Acute cholecystitis: Pathogenesis, clinical features, and diagnosis

Authors:
Salam F Zakko, MD, FACP, AGAF
Nezam H Afdhal, MD, FRCPI
Section Editor:
Sanjiv Chopra, MD, MACP
Deputy Editor:
Shilpa Grover, MD, MPH, AGAF

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Feb 2018. | This topic last updated: Dec 15, 2016.

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".)

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: Clinical
manifestations, diagnosis, and management" 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: Clinical
manifestations, diagnosis, and management".)

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 syndromes in adults:
Epidemiology, definitions, clinical presentation, diagnosis, and prognosis", section on
'Sepsis' 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.)

Contrast enhanced ultrasonography performed in conjunction with intravenous injection of

an ultrasound contrast agent containing microbubbles is advocated by some to allow the
preoperative detection of gangrenous cholecystitis [28]. Theoretically, early diagnosis of this
serious complication of acute cholecystitis would lead to better planning of early intervention
to prevent further more serious complications; however, this test is not widely available [29].

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
90 to 97 percent and 71 to 90 percent, respectively [23,26,30,31]. 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 [32].

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 [33,34]. It was compared with the standard HIDA scan
in a retrospective study where 365 patients who received 2 mg of morphine prior to the scan
were compared with 232 patients who had the standard HIDA scan without morphine
pretreatment. The authors reported its accuracy to be slightly more than the standard HIDA
scan in detecting acute cholecystitis (93 percent versus 84 percent respectively) [35,36]. As
the test has not been well standardized and has a high false positive rate, it 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 [37,38]. However, CT may fail
to detect gallstones because many stones are isodense with bile (image 7) [39,40]. 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 [41,42].

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 [43].

These conditions can usually be differentiated by the clinical setting in which they occur and
by obtaining the appropriate diagnostic studies.

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) [44]. (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 [44].
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
syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, 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.

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 [45].

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) [46]. (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) [47,48]. Other organisms that may be isolated include Escherichia coli (15
percent), staphylococci, streptococci, Pseudomonas, and Klebsiella [48].

Affected patients are often men in their fifth to seventh decade [48], and approximately one-
third to one-half have diabetes [48-50]. 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 [48-50]. In a review of 20 patients with emphysematous cholecystitis,
gallbladder perforation occurred in seven, pericholecystic abscess in nine, and bile
peritonitis in three [50].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines

from selected countries and regions around the world are provided separately. (See "Society
guideline links: Cholecystitis and other gallbladder disorders".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education
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the Basics patient education pieces are longer, more sophisticated, and more detailed.
These articles are written at the 10th to 12th 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 education: Gallstones (The Basics)" and "Patient
education: Gallbladder removal (cholecystectomy) (The Basics)")

●Beyond the Basics topics (see "Patient education: 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".)

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 in the first 24 to 48 hours after admission.

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 anti-inflammatory 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 than morphine [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
infection is suspected on the basis of laboratory (more than 12,500 white cells per cubic
millimeter) or clinical findings (temperature of more than 38.5°C), or in patients with a
diagnosis of acute cholecystitis and radiographic findings indicative of gallbladder rupture,
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 syndromes
in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis".)

When empiric antibiotic therapy is indicated, the chosen agent(s) should cover the most
common pathogens of the Enterobacteriaceae family, including Gram negative rods and
anaerobes; activity against enterococci is not required [8]. 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 [15]. 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). Whenever possible, the chosen agent(s) should also achieve
adequate concentrations in bile.

The guidelines of the Infectious Diseases Society of America recommend the following
antibiotic regimens for patients with acute cholecystitis [10] (table 1):

●For patients with community-acquired acute cholecystitis of mild-to-moderate

severity: cefazolin, cefuroxime, or ceftriaxone.

●For patients with community-acquired acute cholecystitis of severe physiologic

disturbance, advanced age, or immunocompromised state: imipenem-
 cilastatin, meropenem, doripenem, piperacillin-
tazobactam, ciprofloxacin plus metronidazole, levofloxacin plus metronidazole,
or cefepime plus metronidazole.

●For patients with healthcare-associated biliary infection of any severity: imipenem-

cilastatin, meropenem, doripenem, piperacillin-
tazobactam, ciprofloxacin plus metronidazole, levofloxacin plus metronidazole,
or cefepime plus metronidazole, with vancomycin added to each regimen.

The choosing of an antibiotic regimen within each patient category is governed by local
practices, taking into consideration the antibiogram and formulary of each institution. The
chosen agents should subsequently be tailored to culture and susceptibility results when
they become available [7].

The duration of antibiotic therapy 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 [16]. 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'.)

Antibiotic therapy for intra-abdominal infections, including acute cholecystitis, is also

discussed in detail elsewhere. (See "Antimicrobial approach to intra-abdominal infections in
adults".)

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 "Evaluation of cardiac risk prior to noncardiac
surgery" and "Evaluation of preoperative pulmonary risk".)

LOW-RISK PATIENTS

Timing of cholecystectomy — Early cholecystectomy, rather than delayed

cholecystectomy (>7 days after admission), is preferable for patients who require
hospitalization for acute cholecystitis and who are good candidates for cholecystectomy.
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].

The best data come from a meta-analysis of 15 trials including 1625 patients [31]. Compared
with delayed laparoscopic cholecystectomy, early laparoscopic cholecystectomy (performed
within seven days of symptom onset) was associated with less wound infection (relative risk
0.65, 95% CI 0.47-0.91), a shorter hospital stay (mean difference [MD] -3 days, 95% CI -4
to -2), fewer work days lost (MD -11 days, 95% CI -16 to -6), but a longer operative time
(MD 11 minutes, 95% CI 5-18). Early surgery did not increase the rate of mortality, bile duct
injury, bile leakage, conversion to open surgery, or overall complications.

A large administrative database study of over 15,000 cholecystectomies for acute

cholecystitis provided even more granular data on how timing of cholecystectomy can
impact patient outcomes [32]. In that study, the rate of intraoperatively detected biliary injury
was the lowest in patients who underwent surgery on the day of admission; the rate
increased day by day thereafter. The rate of other intraoperative adverse events (eg,
bleeding), as well as 30- and 90-day mortality rates, were lower in patients who underwent
surgery on the first or second day after admission than either on the day of admission or
after the second day after admission. The authors of the study advocated operating within
two days of admission, but after patients have been adequately resuscitated, and when the
most qualified surgeon becomes available. Although there were no data, they speculated
that the slightly higher rate of nonbiliary adverse events that occurred when patients
underwent surgery on the day of admission compared with the day after were due to under-
resuscitation of the patient or a lack of laparoscopic surgical expertise.

Early surgery is also easier to perform, as local inflammation increases 72 hours after 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, albeit with a higher rate of conversion from laparoscopic to open technique
[27,33-35]. In a randomized trial of 86 patients with acute cholecystitis who had more than
72 hours of symptoms, early laparoscopic cholecystectomy during the index admission was
safe [36]. Of 42 patients who received early surgery, only one required conversion to open
surgery; none had a bile leak or bile duct injury. Compared with surgery delayed for six
weeks, early surgery reduced the overall morbidity rate from 39 to 14 percent. Given that
the postoperative complication rates (15 percent early versus 17 percent delayed) were
similar, the difference in morbidity was almost entirely accounted for by morbidities that
occurred during the waiting period in patients who were waiting for delayed surgery (3 failed
initial treatment; 10 required unplanned readmission while awaiting surgery). The length of
stay (four versus seven days), duration of antibiotic therapy (2 versus 10 days), and total
hospital cost (€9349 versus €12,361) were also in favor of early surgery. The authors of this
trial argued that the degree of inflammatory changes associated with acute cholecystitis may
not be time dependent as previously thought [37] and therefore suggested early
laparoscopic cholecystectomy may be offered to patients with acute cholecystitis regardless
of the duration of symptoms.

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 [38-44]. 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 [45,46]. 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'.)

Although other techniques such as single-incision laparoscopy, mini-laparoscopy, robotic-

assisted laparoscopy, and natural orifice transluminal endoscopic surgery (NOTES) have
been used to treat patients with symptomatic cholelithiasis, their role in the treatment of
patients with acute cholecystitis is limited due to the technically demanding dissection
caused by severe inflammation as well as technical challenges associated with the adoption
of these new technologies [47]. (See "Laparoscopic cholecystectomy", section on
'Abdominal access'.)

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
[48,49]. 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 (table 2) [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 [50]. Medical management with
interval cholecystectomy only for recurrent acute cholecystitis may be appropriate in some
patients [51].
However, an initial surgical approach may be preferred in some high-risk patients (eg,
gangrenous or emphysematous cholecystitis) for whom the burden of the ongoing systemic
effects of cholecystitis is deemed to be greater than the risk of surgery. In a study of 483
patients undergoing cholecystectomy for acute cholecystitis, gangrenous cholecystitis was
found in 24 (5 percent) [52]. Patients with gangrenous gallbladders had a much higher
mortality rate than patients who had inflamed but nongangrenous gallbladders (12.5 versus
0.9 percent). In the same study, gallbladder gangrene was associated with an older age,
male sex, and a higher preoperative bilirubin level, as well as comorbid medical conditions
such as diabetes, coronary artery disease, and systemic inflammatory response syndrome.

Antibiotic therapy — For high-risk patients, the initial approach should include antibiotic
therapy and bowel rest, followed by either cholecystectomy for those who improve or
gallbladder drainage for those who fail to improve. (See 'Antibiotics' above.)

Percutaneous cholecystostomy is indicated in patients who fail an initial trial of antibiotic

therapy. In a trial of 123 high-risk patients with acute cholecystitis who were randomly
assigned to percutaneous cholecystostomy or antibiotic therapy, a similar percentage of
patients in each group had resolution of their symptoms (86 versus 87 percent). All
successfully treated patients showed clinical improvement within the first three days [53],
supporting the use of antibiotics as initial therapy of cholecystitis in high-risk patients.
However, gallbladder drainage by percutaneous cholecystostomy in conjunction with
antibiotics may be the best initial treatment for very ill patients (ie, intensive care unit) [54-
57].

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, endoscopic, or surgical

approaches. In one retrospective review of 185 patients, 78 percent were treated with
percutaneous cholecystostomy, and 22 percent with a tube placed surgically [58]. 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 — Percutaneous cholecystostomy is indicated for patients with acute

cholecystitis who have [47]:

●Contraindications to general anesthesia

●Severe cholecystitis
 ●Late presentation (>72 hours after onset of symptoms)

●Failure of medical (antibiotic) therapy

Percutaneous cholecystostomy resolves acute cholecystitis in approximately 90 percent of

patients. Decompressing the gallbladder allows both local inflammation and systemic illness
to resolve, before gallbladder removal could be accomplished with less risk to the patient.
The timing of cholecystectomy after gallbladder drainage can be variable, ranging from
immediately after clinical improvement to after eight weeks. We typically perform
cholecystectomy prior to three days from the onset of symptoms or after six weeks
otherwise. However, some patients benefit from cholecystectomy within these boundaries
when their clinical situation dictates necessity to proceed in order to accelerate delivery of
care.

In a randomized trial comparing percutaneous cholecystostomy followed by early (within six

days) laparoscopic cholecystectomy versus antibiotic therapy followed by delayed (after
eight weeks) laparoscopic cholecystectomy in 70 high-risk patients with acute cholecystitis,
patients who received percutaneous cholecystostomy recovered sooner with a shorter mean
hospital stay (5 versus 15 days) and lower cost ($2612 versus $3735) [59]. All patients in
the percutaneous cholecystostomy group experienced symptomatic relief within 24 hours
after catheter placement, whereas patients in the antibiotic group improved within 48 to 72
hours. In addition, at subsequent cholecystectomy, there was a lower conversion rate from
laparoscopic to open cholecystectomy in the percutaneous cholecystostomy group (6 versus
13 percent).

In a prospective study of 91 high-risk patients with acute cholecystitis, patients were

nonrandomly assigned to either emergency laparoscopic cholecystectomy or percutaneous
cholecystostomy followed by delayed cholecystectomy after four weeks [60]. Patients in the
cholecystostomy group had a lower frequency of conversion to open surgery (8 versus 19
percent), a lower risk of intraoperative bleeding >100 mL (9 versus 33 percent), a shorter
mean hospital stay (3 versus 5.3 days), and a lower risk of complications (9 versus 35
percent) [60]. Similar findings were reached by retrospective studies [61-63].

In retrospective studies, higher mortality and morbidity rates have often been associated
with percutaneous cholecystostomy treatment of acute cholecystitis compared with
cholecystectomy. 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 [64]. This difference is likely due to patient selection bias, as the
healthiest cohort is selected by surgeons for surgical management. Patients who underwent
percutaneous cholecystostomy were usually older, and had a higher ASA classification,
more comorbidities, longer hospital stay, more complications, and more readmissions. In
one time-cohort study, the 30-day mortality rate decreased from 36 to 12 percent when more
“healthy” patients (ASA class I and II: 0 versus 18 percent) underwent the percutaneous
cholecystostomy procedure between 1998 and 2009, compared with the time period from
1989 to 1998 [65]. A randomized prospective trial comparing percutaneous cholecystostomy
with cholecystectomy treatment of acute cholecystitis in high surgical risk patients is
underway [66].

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

various series [54-57]. 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 [67]. 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)
[55,57,68]. In one study, major bleeding complications occurred rarely (0.4 percent) and
were no different between patients with and without coagulopathy [68]. 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.

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 [58,69]. Patients who stabilize but continue to be high risk
for surgery can be considered for percutaneous gallstone extraction with or without
mechanical lithotripsy [70].

Endoscopic — Endoscopic gallbladder drainage can be performed in patients with acute

cholecystitis in whom percutaneous approaches are contraindicated, or are not anatomically
feasible (ie, advanced liver disease, ascites, or coagulopathy) [47,71,72]. Two different
techniques, transpapillary drainage or transmural drainage are available, depending on local
expertise [47].

Transpapillary drainage — Transpapillary drainage utilizes endoscopic retrograde

cholangiography (ERCP) techniques and equipment to place a drainage catheter into the
gallbladder via the cystic duct. The other end of the catheter is either brought out through
the nose (nasobiliary drain) or left to drain internally into the duodenum.

When technically successful (in about 76 to 94 percent of patients), transpapillary drainage

resolves acute cholecystitis in 80 to 90 percent of patients, including those with advanced
liver cirrhosis [73-75]. However, this technique can be technically challenging because the
cystic duct is often narrow and tortuous. In addition, this procedure has all the inherent and
occasionally serious complications associated with endoscopic retrograde cholangiography
(eg, postsphincterotomy bleeding) (see "Endoscopic retrograde cholangiopancreatography:
Indications, patient preparation, and complications").

Transmural drainage — Transmural drainage utilizes endoscopic ultrasound guidance to

access the inflamed gallbladder with a needle puncture, followed by dilation and stent
placement over a guidewire. The introduction of self-expandable, covered, lumen-apposing
metal stents allows direct endoscopic access to the gallbladder for decompression and
stone removal. The transmural drainage technique is technically successful in most cases
(97 percent) and resolves acute cholecystitis in over 95 percent of patients [76].

In a randomized trial involving 59 patients with acute cholecystitis, who did not respond to
initial medical management and were not surgical candidates, transmural drainage was as
effective as percutaneous drainage of the gallbladder in terms of technical (97 versus 97
percent) and clinical success rates (100 versus 96 percent) [77]. Similar proportions of
patients in each group developed complications (7 versus 3 percent) and required
conversion to open surgery when they eventually underwent laparoscopic gallbladder
surgery (9 versus 12 percent). Postprocedure pain was significantly less in the transmural
drainage group.

Endoscopic transmural drainage is used as a bridge to definitive gallbladder surgery.

However, the adhesion created between the gallbladder and duodenum/stomach may
interfere with future cholecystectomy surgery.

Surgical — Although high-risk patients are generally treated with antibiotic therapy with or
without a gallbladder drainage procedure, an initial surgical approach may be preferred in
some patients for whom the burden of the ongoing systemic effects of cholecystitis is
deemed to be greater than the risk of 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 inserted 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'.)

Subsequent care following drainage — For patients who undergo gallbladder drainage,
the approach to subsequent care depends on whether clinical symptoms resolve after
gallbladder drainage has been accomplished.

Effective drainage — 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. Laparoscopic cholecystectomy may be the preferred treatment in high-
risk patients who require surgery. (See "Laparoscopic cholecystectomy".)

Ineffective drainage — A surgical approach may 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. In this setting, laparoscopic
cholecystectomy is preferred but conversion to open surgery may be necessary.
(See "Laparoscopic cholecystectomy" and "Open cholecystectomy".)

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 [55]. 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 [78]. 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'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines

from selected countries and regions around the world are provided separately. (See "Society
guideline links: Gallbladder surgery" and "Society guideline links: Cholecystitis and other
gallbladder disorders".)

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
anti-inflammatory 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 3).
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 transpapillary or transmural drainage.

•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 with
percutaneous cholecystostomy or one of the endoscopic drainage procedures 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 gallbladder drainage 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.