Acute cholecystitis

A 58-year-old woman arrives with 36 hours of constant right upper quadrant pain, fever of 38.4 °C, a white cell count of 16 × 10⁹/L and a positive Murphy sign. Ultrasound shows a distended gallbladder with an impacted stone and a 6 mm wall. Every decision you will make for her — how the diagnosis is actually made, how severe this is, when to operate, what to do if Calot's triangle is frozen, and what to offer the intensive care version of this patient — is mapped by the Tokyo Guidelines and WSES, with trial numbers attached. This page gives you those decisions.

Definition, diagnostic criteria and the severity grading that drives treatment

Acute cholecystitis is acute inflammation of the gallbladder, in the great majority caused by a gallstone impacted in the gallbladder neck or cystic duct; the acalculous form — no stones, a disease of the critically ill — is treated separately below.^[21][15] The working diagnostic framework is the Tokyo Guidelines. TG18 adopted the TG13 diagnostic criteria and severity grading without any modification, on the strength of validation studies showing the severity grading tracks 30-day mortality, length of stay, conversion to open surgery and medical costs.^[1]

The TG18/TG13 diagnostic criteria — learn these verbatim.^[7]

• Item A — local signs of inflammation: (1) Murphy sign; (2) right-upper-quadrant mass, pain or tenderness.
• Item B — systemic signs of inflammation: (1) fever; (2) elevated CRP; (3) elevated white cell count.
• Item C — imaging: findings characteristic of acute cholecystitis.
• Suspected diagnosis: one item in A plus one item in B. Definite diagnosis: one item in A, one item in B, plus C.
• Acute hepatitis, other acute abdominal diseases and chronic cholecystitis must be excluded.

In the multicentre validation behind the criteria (451 patients, six Japanese tertiary centres), definite diagnosis carried sensitivity 91.2% and specificity 96.9% against histopathology — better specificity than the preceding TG07 criteria (93.3%).^[7]

The TG18/TG13 severity grading.^[7]

• Grade III (severe): dysfunction of any one of six organ systems — cardiovascular (hypotension requiring dopamine 5 μg/kg/min or more, or any dose of norepinephrine), neurological (decreased consciousness), respiratory (PaO₂/FiO₂ ratio under 300), renal (oliguria, creatinine over 2.0 mg/dL), hepatic (PT-INR over 1.5), haematological (platelet count under 100,000/mm³).^[7]
• Grade II (moderate): any one of — white cell count over 18,000/mm³; a palpable tender mass in the right upper quadrant; duration of complaints over 72 hours; or marked local inflammation (gangrenous cholecystitis, pericholecystic abscess, hepatic abscess, biliary peritonitis, emphysematous cholecystitis).
• Grade I (mild): meets neither Grade II nor Grade III criteria — cholecystitis in a healthy patient with no organ dysfunction and mild inflammatory change, in whom cholecystectomy is safe and low-risk.

A contemporary narrative review restates the same ladder in prose: grade I is disease confined to the gallbladder without local or systemic complications, grade II adds the local complications or the three clinical markers above, and grade III adds at least one organ failure.^[22] The American alternative, the AAST emergency general surgery grade, was validated across 8 institutions in 861 patients (781 cholecystectomies): it showed only modest discriminatory power — similar to the Tokyo grading and generally lower than the intraoperative Parkland grade — and its authors conclude it should be modified before widespread use.^[17]

Epidemiology and who gets it

Gallstones are common: prevalence reaches 60–70% in American Indians and runs at 10–15% in white adults of developed countries, with ethnic variation throughout (less frequent in black Americans and East Asians, rare in sub-Saharan Africa).^[18] Between 1% and 4% of adults with gallstones become symptomatic each year; 20–40% of patients with gallstones will eventually develop gallstone-related complications, and acute calculous cholecystitis is the first clinical presentation in 10–15% of cases.^[11][8] The WSES/SICG elderly guideline frames the demographic tail: gallstone disease afflicts 20 million people in the USA, and in Europe the overall incidence is 18.8% in women and 9.5% in men, rising with age.^[9]

Risk factors divide into the immutable — female gender, increasing age, ethnicity and family — and the modifiable: obesity, the metabolic syndrome, rapid weight loss, cirrhosis and Crohn disease, gallbladder stasis (spinal cord injury, drugs such as somatostatin), and lifestyle.^[18]

Pathophysiology — one impacted stone, one pressure cascade

In calculous disease, a stone impacts in the gallbladder neck or cystic duct. Increased dilatation and high intraluminal pressure then drive gallbladder inflammation, which may progress to gangrenous change, focal wall necrosis and perforation.^[21] The organisms that colonise the trapped bile are the enteric flora — most frequently E. coli, followed by Klebsiella, Enterococcus and Enterobacter — which is what every empiric regimen on this page is designed to cover.^[22]

The acalculous mechanism is different in kind, not degree: it occurs in critically ill patients — trauma, surgery, shock, burns, sepsis, total parenteral nutrition, prolonged fasting — where stasis and ischaemia, rather than a stone, start the cascade; patients are typically critically ill, often with hypotensive episodes and prolonged gallbladder stasis leading to obstruction, gallbladder ischaemia and inflammation.^[15][21] It carries a high mortality, and early diagnosis with intervention changes that.^[15]

The local complications are the cascade made anatomical: gangrenous cholecystitis (transmural inflammation with ischaemic necrosis, in approximately 20% of cases in the series quoted by the JCM review), gallbladder perforation, pericholecystic abscess, biliary peritonitis, biliary fistula, emphysematous cholecystitis, gallbladder empyema and haemorrhagic cholecystitis.^[22]

Clinical presentation — and the uncomfortable truth about signs

The typical picture is sustained right upper quadrant pain — unlike biliary colic, which is transient — with fever, nausea or vomiting and food intolerance; on examination, right-upper-quadrant tenderness and the Murphy sign (inspiratory arrest on palpation of the right upper quadrant).^[8][22] The JCM review puts a number on the sign's specificity — 87% to 97% — which sounds reassuring until you hear the JAMA Rational Clinical Examination verdict.^[22]

Trowbridge's systematic review of 17 studies is the paper every fellowship examiner knows: no clinical or laboratory finding had a sufficiently high positive or sufficiently low negative likelihood ratio to rule cholecystitis in or out. The Murphy sign managed a positive LR of only 2.8 (95% CI 0.8–8.6) and right-upper-quadrant tenderness a negative LR of 0.4 (0.2–1.1) — both confidence intervals cross 1. The conclusion to quote: no single clinical finding or laboratory test carries sufficient weight to establish or exclude cholecystitis without further testing, such as right-upper-quadrant ultrasound.^[16] WSES hard-codes this as its first statement: do not rely on a single clinical or laboratory finding (QoE high, strong), and diagnose on a combination of history, examination, laboratory tests and imaging.^[8]

The sonographic Murphy trap. The ultrasound probe version of the sign is helpful when positive but relatively insensitive; overreliance on it produces surprisingly low diagnostic accuracy in practice.^[21] The bedside version shares the same fate in the LR data above. Both belong in the diagnostic bundle; neither makes the call alone.^[16][21]

Investigations and the imaging hierarchy

Ultrasound first. WSES recommends abdominal ultrasound as the preferred initial imaging technique — cost-effective, widely available, non-invasive, accurate for gallstone disease (QoE high, strong).^[8] The signs to name go beyond "wall thick over 3 mm": a dilated gallbladder, the bulging fundus of rising intraluminal pressure (the tensile fundus sign), sludge in the setting of right-upper-quadrant pain, wall hyperaemia, loss of mucosal echogenicity, hyperechoic pericholecystic fat, and mucosal discontinuity.^[21]

The accuracy league table. WSES 1.4: the HIDA scan has the highest sensitivity and specificity of any modality for ACC; MRI is as accurate as abdominal ultrasound; and CT's diagnostic accuracy is poor — CT's value is complications, not the primary diagnosis (QoE moderate, strong).^[8] The JCM review agrees: hepatobiliary scintigraphy is the most sensitive and specific test for ACC, while CT is the technique of choice for emphysematous cholecystitis because it detects minute gas bubbles as hypodense spots, and CT or MRI define the full extent of perforation.^[22] On ultrasound, extruded complex fluid next to a wall defect is definitive for gallbladder wall perforation.^[21]

Screening for duct stones while you are at it. WSES is explicit: do not use elevated liver enzymes or bilirubin alone to identify common bile duct stones (QoE moderate, strong), and a dilated duct alone is not sufficient (QoE high, strong). Moderate-risk patients go to preoperative MRCP or EUS, or intraoperative cholangiography or laparoscopic ultrasound, depending on local expertise (QoE high, strong); high-risk patients go to preoperative ERCP, IOC or LUS (QoE high, strong).^[8]

Differential diagnosis

The TG criteria themselves force the exclusions: acute hepatitis, other acute abdominal diseases and chronic cholecystitis must be ruled out before the definite label applies.^[7] In practice the sieve is: biliary colic (transient obstruction, no systemic item-B response — the pain settles and the CRP stays down); choledocholithiasis and cholangitis (jaundice, cholestatic enzymes, duct dilatation — the CBDS pathway above); pancreatitis and hepatitis (enzyme patterns and imaging); and the extra-abdominal mimics of right upper quadrant pain. The JCM review flags the overlap explicitly: variable imaging appearances and overlapping clinical manifestations with biliary colic, acute hepatitis, pancreatitis and cholangiopathies are what make the diagnosis challenging.^[22]

Management — the early-versus-delayed question, settled

The WSES timing windows — quote them exactly. Early laparoscopic cholecystectomy (ELC) should be performed as soon as possible, within 7 days of hospital admission and within 10 days of symptom onset (QoE moderate, strong); delayed laparoscopic cholecystectomy (DLC) is suggested beyond 6 weeks from first presentation when ELC cannot be done (QoE very low, weak).^[8] ELC so defined is preferable to both intermediate surgery (7 days to 6 weeks) and delayed surgery (6 weeks to 3 months).^[8] The JCM review's practical definition is slightly tighter: within 72 hours of admission, or up to 7–10 days from symptom onset.^[22]

The trial evidence. The Cochrane review (six trials contributing data, 488 participants, ELC within 7 days of presentation versus DLC more than 6 weeks later) found no mortality, no significant difference in bile duct injury (ELC 0.4% versus DLC 0.9%; Peto OR 0.49, CI 0.05–4.72), no difference in conversion (19.7% versus 22.1%) — and a total hospital stay shorter by about four days in the early group.^[11] The delayed group's hidden cost: 40 patients (18.3%) suffered non-resolution or recurrence before their planned operation and needed emergency surgery, in whom the conversion rate was 45%.^[11] Lyu's 2018 meta-analysis of 15 RCTs confirms it: no difference in bile duct injury (RR 0.79, CI 0.23–2.79) or bile leak, conversion or total complications; ELC takes modestly longer in theatre within the 7-day window but saves 3.07 days of hospital stay; the authors' conclusion — ELC appears as safe and effective as DLC within 7 days of presentation and may shorten total stay.^[12]

The guideline synthesis. WSES 2020 states it flatly: laparoscopic cholecystectomy is the first-line treatment for ACC (QoE high, strong), and ELC should be the standard of care whenever possible — even in subgroups considered fragile, such as the elderly and those with cardiac disease, renal disease or cirrhosis.^[8] TG18 arrives at the same destination through a fitness gate: Grade I patients get early laparoscopic cholecystectomy if the Charlson comorbidity index is 5 or less and ASA physical status 2 or less; Grade II patients meeting the same criteria get early surgery performed by experienced surgeons — otherwise medical treatment and/or gallbladder drainage first, then cholecystectomy; Grade III patients may have early surgery only under strict criteria — favourable organ system failure, negative predictive factors absent, CCI 3 or less, ASA-PS 2 or less, at an advanced centre with experienced surgeons.^[2] The Grade III negative predictive factors to quote: bilirubin 2 mg/dL or above, and neurological or respiratory dysfunction.^[22] If the patient is not suitable for early surgery, TG18 recommends early/urgent biliary drainage followed by delayed cholecystectomy once the overall condition improves.^[2]

Operative management — safe steps and the bail-out philosophy

The critical view of safety is the operation. TG18's safe-steps doctrine: when Calot's triangle is appropriately retracted and used as a landmark, if a critical view of safety (CVS) cannot be achieved because of nondissectable scarring or severe fibrosis, a bail-out procedure should be chosen. Dissection must stay above (ventral to) the imaginary line connecting the base of the left medial section (segment 4) and the roof of Rouvière's sulcus, and all three CVS criteria must be fulfilled before any structure is divided — because achieving the CVS prevents the misidentification of the cystic duct and common bile duct, the two structures most commonly confused.^[3] The stated purpose of the whole doctrine: avoid any increase in bile duct injury, particularly vasculo-biliary injury, which occurs at a known rate in laparoscopic cholecystectomy.^[3]

The bail-out menu. WSES recommends subtotal cholecystectomy, laparoscopic or open, when anatomic identification is difficult and the risk of iatrogenic injury is high (QoE moderate, strong) — its abstract adds that subtotal cholecystectomy is safe and a valuable option in difficult gallbladder removal.^[8] Conversion from laparoscopic to open is recommended for severe local inflammation, adhesions, bleeding from Calot's triangle, or suspected bile duct injury (QoE moderate, strong).^[8] Two absolute stops: septic shock and absolute anaesthesiological contraindications (QoE high, strong) — that patient is drained, not dissected.^[8]

Antibiotics around the operation. PEANUTS II randomised adults with mild-to-moderate ACC undergoing immediate cholecystectomy to a single preoperative dose of cefazolin 2 g or no prophylaxis: postoperative infectious complications were 7.1% with prophylaxis versus 12.6% without, surgical-site infections 5.3% versus 12.1% (P = 0.010), and non-inferiority of omission was not proven — omitting antibiotic prophylaxis is not recommended.^[19] After the operation, the opposite discipline applies: for uncomplicated ACC with the source controlled by cholecystectomy, WSES recommends against routine postoperative antibiotics (QoE high, strong), on the strength of the Regimbau trial — 414 patients randomised to no antibiotics or 5 further days, with identical postoperative infection rates (17% versus 15%).^[8] Complicated ACC is different: prescribe by presumed pathogens and resistance risk, and adapt to microbiology results (QoE high, strong and moderate, weak respectively).^[8]

The high-risk patient — CHOCOLATE inverted the dogma

This is the section the fellowship viva is built around. The old reflex — "too sick for theatre, put in a cholecystostomy" — rests on confounded observational data. Winbladh's 2009 systematic review (53 studies, 1,918 patients) found percutaneous cholecystostomy technically successful in 85.6%, with procedure mortality of 0.36% — but 30-day mortality of 15.4% after PC versus 4.5% after acute cholecystectomy, a gap that screams selection bias, and the authors concluded honestly that no controlled comparison existed and no definitive recommendation was possible.^[14] The 2013 Cochrane review found just two randomised trials (156 participants) and declared itself unable to determine the role of cholecystostomy in high-risk patients.^[13]

CHOCOLATE (BMJ 2018) filled that gap: 142 high-risk patients with acute calculous cholecystitis (APACHE II score 7 or more) at 11 Dutch hospitals, randomised to laparoscopic cholecystectomy (n=66) or percutaneous catheter drainage (n=68). The trial stopped early at interim analysis. Death did not differ (3% versus 9%, P=0.27) — but major complications occurred in 12% after cholecystectomy versus 65% after drainage (RR 0.19, 95% CI 0.10–0.37); reintervention was needed in 12% versus 66%; recurrent biliary disease in 5% versus 53%; and median stay was 5 versus 9 days.^[10] The conclusion: laparoscopic cholecystectomy reduced major complications in high-risk patients.^[10]

WSES rebuilt its algorithm on this trial. Statement 6.3: immediate laparoscopic cholecystectomy is superior to PTGBD in high-risk patients with ACC and is the first-choice treatment in this group (QoE high, strong). Statement 6.4 — the crucial boundary: gallbladder drainage is for patients not suitable for surgery, because it converts a septic patient with ACC into a non-septic patient (QoE moderate, strong).^[8] The whole architecture turns on a distinction the WSES abstract makes explicit: high-risk patients (sick but operable — the CHOCOLATE population) versus patients not suitable for surgery (septic shock, anaesthesia refusal or impossibility).^[8]

Non-operative management with antibiotics and observation still has a place — for patients refusing surgery or unsuitable for it (WSES 6.1, weak).^[8] But know its price: in the large elderly database series WSES quotes, readmission exceeded 50% after conservative management, and 1-year mortality ran 20.8% for surgery, 27.1% for NOM and 37% for cholecystostomy — observational numbers shaped by who gets which treatment, quoted here to counsel, not to allocate.^[8]

Drainage techniques — when the gallbladder needs a pipe, not a surgeon

For the genuinely unfit, TG18's hierarchy: percutaneous transhepatic gallbladder drainage (PTGBD) should be considered the first alternative to surgical intervention in surgically high-risk patients; endoscopic transpapillary drainage (ETGBD) or EUS-guided gallbladder drainage (EUS-GBD) belong in high-volume institutes with skilled endoscopists.^[4] WSES refines the endoscopic branch: EUS-GBD with lumen-apposing metal stents should be preferred to ETGBD by skilled endoscopists (QoE moderate, strong), and if metal stents are used, remove them within 4 weeks to avoid food impaction and recurrent cholecystitis (QoE low, weak).^[8] Catheter logistics from the WSES elderly guideline: remove the cholecystostomy between 4 and 6 weeks after placement, once a cholangiogram at 2–3 weeks has demonstrated biliary tree patency.^[9] And when periprocedural risk has been reduced, delayed cholecystectomy is suggested to cut readmission from relapse (WSES 6.5, weak).^[8]

Antibiotic therapy — indications, agents, duration

Antimicrobial therapy is a mainstay of management (TG18), but the discipline is in the stopping.^[5]

• Indication logic: empiric agents are chosen by severity grade and community versus healthcare setting, with local antibiogram monitoring and early de-escalation or termination as explicit TG18 doctrine; TG18 systematically reviewed duration for both cholangitis and cholecystitis.^[5] The TG18 management bundles package the whole admission: diagnostic process, severity assessment, patient transfer if necessary, and therapeutic approach at each time point.^[6]
• Agent selection refinements (JCM review): empiric broad-spectrum cover targets the enteric gram-negatives and Enterococcus; a biliary–enteric anastomosis warrants anaerobic therapy such as metronidazole; severe and healthcare-associated infections can be sustained by Pseudomonas species and need antipseudomonal cover; blood and bile cultures guide de-escalation.^[22]
• Duration: for mild or moderate ACC in patients heading to early cholecystectomy, antimicrobials run from diagnosis until surgical intervention, or further if clinically indicated; for adequately source-controlled biliary infections generally, shorter courses of 3–7 days are non-inferior to longer ones.^[22][23] Postoperative antibiotics after uncomplicated ACC with source control: none (Regimbau, WSES 7.1).^[8]
• Perioperative prophylaxis: single preoperative dose (PEANUTS II above).^[19]

Special populations

Elderly. The WSES/SICG elderly guideline suggests same-admission laparoscopic cholecystectomy for elderly patients with ACC, notes that the oldest old age is not by itself a contraindication to surgery, and calls for frailty and surgical risk scores to sharpen judgement.^[9] The supporting meta-analysis (8 studies, 592 patients, mean age 81): conversion 23%, perioperative morbidity 24%, mortality 3.5% — early cholecystectomy is feasible in the elderly, with careful selection.^[20] WSES 2020 extends the same logic: laparoscopic cholecystectomy is suggested for patients over 80, for Child A and B cirrhosis, and in pregnancy (QoE low, weak); for Child C cirrhosis the recommendation is unclear.^[8]

Pregnancy. WSES suggests the laparoscopic approach when surgery is indicated. Its pooled outcome data: maternal death 1 open versus 0 laparoscopic; maternal complications 8.2% open versus 3.5% laparoscopic (OR 0.42); fetal loss 4.3% open versus 0.6% laparoscopic; fetal complications 12.0% open versus 3.9% laparoscopic.^[8]

The critically ill and acalculous disease. Acalculous cholecystitis is a diagnosis of suspicion in the ICU — its findings (right upper quadrant pain, fever, leukocytosis, abnormal liver tests) are all non-specific; sequential sonography and HIDA scanning are the most reliable modalities.^[15] Cholecystectomy is the definitive therapy, but percutaneous drainage can be necessary and life-saving — and may be the only treatment needed.^[15]

Complications and prognosis

The disease complications are the cascade's endpoints: gangrene, emphysematous change, empyema, perforation, pericholecystic abscess, biliary peritonitis, fistula and haemorrhage.^[22] Severity grading earns its keep at prognostication: the TG13/TG18 grade predicts 30-day mortality, length of stay, conversion and cost.^[1] The operation's complications concentrate where the discipline was skipped — the bile duct and vasculo-biliary injuries the CVS doctrine exists to prevent.^[3]

Prognosis by pathway: the fit patient gets early laparoscopic cholecystectomy and goes home about four days sooner than the delayed pathway would have allowed, without paying for it in bile duct injuries.^[11] The high-risk patient does better with surgery than drainage (CHOCOLATE).^[10] The unfit patient is drained, converted from septic to non-septic, and brought back for delayed cholecystectomy once the risk has been reduced.^[8][2]

Revision summary

• Diagnosis is a bundle, not a sign: TG item A (Murphy, RUQ mass/pain/tenderness) + item B (fever, CRP, WBC) = suspected; add item C imaging = definite; sensitivity 91.2%, specificity 96.9%.^[7]
• Grade the severity: Grade III = any of six organ dysfunctions; Grade II = WBC over 18,000, tender RUQ mass, symptoms over 72 h, or marked local inflammation; the grade plus CCI/ASA fitness gates the TG18 flowchart.^[7][2]
• No single finding rules in or out (Murphy LR+ 2.8, CI crosses 1); ultrasound first; HIDA most accurate; CT for gas and perforation; jaundice means think CBDS.^[16][8][22]
• Early laparoscopic cholecystectomy within 7 days of admission / 10 days of onset is the standard — Cochrane (488 participants) and Lyu (15 RCTs) show no BDI penalty, four and three days saved respectively; delayed surgery costs 18.3% emergency crossover at 45% conversion.^[8][11][12]
• CVS before division, above the segment-4–Rouvière line; bail out to subtotal or convert when the view cannot be achieved.^[3][8]
• CHOCOLATE: in APACHE II ≥7 high-risk patients, cholecystectomy beats drainage (major complications 12% vs 65%); drainage is for the patient not suitable for surgery — it converts septic to non-septic.^[10][8]
• Antibiotics: single preoperative dose (PEANUTS II), none postoperatively for uncomplicated disease with source control (Regimbau/WSES 7.1), resistance-adapted for complicated disease, 3–7 days adequate once the source is controlled.^[19][8][23]