Acalculous Cholecystitis

Acalculous Cholecystitis (AAC)

Acalculous cholecystitis (AAC) is acute inflammation of the gallbladder in the absence of gallstones.
It primarily occurs in critically ill or postoperative patients, often those with sepsis, trauma, burns, or prolonged fasting/parenteral nutrition.

AAC represents about 5–10% of all cases of acute cholecystitis, but it carries a much higher morbidity and mortality (30–50%) due to diagnostic delay and underlying systemic illness.

Pathophysiology

AAC is fundamentally an ischemic and inflammatory disease of the gallbladder wall.

1. Ischemia–Reperfusion Injury

• The cystic artery is an end-artery without significant collateral supply.
• Systemic hypotension, vasoconstriction, shock, or vasopressor therapy → ischemia of gallbladder wall → mucosal injury.
• Reperfusion leads to reactive oxygen species and cytokine-mediated inflammation.

2. Bile Stasis and Concentration

• Prolonged fasting, total parenteral nutrition (TPN), and mechanical ventilation with high PEEP cause decreased gallbladder contraction and bile stasis.
• Stagnant bile becomes viscous and concentrated, damaging mucosa and promoting infection.

3. Secondary Infection(due to bile stasis)

• Bacterial translocation from the gut or ascending infection (most commonly E. coli, Klebsiella, Enterococcus) superimposes on the ischemic gallbladder wall.
• Empyema or gangrene may develop.

4. Systemic Inflammation

• AAC often occurs in the setting of sepsis, burns, trauma, or multi-organ failure, where microvascular perfusion is already compromised.

Risk Factors

Clinical Features

AAC is often insidious and difficult to recognize in the ICU, since patients are sedated, intubated, or non-communicative.

Acute acalculous cholecystitis is frequently diagnosed among patients with an admission diagnosis of sepsis and should be considered for any ICU patient with right upper quadrant pain, fevers, and worsening leukocytosis.(irwin rippe)

Symptoms (if awake)

• Right upper quadrant (RUQ) or epigastric pain
• Nausea, vomiting
• Fever

Signs (in ICU)

• Fever of unknown origin
• Leukocytosis
• Unexplained sepsis or hemodynamic instability
• Abnormal liver function tests (LFTs)
• Occasionally, Murphy’s sign (RUQ tenderness with inspiration) if cooperative

Complications at presentation:

• Gangrene (up to 50%)
• Perforation with peritonitis
• Empyema
• Abscess formation

Differential Diagnosis

• Biliary colic—Calculous cholecystitis—Choledocholithiasis
• Cholangitis
• Pancreatitis—Hepatitis
• Gastritis—Peptic Ulcer Disease
• Appenditis 
• Mesenteric ischemia

Investigations

1. Laboratory Findings

• Leukocytosis
• Mild to moderate elevations in AST/ALT, alkaline phosphatase, bilirubin
• Occasionally elevated amylase/lipase
• Sepsis biomarkers (CRP, procalcitonin) elevated but nonspecific

2. Imaging

Ultrasound (first-line)

• Gallbladder wall thickening >3 mm
• Pericholecystic fluid
• Sonographic Murphy’s sign
• Absence of gallstones
• May show sludge or debris inside gallbladder

Sensitivity: ~80%, Specificity: ~90%, but operator-dependent in ICU.

CT Abdomen

• Helpful if ultrasound is inconclusive.
• Findings:
• Wall thickening
• Pericholecystic fluid or edema
• Gas in gallbladder wall (emphysematous cholecystitis)
• Lack of gallstones

HIDA (Hepatobiliary Iminodiacetic Acid) Scan

• Non-visualization of the gallbladder after tracer injection = diagnostic.
• However, often impractical in ICU due to patient instability and false positives with fasting or TPN.

Diagnosis

Clinical suspicion + Imaging findings in a predisposed critically ill patient.

Tokyo Guidelines (TG18) Criteria for Acute Cholecystitis:

Diagnosis requires:

1. Local signs of inflammation (Murphy’s sign, RUQ tenderness/mass)
2. Systemic signs of inflammation (fever, ↑WBC, ↑CRP)
3. Imaging findings consistent with acute cholecystitis

In AAC, criterion (1) may be absent — so diagnosis often rests on imaging + systemic findings.

Management

1. Supportive and Medical Therapy

• Hemodynamic optimization: restore perfusion and oxygen delivery.
• Broad-spectrum IV antibiotics covering:
• Gram-negative bacilli (E. coli, Klebsiella)
• Enterococci
• Anaerobes

Example regimens (ACG 2021):

• Piperacillin–tazobactam
• Cefepime or carbapenem ± metronidazole
• In β-lactam allergy: fluoroquinolone + metronidazole

Continue for 7–10 days or until source control achieved.

2. Source Control

A. Percutaneous Cholecystostomy (PC) Tube  and Stent Placement

• Preferred first-line intervention in unstable ICU patients.
• Ultrasound or CT-guided drainage of gallbladder.
• Rapidly improves sepsis.
• Can serve as definitive therapy in up to 80% of cases, especially if underlying illness resolves.
• The cholecystostomy tube can be removed after 3 weeks.

B. Cholecystectomy

• Laparoscopic or open removal.
• Indicated in:
• Gangrene or perforation
• Failed percutaneous drainage
• Recurrent cholecystitis after recovery

In hemodynamically unstable patients, PC is lifesaving; surgery deferred.

3. Monitoring

• Resolution of fever, leukocytosis
• Serial ultrasound if managed conservatively
• Drain output and culture in PC patients

Complications

Prognosis

• Mortality 30–50%, largely due to underlying disease severity.
• Early recognition and drainage improve outcomes dramatically.
• Recurrence is rare after cholecystectomy; if managed by PC alone, recurrence occurs in 10–20%.

Key Differences: Calculous vs Acalculous Cholecystitis

References

1. Harrison’s Principles of Internal Medicine, 21st ed., Ch. 357 – Gallbladder and Biliary Tract Disease.
2. Barie PS, Eachempati SR. Acalculous Cholecystitis. N Engl J Med. 2003;348: 280–285.
3. ACG Clinical Guideline: Acute Cholecystitis. Am J Gastroenterol. 2021.
4. Tokyo Guidelines 2018 (TG18): J Hepatobiliary Pancreat Sci. 2018;25(1):41–54.
5. Crit Care Med. 2016;44(2):350–357 — “Gallbladder Disease in the Critically Ill.”
6. irwin rippe 9th edition