Clinical review

Acute cholecystitis

Adrian A Indar, surgical fellow, Ian J Beckingham, consultant hepatobiliary and laparoscopic surgeon. 

Section of Gastrointestinal Surgery, University Hospital Nottingham, Nottingham NG7 2UH

Correspondence to: I J Beckingham Ian.Beckingham{at}nottingham.ac.uk

Patients with suspected acute cholecystitis should be referred to hospital and, if the diagnosis is confirmed, early surgery is indicated

Acute cholecystitisinflammation of the gall bladderis most often caused by gall stones. Gall stones are one of the most common disorders of the gastrointestinal tract, affecting about 10% of people in Western society. ^{1 2} More than 80% of people with gall stones are asymptomatic. Acute cholecystitis develops in 1-3% of patients with symptomatic gall stones.³

Helminthic infection (ascariasis) is a major cause of biliary disease in developing countries in Asia, southern Africa, and Latin America.⁴ Obstruction of the cystic duct causes an inflammatory process to start. This results in acute cholecystitis. If the inflammation persists it may cause perforation or gangrene of the gall bladder.

View larger version (40K): [in this window] [in a new window]   Fig 1.   Pathogenesis of acute cholecystitis

Diagnosis of acute cholecystitis is made on the basis of clinical features and is supported by results of ultrasound scanning. Treatment is predominantly surgical, although the timing of surgery is under debate.

Summary points Acute cholecystitis is most often caused by gall stones Patients suspected of having acute cholecystitis should be referred to hospital immediately First line treatments include fasting, intravenous fluids, and analgesia Surgery (cholecystectomy) within 24-48 hours of admission (early) is preferable to delayed or "interval" surgery Percutaneous cholecystostomy is a safe alternative to cholecystectomy for very ill patients or those unfit to undergo surgery In 20% of cases, emergency surgery is needed to treat gangrenous cholecystitis or gallbladder perforation

	Methods

Top Methods Pathogenesis Presentation and diagnosis Management Sequelae of acute cholecystitis Acute cholecystitis and... Acalculous cholecystitis References

We prepared this review by searching Medline for articles in English that included the term "acute cholecystitis." We looked at clinical trials with clear end points and conclusions, and present findings of trials that reflect most of the work published.

	Pathogenesis

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Over 90% of cases of acute cholecystitis result from obstruction of the cystic duct by gall stones or by biliary sludge that has become impacted at the neck of the gall bladder. Obstruction of the cystic duct causes the intraluminal pressure within the gall bladder to increase and, together with cholesterol supersaturated bile, triggers an acute inflammatory response. The trauma caused by the gall stones stimulates the synthesis of prostaglandins I₂ and E₂, which mediate the inflammatory response (fig 1).⁵ Secondary bacterial infection with enteric organisms (most commonly Escherichia coli, Klebsiella, and Streptococcus faecalis) occur in about 20% of cases.

Biliary sludge is a mixture of particulate matter and bile, and it may stimulate microlithiasis. If the sludge persistsfor example, because the patient has already had several pregnancies or is receiving total parenteral nutritiongall stones can form.⁶ Most patients with biliary sludge have no symptoms, but the sludge itself can cause acute cholecystitis.

	Presentation and diagnosis

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Acute cholecystitis is diagnosed on the basis of symptoms and signs of inflammation in patients with peritonitis localised to the right upper quadrant (fig 2). Acute cholecystitis should be differentiated from biliary colic by the constant pain in the right upper quadrant and Murphy's sign (in which inspiration is inhibited by pain on palpation). Patients with acute cholecystitis may have a history of attacks of biliary colic or they may have been asymptomatic until the presenting episode.

In patients with superimposed bacterial infection, septicaemia develops and is associated with increased morbidity and mortality. Patients with severe acute cholecystitis may have mild jaundice (serum concentrations of bilirubin <60 µmol/l) caused by inflammation and oedema around the biliary tract and direct pressure on the biliary tract from the distended gall bladder. Concentrations of bilirubin >60 µmol/l suggest a diagnosis of choledocholithiasis (a gall stone in the common bile duct) or Mirrizzi's syndrome (obstruction by a stone impacted in Hartmann's pouch that compresses the common hepatic duct). All patients suspected of having acute cholecystitis should be referred to hospital.

View larger version (31K): [in this window] [in a new window]   Fig 2.   Clinical features of acute cholecystitis: diagnosis is made when features from all three points of diagnostic triangle are present

Investigations
Ultrasound scanning is the investigation of choice in patients suspected of having acute cholecystitis. Sonograms typically show pericholecystic fluid (fluid around the gall bladder), distended gall bladder, oedematous gallbladder wall, and gall stones, and Murphy's sign can be elicited on ultrasound examination (fig 3). Colour flow Doppler ultrasound shows hyperaemic, pericholecystic blood flow and acute inflammation.⁷ Plain abdominal radiographs show radio-opaque gall stones in about 10% of cases of acute cholecystitis and gas within the gallbladder wall in emphysematous cholecystitis (fig 4).

View larger version (155K): [in this window] [in a new window]   Fig 3.   Ultrasound (B mode) findings in acute cholecystitis

View larger version (167K): [in this window] [in a new window]   Fig 4.   Plain abdominal radiograph showing emphysematous cholecystitis: note gas within the gallbladder wall and air fluid level within the gall bladder

Biliary scintigraphy (hydroxyiminodiacetic acid (HIDA) scan) is the gold standard investigation when the diagnosis remains in doubt after ultrasound scanning. The patient is given an intravenous injection of radiolabelled hydroxyiminodiacetic acid and then the abdomen is scanned; in patients with acute cholecystitis, the gallbladder lumen will not take up any radioactive isotope one to two hours after injection and therefore the gall bladder will not be visible on the scan. Occasionally, an acutely inflamed gall bladder may have delayed filling, leading to a false positive result, but augmentation with morphine reduces this.⁸

	Management

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Medical management
Most patients with acute cholecystitis respond to conservative, first line management: the gall stone disimpacts and falls back into the gall bladder, which allows the cystic duct to empty. If the gall stone does not disimpact, complicationssuch as advanced cholecystitis (gangrenous cholecysytitis or empyema of the gall bladder) or perforationmay result.

Immediate measures should be taken to rest the gall bladder; this will subdue the inflammatory process in most patients. Patients should be fasted, rehydrated with intravenous fluids, and given oxygen therapy and adequate analgesia. Indometacin (25 mg three times daily for a week) can reverse the inflammation of the gall bladder and the contractile dysfunction seen in the early stages (first 24 hours) of cholecystitis. The prokinetic action of indometacin will also improve postprandial emptying of the gall bladder in patients with gallbladder disease.¹⁰ A single intramuscular dose of diclofenac (75 mg) may substantially decrease the rate of progression to acute cholecystitis in patients with symptomatic gall stones.¹¹ Because of the risk of superimposed infection, intravenous antibiotics should be started empirically if the patient has systemic signs or if no improvement is seen after 12-24 hours. A second generation or newer cephalosporin should be used (for example, cefuroxime 1.5 g every 6-8 hours) with metronidazole (500 mg every 8 hours). Non-operative managementsolvent dissolution therapy or extracorporeal shockwave lithotripsyhas been used with variable results to treat chronic cholecystitis in patients unfit for surgery,¹² but it has no place in the management of acute cholecystitis.

Surgical management
About 20% of patients with acute cholecystitis need emergency surgery. Such surgery is indicated if the patient's condition deteriorates or when generalised peritonitis or emphysematous cholecystitis is present. These features suggest gangrene or perforation of the gall bladder.

Cholecystectomy
The timing of surgery for the 80% of patients without evidence of gangrene or perforation is under debate. Open cholecystectomy traditionally has been performed 6-12 weeks after the acute episode to allow the inflammatory process to resolve before the procedure (interval surgery).¹³ Patients with acute cholecystitis who undergo early laparoscopic cholecystectomy (before symptoms have lasted 72-96 hours) have lower complication rates and lower conversion rates than open cholecystectomy and shorter hospital stays than those undergoing interval surgery (table). Early surgery for acute cholecystitis also has a lower conversion rate than delayed surgery (which is performed during the index admission after conservative management and after symptoms have lasted 3-5 days) (table). ^{16 17} Early surgery also avoids complications when conservative treatment fails.¹⁸ A long time between onset of symptoms and presentation is associated with advanced disease (P=0.01).¹⁷

Percutaneous cholecystostomy
Percutaneous cholecystostomy is a minimally invasive procedure that can benefit patients with serious comorbidity who are at high risk from major surgery. Percutaneous cholecystostomy can be performed at the bedside under local anaesthetic and is suitable for patients in intensive care units and those with burns. It is the definitive treatment in patients with acalculous cholecystitis (see below), or it may be used as a temporising measureto drain infected bile and delay the need for definitive treatment.

	Sequelae of acute cholecystitis

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Gangrenous cholecystitis
Gangrenous cholecystitis occurs in 2-30% of cases of acute cholecystitis. Men aged over 50 with a history of cardiovascular disease and leucocytosis (>17 000 leucocytes/ml) have the highest risk of gangrene of the gall bladder.⁹ Gangrene occurs most commonly at the fundus because the vascular supply often becomes compromised. Urgent laparoscopic cholecystectomy should be considered in patients at high risk of gangrene, and the surgeon should have a low threshold for conversion to open cholecystectomy during the procedure.

Gallbladder perforation
The gall bladder is perforated in 10% of cases of acute cholecystitisusually in patients who sought medical attention after a delay or in those who do not respond to conservative management. Perforation most commonly occurs at the fundus. After the gall bladder has perforated, patients may experience transient relief of their symptoms because the gall bladder decompresses, but peritonitis then develops.

Free perforation presents with generalised biliary peritonitis and is associated with a mortality of 30%. Localised perforation, with the formation of pericholecystic abscesses, is more common, because the adherent viscera adjacent to the perforation tend to localise spillage of the contents of the gall bladder. A mass may be palpable in patients with localised perforation, and computed tomography is the most useful investigation.

Cholecystoenteric fistulas
An acutely inflamed gall bladder may create a cholecystoenteric fistula by adhering to and causing a perforation in other parts of the gastrointestinal tract. The most common sites for fistulas are the duodenum and the hepatic flexure of the colon. Decompression of the gall bladder because of a fistula may cause resolution of the acute cholecystitis. Air in the biliary tree (pneumobilia) can be seen on abdominal radiographs, and imaging enhanced with contrast agents may show fistulas.

View larger version (21K): [in this window] [in a new window]   Fig 5.   Pathogenesis and risk factors for acute acalculous cholecystitis

Gallstone ileus
Gallstone ileusobstruction of the small intestine caused by a gall stone passing from the biliary tract into the intestinal tract through a fistulashould be considered in elderly patients with no obvious cause for the intestinal obstruction. Patients may not have a history of cholecystitis. Mortality (15-20%) is attributed to delays before surgery is performed or to coexisting medical illnesses. Classic findings on abdominal radiographs include pneumobilia, intestinal obstructions, and gall stones in unusual sites.

	Acute cholecystitis and pregnancy

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Biliary tract disorders are the second most common general surgical condition in pregnancy, with an incidence of symptomatic gallstone disease of 0.1% (acute appendicitis is the most common surgical condition). Surgical intervention should be delayed until after delivery unless conservative treatment fails or symptoms recur in the same trimester. When surgery is indicated in pregnancy, laparoscopic cholecystectomy has been shown to be safe. ^{20 21}

	Acalculous cholecystitis

Top Methods Pathogenesis Presentation and diagnosis Management Sequelae of acute cholecystitis Acute cholecystitis and... Acalculous cholecystitis References

Acute acalculous cholecystitis is a life threatening condition that occurs in critically ill patients; it accounts for 5-14% of all cases of cholecystitis. The diagnosis is often elusive and is associated with considerable mortality (up to 50%).

Additional educational resources Review articles Kalloo AN, Kantsevoy SV. Gallstones and biliary disease. Prim Care 2001;28:591-606. Svanvik J. Laparoscopic cholecystectomy for acute cholecystitis. Eur J Surg 2000;166(suppl 585):16-7. Strasberg SM. Cholelithiasis and acute cholecystitis. Baillieres Clin Gastroenterol 1997;11:643-61. Websites Collaborative Hypertext of Radiology (http://chorus.rad.mcw.edu)a "quick reference" hypertext for physicians and medical students PathWeb (http://pathweb.uchc.edu/eAtlas/GI/1260.htm)virtual pathology museum Patient information World Book Medical Encyclopedia (www.rush.edu/worldbook/articles/003000a/003000224.html)entry on cholecystitis MediFocus MedCenter (www.solveyourproblem.com/medifocus/gs004.htm)summary longer publication, which is available for a fee Merck Manual of Medical InformationHome Edition (www.merck.com/pubs/mmanual_home/sec10/121.html)article on gallbladder disorders

Acalculous cholecystitis tends to occur in patients hospitalised for multiple trauma or acute non-biliary illness. Risk factors include severe trauma or burns, major surgery (such as cardiopulmonary bypass), long term fasting, total parenteral nutrition, sepsis, diabetes mellitus, atherosclerotic disease, systemic vasculitis, acute renal failure, and AIDS (fig 5).

Over 70% of patients have atherosclerotic disease; this might explain the high prevalence of the condition in elderly men.²²

Immunocompromised patients can develop primary infections caused by opportunistic organisms that result in primary infective cholecystitis (see box B on bmj.com). ^{23 24}

The diagnosis of acute acalculous cholecystitis may be hindered by obtundation of the patient, pre-existing disease, or recent abdominal surgery, and it needs a high index of suspicion. Ultrasound scanning is the investigation of choiceit can detect concomitant lesions, it can be performed in intensive care units, and therapeutic interventions (such as percutaneous drainage) can be done simultaneously.

Percutaneous cholecystostomy is an accepted alternative to cholecystectomy in the treatment of acute acalculous cholecystitis.²⁵ Early cholecystectomy may be appropriate, depending on the patient's clinical condition.

	Acknowledgments

This article is based on a keynote lecture given by IJB to the Association of Upper Gastrointestinal Surgeons at the Royal College of Physicians, Edinburgh, in September 2001.

	Footnotes

Competing interests: None declared.

Supplementary boxes appear on bmj.com

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Top Methods Pathogenesis Presentation and diagnosis Management Sequelae of acute cholecystitis Acute cholecystitis and... Acalculous cholecystitis References

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(Accepted 28 June 2002)