• The plain film can sometimes reveal the presence of pneumobilia which suggests a bilioenteric communication from prior sphincterotomy, surgical bypass, or spontaneous fistula due to stone passage.

Ultrasound is the first screening test that should be obtained,

• and the finding of gallstones and common bile duct dilatation in a patient with jaundice suggests bile duct obstruction resulting from a gallstone.
  
• However, a normal, nondilated biliary ductal system is found in some patients with acute cholangitis early in the disease.
  
• Intrahepatic biliary dilatation and air within the biliary tree, in the absence of biliary-enteric anastomosis, are indicators of biliary infection and obstruction.
  
• The sonographer can also provide information regarding the cause of obstruction, because choledochal cysts and malignant lesions have characteristic appearances on ultrasound.

The technical limitation to abdominal ultrasound examination is

• an obese patient or interference from adjacent bowel gas, which makes examination of the distal bile duct more difficult.
  
• It is also not a very sensitive test for the detection of small common duct stones.

Technetium radionuclide scans employing agents excreted into bile are useful diagnostic measures.

• The absence of flow of contrast material into the bowel is indicative of, although not specific for, bile duct obstruction.
  
• However, opioid agents can cause spasm of the sphincter of Oddi and may lead to false-positive results.
• The presence of infection in the biliary tract also interferes with secretion of the agents into bile.
  
• Patients with cholangitis clear radioisotope quickly from the vascular system, and the liver visualizes within 10 to 15 minutes, but agents do not enter the biliary tract for up to 24 hours.

Computed tomography (CT) of the abdomen can provide useful information, especially in patients with malignant obstruction of the biliary tree.

• Specifically, metastatic disease and the involvement of adjacent structures, especially the portal vein, can be addressed with high-speed CT.
  
• Alternatively, CT portography can be used for extreme resolution of the porta and liver.
  
• Finally, CT is an excellent technique for excluding other upper abdominal diseases that mimic acute cholangitis.

Adjuncts to diagnosis and treatment of acute cholangitis include ERCP and PTC. These procedures provide useful information regarding biliary anatomy and can be therapeutic.

ERCP is performed successfully in 95 to 98% of patients, although success may depend on the operator.

• The one confounding factor is that the patient may be required to lie in the prone position, and this may be difficult if the patient is unstable.
  
• Definition of the lower biliary tract is especially easy with ERCP.
  
• However, higher lesions such as Klatskin's tumors are more difficult to visualize. PTC may be the better test in this situation.
  
• Complication rates from ERCP are reported at 3%, even in the acute setting, and include -
  

1. perforation of the duodenum,
   
2. hemorrhage,
   
3. bile leak,
4. hypotension (possible secondary to sepsis from increased intraductal pressure),
   
5. hemobilia, and
   
6. pancreatitis.
   

• Diagnostic maneuvers including brushings of the duct to make the diagnosis of cancer and sampling of bile to obtain cultures may be performed with ERCP.

PTC is a useful test in proximal biliary lesions or after failed ERCP.

• This test can be done easily in experienced hands even in the absence of biliary dilatation and should have a success rate of at least 90% in this circumstance.
  
• Again, as with ERCP, diagnostic studies can be obtained including brushings and bile cultures.
  
• The reported complication rate from PTC is higher than that from ERCP, which was 7% in one study.
  
• Again, the most common complications are
  

1. bile leak from the tube entrance site into the liver,
   
2. hemobilia,
   
3. hemorrhage,
   
4. sepsis, and
   
5. pneumothorax or hydrothorax, because radiologists may have to go through the chest.

Magnetic resonance cholangiography.

• A satisfactory study requires the patient to lie still for a relatively long time, and the patient must be able to cooperate with breath-holding.
  
• To this extent, it may not be the optimal study for the critically ill patient.
  
• Moreover, therapeutic intervention is not possible in this setting.
  
• We find magnetic resonance cholangiography to be helpful in patients who respond to medical therapy for acute cholangitis because it delineates pancreatic or biliary tumors from stones in patients with a dilated bile or pancreatic duct.

MEDICAL PREPARATION

• Acute cholangitis is a life-threatening medical problem that quickly progresses to sepsis and death.
  
• Patients with persistent fever and chills require hospitalization and prompt intervention because 85% of patients with uncomplicated disease respond to medical support and antibiotics alone.
  
• Regardless, all patients with acute cholangitis should be prepared for invasive radiologic, endoscopic, or surgical procedures.
  
• If not required urgently, invasive procedures will be required electively to diagnose and treat the cause of the episode of cholangitis.
  
• Complications of acute cholangitis, such as acute renal failure, often manifest themselves after an invasive test or procedure.
  
• The stress of the procedure, the use of contrast material, and complications of the procedure such as hemorrhage or hypotension are poorly tolerated by patients with obstructive jaundice.
  
• Such complications may be avoided if the patient is adequately hydrated and if clotting abnormalities are corrected with vitamin K or fresh frozen plasma before any invasive procedure is undertaken.
  
• Antibiotics should begin empirically once blood cultures are drawn.
  
• Vital signs should be monitored closely, and patients who are hemodynamically unstable or who exhibit confusion should be placed in an intensive care unit.

Antibiotics chosen for initial treatment should be broad-spectrum agents that act against the most common organisms isolated from the biliary tract.

• They need to have activity against a wide spectrum of gram-negative organisms, but they must also cover Enterococcus.
  
• The focus of antibiotic treatment may be narrowed later, in response to sensitivities of organisms isolated from blood or bile.
  
• The time-honored combination of ampicillin and aminoglycoside suffices, but it is potentially nephrotoxic.
  
• Two other classes of antibiotics are particularly useful in treatment of acute cholangitis: cephalosporins and ureidopenicillins.
  
• First- and second-generation cephalosporins do not adequately cover gram-negative organisms and are usually reserved for prophylaxis during elective procedures of the biliary tract.
  
• Third-generation cephalosporins give excellent gram-negative coverage, but they have less activity against Staphylococcus and Enterococcus species.
  
• Ampicillin may be added to provide coverage for the latter organism, which is present in at least 34% of patients with acute cholangitis.
  
• If strict conditions are used, anaerobic organisms are frequently cultured from the bile of patients with acute cholangitis.
  
• Metronidazole is frequently added to the regimen.
  
• One prospective, randomized controlled study by Li's group found that ciprofloxacin was equivalent to triple-drug therapy with ceftazidime, ampicillin, and metronidazole.
  
• Piperacillin shows promise as a single agent for patients with cholangitis who are not allergic to penicillin because it is as efficacious as ampicillin and tobramycin, but it is less nephrotoxic.
  
• In biliary obstruction caused by Ascaris or Clonorchis, treatment with praziquantel and pyrantel pamoate, respectively, is recommended.

Patients who respond to medical therapy require prompt, although elective, testing to determine the cause of the episode of acute cholangitis.

• If the underlying problem is not addressed, recurrent and possibly more serious episodes can be expected.
  
• The elective management of common bile duct stones, tumors of the pancreas, bile duct, and ampulla of Vater, and benign strictures of the bile duct are to be considered.
  
• In general, the goals of these procedures are to restore free flow of bile into the intestinal tract and to decrease pressure in the biliary tree.
  
• These goals may be accomplished by removal of obstructing disease, bypass of the obstructing lesions, or placement of intraluminal stents using radiologic, endoscopic or surgical techniques.
  
• If internal drainage is not possible, drainage of bile externally with a T-tube or a percutaneous biliary catheter may palliate the patient.

PATIENT SELECTION

• Patients who present with septic shock or do not respond to medical therapy represent a true medical emergency.
  
• Urgent decompression of the biliary tract is required.
  
• The patient should undergo rapid fluid resuscitation and correction of clotting abnormalities.
  
• Antibiotics should be administered.
  
• The procedure to decompress the biliary tract should be performed as soon as possible.
  
• However, operative therapy carries a high risk of complications and a 21 to 40% risk of death in critically ill patients.
  
• Currently, two effective alternatives to surgery, percutaneous transhepatic drainage (PTD) and endoscopic drainage of the bile duct, are available and are associated with less morbidity.

OPERATIVE APPROACHES

Although effective in experienced hands, PTD and endoscopic drainage require special expertise. Trained interventional radiologists and gastroenterologists are not available in all hospitals.

Emergency surgical decompression of the biliary tract is currently used at locations where interventional radiologists and gastroenterologists are not available or is reserved for patients who do not respond to other therapies.

• The operation is performed by an open technique.
  
• A laparoscopic approach to the bile duct is not recommended because these patients are critically ill and unstable.
  
• They are not likely to tolerate pneumoperitoneum or long anesthetic times.
  
• A right upper quadrant subcostal or midline incision suffices.
  
• The gallbladder and bile duct are exposed, and a tense, distended bile duct is usually found that contains pus or turbid bile under pressure.
  
• A choledochotomy is made in the common bile duct.
  
• If the patient is medically unstable, the operation is limited to gentle irrigation of the duct to remove pus and thick bile, as well as placement of a T-tube.
  
• The gallbladder is left in situ for later treatment.
  
• The cause of cholangitis is not definitively addressed, and definitive treatment is delayed until the patient recovers.

Selected patients whose condition stabilizes after the bile duct is opened may have choledocholithotomy performed.

• Lau and co-workers performed emergency common bile duct exploration in patients with acute cholangitis in whom medical therapy had failed, and the mortality rate was only 4%.
  
• Choledochoscopy was safe in these patients and led to a significantly lower incidence of retained common bile duct stones.
  
• Selection of patients is crucial if morbidity and mortality are to be minimized.
  
• Outcome also correlates with the experience of the surgeon.
  
• In most studies, the decision to proceed with common duct exploration is made on the surgeon's judgment alone.

Several investigators analyzed their experience to determine which factors correlated with morbidity and mortality.

• Lai et al. reviewed results in 86 patients with acute cholangitis who underwent emergency ductal exploration after failed medical therapy.
  
• The overall mortality for the group was 20%, but 55% of patients in septic shock died; this result showed that definitive exploration of the common bile duct is not prudent if patients are hemodynamically unstable.

Five factors correlated with morbidity and mortality:

1. the presence of significant comorbid medical problems,
   
2. a serum pH less than 7.4,
   
3. a serum total bilirubin concentration greater than 5.3 mg/dl,
   
4. a platelet count less than 150,000/ml, and
   
5. a serum albumin level less that 3.0 mg/dl.
   

• When a patient exhibited 3 or more factors, the mortality rate was 99%, whereas it was only 7% if a patient had 2 or fewer factors.
  
• Therefore, patients whose condition stabilizes after the bile duct is opened and who do not have significant jaundice, preexisting medical comorbidities, or significant sequelae of their infection may undergo common bile duct exploration safely.

If the surgeon decides to perform common bile duct exploration, a catheter is placed into the distal and proximal ducts through the choledochotomy already performed.

• The biliary tract is irrigated with saline, to clear it of pus, stones, and sludge.
  
• The duct may then be explored with stone forceps or scoops, but blind exploration is more traumatic and less reliable than choledochoscopy.
  
• We prefer to examine the proximal and distal bile duct with a choledochoscope.
  
• A 6-mm scope is sufficient in a dilated bile duct, but smaller (3-mm) scopes designed for laparoscopic transcystic duct exploration can also be placed through the choledochotomy.
  
• Common duct stones are removed with a stone basket placed through the working channel of the scope.
  
• The surgeon must balance the risks and benefits of persisting with definitive therapy if removal of the obstructing stone is difficult.
  
• The exploration can be aborted at any time and a T-tube can be placed if the surgeon decides that this is in the patient's best interest.
  
• If the exploration is completed successfully, a T-tube is placed, and a closed-suction drain is positioned in the vicinity of the choledochotomy.
  
• Primary closure of the bile duct without T-tube drainage is not prudent in these high-risk patients.

ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY

Leese et al. demonstrated a low mortality rate of 3.8% in patients with acute cholangitis who underwent early endoscopic sphincterotomy (ES). This rate was substantially lower than the mortality of 16 to 59% for patients undergoing surgical management.

• Hence, it is clearly preferable to attempt to manage these patients with endoscopy rather than surgically if at all possible.

The question of the type of decompression to perform has been studied extensively and involves the choice of nasobiliary stenting versus ES and internal stenting.

• Most complications from ERCP are related to the ES.
  
• In fact, Sugiyama and Atomi found an 11% complication rate in an ES group as opposed to a 2% complication rate when a nasobiliary catheter was placed.
  
• Lai's group agreed with this finding and advocated quick placement of a nasobiliary stent without ES in patients with acute cholangitis.

ERCP can provide diagnosis as well as therapy for patients with acute cholangitis during the same procedure.

• For example, cancer of the biliary tree or malignant pancreatic lesions can be documented and stented.
  
• In addition, choledochal cysts can be visualized, and type III choledochoceles can be treated with wide sphincterotomy.
  
• Gallstones, foreign objects, and parasites can be retrieved endoscopically.

Failure to cannulate the bile duct depends on the expertise of the endoscopist and should occur in fewer than 5% of cases.

• In this situation, the patient should be referred for PTC.
  
• Patients with hilar cholangiocarcinomas or extremely proximal obstruction are at especially high risk of complications from ERCP stent placement and should receive PTC preferentially.

After effective drainage of the duct in patients with acute cholangitis, definitive treatment can be undertaken.

• However, in cases of unresectable disease, effective palliation can be performed by stent placement.
  
• Stones and other foreign objects can be removed endoscopically.
  
• Papillary stenosis, which is especially prevalent in patients with HIV infection, can be treated with ES.

PERCUTANEOUS TRANSHEPATIC DRAINAGE

In fact effective decompression was achieved in all cases even when the ducts were not dilated.

• The authors did not advocate obtaining a cholangiogram in the first setting, because the excessive manipulation of the contaminated bile could lead to sepsis.
  
• All patients had resolution of their sepsis within 24 hours of PTD; 3 of 42 patients (7%) had complications. Two patients died within 8 hours of admission (5% mortality rate).
  

The routine use of PTD in patients who have obstructive jaundice has been the topic of debate.

• Pitt et al. noted no benefit and an increased cost of biliary drainage before operative management.
  
• However, experimental data suggest that the presence of jaundice increases the risk of subsequent renal failure.
  
• In most patients with hilar tumors, we believe that preoperative PTD of both lobes of the liver is beneficial and can guide dissection at the time of surgery.
  
• The presence of cholangitis requires preoperative drainage before definitive resection is undertaken.

After PTD, patients can be palliated with stents if they are deemed to have unresectable tumors.

• Patients with strictures that may be related to previous operations, primary sclerosing cholangitis, parasitic infections, or HIV cholangiopathy can often be managed for long periods with stent placement.
  
• and foreign objects can be retrieved by using various baskets.