What is the clinical significance and management of a positive Murphy sign in a patient with right upper quadrant abdominal pain, nausea, and vomiting, suggestive of acute cholecystitis?

Murphy Sign: Clinical Significance and Management

A positive Murphy sign in a patient with right upper quadrant pain, nausea, and vomiting strongly suggests acute cholecystitis and mandates immediate ultrasound imaging followed by early laparoscopic cholecystectomy within 7-10 days of symptom onset. 1

Clinical Significance and Diagnostic Limitations

Murphy's sign has moderate diagnostic utility but insufficient power to establish or exclude acute cholecystitis alone. 2, 3

Diagnostic Performance

• Positive likelihood ratio of 2.8 (95% CI 0.8-8.6), demonstrating limited diagnostic power when used in isolation 2, 3
• Sensitivity ranges from 63% to 86% across studies 4, 5
• Specificity ranges from 35% to 93.6%, with high variability depending on clinical context 4, 5
• Positive predictive value of only 43-72.5%, meaning many false positives occur 4, 5
• Negative predictive value of 82-90.5%, making its absence more useful for ruling out disease 4, 5

Critical Pitfalls to Avoid

• Prior pain medication administration invalidates the reliability of a negative Murphy sign, making timing of examination crucial 2
• The sign may be absent in elderly, diabetic, or immunocompromised patients despite severe gallbladder disease 2
• Murphy's sign is unreliable in separating acute from chronic cholecystitis due to high false-positive rates 4

Mandatory Diagnostic Workup

Ultrasound is the investigation of choice and must be performed immediately in all patients with suspected acute cholecystitis. 1

First-Line Imaging

• Right upper quadrant ultrasound has 96% accuracy for detecting gallstones and 81% sensitivity for acute cholecystitis 2, 6, 7
• Look for: distended gallbladder, edematous gallbladder wall (>3mm), pericholecystic fluid, and gallstones impacted in the cystic duct 1
• Sonographic Murphy sign can be elicited during ultrasound but has relatively low specificity 1, 8

Second-Line Imaging (If Ultrasound Equivocal)

• Hepatobiliary scintigraphy (HIDA scan) is the gold standard when clinical suspicion remains high despite equivocal ultrasound 6, 7
• Sensitivity of 97% and specificity of 90% for acute cholecystitis 6
• CT abdomen with IV contrast can identify complications including gangrene, perforation, or adjacent liver parenchymal hyperemia 6
• MRCP is indicated if common bile duct stones are suspected 1

Management Algorithm

Uncomplicated Acute Cholecystitis

Early laparoscopic cholecystectomy within 7-10 days of symptom onset is the definitive treatment. 1, 7

Immunocompetent, Non-Critically Ill Patients

• Single-shot antibiotic prophylaxis if early intervention performed 1
• No post-operative antibiotics required after early cholecystectomy 1
• Amoxicillin/clavulanate 2g/0.2g q8h if adequate source control achieved 1
• For beta-lactam allergy: Eravacycline 1 mg/kg q12h or Tigecycline 100 mg loading dose then 50 mg q12h 1
• Antibiotic therapy for 2-4 days if source control is adequate 1

Delayed Treatment Option (Second-Line)

• Not recommended for immunocompromised patients 1
• Antibiotic therapy followed by planned delayed cholecystectomy 1
• Antibiotic therapy for no more than 7 days 1

Complicated Acute Cholecystitis

Laparoscopic cholecystectomy remains first-line with open cholecystectomy as alternative. 1

Critically Ill or Immunocompromised Patients

• Piperacillin/tazobactam 6g/0.75g loading dose then 4g/0.5g q6h or 16g/2g by continuous infusion 1
• For beta-lactam allergy: Eravacycline 1 mg/kg q12h 1
• Antibiotic therapy for 4 days in immunocompetent patients if source control adequate 1
• Antibiotic therapy up to 7 days based on clinical conditions and inflammation indices in immunocompromised or critically ill patients 1

Inadequate/Delayed Source Control or High ESBL Risk

• Ertapenem 1g q24h 1
• Alternative: Eravacycline 1 mg/kg q12h 1

Septic Shock

• Meropenem 1g q6h by extended infusion or continuous infusion 1
• Alternatives: Doripenem 500 mg q8h or Imipenem/cilastatin 500 mg q6h by extended infusion 1
• Eravacycline 1 mg/kg q12h is also an option 1

Patients Unfit for Surgery

Cholecystostomy may be considered for patients with multiple comorbidities who do not show clinical improvement after antibiotic therapy. 1

• Antibiotic therapy for 4 days following cholecystostomy 1
• Cholecystostomy is inferior to cholecystectomy in terms of major complications for critically ill patients (65% vs 12% complication rates) 1, 7

Special Populations

During pregnancy, early laparoscopic cholecystectomy is recommended during all trimesters and is associated with lower maternal-fetal complications (1.6% vs 18.4% for delayed management). 7

In patients older than 65 years, laparoscopic cholecystectomy is associated with lower 2-year mortality (15.2%) compared with nonoperative management (29.3%). 7

Red Flags Requiring Diagnostic Investigation

Patients with ongoing signs of infection or systemic illness beyond 7 days of antibiotic treatment warrant diagnostic investigation for complications or alternative diagnoses. 1