Acute cholecystitis: Pathogenesis, clinical features, and diagnosis

Authors

Salam F Zakko, MD, FACP

Nezam H Afdhal, MD, FRCPI

Section Editor

Sanjiv Chopra, MD, MACP

Deputy Editor

Anne C Travis, MD, MSc, FACG, AGAF

All topics are updated as new evidence becomes available and our peer review process is

complete.

Literature review current through: Mar 2015. | This topic last updated: Nov 19, 2013.

INTRODUCTION — Acute cholecystitis predominantly occurs as a complication of gallstone

disease and typically develops in patients with a history of symptomatic gallstones. In a

systematic review, it was seen in 6 to 11 percent of patients with symptomatic gallstones

over a median follow-up of 7 to 11 years [1]. (See"Uncomplicated gallstone disease in

adults", section on 'Natural history'.)

This topic will review the pathogenesis, clinical manifestations, and diagnosis of acute

cholecystitis. The management of uncomplicated gallstone disease, acalculous cholecystitis,

and the treatment of acute cholecystitis are discussed separately. (See "Uncomplicated

gallstone disease in adults" and "Acalculous cholecystitis" and"Treatment of acute calculous

cholecystitis".)

DEFINITIONS — The term cholecystitis refers to inflammation of the gallbladder. It may

develop acutely in association with gallstones (acute cholecystitis) or, less often, without

gallstones (acalculous cholecystitis). It may also develop over time and be discovered

histologically following cholecystectomy (chronic cholecystitis).

Acute cholecystitis — Acute cholecystitis refers to a syndrome of right upper quadrant

pain, fever, and leukocytosis associated with gallbladder inflammation that is usually related

to gallstone disease.

Acalculous cholecystitis — Acalculous cholecystitis is clinically identical to acute

cholecystitis but is not associated with gallstones and usually occurs in critically ill patients. It

accounts for approximately 10 percent of cases of acute cholecystitis and is associated with

high morbidity and mortality rates [2]. (See "Acalculous cholecystitis".)

Chronic cholecystitis — Chronic cholecystitis is the term used to describe chronic

inflammatory cell infiltration of the gallbladder seen on histopathology. It is almost invariably

associated with the presence of gallstones and is thought to be the result of mechanical

irritation or recurrent attacks of acute cholecystitis leading to fibrosis and thickening of the

gallbladder [3-5]. Its presence does not correlate with symptoms since patients with

extensive chronic inflammatory cell inflammation may have only minimal symptoms, and

there is no evidence that chronic cholecystitis increases the risk for future morbidity [6].

Hence, the clinical significance of this entity is questionable. (See "Uncomplicated gallstone

disease in adults".)

Some authors use the phrase "chronic cholecystitis" when referring to gallbladder

dysfunction as a cause of abdominal pain [7]. It is more appropriate in this instance to refer

to the condition based on the disorder present, such as pain due to gallstone disease, pain

due to biliary dyskinesia (which is attributed to sphincter of Oddi dysfunction), or pain due to

functional gallbladder disorder (also called gallbladder dyskinesia). (See "Clinical

manifestations and diagnosis of sphincter of Oddi dysfunction" and "Functional gallbladder

disorder in adults".)

PATHOGENESIS — Acute cholecystitis occurs in the setting of cystic duct obstruction.

However, in contrast to biliary colic, the development of acute cholecystitis is not fully

explained by cystic duct obstruction alone. Studies suggest that an additional irritant

(possibly lysolecithin) is required to develop gallbladder inflammation. Once inflammation of

the gallbladder begins, additional inflammatory mediators are released, further propagating

gallbladder inflammation. In many patients, infection of the biliary system is also involved in

the development of acute cholecystitis.

Studies in animals have demonstrated that ligation of the cystic duct alone does not result in

acute cholecystitis [8,9]. However, acute cholecystitis can be produced by blocking the cystic

duct, followed by deliberate irritation of the gallbladder mucosa (either mechanically with an

indwelling catheter or by infusion of an irritant).

One such irritant used in experimental models, lysolecithin, is produced from lecithin, a

normal constituent of bile. The production of lysolecithin from lecithin is catalyzed by

phospholipase A, which is present in gallbladder mucosa. This enzyme may be released into

the gallbladder following trauma to the gallbladder wall from an impacted gallstone [9].

Supporting this hypothesis is the observation that lysolecithin (normally absent in bile) is

detectable in gallbladder bile in patients with acute cholecystitis [10].

Inflammatory mediators are released in response to gallbladder inflammation and further

propagate the inflammation [11]. Prostaglandins, which are involved in gallbladder

contraction and fluid absorption, probably play a central role in this process. In experimental

models using human gallbladder tissue, the main prostaglandins synthesized by inflamed

human gallbladder microsomes were prostaglandin E2 and 6-keto-prostaglandin F1 alpha,

the concentrations of which were increased four times above normal [12]. The prostaglandin

hypothesis is supported by the observation that prostaglandin inhibitors relieve biliary colic

and can reduce intraluminal cystic pressure [13-15].

Infection of bile within the biliary system probably has a role in the development of

cholecystitis; however, not all patients with cholecystitis have infected bile. This observation

was illustrated in a study of 467 subjects in whom bile samples were obtained from the

gallbladder and common bile duct for aerobic and anaerobic culture [16]. Patients with a

variety of hepatobiliary diseases and a healthy control group were included. Patients with

gallstones, acute cholecystitis, and hydropic gallbladder had similar rates of positive cultures

in the gallbladder and common bile duct, ranging from 22 to 46 percent; cultures were

generally sterile in healthy subjects. The main species isolated were Escherichia coli,

Enterococcus, Klebsiella, and Enterobacter.

Histologic changes of the gallbladder in acute cholecystitis can range from mild edema and

acute inflammation to necrosis and gangrene. Occasionally, prolonged impaction of a stone

in the cystic duct can lead to a distended gallbladder that is filled with colorless, mucoid fluid.

This condition, known as a mucocele with white bile (hydrops), is due to the absence of bile

entry into the gallbladder and absorption of all the bilirubin within the gallbladder.

CLINICAL MANIFESTATIONS — The clinical manifestations of acute cholecystitis include

prolonged (more than four to six hours), steady, severe right upper quadrant or epigastric

pain, fever, abdominal guarding, a positive Murphy's sign, and leukocytosis.

History — Patients with acute cholecystitis typically complain of abdominal pain, most

commonly in the right upper quadrant or epigastrium. The pain may radiate to the right

shoulder or back. Characteristically, acute cholecystitis pain is steady and severe.

Associated complaints may include fever, nausea, vomiting, and anorexia. There is often a

history of fatty food ingestion one hour or more before the initial onset of pain. The episode

of pain is typically prolonged (greater than four to six hours).

Physical examination — Patients with acute cholecystitis are usually ill appearing, febrile,

and tachycardic, and lie still on the examining table because cholecystitis is associated with

true local parietal peritoneal inflammation that is aggravated by movement. Abdominal

examination usually demonstrates voluntary and involuntary guarding. Patients frequently

will have a positive Murphy's sign. (See 'Murphy's sign' below.)

Patients with complications may have signs of sepsis (gangrene), generalized peritonitis

(perforation), abdominal crepitus (emphysematous cholecystitis), or bowel obstruction

(gallstone ileus). (See 'Complications' below and "Sepsis and the systemic inflammatory

response syndrome: Definitions, epidemiology, and prognosis", section on

'Sepsis' and "Diagnostic approach to abdominal pain in adults", section on

'Peritonitis' and "Epidemiology, clinical features, and diagnosis of mechanical small bowel

obstruction in adults", section on 'Gallstones or foreign body' and "Epidemiology, clinical

features, and diagnosis of mechanical small bowel obstruction in adults", section on 'Clinical

presentations'.)

Laboratory evaluation — Patients typically have a leukocytosis with an increased number

of band forms (ie, a left shift). Elevation in the serum total bilirubin and alkaline phosphatase

concentrations are not common in uncomplicated acute cholecystitis since biliary obstruction

is limited to the gallbladder; if present, they should raise concerns about complicating

conditions such as cholangitis, choledocholithiasis, or Mirizzi syndrome (a gallstone

impacted in the distal cystic duct causing extrinsic compression of the common bile duct)

(image 1). (See "Mirizzi syndrome".)

However, there have been reports of mild elevations in serum aminotransferases and

amylase, along with hyperbilirubinemia and jaundice, even in the absence of these

complications [17]. These abnormalities may be due to the passage of small stones, sludge,

or pus.

In patients with emphysematous cholecystitis, mild to moderate unconjugated

hyperbilirubinemia may be present because of hemolysis induced by clostridial infection.

(See 'Emphysematous cholecystitis' below.)

DIAGNOSIS — Acute cholecystitis should be suspected in a patient presenting with right

upper quadrant or epigastric pain, fever, and a leukocytosis. A positive Murphy's sign

supports the diagnosis [18]. However, history, physical examination, and laboratory test

findings are not sufficient to establish the diagnosis. Confirmation of the diagnosis requires

demonstration of gallbladder wall thickening or edema, a sonographic Murphy's sign, or

failure of the gallbladder to fill during cholescintigraphy (algorithm 1). In most cases, the

diagnosis can be confirmed with an abdominal ultrasound. If the diagnosis remains unclear,

cholescintigraphy can be obtained.

Murphy's sign — Patients with acute cholecystitis frequently have a positive "Murphy's

sign". To check for a Murphy's sign, the patient is asked to inspire deeply while the examiner

palpates the area of the gallbladder fossa just beneath the liver edge. Deep inspiration

causes the gallbladder to descend toward and press against the examining fingers, which in

patients with acute cholecystitis commonly leads to increased discomfort and the patient

catching his or her breath.

In one study, using cholescintigraphy as the gold standard, the sensitivity and specificity of a

positive Murphy's sign were 97 and 48 percent, respectively [19]. However, the sensitivity

may be diminished in the elderly [20].

Imaging studies — Physical examination alone cannot determine which abdominal viscera

is the source of inflammation and pain. Thus, patients presenting with clinical features

suggestive of acute cholecystitis should undergo abdominal imaging to confirm the

diagnosis. Ultrasonography is usually the first test obtained and can often establish the

diagnosis. Nuclear cholescintigraphy may be useful in cases in which the diagnosis remains

uncertain after ultrasonography.

Ultrasonography — The presence of stones in the gallbladder in the clinical setting of right

upper quadrant abdominal pain and fever supports the diagnosis of acute cholecystitis but is

not diagnostic. Additional sonographic features include:

●Gallbladder wall thickening (greater than 4 to 5 mm) or edema (double wall sign)

(image 2).

●A "sonographic Murphy's sign" is similar to the Murphy's sign elicited during

abdominal palpation, except that the positive response is observed during palpation

with the ultrasound transducer. This is more accurate than hand palpation because it

can confirm that it is indeed the gallbladder that is being pressed by the imaging

transducer when the patient catches his or her breath.

Several studies have evaluated the accuracy of ultrasonography in the diagnosis of acute

cholecystitis [18,21-26]. A particularly informative systematic review summarized the results

of 30 studies of ultrasonography for gallstones and acute cholecystitis [23]. Adjusted

sensitivity and specificity for diagnosis of acute cholecystitis were 88 percent (95%

confidence interval [CI] 0.74 to 1.00) and 80 percent (95% CI 0.62 to 0.98), respectively.

The sensitivity and specificity of ultrasonography for detection of gallstones are

approximately 84 (95% CI 0.76 to 0.92) and 99 percent (95% CI 0.97 to 1.00), respectively

[23]. Ultrasonography may not detect small stones or sludge as illustrated by a study that

compared ultrasonography with direct percutaneous mini-endoscopy in patients who had

undergone topical gallstone dissolution [27]. Ultrasonography was negative in 12 of 13

patients in whom endoscopy demonstrated 1 to 3 mm stones or fragments (picture 1) [27].

In patients with emphysematous cholecystitis, the ultrasound report may erroneously note

the presence of "overlying bowel gas making adequate visualization of the gallbladder

difficult", when in reality, this reflects air in the wall of the gallbladder. (See 'Emphysematous

cholecystitis' below.)

Cholescintigraphy (HIDA scan) — Cholescintigraphy using 99mTc-hepatic iminodiacetic

acid (generically referred to as a HIDA scan) is indicated if the diagnosis remains uncertain

following ultrasonography. Technetium labeled hepatic iminodiacetic acid (HIDA) is injected

intravenously and is then taken up selectively by hepatocytes and excreted into bile. If the

cystic duct is patent, the tracer will enter the gallbladder, leading to its visualization without

the need for concentration. The HIDA scan is also useful for demonstrating patency of the

common bile duct and ampulla. Normally, visualization of contrast within the common bile

duct, gallbladder, and small bowel occurs within 30 to 60 minutes (image 3). The test is

positive if the gallbladder does not visualize. This occurs because of cystic duct obstruction,

usually from edema associated with acute cholecystitis or an obstructing stone (image 4).

Cholescintigraphy has a sensitivity and specificity for acute cholecystitis of approximately 97

and 90 percent, respectively [23,26,28]. Cystic duct obstruction with a stone or tumor in the

absence of acute cholecystitis can cause a false positive test. Conditions that can cause

false positive results despite a non-obstructed cystic duct include:

●Severe liver disease, which may lead to abnormal uptake and excretion of the tracer.

●Fasting patients receiving total parenteral nutrition, in whom the gallbladder is already

maximally full due to prolonged lack of stimulation.

●Biliary sphincterotomy, which may result in low resistance to bile flow, leading to

preferential excretion of the tracer into the duodenum without filling of the gallbladder.

●Hyperbilirubinemia, which may be associated with impaired hepatic clearance of

iminodiacetic acid compounds. Newer agents commonly used in cholescintigraphy

(diisopropyl and m-bromotrimethyl iminodiacetic acid) have generally overcome this

limitation [29].

False negative results are uncommon since most patients with acute cholecystitis have

obstruction of the cystic duct. When they occur, they may be due to incomplete cystic duct

obstruction.

Morphine cholescintigraphy — A modified version of the HIDA scan has been described in

which patients are given intravenous morphine during the examination. Morphine increases

sphincter of Oddi pressure, thereby causing a more favorable pressure gradient for the

radioactive tracer to enter the cystic duct. This modification is thought to be particularly

useful in critically ill patients, in whom standard HIDA scanning may be associated with false

positive results [30,31]. However, the test has not been well standardized and has not

gained wide acceptance.

Magnetic resonance cholangiography — Magnetic resonance cholangiopancreatography

(MRCP) is a noninvasive technique for evaluating the intrahepatic and extrahepatic bile

ducts (image 5). Its role in the diagnosis of acute cholecystitis was evaluated in a series that

included 35 patients with symptoms of acute cholecystitis who underwent both ultrasound

and MRCP prior to cholecystectomy [7]. MRCP was superior to ultrasound for detecting

stones in the cystic duct (sensitivity 100 versus 14 percent) but was less sensitive than

ultrasound for detecting gallbladder wall thickening (sensitivity 69 versus 96 percent). At the

present time, its role in the diagnosis of acute cholecystitis should remain within clinical

trials. However, MRCP may be appropriate if there is concern that the patient may have a

stone in the common bile duct. (See "Magnetic resonance cholangiopancreatography".)

Computed tomography — Abdominal computed tomography (CT) is usually unnecessary

in the diagnosis of acute cholecystitis, although it can easily demonstrate gallbladder wall

edema associated with acute cholecystitis (image 6). Other CT findings include

pericholecystic stranding and fluid, and high-attenuation bile [32,33]. However, CT may fail

to detect gallstones because many stones are isodense with bile (image 7) [34,35]. CT can

be useful when complications of acute cholecystitis (such as emphysematous cholecystitis

or gallbladder perforation) are suspected or when other diagnoses are being considered.

(See 'Complications' below.)

Oral cholecystography — Oral cholecystography has no role in the diagnosis of acute

cholecystitis since it cannot show gallbladder wall edema and requires days to complete.

(See "Uncomplicated gallstone disease in adults", section on 'Oral cholecystography'.)

DIFFERENTIAL DIAGNOSIS — The greatest initial challenge in the diagnosis of acute

cholecystitis is distinguishing it from the more benign condition of biliary colic. Biliary colic is

usually caused by the gallbladder contracting in response to a fatty meal, pressing a stone

against the gallbladder outlet or cystic duct opening. This then results in increased intra-

gallbladder pressure and pain. As in acute cholecystitis, biliary colic causes pain in the right

upper quadrant. However, unlike acute cholecystitis, the pain is entirely visceral in origin,

without true gallbladder wall inflammation, so peritoneal signs are absent. In addition,

patients with biliary colic are afebrile with normal laboratory studies. As the gallbladder

relaxes, the stones often fall back from the cystic duct. As a result, the attack reaches a

crescendo over a number of hours and then resolves completely. (See "Uncomplicated

gallstone disease in adults", section on 'Biliary colic'.)

Most patients who develop acute cholecystitis have had previous attacks of biliary colic,

which may further confuse the diagnosis or lead patients to delay seeking medical attention.

The following features may help to distinguish an attack of biliary colic from acute

cholecystitis. However, such patients usually require imaging studies to help establish the

diagnosis:

●The pain of biliary colic typically reaches a crescendo, and then resolves completely.

Pain resolution occurs when the gallbladder relaxes, permitting stones to fall back from

the cystic duct. An episode of right upper quadrant pain lasting for more than four to six

hours should raise suspicion for acute cholecystitis.

●Patients with constitutional symptoms such as malaise or fever are more likely to

have acute cholecystitis.

Symptoms that are not suggestive of a biliary etiology include fatty food intolerance not in

the form of pain, nausea not in association with pain, pain only a few minutes after a meal,

irregular bowel habits, or belching [36,37].

A variety of other conditions can give rise to symptoms in the upper abdomen, which may be

confused with biliary colic or acute cholecystitis. These include:

●Acute pancreatitis.

●Appendicitis.

●Acute hepatitis.

●Peptic ulcer disease.

●Nonulcer dyspepsia.

●Irritable bowel disease.

●Functional gallbladder disorder.

●Sphincter of Oddi dysfunction.

●Diseases of the right kidney.

●Right-sided pneumonia.

●Fitz-Hugh-Curtis syndrome (perihepatitis caused by gonococcal infection). Right

upper quadrant pain with fever and even a possible positive Murphy's sign in patients

at high risk for sexually transmitted diseases should raise this possibility. The HIDA

scan is usually negative, but pericholecystic fluid may be confused with acute

cholecystitis (image 8).

●Subhepatic or intraabdominal abscess.

●Perforated viscus.

●Cardiac ischemia.

●Black widow spider envenomation [38].

These conditions can usually be differentiated by the clinical setting in which they occur and

by obtaining the appropriate diagnostic studies. (See "Differential diagnosis of abdominal

pain in adults", section on 'Upper abdominal pain syndromes' and "Diagnostic approach to

abdominal pain in adults", section on 'Acute abdominal pain'.)

COMPLICATIONS — Left untreated, symptoms of cholecystitis may abate within 7 to 10

days. However, complications are common, so patients with suspected acute cholecystitis

require definitive treatment (eg, cholecystectomy). The most common complication is the

development of gallbladder gangrene (up to 20 percent of cases) (image 9) with subsequent

perforation (2 percent of cases) [39]. (See "Treatment of acute calculous cholecystitis".)

Gangrene — Gangrenous cholecystitis is the most common complication of cholecystitis,

particularly in older patients, patients with diabetes, or those who delay seeking therapy [39].

The presence of a sepsis-like picture in addition to the other symptoms of cholecystitis

suggests the diagnosis, but gangrene may not be suspected preoperatively. (See "Sepsis

and the systemic inflammatory response syndrome: Definitions, epidemiology, and

prognosis", section on 'Sepsis'.)

Perforation — Perforation of the gallbladder usually occurs after the development of

gangrene. It is often localized, resulting in a pericholecystic abscess (image 10). Less

commonly, perforation is free into the peritoneum, leading to generalized peritonitis (image

11). Such cases are associated with a high mortality rate. (See"Diagnostic approach to

abdominal pain in adults", section on 'Peritonitis'.)

Cholecystoenteric fistula — A cholecystoenteric fistula may result from perforation of the

gallbladder directly into the duodenum or jejunum. Fistula formation is more often due to

long standing pressure necrosis from stones than to acute cholecystitis [40].

Gallstone ileus — Passage of a gallstone through a cholecystoenteric fistula may lead to

the development of mechanical bowel obstruction, usually in the terminal ileum (gallstone

ileus) (image 12) [41]. (See "Gallstone ileus" and "Epidemiology, clinical features, and

diagnosis of mechanical small bowel obstruction in adults", section on 'Clinical

presentations' and "Epidemiology, clinical features, and diagnosis of mechanical small bowel

obstruction in adults", section on 'Gallstones or foreign body'.)

Emphysematous cholecystitis — Emphysematous cholecystitis is caused by secondary

infection of the gallbladder wall with gas-forming organisms (such as Clostridium welchii)

(image 13) [42,43]. Other organisms that may be isolated include Escherichia coli (15

percent), staphylococci, streptococci, Pseudomonas, and Klebsiella [43].

Affected patients are often men in their fifth to seventh decade [43], and approximately one-

third to one-half have diabetes [43-45]. Gallstones are present in about one-half of patients.

Like other patients with acute cholecystitis, patients with emphysematous cholecystitis

usually present with right upper quadrant pain, nausea, vomiting, and low-grade fever.

Peritoneal signs are usually absent, but crepitus in the abdominal wall adjacent to the gall

bladder may rarely be detected. When such crepitus is present, it is an important clue to the

diagnosis. Mild to moderate unconjugated hyperbilirubinemia may be present (caused by

hemolysis induced by clostridial infection). The ultrasound report may erroneously note the

presence of "overlying bowel gas making adequate visualization of the gallbladder difficult",

when in reality, this reflects air in the wall of the gallbladder.

Emphysematous cholecystitis often heralds the development of gangrene, perforation, and

other complications [43-45]. In a review of 20 patients with emphysematous cholecystitis,

gallbladder perforation occurred in seven, pericholecystic abscess in nine, and bile peritonitis

in three [45].

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education

materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are

written in plain language, at the 5th to 6

th grade reading level, and they answer the four or five

key questions a patient might have about a given condition. These articles are best for

patients who want a general overview and who prefer short, easy-to-read materials. Beyond

the Basics patient education pieces are longer, more sophisticated, and more detailed.

These articles are written at the 10th to 12

th grade reading level and are best for patients who

want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to

print or e-mail these topics to your patients. (You can also locate patient education articles

on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient information: Gallstones (The Basics)" and "Patient

information: Gallbladder removal (cholecystectomy) (The Basics)")

●Beyond the Basics topics (see "Patient information: Gallstones (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Acute cholecystitis refers to a syndrome of right upper quadrant pain, fever, and

leukocytosis associated with gallbladder inflammation and is usually related to

gallstone disease. (See 'Definitions' above.)

●Patients with acute cholecystitis typically complain of abdominal pain, most commonly

in the right upper quadrant or epigastrium. The pain may radiate to the right shoulder or

back. Characteristically, acute cholecystitis pain is prolonged (more than four to six

hours), steady, and severe. Associated complaints may include nausea, vomiting, and

anorexia. (See 'Clinical manifestations' above.)

●Acute cholecystitis should be suspected in a patient presenting with right upper

quadrant or epigastric pain, fever, and a leukocytosis. A positive Murphy's sign

supports the diagnosis. However, history, physical examination, and laboratory test

findings are not sufficient to make the diagnosis. Confirmation of the diagnosis requires

demonstration of gallbladder wall thickening or edema, a sonographic Murphy's sign, or

failure of the gallbladder to fill during cholescintigraphy (algorithm 1).

(See 'Diagnosis' above.)

●Acute cholecystitis must be distinguished from the more benign condition of biliary

colic, which presents with the same type of pain. Most patients who develop acute

cholecystitis have had previous attacks of biliary colic. The following features may help

to distinguish an attack of biliary colic from acute cholecystitis, though such patients

usually require imaging studies to help establish the diagnosis (see 'Differential

diagnosis' above and "Uncomplicated gallstone disease in adults", section on 'Biliary

colic'):

•The pain of biliary colic typically reaches a crescendo and then resolves

completely. Pain resolution occurs when the gallbladder relaxes, permitting

stones to fall back from the cystic duct. An episode of right upper quadrant pain

lasting for more than four to six hours should raise suspicion for acute

cholecystitis.

•Patients with constitutional symptoms such as malaise or fever are more likely to

have acute cholecystitis.

•Patients with biliary colic do not have signs of peritonitis on examination and

have normal laboratory tests.

●Left untreated, symptoms of cholecystitis may abate within 7 to 10 days. However,

complications are common, so patients with suspected acute cholecystitis require

definitive treatment (eg, cholecystectomy). The most common complication of acute

cholecystitis is the development of gallbladder gangrene (up to 20 percent of cases)

with subsequent perforation (2 percent of cases). (See 'Complications' above

and "Treatment of acute calculous cholecystitis".)

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REFERENCES

1. Friedman GD. Natural history of asymptomatic and symptomatic gallstones. Am J Surg 1993; 165:399.

2. Barie PS, Fischer E. Acute acalculous cholecystitis. J Am Coll Surg 1995; 180:232. 3. Ziessman HA. Cholecystokinin cholescintigraphy: clinical indications and proper

methodology. Radiol Clin North Am 2001; 39:997. 4. Kalloo AN, Kantsevoy SV. Gallstones and biliary disease. Prim Care 2001; 28:591. 5. Ahmed A, Cheung RC, Keeffe EB. Management of gallstones and their complications. Am

Fam Physician 2000; 61:1673. 6. Nahrwold DL, Rose RC, Ward SP. Abnormalities in gallbladder morphology and function in

patients with cholelithiasis. Ann Surg 1976; 184:415. 7. Park MS, Yu JS, Kim YH, et al. Acute cholecystitis: comparison of MR cholangiography and

US. Radiology 1998; 209:781. 8. MORRIS CR, HOHF RP, IVY AC. An experimental study of the role of stasis in the etiology

of cholecystitis. Surgery 1952; 32:673. 9. Roslyn JJ, DenBesten L, Thompson JE Jr, Silverman BF. Roles of lithogenic bile and cystic

duct occlusion in the pathogenesis of acute cholecystitis. Am J Surg 1980; 140:126. 10. Kaminski DL. Arachidonic acid metabolites in hepatobiliary physiology and disease.

Gastroenterology 1989; 97:781. 11. Jivegård L, Thornell E, Svanvik J. Pathophysiology of acute obstructive cholecystitis:

implications for non-operative management. Br J Surg 1987; 74:1084. 12. Myers SI, Bartula L. Human cholecystitis is associated with increased gallbladder

prostaglandin I2 and prostaglandin E2 synthesis. Hepatology 1992; 16:1176. 13. Thornell E, Jansson R, Svanvik J. Indomethacin reduces raised intraluminal gallbladder

pressure in acute cholecystitis. Acta Chir Scand 1985; 151:261. 14. Thornell E, Jansson R, Svanvik J. Indomethacin intravenously--a new way for effective relief

of biliary pain: a double-blind study in man. Surgery 1981; 90:468. 15. Akriviadis EA, Hatzigavriel M, Kapnias D, et al. Treatment of biliary colic with diclofenac: a

randomized, double-blind, placebo-controlled study. Gastroenterology 1997; 113:225.

16. Csendes A, Burdiles P, Maluenda F, et al. Simultaneous bacteriologic assessment of bile from gallbladder and common bile duct in control subjects and patients with gallstones and common duct stones. Arch Surg 1996; 131:389.

17. Kurzweil SM, Shapiro MJ, Andrus CH, et al. Hyperbilirubinemia without common bile duct abnormalities and hyperamylasemia without pancreatitis in patients with gallbladder disease. Arch Surg 1994; 129:829.

18. Trowbridge RL, Rutkowski NK, Shojania KG. Does this patient have acute cholecystitis? JAMA 2003; 289:80.

19. Singer AJ, McCracken G, Henry MC, et al. Correlation among clinical, laboratory, and hepatobiliary scanning findings in patients with suspected acute cholecystitis. Ann Emerg Med 1996; 28:267.

20. Adedeji OA, McAdam WA. Murphy's sign, acute cholecystitis and elderly people. J R Coll Surg Edinb 1996; 41:88.

21. Ralls PW, Colletti PM, Lapin SA, et al. Real-time sonography in suspected acute cholecystitis. Prospective evaluation of primary and secondary signs. Radiology 1985; 155:767.

22. Cooperberg PL, Burhenne HJ. Real-time ultrasonography. Diagnostic technique of choice in calculous gallbladder disease. N Engl J Med 1980; 302:1277.

23. Shea JA, Berlin JA, Escarce JJ, et al. Revised estimates of diagnostic test sensitivity and specificity in suspected biliary tract disease. Arch Intern Med 1994; 154:2573.

24. Kalimi R, Gecelter GR, Caplin D, et al. Diagnosis of acute cholecystitis: sensitivity of sonography, cholescintigraphy, and combined sonography-cholescintigraphy. J Am Coll Surg 2001; 193:609.

25. Chatziioannou SN, Moore WH, Ford PV, Dhekne RD. Hepatobiliary scintigraphy is superior to abdominal ultrasonography in suspected acute cholecystitis. Surgery 2000; 127:609.

26. Kiewiet JJ, Leeuwenburgh MM, Bipat S, et al. A systematic review and meta-analysis of diagnostic performance of imaging in acute cholecystitis. Radiology 2012; 264:708.

27. Zakko SF, Srb S, Ramsby GR. Sensitivity of percutaneous endoscopy compared with ultrasonography in the detection of residue or mucosal lesions after topical gallbladder stone dissolution. Gastrointest Endosc 1995; 42:434.

28. Fink-Bennett D, Freitas JE, Ripley SD, Bree RL. The sensitivity of hepatobiliary imaging and real-time ultrasonography in the detection of acute cholecystitis. Arch Surg 1985; 120:904.

29. Kim EE, Moon TY, Delpassand ES, et al. Nuclear hepatobiliary imaging. Radiol Clin North Am 1993; 31:923.

30. Flancbaum L, Choban PS, Sinha R, Jonasson O. Morphine cholescintigraphy in the evaluation of hospitalized patients with suspected acute cholecystitis. Ann Surg 1994; 220:25.

31. Oates E, Selland DL, Chin CT, Achong DM. Gallbladder nonvisualization with pericholecystic rim sign: morphine-augmentation optimizes diagnosis of acute cholecystitis. J Nucl Med 1996; 37:267.

32. Paulson EK. Acute cholecystitis: CT findings. Semin Ultrasound CT MR 2000; 21:56. 33. Fidler J, Paulson EK, Layfield L. CT evaluation of acute cholecystitis: findings and

usefulness in diagnosis. AJR Am J Roentgenol 1996; 166:1085. 34. Barakos JA, Ralls PW, Lapin SA, et al. Cholelithiasis: evaluation with CT. Radiology 1987;

162:415. 35. Benarroch-Gampel J, Boyd CA, Sheffield KM, et al. Overuse of CT in patients with

complicated gallstone disease. J Am Coll Surg 2011; 213:524. 36. Barbara L, Sama C, Morselli Labate AM, et al. A population study on the prevalence of

gallstone disease: the Sirmione Study. Hepatology 1987; 7:913.

37. Kraag N, Thijs C, Knipschild P. Dyspepsia--how noisy are gallstones? A meta-analysis of epidemiologic studies of biliary pain, dyspeptic symptoms, and food intolerance. Scand J Gastroenterol 1995; 30:411.

38. Bush SP. Black widow spider envenomation mimicking cholecystitis. Am J Emerg Med 1999; 17:315.

39. Reiss R, Nudelman I, Gutman C, Deutsch AA. Changing trends in surgery for acute cholecystitis. World J Surg 1990; 14:567.

40. Roslyn JJ, Thompson JE Jr, Darvin H, DenBesten L. Risk factors for gallbladder perforation. Am J Gastroenterol 1987; 82:636.

41. Clavien PA, Richon J, Burgan S, Rohner A. Gallstone ileus. Br J Surg 1990; 77:737. 42. Lorenz RW, Steffen HM. Emphysematous cholecystitis: diagnostic problems and differential

diagnosis of gallbladder gas accumulations. Hepatogastroenterology 1990; 37 Suppl 2:103. 43. Sarmiento RV. Emphysematous cholecystitis. Report of four cases and review of the

literature. Arch Surg 1966; 93:1009. 44. Mentzer RM Jr, Golden GT, Chandler JG, Horsley JS 3rd. A comparative appraisal of

emphysematous cholecystitis. Am J Surg 1975; 129:10. 45. Garcia-Sancho Tellez L, Rodriguez-Montes JA, Fernandez de Lis S, Garcia-Sancho Martin

L. Acute emphysematous cholecystitis. Report of twenty cases. Hepatogastroenterology 1999; 46:2144.

Ultrasound from a patient with acute cholecystitis and Mirizzi syndrome

Transabdominal ultrasound from a patient with acute cholecystitis and Mirizzi syndrome. The

patient presented with right upper quadrant pain and jaundice. Acute cholecystitis and

Mirizzi syndrome are confirmed by the ultrasound findings of a positive sonographic

Murphy's sign (pain with compression of the gallbladder by the ultrasound probe), a large

shadowing stone impacted in the infundibulum of the gallbladder (white arrow), cholestasis

with sludge (yellow arrowhead), and a dilated common hepatic duct (white arrowheads in

B).Graphic 86878 Version 1.0

Algorithm for the diagnosis of acute cholecystitis

GB: gallbladder; U/S: ultrasound.Graphic 50032 Version 3.0

Acute cholecystitis with pericholecystic fluid seen on

ultrasound

(A) Longitudinal view of the gallbladder showing small shadowing stones in the dependent

part of the gallbladder (green arrow). The ultrasound also shows a thickened wall in both

the longitudinal projection (white arrow) and transverse projection (B). (B) A small amount

of pericholecystic fluid is noted (yellow arrow). (C) The Doppler study shows an increase in

blood flow to the wall (red arrow) reminiscent of the hyperemia of an inflammatory process.

These findings are consistent with acute calculous cholecystitis. Graphic 83042 Version 2.0

Percutaneous gallbladder endoscopy showing gallstone

Percutaneous gallbladder endoscopy shows a small gallstone that was not detected on

ultrasonography. Courtesy of Salam Zakko, MD, FACP. Graphic 65714 Version 2.0

Normal HIDA scan

This is an example of a normal 99mTc-hepatic iminodiacetic acid (HIDA) scan and shows

early filling of the gallbladder at 15 minutes (white arrow) and complete filling by 25

minutes (white arrowhead), indicating a patent cystic duct. Graphic 59241 Version 3.0

HIDA scan in a patient with acute cholecystitis

The hepatic iminodiacetic acid (HIDA) scan is abnormal and shows absence of filling of the

gallbladder, indicating obstruction of the cystic duct. The duodenum starts to fill with

radioisotope at about 20 minutes (white arrow). The radioisotope flows directly into the

duodenum (white arrow) starting at 20 minutes. The gallbladder never fills during the

course of the 60 minute examination. These findings are consistent with the diagnosis of

acute cholecystitis. Graphic 86879 Version 1.0

Magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) in a patient with acute

cholecystitis

MRI and MRCP images from a patient with acute cholecystitis. Contrast enhanced (A) and fat

saturated T2-weighted imaging (B) reveal a hyperemic gallbladder wall (white arrowheads).

Multiple small stones are noted lying dependently in the base of the gallbladder (white

arrow). The MRCP in the coronal projections (C and D) reveals accumulation of

pericholecystic fluid (short yellow arrows). These findings are consistent with the diagnosis of

acute cholecystitis Graphic 86864 Version 2.0

Computed tomographic (CT) scan from a patient with acute cholecystitis

The CT scan shows a distended gallbladder with an edematous and hyperemic wall (thick

arrow) and inflammatory induration in the fat surrounding the gallbladder (arrowheads). A

calcified stone is visible lying dependently at the base of the gallbladder (thin arrow).

Graphic 77336 Version 3.0

Computed tomographic (CT) scan and ultrasound in a patient with acute

cholecystitis

The CT scan (A and B) shows a thick walled and distended gallbladder (thick white arrow)

with pericholecystic induration (yellow arrowheads). However, it does not reveal

gallstones. The radiologic differential diagnosis includes acute calculous and acalculous

cholecystitis. The ultrasound (C and D) confirms the presence of a distended gallbladder

(thick white arrow) with stones (black arrow), and the presence of tumefactive sludge

(short yellow arrow). The thin white arrow shows a small amount of fluid in the gallbladder

fossa. These findings are consistent with acute calculous cholecystitis. Graphic 86866

Version 1.0

Fitz-Hugh Curtis syndrome

A CT-scan image (left) of a young female with Fitz-Hugh Curtis Syndrome. Note the

contracted gallbladder in the very center giving the appearance of a gallstone and the large

amount of pericholecystic fluid around it. The ultrasound image (right) confirms the

contracted gallbladder with the double wall sign. Courtesy of Salam F Zakko, MD,

FACP.Graphic 65754 Version 3.0

Gallbladder gangrene on transabdominal ultrasound

Transabdominal ultrasound of a gangrenous gallbladder showing evidence of necrotic and

denuded mucosa. The longitudinal view of the base of the gallbladder (A) shows a distended

gallbladder, with multiple stones within gallbladder sludge (thin yellow arrow) casting an

acoustic shadow (thick yellow arrow). The longitudinal view of the fundus (B) demonstrates

denuded mucosa (yellow arrowhead), indicating early necrosis of the gallbladder wall.

Graphic 86863 Version 1.0

Liver abscess complicating acute cholecystitis

Computed

tomographic (CT) scan in a patient with acute cholecystitis complicated by perforation and

liver abscess formation. (A) The CT scan shows a gall stone (yellow arrow) surrounded by

an irregular accumulation of fluid with a hyperemic rim (yellow arrowhead). (B) The fluid

can be seen extending from the gallbladder fossa into the liver parenchyma (yellow

arrowhead). (C) Percutaneous aspiration of pus confirmed the presence of an abscess and a

drain was placed (yellow arrow). Following drainage of the abscess, a small amount of

contrast was injected into the decompressed cavity. Graphic 86867 Version 1.0

Contained gallbladder perforation in a patient with acute cholecystitis

Computed

tomographic (CT) scan showing a sealed perforation of the gallbladder. Transverse (A) and

reformatted coronal projections (B) of the CT scan demonstrate a focal accumulation of fluid

near the fundus of the gallbladder (white arrowhead) with significant induration in the

pericholecystic fat (yellow arrow). At surgery a necrotic and perforated gallbladder was

identified. Graphic 86865 Version 1.0

Gallstone ileus seen on computed tomography (CT) scan

CT scan in a 75-year-old woman with small bowel obstruction due to gallstone ileus. Left

panel: Free air is seen in the biliary tree and gallbladder (arrow). Right panel: Dilated loops

of small bowel with large gallstone with a calcified rim (arrow) impacted in the terminal

ileum. Courtesy of Nezam Afdhal, MD. Graphic 80522 Version 5.0

Emphysematous cholecystitis seen on computed tomographic scan

(A) An axial image of a contrast enhanced computed tomographic (CT) scan demonstrating air within the gallbladder lumen (arrows). (B) A coronal reformat of a contrast enhanced CT demonstrating air within the wall of the gallbladder (arrow).

Treatment of acute calculous cholecystitis

Authors

Charles M Vollmer, Jr, MD

Salam F Zakko, MD, FACP

Nezam H Afdhal, MD, FRCPI

Section Editor

Stanley W Ashley, MD

Deputy Editor

Kathryn A Collins, MD, PhD, FACS

All topics are updated as new evidence becomes available and our peer review process is

complete.

Literature review current through: Mar 2015. | This topic last updated: Feb 03, 2015.

INTRODUCTION — Acute cholecystitis refers to a syndrome of right upper quadrant pain,

fever, and leukocytosis associated with gallbladder inflammation, which is usually related to

gallstone disease (ie, acute calculous cholecystitis). Complications include the development

of gangrene and gallbladder perforation, which can be life-threatening.

The treatment of acute calculous cholecystitis will be reviewed here. The approach to

patients with asymptomatic gallstones, the approach to the pregnant patient with gallstones,

and the clinical manifestations and diagnosis of biliary colic, acute cholecystitis and related

conditions, such as acalculous and xanthogranulomatous cholecystitis, are discussed

separately. (See "Uncomplicated gallstone disease in adults" and "Approach to the patient

with incidental gallstones" and"Choledocholithiasis: Clinical manifestations, diagnosis, and

management" and "Gallstones in pregnancy" and "Acute cholecystitis: Pathogenesis, clinical

features, and diagnosis" and "Acalculous cholecystitis" and "Xanthogranulomatous

cholecystitis".)

OVERVIEW OF TREATMENT — Once a patient develops symptoms or complications

related to gallstones (biliary colic, acute cholecystitis, cholangitis, and/orpancreatitis),

definitive therapy (cholecystectomy, cholecystostomy, endoscopic sphincterotomy, medical

gallstone dissolution) is recommended. Without treatment to eliminate the gallstones, the

likelihood of subsequent symptoms or complications is high. Complications include the

development of gangrene and gallbladder perforation, which can be life-threatening.

(See 'Morbidity and mortality' below.)

●In the National Cooperative Gallstone Study, a trial of nonsurgical treatment with

chenodiol for biliary tract pain, demonstrated that the risk of recurrent symptoms for

untreated patients was approximately 70 percent during the two years following initial

presentation [1].

●In a cohort study of 25,397 patients from Ontario, Canada with a first episode of

uncomplicated acute cholecystitis, 10,304 did not undergo cholecystectomy on their

first admission [2]. During a median 3.4 years of follow-up, 24 percent of patients had a

gallstone-related event with the majority of events occurring within the first year (88

percent). The risk was highest among 18 to 34-year-old patients. Among the events, 30

percent were for biliary obstruction or pancreatitis.

●A review of the United States Medicare database that included 29,818 elderly patients

with acute cholecystitis, found a higher risk for mortality over the following two years in

patients who were discharged without surgery compared with patients who underwent

cholecystectomy in the initial hospitalization (hazard ratio 1.56, 95% CI 1.47-1.65) [3].

Our treatment approach is as follows (algorithm 1):

●Patients with acute cholecystitis should be admitted to the hospital for supportive

care, which includes intravenous fluid therapy, correction of electrolyte disorders, and

control of pain. Antibiotics may also be indicated. (See 'Supportive care' below.)

●The selection and timing of definitive therapy depends upon the severity of symptoms

and the patient's overall risk for cholecystectomy. (See 'Medical risk

assessment' below.)

●If gangrene or perforation are suspected, or if the patient develops progressive

symptoms and signs such as fever, hemodynamic instability, or intractable pain while

on supportive therapy, emergency cholecystectomy or gallbladder drainage may be

needed (image 1). (See 'Timing of cholecystectomy' below and 'Indications for surgery

in high-risk patients' below.)

●Low-risk patients without emergent indications for intervention generally undergo

laparoscopic cholecystectomy preferably during the same admission. (See 'Low-risk

patients' below.)

●High-risk patients without emergent indications for intervention are treated with a

gallbladder drainage procedure if symptoms do not improve with supportive care. For

patients whose medical status can be optimized to allow surgery, cholecystectomy can

be considered. (See 'High-risk patients' below.)

SUPPORTIVE CARE — Patients diagnosed with acute calculous cholecystitis should be

admitted to the hospital. Patients have often been ill for days prior to seeking medical

attention, making intravenous hydration and correction of any associated electrolyte

disorders an important initial measure.

Patients should be kept fasting, and although uncommonly needed, those who are vomiting

should have placement of a nasogastric tube. (See "Nasogastric and nasoenteric tubes".)

Pain control — Pain control in patients with acute cholecystitis can usually be achieved with

nonsteroidal antiinflammatory drugs (NSAIDs) or opioids. Progression of pain during

treatment for acute cholecystitis, despite adequate analgesia, is an indicator of a clinical

progression.

We prefer ketorolac (30 to 60 mg adjusted for age and renal function given in a single

intramuscular dose) for patients with biliary colic. Treatment usually relieves symptoms

within 20 to 30 minutes. Opioids, such as morphine, hydromorphone, or meperidine are

appropriate therapy for patients who have contraindications to NSAIDs or who do not

achieve adequate pain relief with an NSAID, which may be more common in patients with

acute cholecystitis compared with uncomplicated gallstone disease.

It was traditionally thought that meperidine was the opioid of choice in patients with gallstone

disease because it has less of an effect on sphincter of Oddi motility thanmorphine [4-6].

However, a systematic review found that all opioids increase sphincter of Oddi pressure [5].

There are insufficient data to suggest that morphine should be avoided. Morphine has an

advantage that it requires less frequent dosing than meperidine, which has a shorter half-life.

Antibiotics — Acute cholecystitis is primarily an inflammatory process, but secondary

infection of the gallbladder can occur as a result of cystic duct obstruction and bile stasis

[7,8]. The rate of empyema and pericholecystic abscess is overall low, but patients can

easily develop life-threatening gram negative sepsis from uncomplicated, acute cholecystitis.

Thus, antibiotics are commonly administered at the outset to protect against sepsis and

wound infection [9]. Studies are conflicting as to whether antibiotics are required for the

treatment of uncomplicated, acute cholecystitis [7,8,10-12]. One study of 302 patients

showed a lower rate of bacteremia and wound infection, but no difference in the

development of empyema of the gallbladder or pericholecystic abscesses with the

administration of antibiotics [13]. This is likely due to the obstruction to bile flow that

interferes with achieving adequate gallbladder bile concentrations of antibiotics.

Many clinicians routinely administer antimicrobial therapy to all patients diagnosed with

acute cholecystitis, which are continued until the gallbladder is removed or the cholecystitis

clinically resolves. Others advocate that antimicrobial therapy should only be instituted if

sepsis is suspected on the basis of laboratory (more than 12,000 white cells per cubic

millimeter) or clinical findings (temperature of more than 38.3°C, <36°C), or in patients with a

diagnosis of acute cholecystitis and radiographic findings indicative of gallbladder ischemia

or necrosis (eg, air in the gallbladder or gallbladder wall). Routine antibiotics are also

recommended in older patients or those with diabetes or immunodeficiency with a diagnosis

of acute cholecystitis regardless of these signs [10,14]. (See "Sepsis and the systemic

inflammatory response syndrome: Definitions, epidemiology, and prognosis".)

When antibiotic therapy is initiated, the duration of postoperative treatment is generally

tailored to the clinical situation. A multicenter trial randomly assigned 414 patients

hospitalized for mild or moderate calculous cholecystitis to continue their preoperative

antibiotic regimen for five days (2 g amoxicillin plus clavulanic acid, three times daily) or to

receive no antibiotics following cholecystectomy [15]. No significant differences in

postoperative infection rates (17 versus 15 percent) were found. These results support our

current practice of discontinuing antibiotics the day after the cholecystectomy for patients

with uncomplicated cholecystitis. Clinical judgement should dictate antibiotic management in

more complicated scenarios, such as in the septic postoperative patient.

The need for prophylactic antibiotics at the time of surgery in the absence of

clinical symptoms/signs of biliary infection is discussed elsewhere. (See "Open

cholecystectomy", section on 'Prophylactic antibiotics' and "Laparoscopic cholecystectomy",

section on 'Antibiotics'.)

Empiric antibiotic therapy should include activity against the most common pathogens. In a

study of 467 patients, including a control group of 42 with normal biliary trees, positive bile

cultures were found in 22 percent of patients with symptomatic gallstones and 46 percent of

patients with acute cholecystitis [16]. The most frequent isolates from the gallbladder or

common bile duct were Escherichia coli (41 percent), Enterococcus (12 percent), Klebsiella

(11 percent), and Enterobacter (9 percent). Empiric antibiotic therapy options and doses are

provided in the table (table 1). Antibiotic therapy should subsequently be tailored to culture

and susceptibility results when available [7]. Thus, broad-spectrum antibiotics should cover

gram-negative organisms and anaerobes. Commonly used regimens are piperacillin-

tazobactam, ceftriaxoneplus metronidazole, or levofloxacin plus metronidazole.

MEDICAL RISK ASSESSMENT — The American Society of Anesthesiologists (ASA)

physical status classification is commonly used to stratify the risk of surgery (table 2) [17].

Other methods to specifically assess cardiac or pulmonary risk are discussed elsewhere.

(See "Overview of anesthesia and anesthetic choices" and "Evaluation of cardiac risk prior to

noncardiac surgery" and "Evaluation of preoperative pulmonary risk".)

LOW-RISK PATIENTS

Timing of cholecystectomy — Early cholecystectomy, rather than antibiotic therapy and

delayed (>7 days after admission) may be preferred among patients who require

hospitalization for acute cholecystitis and who are good candidates for cholecystectomy. The

bulk of the evidence from large database reviews and randomized trials show that

cholecystectomy performed early during the initial hospitalization may be associated with

reduced perioperative morbidity and mortality in some patients, and reduces the length of

hospital stay and cost [3,18-30]. Early surgery is also easier to perform as local inflammation

increases 72 hours past the initial onset of symptoms making dissection less precise,

increasing the severity of surgical complications, and making open conversion more likely.

Nevertheless, there are data to suggest that surgery is still safe even after 72 hours of

symptom onset [27,31,32].

An early systematic review that included predominantly open, but also laparoscopic

cholecystectomy in patients with acute calculous cholecystitis found no significant

differences in perioperative morbidity or mortality, but a significantly shorter length of hospital

stay for the early surgery group (9.6 versus 5.8 days) [26]. More than 20 percent of patients

in the delayed surgery group failed to respond to conservative management or suffered

recurrent cholecystitis in the interval period. A coincident Cochrane review (2004) that

included five trials limited to laparoscopic cholecystectomy concluded that early laparoscopic

cholecystectomy (ranging from immediate cholecystectomy to cholecystectomy within seven

days of symptoms) is safe and significantly shortens hospital stay [18]. No significant

differences were seen between the groups for the rate of bile duct injury or conversion to

open cholecystectomy. An updated Cochrane review (2013) limited to laparoscopic

cholecystectomy included two additional trials [28,30], but had similar findings [27]. The

incidence of bile duct injury in the early group was 0.4 percent, while that in the delayed

group was 0.9 percent, a difference that was not significant. Conversion rates were 19.7

versus 22.1 percent in the early versus late groups, respectively. Among four trials, the total

hospital stay was shorter in the early compared with the delayed group (mean difference -

4.12 days; 95% CI -5.22 to -3.03). It is important to note that significant complications such

as bile duct injury occur rarely, and the included trials (and likely any future clinical trials)

were not adequately powered to detect differences in the rates of bile duct injury and other

serious complications. Although the Cochrane reviews suggest similar conversion rates for

open procedures in patients operated on within seven days, they do not specify how many of

the “early surgery” patients were symptomatic for less than 72 hours. Some studies suggest

that patients who have surgery more than three days after the onset of symptoms have a

higher rate of conversion to open surgery compared with those who have had symptoms for

less than three days [33].

A later multicenter trial not included in the Cochrane metaanalyses, the Acute Cholecystitis-

early laparoscopic surgery versus antibiotic therapy and Delayed elective Cholecystectomy

(ACDC) trial (NCT00447304), randomly assigned patients to surgery within 24 hours of

hospital admission (n = 304) or initial antibiotic treatment followed by laparoscopic

cholecystectomy delayed more than seven days (n = 314 patients) [23]. The overall rate of

morbidity was significantly lower in the immediate compared with delayed cholecystectomy

group (11.8 versus 34.4 percent). The rate of conversion to open surgery and mortality did

not differ significantly between groups. Mean length of hospital stay (5.4 days versus 10.0

days) and total hospital costs were significantly lower in the immediate cholecystectomy

group.

Large database reviews have identified similar benefits for prompt surgical intervention, as

well as possible reductions in morbidity and improved late outcomes [22,25,29].

●In a large cohort study from Ontario, Canada, a significantly lower rate of major bile

duct injury (0.28 versus 0.53 percent) and shorter length of hospital stay (mean

difference -1.9 days) were seen for early compared with delayed cholecystectomy (≥7

days) among 14,220 patients with a first episode of acute cholecystitis [25].

●In a review from the American College of Surgeons National Surgical Quality

Improvement Program (NSQIP), those who underwent operation later in the course of

admission were more likely to require an open procedure [22].

Surgical approach — Laparoscopic cholecystectomy is considered the standard approach

for the surgical treatment of acute calculous cholecystitis. Compared with open

cholecystectomy, laparoscopic cholecystectomy reduces postoperative pain and significantly

shortens hospital length of stay and convalescence, and time away from work, and is

preferred by many patients from a cosmetic viewpoint [34-40]. However, the overall serious

complication rate in laparoscopic cholecystectomy remains higher than that seen with open

cholecystectomy; thus, the threshold for conversion to an open procedure should be low

[41,42]. Factors which may lead the surgeon to primarily choose, or convert to, an open

approach are discussed in detail elsewhere. (See "Open cholecystectomy", section on

'Indications for open surgery' and"Laparoscopic cholecystectomy", section on 'Intraoperative

complications'.)

For selected patients in whom the risk for injury or excessive blood loss is deemed too high

to perform cholecystectomy, a cholecystostomy or a subtotal cholecystectomy can be

performed. The latter procedure achieves control of the cystic duct at the level of the neck of

the gallbladder and leaves the dome of the gallbladder adherent to the liver fossa in situ

[43,44]. Biliary leaks can still occur, but these can generally be managed conservatively.

(See "Laparoscopic cholecystectomy" and "Complications of laparoscopic

cholecystectomy" and "Repair of common bile duct injuries".)

HIGH-RISK PATIENTS — Patients categorized as ASA classes III, IV, or V, have

perioperative mortality rates ranging from 5 to 27 percent, and are considered high risk for

cholecystectomy [17].

For these patients, the risk of cholecystectomy likely outweighs the potential benefits, and an

initial nonoperative approach should be undertaken that includes antibiotic therapy and

bowel rest. For those who fail to improve, gallbladder drainage should be implemented with

the eventual goal of performing cholecystectomy. Once cholecystitis resolves, the patient’s

risk for surgery should be reassessed. Patients who have become reasonable candidates for

surgery should undergo elective cholecystectomy [45]. Medical management with interval

cholecystectomy only for recurrent acute cholecystitis may be appropriate in some patients

[46].

Gallbladder drainage — Some form of gallbladder drainage is required for high-risk

patients managed conservatively but who show no appreciable improvement and progress

to severe symptoms. The goal of drainage is to direct purulent material away from the

obstructed gallbladder which also allows for resolution of edema, which often “opens” up the

obstructed cystic duct.

Gallbladder drainage can be accomplished via percutaneous, open surgical, or endoscopic

approaches. In one retrospective review of 185 patients, 78 percent were treated with

percutaneous cholecystostomy, and 22 percent with a tube placed surgically [47]. Over half

the patients (57 percent) subsequently underwent laparoscopic cholecystectomy.

Regardless of cholecystostomy tube approach, surgical or percutaneous, there were no

differences in the proportion of patients who underwent laparoscopic cholecystectomy as

definitive treatment.

Percutaneous and endoscopic methods are reviewed in the next sections. Open

cholecystostomy is discussed below. (See 'Indications for surgery in high-risk

patients'below.)

Percutaneous — Gallbladder drainage by percutaneous cholecystostomy in conjunction

with antibiotics may be the best initial treatment for very ill patients [48-51]. Percutaneous

cholecystostomy is often performed with the intent of delayed cholecystectomy; however,

many patients do not actually go on to receive cholecystectomy due to ongoing

contraindications [47,52].

A Cochrane review identified only two trials comparing outcomes for patients treated with

cholecystostomy for acute cholecystitis [53]. Neither of these trials found any significant

differences in mortality for the approaches studied, which included percutaneous

cholecystostomy and early laparoscopic cholecystectomy compared with delayed

laparoscopic cholecystectomy in one trial, and percutaneous cholecystostomy compared

with conservative treatment in the other trial. Although mortality differences have been found

in observational studies, in these studies, the healthiest cohort is selected by surgeons for

surgical management. As an example, in one retrospective review that included 1918

patients, 30-day mortality after percutaneous cholecystostomy was 15.4 percent, but only

4.5 percent for cholecystectomy [54]. Patients who underwent percutaneous

cholecystostomy were older, had a higher ASA classification, more comorbidities, longer

hospital stay, more complications, and more readmissions; most ultimately required

cholecystectomy. A time-cohort study had similar findings and noted that compared with

patients treated with cholecystostomy between 1989 and 1998, a significantly lower

percentage of patients treated between 1998 and 2009 had low ASA classification (zero

versus 18 percent) [55].

The technical success of percutaneous cholecystostomy ranges from 82 to 100 percent in

various series [48-51]. In a retrospective review, the outcomes of 106 patients with acute

cholecystitis (calculous and acalculous) treated by percutaneous cholecystostomy were

evaluated over a 10-year period; 67 percent presented to the emergency room and 23

percent were inpatients admitted initially for other conditions [56]. About half in each group

had gallstones. After cholecystostomy tube placement, clinical improvement was seen

overall in 68 percent, whereas 32 percent showed no improvement or clinically worsened.

More patients who presented to the emergency department primarily with acute cholecystitis

showed improvement compared with the inpatients (84 versus 34 percent).

Minor complications of percutaneous drainage include bleeding, catheter blockage and

dislodgement (10 to 15 percent), and failure to resolve the acute cholecystitis (10 percent)

[49,51,57]. In one study, major bleeding complications occurred rarely (0.4 percent) and

were no different between patients with and without coagulopathy [57]. Failure is usually

related to ineffective drainage due to thick sludge or pus. We generally irrigate the

gallbladder contents manually with normal saline through the catheter. If irrigation is

ineffective, the percutaneous pigtail catheter can be replaced over a wire with a larger one to

achieve more effective irrigation.

Patients who stabilize but continue to be high risk for surgery can be considered for

percutaneous gallstone extraction with or without mechanical lithotripsy [58].

Endoscopic — Endoscopic transpapillary gallbladder drainage has also been reported in

patients with acute cholecystitis in whom percutaneous approaches are contraindicated, or

are not anatomically feasible [59,60]. The technique can be technically challenging. In

addition, this procedure has all the inherent and occasionally serious complications

associated with endoscopic retrograde cholangiography. (See "Endoscopic retrograde

cholangiopancreatography: Indications, patient preparation, and complications".)

Indications for surgery in high-risk patients — The risk for surgery should be

reconsidered once cholecystitis resolves in patients treated conservatively with antibiotics

and gallbladder drainage. Patients who have become reasonable candidates for surgery

should undergo elective cholecystectomy.

An initial surgical approach may be preferred in some high-risk patients for whom the burden

of the ongoing systemic effects of cholecystitis is deemed to be greater than the risk of

surgery. A surgical approach may also become necessary if the less-invasive techniques

discussed above are not technically feasible, are unsuccessful at providing adequate

drainage, or if the patient does not improve following drainage, which suggests that the

gallbladder may have progressed to gangrene.

Laparoscopic cholecystectomy may be the preferred treatment in high-risk patients who

require surgery. If cholecystectomy is not feasible, a subtotal cholecystectomy can be

performed instead, but if medical risk precludes gallbladder removal, a surgical

cholecystostomy tube can be performed through a limited laparotomy in the operating room,

or at the bedside in the intensive care unit setting, if necessary. (See "Open

cholecystectomy", section on 'Open cholecystostomy tube placement'.)

MORBIDITY AND MORTALITY — The overall mortality of a single episode of acute

cholecystitis is approximately 3 percent. However, the risk in a given patient depends upon

the patient's health and surgical risk [49]. Mortality is less than 1 percent in young, otherwise

healthy patients, but approaches 10 percent in high-risk patients, or in those with

complications. Perioperative morbidity and mortality associated with specific treatments are

reviewed elsewhere. (See "Open cholecystectomy", section on 'Perioperative morbidity and

mortality' and "Laparoscopic cholecystectomy", section on 'Postoperative complications'.)

A study of the American College of Surgeons National Surgical Quality Improvement

Program (NSQIP) database evaluated outcomes following treatment of acute cholecystitis in

5460 patients with and without diabetes [61]. Mortality among 770 patients with diabetes was

significantly higher than in the 4690 patients without diabetes (4.4 versus 1.4 percent). The

risk for complications including cardiovascular events and renal failure was also significantly

increased.

Prevention of recurrent gallstones — Following cholecystectomy, or other nonsurgical

means to remove gallstones, patients who remain at high risk for developing recurrent

gallstones may benefit from certain medical therapies. These are discussed elsewhere.

(See "Patient selection for the nonsurgical treatment of gallstone disease", section on

'Prophylaxis in patients at high risk for developing symptomatic gallstone disease'.)

SUMMARY AND RECOMMENDATIONS

●Acute cholecystitis refers to a syndrome of right upper quadrant pain, fever, and

leukocytosis associated with gallbladder inflammation, which is usually related to

gallstone disease. Once a patient develops acute cholecystitis, definitive therapy aimed

at eliminating the gallstones is recommended. Without definitive therapy, the likelihood

of recurrent symptoms or complications is high. (See 'Introduction' above

and 'Overview of treatment' above.)

●Patients diagnosed with acute cholecystitis should be admitted to the hospital. Initial

supportive care includes intravenous fluid therapy, correction of electrolyte disorders,

and control of pain. Adequate pain control can usually be achieved with nonsteroidal

antiinflammatory drugs (NSAIDs) or opioids. Patients should be kept fasting and those

who are vomiting may need placement of a nasogastric tube. (See 'Supportive

care' above.)

●Acute cholecystitis is primarily an inflammatory process, but secondary infection of

the gallbladder can occur as a result of cystic duct obstruction and bile stasis. Many

clinicians routinely administer antimicrobial therapy to all patients diagnosed with acute

cholecystitis, which are continued until the gallbladder is removed or the cholecystitis

clinically resolves. If sepsis is suspected (laboratory or clinical findings), or radiographic

findings are indicative of gallbladder ischemia or necrosis, we suggest empiric antibiotic

therapy (Grade 2C). Antibiotic options and doses are provided in the table (table 1).

For patients with uncomplicated cholecystitis, we discontinue antibiotics the day after

the cholecystectomy. (See 'Antibiotics' above.)

●The choice and timing of intervention for acute cholecystitis (cholecystectomy,

gallbladder drainage) depends upon the severity of symptoms and the patient's overall

risk of surgery. Drainage options include percutaneous or open cholecystostomy and

endoscopic sphincterotomy.

•Emergent intervention is indicated for patients with:

-Progressive symptoms and signs such as high fever, hemodynamic

instability, or intractable pain in spite of adequate pain medication.

-Suspicion of gallbladder gangrene or gallbladder perforation

•For patients without emergent indications for definitive therapy who are low risk

for surgery, we recommend cholecystectomy during the initial hospitalization

(Grade 1A). Cholecystectomy performed early rather than later in the

hospitalization may be associated with reduced perioperative morbidity and

mortality. Low-risk patients generally undergo laparoscopic cholecystectomy.

Compared with open cholecystectomy, laparoscopic cholecystectomy reduces

postoperative pain and significantly shortens the length of hospital stay and

convalescence. (See 'Timing of cholecystectomy' above and 'Low-risk

patients'above.)

•For patients without emergent indications for definitive therapy, and in whom the

risk of cholecystectomy outweighs the potential benefits, gallbladder drainage

(percutaneous cholecystostomy, endoscopic sphincterotomy, open

cholecystostomy) is indicated if symptoms do not improve with supportive care.

Once cholecystitis resolves, the patient’s risk for surgery should be reassessed.

Patients who have become reasonable candidates for surgery should undergo

elective cholecystectomy. Patients who stabilize with a cholecystostomy tube but

continue to be at high-risk for surgery can be considered for percutaneous

gallstone extraction with or without mechanical lithotripsy. (See 'Gallbladder

drainage' above.)

●Mortality associated with a single episode of acute cholecystitis depends upon the

patient's health and surgical risk. Overall mortality is approximately 3 percent, but is

less than 1 percent in young, otherwise healthy patients, and approaches 10 percent in

high-risk patients, or in those with complications.

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REFERENCES

1. Thistle JL, Cleary PA, Lachin JM, et al. The natural history of cholelithiasis: the National Cooperative Gallstone Study. Ann Intern Med 1984; 101:171.

2. de Mestral C, Rotstein OD, Laupacis A, et al. A population-based analysis of the clinical course of 10,304 patients with acute cholecystitis, discharged without cholecystectomy. J Trauma Acute Care Surg 2013; 74:26.

3. Riall TS, Zhang D, Townsend CM Jr, et al. Failure to perform cholecystectomy for acute cholecystitis in elderly patients is associated with increased morbidity, mortality, and cost. J Am Coll Surg 2010; 210:668.

4. Elta GH, Barnett JL. Meperidine need not be proscribed during sphincter of Oddi manometry. Gastrointest Endosc 1994; 40:7.

5. Thompson DR. Narcotic analgesic effects on the sphincter of Oddi: a review of the data and therapeutic implications in treating pancreatitis. Am J Gastroenterol 2001; 96:1266.

6. Thune A, Baker RA, Saccone GT, et al. Differing effects of pethidine and morphine on human sphincter of Oddi motility. Br J Surg 1990; 77:992.

7. Fuks D, Cossé C, Régimbeau JM. Antibiotic therapy in acute calculous cholecystitis. J Visc Surg 2013; 150:3.

8. Strasberg SM. Clinical practice. Acute calculous cholecystitis. N Engl J Med 2008; 358:2804. 9. Järvinen H, Renkonen OV, Palmu A. Antibiotics in acute cholecystitis. Ann Clin Res 1978;

10:247. 10. Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated

intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis 2010; 50:133.

11. Kanafani ZA, Khalifé N, Kanj SS, et al. Antibiotic use in acute cholecystitis: practice patterns in the absence of evidence-based guidelines. J Infect 2005; 51:128.

12. Mazeh H, Mizrahi I, Dior U, et al. Role of antibiotic therapy in mild acute calculus cholecystitis: a prospective randomized controlled trial. World J Surg 2012; 36:1750.

13. Kune GA, Burdon JG. Are antibiotics necessary in acute cholecystitis? Med J Aust 1975; 2:627.

14. Landau O, Kott I, Deutsch AA, et al. Multifactorial analysis of septic bile and septic complications in biliary surgery. World J Surg 1992; 16:962.

15. Regimbeau JM, Fuks D, Pautrat K, et al. Effect of postoperative antibiotic administration on postoperative infection following cholecystectomy for acute calculous cholecystitis: a randomized clinical trial. JAMA 2014; 312:145.

16. Csendes A, Burdiles P, Maluenda F, et al. Simultaneous bacteriologic assessment of bile from gallbladder and common bile duct in control subjects and patients with gallstones and common duct stones. Arch Surg 1996; 131:389.

17. Feigal DW, Blaisdell FW. The estimation of surgical risk. Med Clin North Am 1979; 63:1131. 18. Gurusamy KS, Samraj K. Early versus delayed laparoscopic cholecystectomy for acute

cholecystitis. Cochrane Database Syst Rev 2006; :CD005440.

19. Norrby S, Herlin P, Holmin T, et al. Early or delayed cholecystectomy in acute cholecystitis? A clinical trial. Br J Surg 1983; 70:163.

20. Lahtinen J, Alhava EM, Aukee S. Acute cholecystitis treated by early and delayed surgery. A controlled clinical trial. Scand J Gastroenterol 1978; 13:673.

21. McArthur P, Cuschieri A, Sells RA, Shields R. Controlled clinical trial comparing early with interval cholecystectomy for acute cholecystitis. Br J Surg 1975; 62:850.

22. Brooks KR, Scarborough JE, Vaslef SN, Shapiro ML. No need to wait: an analysis of the timing of cholecystectomy during admission for acute cholecystitis using the American College of Surgeons National Surgical Quality Improvement Program database. J Trauma Acute Care Surg 2013; 74:167.

23. Gutt CN, Encke J, Köninger J, et al. Acute cholecystitis: early versus delayed cholecystectomy, a multicenter randomized trial (ACDC study, NCT00447304). Ann Surg 2013; 258:385.

24. Banz V, Gsponer T, Candinas D, Güller U. Population-based analysis of 4113 patients with acute cholecystitis: defining the optimal time-point for laparoscopic cholecystectomy. Ann Surg 2011; 254:964.

25. de Mestral C, Rotstein OD, Laupacis A, et al. Comparative operative outcomes of early and delayed cholecystectomy for acute cholecystitis: a population-based propensity score analysis. Ann Surg 2014; 259:10.

26. Papi C, Catarci M, D'Ambrosio L, et al. Timing of cholecystectomy for acute calculous cholecystitis: a meta-analysis. Am J Gastroenterol 2004; 99:147.

27. Gurusamy KS, Davidson C, Gluud C, Davidson BR. Early versus delayed laparoscopic cholecystectomy for people with acute cholecystitis. Cochrane Database Syst Rev 2013; 6:CD005440.

28. Macafee DA, Humes DJ, Bouliotis G, et al. Prospective randomized trial using cost-utility analysis of early versus delayed laparoscopic cholecystectomy for acute gallbladder disease. Br J Surg 2009; 96:1031.

29. Dua A, Dua A, Desai SS, et al. Gender based differences in management and outcomes of cholecystitis. Am J Surg 2013; 206:641.

30. Yadav RP, Adhikary S, Agrawal CS, et al. A comparative study of early vs. delayed laparoscopic cholecystectomy in acute cholecystitis. Kathmandu Univ Med J (KUMJ) 2009; 7:16.

31. Farooq T, Buchanan G, Manda V, et al. Is early laparoscopic cholecystectomy safe after the "safe period"? J Laparoendosc Adv Surg Tech A 2009; 19:471.

32. Litwin DE, Cahan MA. Laparoscopic cholecystectomy. Surg Clin North Am 2008; 88:1295. 33. Pessaux P, Tuech JJ, Regenet N, et al. [Laparoscopic cholecystectomy in the treatment of

acute cholecystitis. Prospective non-randomized study]. Gastroenterol Clin Biol 2000; 24:400.

34. Soper NJ, Stockmann PT, Dunnegan DL, Ashley SW. Laparoscopic cholecystectomy. The new 'gold standard'? Arch Surg 1992; 127:917.

35. Wiesen SM, Unger SW, Barkin JS, et al. Laparoscopic cholecystectomy: the procedure of choice for acute cholecystitis. Am J Gastroenterol 1993; 88:334.

36. Wilson RG, Macintyre IM, Nixon SJ, et al. Laparoscopic cholecystectomy as a safe and effective treatment for severe acute cholecystitis. BMJ 1992; 305:394.

37. Johansson M, Thune A, Nelvin L, et al. Randomized clinical trial of open versus laparoscopic cholecystectomy in the treatment of acute cholecystitis. Br J Surg 2005; 92:44.

38. Yamashita Y, Takada T, Kawarada Y, et al. Surgical treatment of patients with acute cholecystitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg 2007; 14:91.

39. Overby DW, Apelgren KN, Richardson W, et al. SAGES guidelines for the clinical application of laparoscopic biliary tract surgery. Surg Endosc 2010; 24:2368.

40. NIH releases consensus statement on gallstones, bile duct stones and laparoscopic cholecystectomy. Am Fam Physician 1992; 46:1571.

41. Vollmer CM Jr, Callery MP. Biliary injury following laparoscopic cholecystectomy: why still a problem? Gastroenterology 2007; 133:1039.

42. Khan MH, Howard TJ, Fogel EL, et al. Frequency of biliary complications after laparoscopic cholecystectomy detected by ERCP: experience at a large tertiary referral center. Gastrointest Endosc 2007; 65:247.

43. Bernard HR, Hartman TW. Complications after laparoscopic cholecystectomy. Am J Surg 1993; 165:533.

44. National Institutes of Health Consensus Development Conference Statement on Gallstones and Laparoscopic Cholecystectomy. Am J Surg 1993; 165:390.

45. Morse BC, Smith JB, Lawdahl RB, Roettger RH. Management of acute cholecystitis in critically ill patients: contemporary role for cholecystostomy and subsequent cholecystectomy. Am Surg 2010; 76:708.

46. McGillicuddy EA, Schuster KM, Barre K, et al. Non-operative management of acute cholecystitis in the elderly. Br J Surg 2012; 99:1254.

47. Cherng N, Witkowski ET, Sneider EB, et al. Use of cholecystostomy tubes in the management of patients with primary diagnosis of acute cholecystitis. J Am Coll Surg 2012; 214:196.

48. Melin MM, Sarr MG, Bender CE, van Heerden JA. Percutaneous cholecystostomy: a valuable technique in high-risk patients with presumed acute cholecystitis. Br J Surg 1995; 82:1274.

49. Ito K, Fujita N, Noda Y, et al. Percutaneous cholecystostomy versus gallbladder aspiration for acute cholecystitis: a prospective randomized controlled trial. AJR Am J Roentgenol 2004; 183:193.

50. Davis CA, Landercasper J, Gundersen LH, Lambert PJ. Effective use of percutaneous cholecystostomy in high-risk surgical patients: techniques, tube management, and results. Arch Surg 1999; 134:727.

51. Byrne MF, Suhocki P, Mitchell RM, et al. Percutaneous cholecystostomy in patients with acute cholecystitis: experience of 45 patients at a US referral center. J Am Coll Surg 2003; 197:206.

52. de Mestral C, Gomez D, Haas B, et al. Cholecystostomy: a bridge to hospital discharge but not delayed cholecystectomy. J Trauma Acute Care Surg 2013; 74:175.

53. Gurusamy KS, Rossi M, Davidson BR. Percutaneous cholecystostomy for high-risk surgical patients with acute calculous cholecystitis. Cochrane Database Syst Rev 2013; 8:CD007088.

54. Abi-Haidar Y, Sanchez V, Williams SA, Itani KM. Revisiting percutaneous cholecystostomy for acute cholecystitis based on a 10-year experience. Arch Surg 2012; 147:416.

55. Smith TJ, Manske JG, Mathiason MA, et al. Changing trends and outcomes in the use of percutaneous cholecystostomy tubes for acute cholecystitis. Ann Surg 2013; 257:1112.

56. Joseph T, Unver K, Hwang GL, et al. Percutaneous cholecystostomy for acute cholecystitis: ten-year experience. J Vasc Interv Radiol 2012; 23:83.

57. Dewhurst C, Kane RA, Mhuircheartaigh JN, et al. Complication rate of ultrasound-guided percutaneous cholecystostomy in patients with coagulopathy. AJR Am J Roentgenol 2012; 199:W753.

58. Burhenne HJ, Stoller JL. Minicholecystostomy and radiologic stone extraction in high-risk cholelithiasis patients. Preliminary experience. Am J Surg 1985; 149:632.

59. Itoi T, Sofuni A, Itokawa F, et al. Endoscopic transpapillary gallbladder drainage in patients with acute cholecystitis in whom percutaneous transhepatic approach is contraindicated or anatomically impossible (with video). Gastrointest Endosc 2008; 68:455.

60. Kjaer DW, Kruse A, Funch-Jensen P. Endoscopic gallbladder drainage of patients with acute cholecystitis. Endoscopy 2007; 39:304.

61. Karamanos E, Sivrikoz E, Beale E, et al. Effect of diabetes on outcomes in patients undergoing emergent cholecystectomy for acute cholecystitis. World J Surg 2013; 37:2257.

Treatment of acute cholecystitis

Ruptured gallbladder with biloma

Axial CT scan of the upper abdomen without intravenous but with oral contrast

demonstrates a ruptured gallbladder with a collection of bile (biloma) in the

gallbladder fossa. Note that there are multiple gallstones that are located outside of

the gallbladder. There is also a small amount of fluid around the liver.

Courtesy of J Pierre Sasson, MD. Graphic 74614 Version 3.0

Empiric antibiotic therapy for gram-negative and anaerobic pathogens

Regimen Dose (adult)*

First choice

Monotherapy with a beta-lactam/beta-lactamase inhibitor:

Ampicillin-sulbactam• 3 g IV every six hours

Piperacillin-tazobactamΔ 3.375 or 4.5 g IV every six hours

Ticarcillin-clavulanate 3.1 g IV every four hours

Combination third generation cephalosporin PLUS metronidazole:

Ceftriaxone plus 1 g IV every 24 hours or 2 g IV every 12 hours for CNS infections

Metronidazole 500 mg IV every eight hours

Alternative empiric regimens

Combination fluoroquinolone◊ PLUS metronidazole:

Ciprofloxacin or 400 mg IV every 12 hours

Levofloxacin plus 500 or 750 mg IV once daily

Metronidazole 500 mg IV every eight hours

Monotherapy with a carbapenem§:

Imipenem-cilastatin 500 mg IV every six hours

Meropenem 1 g IV every eight hours

Doripenem 500 mg IV every eight hours

Ertapenem¥ 1 g IV once daily

* Antibiotic doses should be adjusted appropriately for patients with renal insufficiency

or other dose-related consideration. • E coli resistance to Ampicillin-sulbactam is

merging in some areas; check local susceptibility data.

Δ Some clinicians use 4.5 g every eight hours for empiric therapy since the percent

time above the MIC is similar between the regimens for most pathogens; however, this

regimen is NOT recommended for nosocomial pneumonia or Pseudomonas coverage.

Please refer to UpToDate topics on the "Treatment of hospital-acquired, ventilator-

associated, and healthcare-associated pneumonia in adults" and "Treatment

of Pseudomonas aeruginosainfections". ◊ Fluoroquinolones are generally avoided in

pregnant women due to potential fetal toxicity. § Use carbapenems cautiously in

patients with immediate-type hypersensitivity to beta-lactams. ¥ Ertapenem lacks

activity against Acinetobacter and Pseudomonas and is not an appropriate choice for

severe or nosocomial infection.

American Society of Anesthesiologists (ASA) Physical Status Classification System

ASA 1 A normal healthy patient

ASA 2 A patient with mild systemic disease

ASA 3 A patient with severe systemic disease

ASA 4 A patient with severe systemic disease that is a constant threat to life

ASA 5 A moribund patient who is not expected to survive without the operation

ASA 6 A declared brain-dead patient whose organs are being removed for donor purposes

ASA Physical Status Classification System is reprinted with permission of the American

Society of Anesthesiologists, 520 N. Northwest Highway, Park Ridge, Illinois 60068-

2573.