Calculous and acalculous cholecystitis

Risk factors and pathophysiology

In the general population, acute cholecystitis is associated with the presence of gallstones, which develop as a result of decreased solubility of cholesterol and bile salts in bile. Risk factors for gallstones include age, female sex, recent pregnancy, positive family history for gallstones, and hemolysis. Patients with gallstones may develop acute cholecystitis at any time. Rarely, acute calculous cholecystitis can occur during hospitalization for other reasons.

Acalculous cholecystitis can occur spontaneously under certain circumstances. In outpatients, risk factors for acalculous cholecystitis include diabetes mellitus, vasculitis, older age, and male sex.

Acute cholecystitis has been described as a complication of a variety of surgical procedures, ^, burns, sepsis, cardiovascular diseases, and malignancy. Trauma patients are also at increased risk, perhaps because of the development of sludge over time, which may also increase the risk for pancreatitis. ^,

There is an association between total parenteral nutrition and biliary stasis. Though lack of enteral feeding may play a significant role, parenteral nutrition can directly decrease bile production, worsening biliary stasis. Biliary sludge can be found in almost all patients on long-term parenteral nutrition. Many go on to form gallstones. The fatty acid derivatives of lipid emulsions, large amounts of dextrose, and specific deficiencies, such as choline and taurine, may also play a role.

Theories regarding the pathogenesis of acalculous cholecystitis in critically ill and postoperative patients have evolved over the years. Presumptive causes have included gastrointestinal hypomotility, biliary stasis, and lack of enteral feeding in the postoperative period, leading to increased concentrations of bile salts and cholesterol in bile. The rarely observed acute onset of cholecystitis with refeeding suggests impaction of stones or viscous bile in the cystic duct with gallbladder contractions.

Gallbladder mucosal necrosis, arterial thrombosis, gangrene, and perforation suggest that hypoperfusion may be another critical mechanism for acalculous cholecystitis. Histopathologic studies confirm microvascular changes and ischemic cholecystitis histologically. Hypoperfusion, particularly of the splanchnic circulation, is common in critically ill patients because of hemorrhage, dehydration, heart failure, and sepsis. Vasopressors can exacerbate the situation. Mechanical ventilation with positive end-expiratory pressure can increase hepatic venous pressure and thereby decrease portal perfusion.

In addition to hypoperfusion, increased intraluminal pressure from biliary stasis secondary to fasting and narcotics may be a critical factor. The combination of hypoperfusion and increased intraluminal pressure leads to a decrease in gallbladder perfusion pressure, wall ischemia, bacterial invasion, and cholecystitis.

Incidence

The incidence of acute cholecystitis in the ICU is difficult to determine, given the great diversity in ICU patient populations and illness severity. Visceral hypoperfusion related to left ventricular dysfunction has been implicated as an etiologic factor, particularly in the cardiac surgery population. Early predictors of acute cholecystitis in these patients include arterial occlusive disease, low preoperative oxygen delivery, longer cardiopulmonary bypass times, need for surgical reexploration, cardiac arrhythmias, mechanical ventilation for ≥3 days, bacteremia, and nosocomial infections. The common threads among these factors include decreased tissue perfusion and oxygenation, significant surgical trauma with the expected inflammatory response, and perhaps bacterial translocation from the gut lumen. Because of high risk, some have suggested ultrasound screening of patients who have had complicated courses after cardiovascular surgical procedures.

In the general population of postoperative patients, acute cholecystitis appears to occur with or without gallstones. Among trauma patients, about 90% of the acute cholecystitis cases are acalculous. Because the incidence of the disease is low but the many risk factors for the disease are common, it is difficult to identify specific groups of ICU patients who might benefit from selective screening for acute cholecystitis.

Clinical presentation

The signs and symptoms of acute cholecystitis do not generally differ between calculous and acalculous disease. Typically, patients with acute cholecystitis present with right upper quadrant or epigastric pain, often after ingesting a fatty meal. The pain may radiate to the back. Anorexia, nausea, and vomiting are common findings, as are fever and chills. If the patient is receiving enteral nutrition, the symptoms may be related to meals or tube feedings.

On examination, the most consistent finding is fever. Focal tenderness in the right upper quadrant or epigastrium is typically found, often with evidence of peritoneal irritation. Rarely, the gallbladder is palpable. There may be abdominal distention and loss of bowel sounds. In critically ill patients, symptoms and physical examination findings are frequently difficult to assess or absent because of alterations in the patient’s mental status and concurrent disease.

The most consistent laboratory finding is a leukocytosis. Serum levels of liver enzymes and bilirubin are usually normal unless choledocholithiasis, Mirizzi syndrome (external compression of the common hepatic duct by a stone impacted in the cystic duct), or liver dysfunction from sepsis is present. Thus jaundice is rare. Clinical findings and laboratory studies are not very sensitive or specific for cholecystitis, even in the general population, and are less so in critically ill patients.

Given that the underlying pathophysiology of cholecystitis in the ICU often involves gallbladder wall ischemia, there is significant risk for rapid progression to gangrene and perforation. Consequently, even though other causes of sepsis in the ICU are more common, one needs to have a low threshold for considering cholecystitis in the differential diagnosis of patients who may have intraabdominal sepsis. Imaging of the gallbladder should be the next step.

Imaging studies

Ultrasonography is usually the first test of choice for acute cholecystitis in the general population and in critically ill patients. In the ICU, the presence or absence of gallstones does not help with the diagnosis. The most useful ultrasonographic findings are thickening of the gallbladder wall and pericholecystic fluid ( Fig. 88.1 ). These findings correlate well with operative findings. False-positive findings may occur with sludge, nonshadowing stones, cholesterolosis, ascites, hypoalbuminemia, and portal hypertension. Other ultrasonographic findings indicative of acute cholecystitis include the following: the “double wall sign,” representing edema of the gallbladder wall; the “halo sign,” representing sloughed gallbladder mucosa; intramural gas; distention of the gallbladder; and the “sonographic Murphy sign,” demonstrating point tenderness by pressing the ultrasound probe directly over the gallbladder. The sensitivity of ultrasound for detecting acalculous cholecystitis is 81%–92%. The specificity is 60%–96%, ^, but these results are operator dependent.

One problem in the ICU is that the typical ultrasonographic findings of cholecystitis can be seen in ICU patients without the condition. For example, Boland and colleagues performed ultrasound examinations of the gallbladder twice a week in a variety of ICU patients. Half of the patients without calculi developed at least one ultrasonographic finding of acute cholecystitis. Patients with several findings should undergo more aggressive diagnostic evaluation and, perhaps, therapeutic interventions. In equivocal cases, serial examinations may demonstrate increasing wall thickness, which should increase the suspicion for cholecystitis.

Computed tomography (CT) of the abdomen can be used to make the diagnosis of acute cholecystitis. The criteria for a positive study include wall thickness >4 mm, pericholecystic fluid, intramural gas, sloughed mucosa, or subserosal edema without ascites ( Fig. 88.2 ). If intravenous contrast is administered, enhancement of the gallbladder wall may be seen. Although CT may not be as sensitive as ultrasound for determining the presence of gallstones or acute cholecystitis, it can help to detect or rule out other causes of intraabdominal sepsis. A great disadvantage of CT for critically ill patients, however, is the need to transport the patient to the scanner. In critically ill patients with suspected cholecystitis, ultrasound remains the first test of choice. Frequently, however, additional studies are necessary.

Scintigraphy of the gallbladder has been used when acute cholecystitis is suspected but findings from other tests such as ultrasound or CT are inconclusive or contradictory. Gallbladder scintigraphy is performed by administering technetium-labeled iminodiacetic acid (IDA). Cholecystitis is diagnosed if the radioactive tracer is visualized in the small bowel without visualization of the gallbladder within 4 hours, suggesting occlusion of the cystic duct ( Fig. 88.3 ). Delayed visualization of the gallbladder may represent chronic cholecystitis. The rate of false-positive tests is significant in fasting patients, particularly those receiving parenteral nutrition, as the gallbladder may already be maximally filled. The use of intravenous morphine to increase tone in the sphincter of Oddi and thereby increase pressure within the biliary system can decrease the risk of a false-positive test. In patients with severe liver disease, there may be inadequate uptake and excretion of the tracer to provide visualization of the biliary tree. Also, if a patient has had a biliary sphincterotomy, the tracer may pass too quickly through the biliary tree. Overall, the sensitivity of scintigraphy is 91%–97% and the specificity is 38%–99%. Scintigraphy is a useful complement to ultrasonography for early decision making regarding intervention.