Acute cholecystitis
BMJ 2002; 325 doi: https://doi.org/10.1136/bmj.325.7365.639 (Published 21 September 2002) Cite this as: BMJ 2002;325:639
- Adrian A Indar, surgical fellow,
- Ian J Beckingham (Ian.Beckingham{at}nottingham.ac.uk), consultant hepatobiliary and laparoscopic surgeon
- Correspondence to: I J Beckingham
- Accepted 28 June 2002
Acute cholecystitis—inflammation of the gall bladder—is 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.
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
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
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 I2and E2, which mediate the inflammatory response (fig 11).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 persists—for example, because the patient has already had several pregnancies or is receiving total parenteral nutrition—gall stones can form.6 Most patients with biliary sludge have no symptoms, but the sludge itself can cause acute cholecystitis.
Presentation and diagnosis
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.
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).
Ultrasound (B mode) findings in acute cholecystitis
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
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, complications—such as advanced cholecystitis (gangrenous cholecysytitis or empyema of the gall bladder) or perforation—may 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 management—solvent dissolution therapy or extracorporeal shockwave lithotripsy—has 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
Conversion rate to open surgery and outcomes after surgery for acute cholecystitis in prospective randomised studies. Values are numbers (percentages) unless otherwise specified
Early laparoscopic surgery is safe and feasible in patients with acute cholecystitis. If early intervention—less than 72 hours after symptoms started—can be achieved, “oedema planes” presentduring this period allow the gall bladder to be dissected laparoscopically. Although it is desirable to operate within this time period, it is often difficult to do so in clinical practice. By the time inflammation has been present for more than 72 hours, features of chronic inflammation (such as fibrosis) predominate and make it more difficult to dissect the gall bladder (see box A on bmj.com). The optimal treatment for patients presenting with acute cholecystitis should be resuscitation followed by laparoscopic cholecystectomy on the next available surgical list.
Patients with fever, serum bilirubin >170 μmol/l, male sex, body temperature >38°C, and advanced cholecystitis are more likely to have complications. 17 19
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 measure—to drain infected bile and delay the need for definitive treatment.
Percutaneous cholecystostomy gives clinical improvement in about three quarters of patients. Mortality after this procedure is related to comorbidity (for example, pneumonia or myocardial infarction) or pre-existing sepsis. An incomplete or poor response to cholecystostomy within the first 48 hours may indicate causes of sepsis other than cholecystitis, inadequate antibiotic coverage, possible complications (such as dislodgement of the drainage tube), or necrosis of the wall of the gall bladder.
Patients can undergo cholecystectomy after percutaneous cholecystostomy. In patients unfit to be given a general anaesthetic, the drain can be left in place for more than six weeks to allow radiological extraction of calculi at a later date.
Sequelae of acute cholecystitis
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 cholecystitis—usually 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.
Pathogenesis and risk factors for acute acalculous cholecystitis
Gallstone ileus
Gallstone ileus—obstruction of the small intestine caused by a gall stone passing from the biliary tract into the intestinal tract through a fistula—should 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
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
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” hypertextfor 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 Information—Home Edition (http://www.merck.com/pubs/mmanual_home/sec10/121.htm)—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 choice—it 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