Description

Acalculous cholecystitis, also known as acute alithiasic cholecystitis (AAC), is an acute necroinflammatory disease of the gallbladder occurring in the absence of cholelithiasis (1) with a multifactorial pathogenesis (2).

Epidemiology

• AAC accounts 10% of all cases of acute cholecystitis (1,2,3,4). AAC most frequently presents in critically ill patients (status—postsurgical intervention; extensive burn injuries) and the elderly.
• Diabetes mellitus, atherosclerosis, and connective tissue disease are also linked with AAC (2,3).
• Complications occur in about 40% of cases (gangrene, perforation, peritonitis, sepsis, shock).
• Mortality depends on underlying comorbidities reaching as high as 90% in critically ill patients (1).

Etiology and Pathophysiology

The pathogenesis of AAC is multifactorial. Bile stasis and ischemia both likely contribute. Bile stasis can be caused by fasting, obstruction, procedural irritation, and/or ileus. This can lead to bile inspissation that is directly toxic to the gallbladder epithelium. Ischemia may occur as a result of systemic inflammation, iatrogenesis, or shock. Trauma, total parenteral nutrition, viral (hepatotropic virus) or bacterial (mostly gram-negative or anaerobic) infections are also associated with AAC (1,2).

Risk Factors

• Critically ill hospitalized patients
• Recent surgery
• Elderly
• Connective tissue and autoimmune disease
• Extensive burns
• Shock and ischemia
• Trauma
• Parenteral nutrition

History

• Right upper quadrant pain, radiating to right shoulder and/or back
• Fever
• Nausea and vomiting

Physical Exam

• A palpable right upper quadrant mass may be present.
• Jaundice (20%)
• Murphy sign (pain during inspiration while palpating the right upper quadrant)
• In calculous cholecystitis, jaundice and an abdominal mass are less common (2).

Differential Diagnosis

• Chronic cholecystitis
• Acute calculous cholecystitis
• Peptic ulcer disease (with or without perforation)
• Right-sided pneumonia
• Acute pancreatitis
• Hepatic or subphrenic abscess
• Right-sided pyelonephritis
• Sepsis due to other causes (e.g., pneumonia, urinary tract infection)
• Patients suspected of having acalculous cholecystitis should also have laboratory testing for pancreatitis (i.e., serum amylase and lipase), a urinalysis to look for evidence of urosepsis, and a chest radiograph or computed tomography (CT) scan to rule out pneumonia. Usually, upper endoscopy isn’t performed to look for evidence of peptic ulcer disease unless there is evidence of gastrointestinal bleeding. Upper endoscopy should not be performed in patients suspected of having a perforated peptic ulcer (2).

Diagnostic Tests & Interpretation

Initial Tests (lab, imaging)

• Laboratory tests in patients with acalculous cholecystitis are nonspecific. Leukocytosis with a left shift is seen in 70–85% of patients. Abnormal liver tests are more common in acalculous cholecystitis than in calculous cholecystitis. These include hyperbilirubinemia and a mild increase in serum alkaline phosphatase and serum aminotransferases.
• Obtain blood cultures in all patients with suspected acalculous cholecystitis. If a pathogen is detected, it can be used to guide antibiotic therapy.
• Confirmation of AAC typically requires imaging, most commonly abdominal ultrasound. If the diagnosis remains unclear, cholescintigraphy can be obtained.
  • Cholescintigraphy (HIDA scanning) can be performed in stable patients. Failure to opacify the gallbladder is the most sensitive finding. Leakage into the pericholecystic space suggests perforation. Cholescintigraphy is not recommended in critically ill patients in whom a delay in therapy can be potentially fatal. The specificity of cholescintigraphy for acalculous cholecystitis is high. The following may lead to false-positive results:
    • Severe liver disease
    • Fasting or administration of total parenteral nutrition
    • Biliary sphincterotomy
    • Hyperbilirubinemia
• Ultrasonography: Wall thickening is the most reliable finding. Nuclear cholescintigraphy may be useful in cases in which the diagnosis remains uncertain after ultrasonography (2).
• CT scanning: may be particularly useful if disorders not readily seen with ultrasonography are also being considered (e.g., pneumonia). The accuracy of CT scanning is similar to ultrasonography. Findings suggestive of acalculous cholecystitis include:
  • Absence of gallstones or sludge
  • Gallbladder wall thickening
  • Subserosal halo sign
  • Pericholecystic infiltration of fat
  • Pericholecystic fluid
  • Mucosal sloughing
  • Intramural gas
  • Gallbladder distention
• Magnetic resonance cholangiopancreatography (MRCP) is superior to ultrasound for detecting stones in the cystic duct (sensitivity 100% vs. 14%) but is less sensitive than ultrasound for detecting gallbladder wall thickening (sensitivity 69% vs. 96%) (2).

Medication

• Early treatment is essential for patients with AAC due to the risk of gangrene and perforation (4).
• Early empiric antibiotic therapy should be initiated to cover gram-negative bacteria and anaerobes. The bacteria most commonly isolated from the gallbladder and bile duct include Escherichia coli (41%), Enterococcus spp. (12%), Klebsiella spp. (11%), and Enterobacter spp. (9%) (4).
• Patients recently on broad-spectrum antibiotics can be treated with a 3rd-generation cephalosporin plus metronidazole or imipenem/cilastatin plus or minus antifungal therapy (usually fluconazole).
• Add vancomycin if nosocomial infection with MRSA is known or suspected to be likely.
• For antibiotic-naive patients, empiric therapy with piperacillin/tazobactam, ampicillin/sulbactam, or imipenem is appropriate.
• Avoid aminoglycosides in the elderly or those with renal insufficiency if possible. 1 or 2 doses can be given empirically pending microbiologic results in patients without serious risk (2).

Additional Therapies

• Gallbladder drainage is necessary to remove purulent material. Drainage may be accomplished percutaneously or endoscopically.
• Percutaneous cholecystostomy (PCo) has success rates ranging from 56% to 100%.
• Endoscopic drainage of the gallbladder may be performed in patients where PCo is contraindicated or anatomically unfeasible. The most common approach is transpapillary (when technically feasible) which resolves the condition in 80–90% of patients (4).

Surgery/Other Procedures

The definitive therapy for acalculous cholecystitis is cholecystectomy with drainage of any associated abscess (cholecystostomy is often preferred because it is less invasive). Both open and laparoscopic cholecystectomy have been used. Timely cholecystectomy is associated with survival rates of >90% in patients with acute cholecystitis related to trauma. Lower survival rates are associated with acalculous cholecystitis in the setting of a critical illness (2).

Prognosis

• Acalculous cholecystitis is associated with several complications and a high mortality rate.
• If treatment is delayed, mortality rates may be as high as 75%.
• Gallbladder gangrene develops in approximately 50% of patients with acalculous cholecystitis and can result in gallbladder perforation.
• Emphysematous cholecystitis puts patients at risk for perforation. Overall, perforation occurs in approximately 10% of patients with acalculous cholecystitis.
• Mortality in patients with acalculous cholecystitis depends on comorbidities and the speed of diagnosis.
• Gallbladder necrosis, gangrene, and perforation are frequently present at the time of diagnosis, particularly in the critically ill and are associated with poor outcomes.
• Mortality rates range from 10% to 90%, depending on the severity of underlying illness.

ICD-10

• K81 Cholecystitis
• K81.0 Acute cholecystitis
• K81.1 Chronic cholecystitis
• K81.2 Acute cholecystitis with chronic cholecystitis
• K81.9 Cholecystitis

ICD-9

• 575.1 Other cholecystitis
• 575.10 Cholecystitis
• 575.11 Chronic cholecystitis
• 575.12 Acute and chronic cholecystitis

SNOMED

• 19968009 Cholecystitis without calculus
• 34346002 Acute cholecystitis without calculus
• 53928001 Chronic cholecystitis without calculus