Acute Acalculous Cholecystitis

Acute acalculous cholecystitis (AAC) is acute gallbladder inflammation without gallstones. It accounts for 5 to 10% of acute cholecystitis in adults and occurs predominantly in the critically ill. It is also seen in children (viral infections, Salmonella, Leptospira, Kawasaki disease), in HIV and AIDS (cytomegalovirus, cryptosporidium and microsporidia causing AIDS cholangiopathy), and after trauma or burns.

Pathophysiology is multifactorial, with gallbladder ischaemia and bile stasis central. Prolonged fasting, total parenteral nutrition and critical illness cause gallbladder hypomotility, concentrated viscous bile, sludge and raised intraluminal pressure.

Hypoperfusion (shock, vasopressors, mesenteric hypoperfusion), reperfusion injury and endotoxin cause mucosal ischaemia and necrosis.

Secondary bacterial invasion (enteric Gram negative organisms, enterococci, anaerobes, Candida) follows, and gangrene, perforation or emphysematous cholecystitis can develop rapidly.

Risk factors and settings:

• Critical illness: sepsis, major burns, trauma, major non-biliary surgery (cardiac and aortic), prolonged mechanical ventilation, multi organ failure, long ICU stay
• Total parenteral nutrition and prolonged fasting
• Opioids, positive end expiratory pressure, rapid weight loss
• Diabetes, atherosclerotic vascular disease, vasculitis (polyarteritis nodosa, systemic lupus erythematosus), immunosuppression
• Elderly men are particularly vulnerable
• Infections: bacterial (Salmonella, Vibrio cholerae, Leptospira, streptococci), viral (Epstein-Barr virus, hepatitis A, cytomegalovirus, dengue), parasitic (Cryptosporidium)

Mortality is 15 to 50% in the critically ill, compared with 1 to 5% for calculous disease, reflecting underlying illness, delayed diagnosis and gangrene (40 to 60%) and perforation (10 to 20%).

Presentation is often subtle and masked in sedated, ventilated patients. Classic right upper quadrant pain, tenderness and Murphy sign are absent in many. Look for:

• Unexplained fever, sepsis or rising inflammatory markers without another source
• Right upper quadrant tenderness, guarding or a palpable mass
• Nausea, vomiting, ileus, intolerance of enteral feeding, abdominal distension
• Mild jaundice from inflammation; marked jaundice suggests bile duct involvement or another cause
• Leucocytosis and raised C-reactive protein and procalcitonin
• Haemodynamic instability, worsening organ dysfunction, unexplained metabolic acidosis (raised lactate)
• Complications: gangrenous cholecystitis (peritonitis, shock), perforation with bile peritonitis or pericholecystic abscess, emphysematous cholecystitis (gas forming organisms such as Clostridium and E. coli, common in diabetics), cholangitis

Differential diagnosis: pancreatitis, hepatitis, hepatic abscess, peptic ulcer, perforated viscus, mesenteric ischaemia, pyelonephritis, right lower lobe pneumonia, and ventilator associated complications.

A high index of suspicion is essential in the critically ill. No single test is both sensitive and specific.

• Laboratory: raised white cell count and C-reactive protein, liver tests (raised bilirubin, alkaline phosphatase, gamma glutamyl transferase, often mildly raised aminotransferases), amylase or lipase to exclude pancreatitis, lactate, blood cultures
• Bedside ultrasound is first line:
  • Gallbladder wall thickening above 3.5 to 4 mm (non-specific with hypoalbuminaemia or ascites).
  • Distension (transverse diameter above 5 cm), pericholecystic fluid, intramural gas, sloughed mucosa (striated wall).
  • Sonographic Murphy sign (unreliable in sedated patients), and sludge (common in critical illness and non-specific).
  • Gallstones must be absent.
  • Sensitivity is about 80 to 90% in the correct clinical context.
• Contrast CT: wall thickening or oedema, pericholecystic stranding or fluid, mucosal hyperenhancement or non-enhancement (gangrene), gas in the wall or lumen, and perforation; it also excludes other diagnoses and is more reliable than ultrasound in the critically ill
• Hepatobiliary iminodiacetic acid (HIDA) scan: non-visualisation of the gallbladder 60 minutes after tracer (or after morphine augmentation 0.04 mg/kg IV) suggests cystic duct obstruction, with sensitivity of 90 to 95%; false positives occur with fasting, parenteral nutrition and severe illness
• Diagnosis rests on local signs of inflammation (Murphy sign, right upper quadrant mass, pain or tenderness), systemic signs (fever, raised CRP, raised white count) and characteristic imaging. Severity grades: mild (I), moderate (II: white count above 18,000, palpable mass, duration over 72 hours, or marked local inflammation), and severe (III: organ dysfunction)

General. Treat as sepsis: resuscitate, keep nil by mouth, decompress the stomach for ileus, correct electrolytes and coagulopathy, and give analgesia (fentanyl infusion is often preferred in the critically ill). Remove gallbladder toxic factors where possible: reduce vasopressors, switch from parenteral to enteral feeding, and stop unnecessary opioids.

Antibiotics. Start broad spectrum antibiotics immediately after cultures, covering enteric Gram negative bacilli, enterococci and anaerobes. Options are piperacillin tazobactam 4.5 g IV every 6 hours (or 4.5 g every 8 hours as an extended infusion), or meropenem 1 g IV every 8 hours for critically ill patients and those at risk of resistant organisms.

Add vancomycin 15 to 20 mg/kg every 8 to 12 hours for enterococcal or MRSA concern, and an antifungal (fluconazole or an echinocandin) for Candida risk. Alternatives: ceftriaxone 2 g daily with metronidazole 500 mg every 8 hours, or ciprofloxacin 400 mg every 12 hours with metronidazole.

Duration: for mild to moderate disease with cholecystectomy, a single dose or up to 24 hours after surgery; for severe disease, 4 to 7 days after source control; 2 weeks for bacteraemia with Gram positive cocci or incomplete drainage.

Source control.

• Percutaneous cholecystostomy:
  • Ultrasound guided transhepatic (preferred) or transperitoneal 8 to 10 Fr pigtail drain under local anaesthetic.
  • Success is 85 to 95%, with improvement in 24 to 72 hours, so it is the preferred first step in critically ill or high risk patients unfit for general anaesthesia.
  • Aspirate and culture bile.
  • Leave the drain for at least 2 to 6 weeks to mature the tract; cholangiography through the tube after recovery confirms cystic duct patency.
  • Complications: bile leak, dislodgement, bleeding, vasovagal events.
  • Failure to improve in 48 to 72 hours suggests gangrene or perforation needing surgery.
• Cholecystectomy is definitive in patients fit for surgery.
  • Laparoscopic cholecystectomy within 72 hours (or up to 7 days) of onset for mild to moderate disease.
  • Open or subtotal cholecystectomy for difficult, inflamed anatomy to reduce the risk of bile duct injury.
  • Urgent surgery for gangrene, perforation or emphysematous disease.
  • Obtain the critical view of safety or an intraoperative cholangiogram.
  • After cholecystostomy, interval cholecystectomy at 6 to 8 weeks once recovered; in patients who remain high risk with a patent cystic duct, the drain can be removed with about 10% recurrence at 1 year.
• Endoscopic transpapillary gallbladder drainage or endoscopic ultrasound guided gallbladder drainage with a lumen apposing metal stent for patients who cannot have percutaneous drainage

Supportive and after care. Organ support in the ICU, enteral nutrition, glycaemic control, and monitoring for complications (bile leak, abscess, bleeding). Prevention in the ICU: early enteral feeding, minimising parenteral nutrition, and avoiding hypovolaemia.