According to the Tokyo Guidelines, how is acute cholecystitis diagnosed, severity‑graded, and what are the recommended antibiotic regimens, timing of cholecystectomy, and drainage strategies for each severity grade?

Tokyo Guidelines for Acute Cholecystitis: Diagnosis, Severity Grading, and Management

The Tokyo Guidelines provide a severity-based algorithmic approach to acute cholecystitis, where Grade I (mild) patients undergo early laparoscopic cholecystectomy, Grade II (moderate) patients receive early surgery by experienced surgeons or drainage followed by delayed surgery, and Grade III (severe) patients require organ support with urgent drainage followed by delayed cholecystectomy once stabilized. 1, 2

Diagnostic Criteria

Definite diagnosis of acute cholecystitis requires:

• Local signs of inflammation: Murphy's sign, mass/pain/tenderness in right upper quadrant 3, 4
• Systemic signs of inflammation: Fever, elevated WBC count, elevated CRP 3, 4
• Imaging confirmation: Ultrasound, CT, or other modalities demonstrating gallbladder inflammation 3, 4

The revised Tokyo 2013 criteria achieved 91.2% sensitivity and 96.9% specificity, improving accuracy from 92.7% to 94.0% compared to the original 2007 criteria 4. This represents a significant reduction in false positives from 15.5% to 5.9% 5.

Severity Grading System

Grade I (Mild Acute Cholecystitis)

• No organ dysfunction 3, 2
• Limited disease in the gallbladder making cholecystectomy a low-risk procedure 3
• Represents approximately 33.9% of cases 6

Grade II (Moderate Acute Cholecystitis)

• No organ dysfunction but extensive local disease 3, 2
• Characterized by: Elevated WBC count >18,000/mm³, palpable tender mass in RUQ, symptom duration >72 hours, marked local inflammation on imaging 3, 4
• Represents approximately 56.8% of cases 6

Grade III (Severe Acute Cholecystitis)

• Presence of organ dysfunction in any of the following systems: cardiovascular, neurological, respiratory, renal, hepatic, or hematological 3, 2
• Represents approximately 9.3% of cases 6
• Associated with 18% mortality and 49% complication rate 6

Management Algorithm by Severity Grade

Grade I (Mild) Management

Early laparoscopic cholecystectomy is the preferred treatment for patients meeting criteria of Charlson Comorbidity Index (CCI) ≤5 and ASA-PS ≤2 1, 2. This approach is associated with only 3.6% postoperative complications and 0% mortality 6.

Grade II (Moderate) Management

For patients with CCI ≤5 and ASA-PS ≤2: Early laparoscopic cholecystectomy performed by experienced surgeons is recommended 1.

For patients not meeting these criteria or with extensive local inflammation: Initial management with percutaneous gallbladder drainage followed by delayed elective cholecystectomy after clinical improvement 1, 2. This staged approach reduces surgical risk in patients with significant comorbidities or extensive inflammation.

Postoperative complications occur in 12.2% with 0.5% mortality when appropriately managed 6.

Grade III (Severe) Management

Initial management requires:

• Immediate organ support: Ventilatory and circulatory management as needed 2
• Hemodynamic stabilization before any intervention 1, 2

After stabilization, urgent biliary drainage (endoscopic or percutaneous transhepatic) should be performed 2.

Laparoscopic cholecystectomy may be considered only in highly selected Grade III patients at advanced centers with experienced surgeons when patients meet ALL of the following strict criteria 1:

• Favorable organ system failure pattern
• Negative predictive factors
• CCI ≤3 (note: more restrictive than Grade I/II)
• ASA-PS ≤2
• Treatment at specialized center

For biliary peritonitis due to gallbladder perforation: Urgent cholecystectomy and/or drainage is indicated regardless of severity grade 2.

If early surgery is not appropriate: Delayed elective cholecystectomy should be performed after gallbladder drainage and improvement of overall condition 1, 2.

Antibiotic Therapy

While the Tokyo Guidelines focus primarily on surgical management, complementary guidelines address antibiotic therapy:

For patients with previous biliary infection or preoperative drainage: Broad-spectrum antibiotics (4th-generation cephalosporins) are recommended with adjustments per antibiogram 7.

For prophylaxis during uncomplicated cholecystectomy: Cefazolin, cefamandole, or cefuroxime (substitute with gentamicin and clindamycin if allergic) for no more than 24 hours 7.

For severe sepsis or biliary peritonitis: Piperacillin/tazobactam, imipenem/cilastatin, meropenem, or ertapenem should be started within 1 hour, with amikacin added in shock states and fluconazole in fragile patients 7.

Critical Pitfalls to Avoid

Do not perform straightforward laparoscopic cholecystectomy in Grade III patients unless they meet the strict criteria outlined above at specialized centers 1. The 49% complication rate and 18% mortality in severe cases demands careful patient selection 6.

Do not delay biliary drainage in Grade III patients once hemodynamic stabilization is achieved—urgent drainage is required 2.

Do not attempt early surgery in Grade II patients with extensive inflammation without considering initial drainage followed by delayed surgery 1, 2.

Ensure accurate severity grading as it directly determines management strategy and has profound implications for morbidity and mortality 3, 6.