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Holzheimer RG, Mannick JA, editors. Surgical Treatment: Evidence-Based and Problem-Oriented. Munich: Zuckschwerdt; 2001.

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Surgical Treatment: Evidence-Based and Problem-Oriented.

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Acute acalculous cholecystitis

, M.D.

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Acute acalculous cholecystitis (AAC) may develop without gallstones in critically ill or injured patients, and appears to be increasing in incidence. In addition to injured or postoperative patients, patients with diabetes, malignant tumors, vasculitis, congestive heart failure, and shock or cardiac arrest may develop AAC. Ischemia/reperfusion injury is a central pathogenic feature, but bile stasis, opioid therapy, positive-pressure ventilation, and total parenteral nutrition have all been implicated as co-factors. Ultrasound of the gallbladder is most accurate for the diagnosis of AAC in critically ill patients. The primary therapy for AAC has been cholecystectomy, but percutaneous cholecystostomy is gaining acceptance as an alternative. Percutaneous drainage controls AAC in about 85% of patients, and appears to be equivalent to open procedures (~30% mortality). Unfortunately, this literature is essentially devoid of Class I data.


Acute acalculous cholecystitis (AAC) is especially dangerous during a serious illness or following major surgery (1). The incidence of AAC appears to be increasing (2); it is likely that increased awareness and improved imaging studies are identifying more cases (3). The mortality rate remains about 30% because the diagnosis remains challenging, the affected patients are critically ill, and because the disease itself can progress rapidly because of a high incidence of gangrene (> 50%) and perforation (> 10%).

Patterns of clinical illness

Reports of acute cholecystitis complicating surgery, multiple trauma, or burns are widespread. More than 80% of patients who develop AAC following non-trauma-related surgical procedures are men (4). The incidence of AAC following abdominal aortic reconstruction is about 1%, with a predilection for ruptured aneurysm cases. The incidence of acute cholecystitis was 0.12% (42% AAC) in collected reports encompassing 31,710 patients, with an overall mortality rate of 45% (4). Acute acalculous cholecystitis also has a predilection to occur in males following trauma and burns (5).

The development of AAC is not limited to surgical or injured patients, or even to the intensive care unit. Diabetes, abdominal vasculitis, congestive heart failure, cholesterol embolization, and resuscitation from shock or cardiac arrest have been associated with AAC (4). Patients with cancer are at risk from metastasis to the porta hepatis, therapy with interleukin-2 and lymphokine-activated killer cells for metastatic disease, or percutaneous transhepatic decompression of extrahepatic biliary obstruction. Acalculous cholecystitis may also develop from secondary infection of the gallbladder, including Candida infections, Salmonella infections, cholera, and tuberculosis (4).


Gallbladder ischemia/reperfusion injury

Gallbladder ischemia/reperfusion injury is a critical factor in the pathogenesis of AAC. Bacterial invasion of ischemic tissue is believed to be a secondary phenomenon; an increasing duration of ischemia increases mucosal phospholipase A2 and superoxide dismutase activities, and increases mucosal lipid peroxide content. Longer periods of reperfusion produce further increases in mediator activity. The humoral response to gram-negative bacteremia or splanchnic ischemia and mediator release may be of primary importance. Lipopolysaccharide induces a marked host response, including the activation of the coagulation cascades and generation of platelet-activating factor, both of which have been implicated in animal studies of pathogenesis (7, 8). Numerous observations of clinical low-flow states support this hypothesis (4), as does the pathologic observation of high rates of gallbladder necrosis and perforation. Gallbladder specimen arteriography reveals marked differences between acute calculous and AAC in humans (9). Whereas gallstone-related disease is associated with arterial dilatation and extensive venous filling, AAC is associated with multiple arterial occlusions and minimal to-absent venous filling.

Bile Stasis

Volume depletion may lead to concentration and stasis of bile, which can inspissate in the absence of gallbladder emptying. Opioid analgesics induce increased biliary pressure due to spasm of the sphincter of Oddi. Bile stasis may also be induced by positive-pressure mechanical ventilation with positive end-expiratory pressure (PEEP) (10). Bile stasis increases the concentration of lysophosphatidyl choline in bile, which promotes local injury of the gallbladder mucosa by disrupting normal water transport across gallbladder mucosa. Other compounds present in bile, such as beta-glucuronidase, have also been implicated in the pathogenesis of AAC (11). Long-term therapy with TPN causes bile stasis, and may be associated with an incidence of AAC of up to 30% (12). Serial gallbladder ultrasound studies in patients on long-term TPN (13) show that the incidence of gallbladder “sludge”, only 6% during the first week of TPN, increases to 50% at 4 weeks and 100% at 6 weeks. Unfortunately, periodic stimulation of gallbladder contraction with cholecystokinin does not prevent AAC in critically ill patients, nor does enteral hyperlimentation, which preserves gallbladder motility (14).


Most patients with AAC are critically ill, which makes the diagnosis challenging to make. Cholecystitis is but one of many potential causes of systemic inflammatory response syndrome or sepsis that may develop in such patients. Moreover, the differential diagnosis of jaundice in the critically ill patient is complex, and includes intrahepatic cholestasis from sepsis or drug toxicity and “fatty liver” induced by TPN, in addition to AAC. Rapid and accurate diagnosis is essential, as ischemia can progress rapidly to gangrene and perforation. A calculous cholecystitis is sufficiently common that the diagnosis should be considered in every critically ill or injured patient with a clinical picture of sepsis and no other obvious source. Physical examination and laboratory studies are too non-specific to be reliable (15).


Ultrasound of the gallbladder is the most accurate modality to diagnose AAC in the critically ill patient. Thickening of the gallbladder wall is the most reliable criterion. Deitch (16) reported specificity of 90% using 3.0 mm and 98.5% at a 3.5 mm wall thickness, whereas sensitivity was 100% at 3.0 mm but only 80% at 3.5 mm. Based on the above findings, Deitch and Engel recommended acceptance of gallbladder wall thickness of 3.5 mm or greater as definitive evidence of acute cholecystitis, whereas 3.0 mm is suggestive but not conclusive evidence (17). False-positives may occur when conditions including sludge, nonshadowing stones, cholesterolosis, hypoalbuminemia, or ascites mimic a thickened wall (17). Other helpful ultrasonographic findings for AAC include pericholecystic fluid, or the presence of intramural gas or a sonolucent intramural layer or “halo” that represents intramural edema.

Radionuclide studies

Hepatobiliary imaging has limited value in critically ill of injured patients (18) because of a high incidence of false-positive scans, which may be due to fasting, liver disease, or TPN. A sensitivity rate as low as 68% has been reported in studies of hepatobiliary imaging for AAC. Intravenous morphine (0.01 mg/kg) may increase the accuracy of cholescintigraphy in critically ill patients by enhanced gallbladder filling due to increased biliary secretory pressure (19), but the technique is not practiced widely.

Computed tomography

Computed tomography (CT) is as accurate as ultrasound in the diagnosis of AAC (20). Appropriate criteria for diagnosis of AAC by CT are similar to the criteria described for ultrasound. Only a single retrospective study has compared all three modalities (ultrasonography, hepatobiliary scanning, and CT) (21); ultrasonography and CT were comparably accurate and superior to hepatobiliary imaging. Comparable accuracy, low cost and bedside availability make ultrasonography the diagnostic modality of choice for AAC. Preference may be given to CT if other abdominal pathology is considered more likely.


Laparoscopy has been reported to be successful for both the diagnosis and therapy of AAC (22), although reports are limited to small series and there has been no randomized trial. Laparoscopy can be performed under local anesthesia and intravenous sedation at the bedside, and may be advisable to attempt if open surgical drainage is otherwise contemplated. Laparoscopy is possible in patients who have undergone recent abdominal surgery if “gasless” techniques are used. Diagnostic accuracy is high, and both laparoscopic cholecystostomy and cholecystectomy have been performed.


The mainstay of therapy for AAC has been cholecystectomy. Pericholecystic fluid collections may be drained if necessary, and other acute problems that may mimic acute cholecystitis (e.g., perforated ulcer, cholangitis, pancreatitis) may be identified and managed if AAC is not present. Cholecystostomy can be a lifesaving alternative in the patient considered too unstable to undergo general anesthesia (23), but provides inadequate drainage of the common bile duct for concomitant cholangitis. Successful cholecystostomy is followed by cholangiography after the patient has recovered. If gallstones are absent (true AAC), cholecystectomy is usually not indicated and the catheter can be removed (24). Percutaneous cholecystostomy is gaining acceptance as an alternative to open procedures (2426). although randomized trials have not been published, class II and III of evidence lends credence to the procedure. The advantages of percutaneous cholecystostomy are bedside applicability, local anesthesia, and avoidance of an open procedure. The technique controls the acute syndrome in about 85% of patients. If percutaneous cholecystostomy does not result in improvement within 24 hours, an open procedure should be performed expediently. Reported causes of failure include gangrenous cholecystitis, catheter dislodgment, bile leakage causing peritonitis, and an erroneous diagnosis. Perforated ulcer, pancreatic abscess, pneumonia, and pericarditis have been discovered in the aftermath of percutaneous cholecystostomy when patients failed to improve (27). In the largest reported series 262), major complications were reported in 11 patients (8.7%), including dislodgment of the catheter, acute respiratory distress, bile peritonitis, hemorrhage, cardiac arrhythmia, and hypotension due to procedure-related bacteremia. Minor complications occurred in an additional five patients (3.9%). Throughout the literature, the 30-day mortality of percutaneous and open cholecystostomy appear to be similar.

Empiric percutaneous cholecystostomy has been advocated on patients who have sepsis but no demonstrable source (25). Fifteen of 24 patients required vasopressor therapy for septic shock at the time of the procedure. 14 patients (58%) improved as a result of the cholecystostomy. Pneumonia was subsequently diagnosed in three of the ten non-responders, but an infection was never found in the other seven patients.

Antibiotic therapy does not substitute for removal or drainage of AAC, but remains an important adjunct. The most common bacteria isolated from bile in acute cholecystitis are E. coli, Klebsiella, and Enterococcus faecalis, thus antibiotic therapy should be directed against these organisms. However, critical illness and prior antibiotic therapy alter host flora, and resistant or opportunistic pathogens may be encountered. Pseudomonas, staphylococci (including methicillin-resistant strains), Enterobacter and related species, anaerobic organisms (Clostridium, Bacteroides), and fungi may be recovered. Anaerobes are particularly likely to be isolated from bile in diabetes, in patients older than 70 years, and from patients whose biliary tracts have been instrumented previously.


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Copyright © 2001, W. Zuckschwerdt Verlag GmbH.
Bookshelf ID: NBK6881


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