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their habits of critical inquiry and balanced judgement, and to contribute to better patient care. Disclosures: Badri Man Shrestha, MS, MPhil, MD,

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Acute Cholecystitis View online at http://pier.acponline.org/physicians/diseases/d642/d642.html

Module Updated: 2013-02-20

CME Expiration: 2016-02-20

Author

Badri Man Shrestha, MS, MPhil, MD, FRCS

Table of Contents

1. Prevention .........................................................................................................................2

2. Diagnosis ..........................................................................................................................4

3. Consultation ......................................................................................................................8

4. Hospitalization ...................................................................................................................11

5. Therapy ............................................................................................................................12

6. Patient Education ...............................................................................................................16

7. Follow-up ..........................................................................................................................17

References ............................................................................................................................19

Glossary................................................................................................................................23

Tables ...................................................................................................................................25

Figures .................................................................................................................................30

http://pier.acponline.org/physicians/diseases/d642/d642.html

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1. Prevention Top

Consider medical therapy and prophylactic cholecystectomy in patients with symptomatic gallstones.

1.1 Consider UDCA to dissolve symptomatic cholesterol gallstones.

Recommendations

• Consider prescribing oral UDCA, 8 to 12 mg/kg·d.

Evidence

• In a meta-analysis of trials published from 1966 to 1992 comprising 1949 patients, complete

dissolution was achieved in 18.2% of patients with CDCA, 37.3% with UDCA, and 62.8% with

combination therapy (1).

• A double-blind, randomized, controlled study showed up to 55% partial dissolution and up to 29%

complete dissolution of radiolucent gallstones with UDCA. Dissolution was most effective in stones

<5 mm in diameter (2).

• A randomized, double-blind study showed that in patients treated with UDCA, there was a

significant reduction in biliary cholesterol concentration, formation of cholesterol crystals, and bile

viscosity (3).

• A 2008 meta-analysis of five randomized, controlled trials including 521 patients showed significant

reduction of gallstone formation after bariatric surgery (RR, 0.43 [CI, 0.22 to 0.83]), with 8.8% of

those taking UDCA developing gallstones compared with 27.7% of those taking placebo (P=0.01)

(4).

• In a prospective study of 1059 patients who had laparoscopic cholecystectomy for symptomatic

gallstones, risk factors for developing acute cholecystitis were analyzed. Age older than 60 years,

male sex, the presence of cardiovascular disease, the presence of diabetes mellitus, and a history

of cerebrovascular accident (ischemic stroke or cerebral hemorrhage) were identified as

independent risk factors for acute cholecystitis after multivariate analysis. Acute cholecystitis was

associated with greater operative difficulty and more postoperative morbidity than chronic

cholecystitis. Therefore, an early cholecystectomy was recommended for the patients with risk

factors for acute cholecystitis (5).

Rationale

• UDCA can dissolve gallstones, decrease cholesterol crystal formation, and reduce the bile

saturation index.

Comments

• Patients must have a functioning gallbladder, and gallstones must be radiolucent in order to use

UDCA. Gallstones optimally should be <5 mm in diameter.

• Significant diarrhea will develop in 5% to 10% of patients taking UDCA.

• The most definitive preventive strategy for cholecystitis is cholecystectomy. Because of suboptimal

response rates and prolonged time needed for dissolution, medical therapy should be reserved for

patients unable to have surgery. A study comprising 177 patients concluded that UDCA does not

reduce biliary symptoms in highly symptomatic patients and that early cholecystectomy is

warranted in patients with symptomatic gallstones (6).

1.2 Consider diclofenac in patients with biliary colic.

Recommendations

• Consider administering diclofenac, 75 mg, intramuscularly in a single injection.

Evidence

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• A 2008 systematic review and meta-analysis that included seven randomized, controlled trials

(n=349 patients) comparing the efficacy of NSAIDs with other analgesic agents in the treatment of

biliary colic showed NSAIDs to be the analgesics of choice for biliary colic in limiting the progression

of colic to acute cholecystitis (7).

• A randomized, double-blind study of diclofenac showed satisfactory pain relief and decrease in

progression to acute cholecystitis. Four of 27 patients treated with diclofenac developed acute

cholecystitis compared with 11 of 26 placebo patients (P=0.04) (8).

• A randomized, double-blind study of diclofenac vs. hyoscine for acute biliary colic showed faster

and more effective pain relief in the diclofenac arm. A smaller percentage of patients in the

diclofenac group (16.7%) progressed to acute cholecystitis compared with the hyoscine group

(52.8%) (9).

Rationale

• Diclofenac provides pain relief in biliary colic and decreases the risk for acute cholecystitis.

1.3 Consider cholecystectomy for symptomatic gallstones.

Recommendations

• Consider laparoscopic cholecystectomy for patients with symptomatic gallstones.

Evidence

• A randomized, prospective study showed that in patients with biliary colic, 38% per year had

recurrent biliary pain and 2% per year required cholecystectomy for significant biliary symptoms

(10).

• Based on simulation modeling, prophylactic cholecystectomy may decrease mortality more than

conservative management in patients with symptomatic gallstones (11).

• There are no randomized trials comparing cholecystectomy vs. no cholecystectomy in patients with

silent gallstones. Further evaluation of observational studies, which measure such outcomes as

obstructive jaundice, gallstone-associated pancreatitis, and/or gallbladder cancer for sufficient

duration of follow-up, is necessary before randomized trials are designed to evaluate whether

cholecystectomy or no cholecystectomy is better for asymptomatic gallstones (12).

• The need for cholecystectomy was demonstrated in a study comparing outcomes in non-

gangrenous (n=174) vs. gangrenous cholecystitis (n=106). Mortality was significantly higher in the

latter group (0% vs. 4%; P=0.017). The risk factors associated with gangrenous cholecystitis

included older age (69 years vs. 57 years; P=0.001) and diabetes (19% vs. 10%; P=0.049). There

was no overall difference in complication rates between the non-gangrenous and gangrenous

cholecystitis groups (22% vs. 14%; P=0.102) when treated in a specialized unit (13).

Rationale

• A large percentage of patients with symptomatic gallstones will have recurrent symptoms and may

develop more serious complications.

Comments

• Surgical removal of the gallbladder and gallstones is the definitive therapy for preventing acute

cholecystitis.

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2. Diagnosis Top

Base the diagnosis of acute cholecystitis on the history, physical exam, laboratory data, and radiologic studies.

2.1 Obtain patient history for features suggestive of acute cholecystitis.

Recommendations

• Ask about:

Details of pattern, duration, location, and radiation of pain

Related symptoms, such as fever, chills, nausea, or vomiting

Dark urine

Previous biliary colic

Patient's age

Presence of diabetes

• Note that the typical pain is mid-epigastric, progressing to right upper quadrant. Pain may also

radiate to right scapula, right shoulder, back, or lower abdomen.

Evidence

• A retrospective study showed that 73.5% of patients with acute cholecystitis had pain persisting

less than 24 hours, 54% had right upper quadrant pain, and 34% had mid-epigastric pain (14).

• A prospective study showed that 32.2% of patients with acute cholecystitis had fever, and 75%

had previous episodes of biliary colic (15).

• A retrospective study showed that in acute acalculous cholecystitis, advanced age was associated

with the presence of severe gallbladder complications (16).

• A retrospective study showed that a history of diabetes was significantly associated with the

development of gangrenous cholecystitis (17).

Rationale

• The history of acute cholecystitis often includes previous episodes of biliary colic, mid-epigastric

visceral pain radiating to the right upper quadrant, parietal pain, fever, chills, nausea, and

vomiting.

• Advanced age may correlate with the development of complications in acute cholecystitis.

• Diabetes may play a role in the development of complications in acute cholecystitis.

Comments

• In elderly patients (especially those with diabetes) with leukocytosis and acute cholecystitis,

consider early surgical evaluation owing to the increased risk for developing gallbladder

complications (16).

2.2 Perform physical exam for features suggestive of acute cholecystitis.

Recommendations

• Look for:

Abdominal tenderness

Murphy's sign (palpation of the right upper quadrant causing pain and arrest of inspiration)

Right upper quadrant mass

Fever

Jaundice

Peritoneal signs

Signs of hemodynamic instability

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Evidence

• A retrospective study showed that a positive Murphy's sign had a sensitivity of 97.2% and was

highly predictive (93.3%) of a positive hepatobiliary scintigraphic scan in the diagnosis of acute

cholecystitis (14).

• A retrospective study showed that 85% of patients with acute cholecystitis had right upper

quadrant tenderness, and 40% had tenderness elicited in other regions (18).

• A retrospective study showed that 23% of patients with acute cholecystitis had a palpable

gallbladder (19).

Rationale

• Classic findings on the exam of acute cholecystitis include right upper quadrant or mid-epigastric

tenderness with Murphy's sign.

• A right upper quadrant mass (palpable gallbladder) may be present.

• Peritoneal signs imply a perforated viscus.

Comments

• Peritoneal signs require immediate surgical evaluation.

2.3 Recognize the clinical setting of acute acalculous cholecystitis.

Recommendations

• Consider the diagnosis of acute acalculous cholecystitis in critically ill patients.

• Understand that the classic signs and/or symptoms of acute cholecystitis may be absent in

acalculous disease.

Evidence

• A retrospective study showed that 14% of all cases of acute cholecystitis were acalculous; 63% of

the patients had had surgery, 52% were in the ICU, 37% were on a ventilator, 33% were

hypotensive, 33% were fasting, and 18% were on TPN (20).

• A retrospective study showed that only 66.7% of patients with acute acalculous cholecystitis had

right upper quadrant pain (21).

Rationale

• Five percent to 15% of cases of acute cholecystitis are acalculous.

• Acute acalculous cholecystitis generally occurs in critically ill, septic patients.

• The classic findings of right upper quadrant pain, Murphy's sign, and fever may be absent in

intubated, unresponsive patients.

2.4 Use laboratory data to establish the diagnosis.

Recommendations

• Look for evidence of leukocytosis.

• Evaluate LFTs.

• Use laboratory data to exclude other diseases.

• See table Laboratory and Other Studies for Acute Cholecystitis.

Evidence

• A prospective study showed that 41% of patients with acute cholecystitis had elevated bilirubin

levels, 26% had elevated alkaline phosphatase levels, 12% had elevated ALT levels, and 51% had

leukocytosis (>10,000 103/µL) (15).

• A prospective study showed that 29% of patients with acute cholecystitis had hyperbilirubinemia.

The average bilirubin level in patients without common bile-duct stones was 2.7 mg/dL. The

average bilirubin level in patients with common bile-duct stones was 6.7 mg/dL (22).

• Two retrospective studies showed that leukocytosis was present in 60% and 63% of patients with

acute cholecystitis (14; 23).

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• In a review of 216 patients with acute calculous cholecystitis, elevated serum γ-glutamyl

transpeptidase >90 U/L was associated with a 33% chance of having choledocholithiasis (24).

• In a retrospective review of 177 patients aged 16 to 65 years who had right hypochondrial pain,

statistically significant predictors of acute cholecystitis were alkaline phosphatase, Murphy's sign,

elevated leukocyte count, and elevated bilirubin level (25).

Rationale

• Leukocytosis, mild LFT abnormalities, and mild hyperbilirubinemia are common in acute

cholecystitis.

• Leukocytosis may correlate with outcome in acute cholecystitis.

• Bilirubin >4 mg/dL is not a feature of uncomplicated acute cholecystitis.

Comments

• Bilirubin levels >4 mg/dL suggest possible common bile-duct stone, cholangitis, or Mirizzi's

syndrome, a rare condition in which a gallstone impacting the cystic duct obstructs the common

bile duct by edema and extrinsic compression.

• In elderly patients with acute cholecystitis and leukocytosis, consider early surgical evaluation

owing to the increased risk for developing gallbladder complications (16; 17).

2.5 Use imaging studies to establish the diagnosis.

Recommendations

• Obtain the following:

Transcutaneous ultrasound to diagnose acute cholecystitis

Cholescintigraphy scans (e.g., HIDA scan) as an alternative to diagnose acute cholecystitis or when ultrasound is equivocal

CT scan when other studies are equivocal or when complications of acute cholecystitis are suspected

MRCP scan if there is suspicion of calculi in the bile duct

• See table Laboratory and Other Studies for Acute Cholecystitis.

• See figure Gallbladder Ultrasound Showing Gallstones.

• See figure Acalculous Cholecystitis.

• See figure Normal Gallbladder Ultrasound.

• See figure Gallstone Ileus.

Evidence

• A prospective study showed that when ultrasound revealed gallstones and a positive sonographic

Murphy's sign, the positive predictive value for acute cholecystitis was 92.2%. When the patient

had gallstones and gallbladder-wall thickening (≥3 mm), the positive predictive value was 95.2%

for acute cholecystitis (26).

• Multiple (>20) prospective and retrospective studies have showed ultrasound to have 81% to 98%

sensitivity and 70% to 98% specificity for acute cholecystitis (26; 27; 28; 29; 30).

• Various retrospective and prospective trials have compared ultrasound with HIDA scanning for the

diagnosis of acute cholecystitis. A retrospective analysis of patients with acute cholecystitis showed

ultrasound scans to be less sensitive than HIDA scans for initial diagnosis (48% vs. 86%) (30).

• A retrospective study showed ultrasound to have a sensitivity of 86% vs. 97% for HIDA scans (28).

• A retrospective study showed ultrasound to have an accuracy of 94% vs. 93% for HIDA scans (27).

• A meta-analysis from 1994 of 30 articles showed ultrasound to have 94% sensitivity and 78%

specificity, compared with HIDA scans, which have a 97% sensitivity and a 90% specificity for the

diagnosis of acute cholecystitis (29).

• A retrospective study showed that 50.9% of patients with acute cholecystitis showed evidence of a

thickened gallbladder wall on unenhanced CT scan. In addition, 66.7% of patients with this finding

had gangrenous cholecystitis on histology (31).

• A 2003 meta-analysis of 67 studies including 4711 patients showed that MRCP is a non-invasive

imaging test with excellent overall sensitivity (95%) and specificity (97%) for showing the level

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and presence of biliary obstruction, although it was less sensitive for identifying stones (88%) and

malignant lesions (92%) (32).

Rationale

• Both ultrasound and HIDA scans are accurate for the diagnosis of acute cholecystitis. The general

recommendation has been to obtain an ultrasound scan first, followed by an HIDA scan, if

necessary.

• The classic findings of acute cholecystitis on ultrasound are pericholecystic fluid and a thickened

gallbladder wall of 3 mm to 4 mm; sonographic Murphy's sign further confirms the diagnosis.

• The classic finding of acute cholecystitis on HIDA scan is non-visualization of the gallbladder.

• An enhanced CT scan can show gallstones, gallbladder-wall thickening, gallbladder distension,

pericholecystic fluid, and inflammation of the pericholecystic fat. An unenhanced CT scan can show

gallstones and a hyperdense gallbladder wall, which can suggest the presence of gangrenous

cholecystitis.

Comments

• Despite most organizations recommending ultrasound as the primary diagnostic tool for acute

cholecystitis, the literature shows that an HIDA scan has equal or better sensitivity and specificity;

however, cost and ease of access favor the use of ultrasound.

• Ultrasound can be less accurate in patients with ascites, hypoalbuminemia, hepatitis, obesity, and

heart failure.

• HIDA scans can give false-positive results in critically ill, fasting patients. Furthermore, HIDA scans

are not accurate with bilirubin levels >5 mg/dL, in which case more specialized tests, such as

DISIDA scan, can be used.

• CT scan should be reserved for cases of diagnostic dilemma and to detect possible complications of

acute cholecystitis (31).

• MRCP is commonly used to diagnose obstruction of the biliary tree caused by stones or malignant

lesions.

2.6 Consider the broad differential diagnosis.

Recommendations

• When considering the differential diagnosis of acute cholecystitis, include acute disease processes

on both sides of the diaphragm.

• See table Differential Diagnosis of Acute Cholecystitis.

Evidence

• Consensus.

Rationale

• Many intra-abdominal and thoracic conditions can mimic acute cholecystitis.

• The correct diagnosis must be made to separate routine conditions from emergent conditions.

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3. Consultation Top

Obtain surgical and possibly GI consultation to aid in the diagnosis. Consult a surgeon and a gastroenterologist as needed for management of patients.

3.1 Obtain surgical consultation for suspected cases of acute cholecystitis.

Recommendations

• Obtain surgical consultation to aid in diagnosing acute calculous and acalculous cholecystitis.

Evidence

• Consensus.

Rationale

• The differential diagnosis of acute cholecystitis is extensive; several surgical conditions can mimic

acute cholecystitis.

• Acute acalculous cholecystitis can present with subtle signs and symptoms in critically ill patients.

• A surgical consultant can establish a diagnosis and formulate a treatment plan.

3.2 Obtain GI consultation in certain cases.

Recommendations

• Obtain GI consultation in cases of suspected acute cholecystitis with a bilirubin level >4 mg/dL

and/or significantly elevated LFTs.

Evidence

• A prospective study of patients with acute cholecystitis who had hyperbilirubinemia and subsequent

biliary-tract exploration showed that 68.4% had common bile-duct stones (22).

Rationale

• Acute cholecystitis is generally not associated with significant jaundice or elevation of LFTs; these

findings suggest either common bile-duct stones or Mirizzi's syndrome, a rare condition in which a

gallstone impacting the cystic duct obstructs the common bile duct by edema and extrinsic

compression.

• MRC is useful in detecting stones in the common bile duct before or after cholecystectomy and may

be indicated.

• Endoscopic evaluation of the biliary tree may be warranted.

3.3 Obtain joint surgical and obstetric consultations in cases of suspected acute cholecystitis during pregnancy.

Recommendations

• Obtain joint surgical and obstetric consultations in cases of suspected acute cholecystitis during

pregnancy.

Evidence

• In a study of 6221 women with gallstone-related hospitalization during pregnancy and postpartum,

76% were diagnosed with uncomplicated cholelithiasis, 16% with pancreatitis, 9% with acute

cholecystitis, and 8% with cholangitis. Seventy-three percent of the hospitalized women underwent

cholecystectomy and 5% underwent ERCP (39).

• In a prospective observational study of 122 patients with biliary disease (41 with acute

cholecystitis), conservative treatment failed in 69 (56.5%) patients and 54 of this group underwent

laparoscopic cholecystectomy during second trimester with no fetal or maternal mortality (40).

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• In a study of 49 patients admitted with an acute abdomen in pregnancy due to cholecystitis, 15

patients (31%) had emergency cholecystectomy within the first week. Thirty-four patients (69%)

were treated conservatively, of whom 24 relapsed many times and had to be readmitted to the

hospital. Of the remaining 10 patients on conservative management, 3 had emergency

cholecystectomy and 7 reached term safely. Maternal morbidity was significantly less in the

surgically treated group (P<0.0001), but there was no significant difference in perinatal outcome.

Although tocolytics were used in 13 cases, they did not improve the fetal outcome significantly and

had maternal and fetal side effects. This article concluded that early surgical intervention is

recommended and the use of tocolytics did not improve the perinatal outcome (41).

• In a population-based measurement of outcomes of cholecystectomy during pregnancy among

9714 pregnant women (89% underwent laparoscopic cholecystectomy), maternal and fetal

complication rates were 4.3% and 5.8%, respectively. Compared with pregnant women who

underwent open procedures, pregnant women who underwent laparoscopic cholecystectomy had

higher rates of surgical (19% vs. 10%), maternal (9% vs. 4%), and fetal (11% vs. 5%)

complications; longer length of stay (6 vs. 4 days); and higher cost ($13,198 vs. $9,229) (all

P<0.0001) (42).

Rationale

• Acute cholecystitis during pregnancy, although classically managed conservatively, can be

associated with recurrent symptoms requiring cholecystectomy.

• Acute cholecystitis during pregnancy can be safely treated with minimally invasive techniques

including percutaneous aspiration, cholecystostomy, laparoscopic cholecystectomy, and ERCP,

depending on the pregnancy trimester and underlying diagnosis.

3.4 Consult a surgeon immediately for management of patients.

Recommendations

• Consult a surgeon immediately for cholecystectomy.

• Consider surgical consult even in patients who are poor surgical candidates or deemed inoperable

who may benefit from cholecystectomy.

Evidence

• A prospective, randomized trial compared early cholecystectomy with delayed cholecystectomy in

patients with acute cholecystitis. In the delayed group, 13% of patients required emergent surgery

within 90 days owing to cholangitis, empyema, or peritonitis. Another 15% of patients developed

acute recurrent symptoms within the 90-day period (54).

• Two prospective, randomized, controlled trials have examined the issue of ‘early’ vs. ‘delayed’

laparoscopic cholecystectomy in acute cholecystitis. Both showed no difference in complication

rates, rates of conversion to open procedure, morbidity, or mortality. There was a shorter hospital

stay in the early group (P<0.001) (75; 76).

• A retrospective Veterans Administration study of acute cholecystitis patients with multiple medical

comorbidities evaluated 24 patients treated with cholecystostomy tubes (22 ultrasound/CT guided,

2 surgically placed), of whom 78% had clinical improvement within 48 hours. There was a 25%

periprocedural mortality rate (77).

• A retrospective study of inoperable patients treated with percutaneous cholecystostomy showed

98% successful biliary drainage; 96% of these patients showed clinical improvement within 72

hours, and 93% were discharged from the hospital with plans for a subsequent cholecystectomy

(65).

• A prospective study showed that 92.3% of patients with acute acalculous cholecystitis treated with

percutaneous cholecystostomy had good clinical response. All patients had subsequent catheter

removal without the need for cholecystectomy (66).


percutaneous cholecystostomy had significant clinical improvement; 13 of 14 patients who

responded had catheter removal and required no further therapy (67).

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Rationale

• Cholecystectomy is definitive therapy in most patients with acute cholecystitis.

• Early laparoscopic cholecystectomy can be safely done in most patients with acute cholecystitis.

• Inoperable and high-risk surgical candidates may need interventions, such as cholecystostomy,

which can be coordinated by a surgical consultant.

3.5 Consult a gastroenterologist in certain cases.

Recommendations

• Consult a gastroenterologist in patients for possible ERCP with acute cholecystitis and:

Jaundice

Common bile-duct dilation

Significantly elevated LFT levels

Significantly elevated pancreatic enzymes

Evidence

• A prospective, randomized study showed that 100% of patients presenting with acute cholangitis

had successful biliary drainage by ERCP. There was a trend toward fewer complications in the ERCP

group vs. the surgery group (P>0.05), and there was less mortality in the ERCP group (P<0.03)

(78).

• A retrospective study showed that 97% of patients with acute cholangitis were able to have

successful biliary drainage by ERCP. The overall mortality was 4.7% (compared with the quoted

historical, surgical mortality rate of 16.5% to 40%) (79).

Rationale

• Patients with acute cholecystitis and significantly elevated LFTs, bilirubin, pancreatic enzymes, or

dilated bile ducts may have common bile-duct stones or Mirizzi's syndrome.

• ERCP may be diagnostic and/or therapeutic in this subset of patients.

Comments

• MRC is a non-invasive method of detecting stones in the common bile duct in patients with risk

factors for common bile-duct calculi, thereby helping avoid ERCP, which is an invasive test with

potential complications. A prospective study evaluated the predictive value of MRC in detecting

stones in the common bile duct before laparoscopic cholecystectomy. MRC had a sensitivity of

100%, a specificity of 96.3%, a positive predictive value of 91.8%, and a negative predictive value

of 100% for the detection of common bile-duct stones (80).

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4. Hospitalization Top

Hospitalize patients with acute cholecystitis.

4.1 Hospitalize patients with acute cholecystitis for definitive diagnosis and treatment.

Recommendations

• Hospitalize patients to:

Provide analgesia, hydration, supportive care, and possibly antibiotics

Obtain surgical consultation

Prepare patient for possible cholecystectomy

• See Therapy.

Evidence

• Consensus.

Rationale

• Many patients with acute cholecystitis will have nausea, vomiting, or anorexia requiring iv

hydration and supportive care, and many will also require parenteral analgesia.

• Most patients will require definitive surgical therapy.

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5. Therapy Top

Consider cholecystectomy as definitive therapy.

5.1 Consider the use of antibiotics in certain patients.

Recommendations

• Consider using broad-spectrum antibiotics in acute cholecystitis patients with sepsis, fever,

leukocytosis, or evidence of complications.

• See table Drug Treatment for Acute Cholecystitis.

Evidence

• A prospective study of 467 patients with acute cholecystitis showed positive bile cultures in 46%;

the most common organisms were E. coli, Klebsiella sp., group D Streptococcus sp., and

Enterobacter sp. Patients aged over 60 years had the highest rate of biliary infection (43).

• Cases of acute cholecystitis are reported to be caused by such organisms as Vibrio cholerae (44),

Haemophilus influenzae (45), Moellerella wisconsensis (46), Salmonella sp. (47), Cytomegalovirus

(48), Cellulomonas denverensis (49), and Candida lusitaniae (50).

• A retrospective study of 302 patients with acute cholecystitis showed no difference in local septic

complications, such as empyema or pericholecystic abscess, in those treated with or without

antibiotics. There was a lower incidence of wound infections and postoperative bacteremia in

patients treated with antibiotics (51).

Rationale

• A significant percentage of patients with acute cholecystitis will have positive blood and bile

cultures. Antibiotics would be expected to benefit this group.

Comments

• Definitive evidence regarding the use of antibiotics in acute cholecystitis is lacking; however, it

would seem prudent to consider using antibiotics in toxic-appearing patients.

• The recommended regimens vary from single- to triple-coverage; the choice of antibiotic should be

based on suspected organisms and local antibiotic resistance patterns.

5.2 Ensure appropriate use of pain medications.

Recommendations

• Consider using:

NSAIDs in patients with biliary colic or acute cholecystitis with mild to moderate abdominal pain

Narcotic analgesics in patients with moderate to severe abdominal pain

• See module Pain.

Evidence

• Retrospective studies of patients presenting with acute cholecystitis show that abdominal pain

occurs in 73.5% (14) and abdominal tenderness occurs in 85% (18).

• A randomized, double-blind study of diclofenac showed satisfactory pain relief and decrease in

progression to acute cholecystitis. Four of 27 patients who received diclofenac developed acute

cholecystitis compared with 11 of 26 patients who received placebo (P=0.04) (8).

• A 2008 systematic review and meta-analysis that included seven randomized, controlled trials

(n=349 patients) assessing the efficacy of NSAIDs in comparison to other analgesic agents in the

treatment of biliary colic showed NSAIDs to be the analgesics of choice for biliary colic in limiting

the progression of colic to acute cholecystitis (7).

• A randomized, double-blind study evaluated the efficacy of iv ketorolac compared with butorphanol

for the treatment of biliary colic pain in the emergency department. Patients presenting with

abdominal pain suspected to be biliary colic were randomized to receive either ketorolac, 30 mg iv,


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or butorphanol, 1 mg iv. The mean (+/- SD) pain score (visual analogue scale) in the butorphanol

group decreased from 7.1 (+/-1.7) to 2.1 (+/-2.2) after 30 minutes. The mean (+/-SD) pain score

in the ketorolac group decreased from 7.4 (+/-2.0) to 3.1 (+/-3.3) after 30 minutes. This study

showed that both ketorolac and butorphanol provide pain relief in biliary colic and were suitable

especially in patients who require HIDA scan (52).

Rationale

• Over 80% of patients with acute cholecystitis present with abdominal pain or tenderness, and pain

medications can provide analgesia while awaiting definitive therapy.

• NSAIDs provide pain relief in biliary colic and may decrease the risk for progression to acute

cholecystitis.

Comments

• A prospective, non-blinded study using sphincter of Oddi manometry showed that morphine

increased sphincter phasic wave amplitude and basal pressure (P<0.05) (53).

• Older studies suggested that meperidine might be preferable to morphine in the treatment of pain

in patients with acute cholecystitis because it increases pressure at the sphincter of Oddi less than

other opiates, but evidence is not strong enough to support a recommendation of one opiate

analgesic over another. Meperidine should be avoided in elderly patients and those with renal

dysfunction because of possible accumulation of a toxic metabolite with neuroexcitatory effects.

5.3 Consider early cholecystectomy.

Recommendations

• Consider laparoscopic cholecystectomy to be the preferred surgical approach in patients with acute

cholecystitis.

• Perform cholecystectomy within 24 to 48 hours of diagnosis.

• Note that technical aspects, such as anatomy and complications, may require an open surgical

approach in certain patients.

Evidence





• A retrospective study evaluated 609 patients with acute cholecystitis treated by laparoscopic

cholecystectomy. The overall complication rate was 15%; specific complication rates were bile

leaks, 1.97%, and biliary-tract injury, 0.66%; mortality was 0.66%. These rates were comparable

to previous open cholecystectomy series (55).

• A randomized, controlled trial comparing open and laparoscopic cholecystectomy in acute

cholecystitis showed a significantly lower postoperative complication rate (P=0.0048), shorter

hospitalization (P=0.0063), and lower hospital cost for laparoscopy (56).

• A 2008 meta-analysis examined the issue of ‘early’ vs. ‘delayed’ laparoscopic cholecystectomy in

patients with acute cholecystitis. Early laparoscopic cholecystectomy resulted in a significantly

shorter total hospital stay at the cost of a significantly longer operation time, with no significant

difference in conversion rates or complications (57).

• A 2010 systematic review with meta-analysis of randomized clinical trials of early laparoscopic

cholecystectomy (done within 1 week of onset of symptoms) vs. delayed laparoscopic

cholecystectomy (done at least 6 weeks after symptoms settled) for acute cholecystitis, which

included five trials with 451 patients, showed no significant difference between the two groups in

terms of bile-duct injury (RR, 0.64 [CI, 0.15 to 2.65]) or conversion to open cholecystectomy (RR,

0.88 [CI, 0.62 to 1.25]). The total hospital stay was 4 days shorter for early laparoscopic

cholecystectomy (mean difference, -4.12 [CI, -5.22 to -3.03] days). Early laparoscopic

cholecystectomy during acute cholecystitis appears safe and shortens the total hospital stay (58).

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• A 2008 Cochrane review, which included five trials with 429 patients randomly assigned to the day-

case group (n=215) and overnight-stay group (n=214), showed no significant difference between

the two groups regarding morbidity, prolongation of hospital stay, readmission rates, pain, quality

of life, patient satisfaction, and return to normal activity and work. The day-case elective

laparoscopic cholecystectomy was safe and effective in selected patients with symptomatic

gallstones who had no or minimal systemic disease and were within easy reach of the hospital

(59).

• In a prospective study from the UK that included 106 patients who had day-case laparoscopic

cholecystectomy, 84% were discharged on the day of surgery. Mean surgery time was 62 minutes,

with an average total stay on the day-case unit of 426 minutes. Both the readmission rate after

surgery and rate of conversion to open surgery were 2%. Introduction of day-case laparoscopic

cholecystectomy in the UK was feasible and acceptable to patients (60).

• Cholecystectomy using rigid-hybrid transvaginal natural orifice transluminal endoscopic surgery

reduces abdominal-wall incisions and might decrease surgical trauma by combining endoluminal

access and laparoscopic techniques. In one study, 102 of 137 consecutive patients (74.5 %) with

symptomatic cholecystolithiasis (n=74) or cholecystitis (n=28) were scheduled for this type of

surgery. There were no intraoperative complications. At 6 weeks postoperatively, there were fewer

dyspareunia symptoms than preoperatively (P=0.049). This technique is feasible and safe in

routine practice for symptomatic cholecystolithiasis and acute cholecystitis (61).

• Percutaneous transhepatic gallbladder drainage is a procedure to resolve acute cholecystitis, which

decreases the technical difficulty of laparoscopic cholecystectomy and facilitates successful surgery

when a patients' condition improves. Early laparoscopic cholecystectomy (within 72 hours, n=21)

vs. delayed (after 72 hours; n=46) laparoscopic cholecystectomy after percutaneous transhepatic

gallbladder drainage showed a higher complication rate and longer operating time, but shorter

hospital stay in the former group (62).

• In a retrospective study involving 809 patients with acute cholecystitis, laparoscopic

cholecystectomy (done in 82% of patients) was associated with significantly better outcomes,

including shorter postsurgical stay and fewer complications compared with open cholecystectomy

and cholecystostomy (63).

Rationale

• Laparoscopic cholecystectomy is safer, less expensive, and associated with shorter hospitalizations

than open procedures.

• Early cholecystectomy is associated with a shorter recovery period and fewer complications, such

as gangrene and empyema of the gallbladder.

• Acute cholecystitis and/or other serious complications of gallstone disease can recur in untreated

patients.

Comments

• The exact surgical approach may vary based on local surgical expertise.

• Patients should understand that conversion from a laparoscopic to an open procedure may be

necessary.

• Day-case laparoscopic cholecystectomy is not suitable for acute cholecystitis.

• Natural orifice transluminal endoscopic surgery is being increasingly practiced with encouraging

results.

• Single-incision laparoscopic cholecystectomy is a variation in which trocar scars are hidden in the

umbilicus. In a study including 205 cases of single-incision laparoscopic cholecystectomy, the mean

operating time was 60 minutes and complications occurred in 4% of cases. Single-incision

laparoscopic cholecystectomy can be done safely and offers a better cosmetic result, which may

lead to greater patient satisfaction (64).

5.4 Consider cholecystostomy in certain patients.

Recommendations

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• Consider cholecystostomy as temporizing or definitive therapy for inoperable or high-risk patients

with calculous or acalculous cholecystitis.

Evidence

• A retrospective study of inoperable patients treated with percutaneous cholecystostomy showed

98% successful biliary drainage; 96% of these patients showed clinical improvement within 72

hours, and 93% were discharged from the hospital with plans for a subsequent cholecystectomy

(65).


percutaneous cholecystostomy had good clinical response. All patients had subsequent catheter

removal without the need for cholecystectomy (66).


percutaneous cholecystostomy had significant clinical improvement; 13 of 14 patients who

responded had catheter removal and required no further therapy (67).

• A retrospective study of 45 patients having cholecystostomy for acute cholecystitis showed a 100%

technically successful gallbladder drainage rate. 78% of the patients improved clinically within 5

days (68).

• A prospective study randomizing patients with acute calculous cholecystitis into those having

percutaneous cholecystostomy followed by an early laparoscopic cholecystectomy (n=31) and

those having an initial conservative treatment followed by a delayed laparoscopic cholecystectomy

(n=30) showed significantly shorter hospital stay and lower cost in the first group (69).

• In a study involving 106 patients with acute cholecystitis, percutaneous cholecystostomy led to

clinical improvement in 72 patients (68%), whereas 34 (32%) showed no improvement or clinical

deterioration. Patients who presented to the emergency department primarily with acute

cholecystitis fared better (84% of patients showed improvement) than inpatients (34% showed

improvement; P<0.0001). Gallstones were identified in 54% of patients who presented to the

emergency department, whereas acalculous cholecystitis was more commonly diagnosed in

inpatients (54%). Patients with sepsis had worse outcomes overall (P<0.0001). Patients fare better

after percutaneous cholecystostomy for acute cholecystitis when the disease is primary and not

precipitated by concurrent illness (70).

Rationale

• The mortality rate of critically ill patients having cholecystectomy for acute cholecystitis can be

10% to 30%.

• Because patients with acute acalculous cholecystitis are often critically ill and may not be operative

candidates, cholecystostomy may allow biliary drainage that may temporize the patient until

surgery can be safely done or even provide definitive therapy for the patient.

• Acalculous cholecystitis may resolve when the precipitating factors, such as TPN, sepsis, shock, or

fasting, improve.

• Cholecystostomy may allow time to resolve these precipitating factors and thus be curative.

Comments

• Cholecystostomy is indicated in high-risk patients who are not candidates for cholecystectomy.

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6. Patient Education Top

Inform patients of the natural history of acute cholecystitis.

6.1 Inform patients of the natural history and therapeutic options for acute cholecystitis.

Recommendations

• Explain the natural course of acute cholecystitis.

• Inform the patient of the treatment options available.

• Explain why surgical options are preferred in most cases.

Evidence

• A retrospective study of patients at initial presentation with acute cholecystitis showed 7.1% had

gangrenous cholecystitis, 6.3% had empyema of the gallbladder, 3.3% had gallbladder perforation,

and 0.5% had emphysematous cholecystitis (71).





• A prospective, randomized clinical trial compared the outcomes of early (within 7 days of onset of

symptoms) with delayed (6 to 8 weeks after initial conservative treatment) laparoscopic

cholecystectomy. Twenty-six percent of patients in the delayed cholecystectomy group required

emergency cholecystectomy for failure of conservative treatment. There was no significant

difference in the conversion rate, operating time, or complications. The greatest advantage was a

reduced length of hospital stay in the early cholecystectomy group (72).

• A 2008 meta-analysis of 20 randomized, controlled trials including 3860 patients showed day-case

laparoscopic cholecystectomy to be safe in a selected group of patients who do not have acute

cholecystitis, bile-duct stones, or previous upper-abdominal surgery (73).

• In 185 adult patients admitted with acute cholecystitis (mean age 71 years; 80% had more than

one comorbidity), percutaneous cholecystostomy was done in 78% of cases and open surgical

cholecystostomy was done in 22%. In both groups, 85% patients underwent laparoscopic

cholecystectomy as definitive treatment, thereby confirming that cholecystostomy is a useful

alternative to open cholecystectomy in patients with acute cholecystitis that allows patients to

undergo laparoscopic cholecystectomy at a later date (74).

Rationale

• The risk for advanced disease and complications at the time of presentation is significant.

• The risk for recurrent acute cholecystitis in the untreated patient is significant.

• Surgical therapies are definitive, effective, and safe.

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7. Follow-up Top

Schedule follow-up of patients treated for acute cholecystitis based on hospital course.

7.1 Ensure that patients who have had cholecystectomy follow-up with their surgeon.

Recommendations

• Advise patients to follow-up with their surgeon routinely, and immediately if they have right upper

quadrant pain, fever, or wound-site complaints which suggest postoperative biliary tract

complications such as retained bile-duct stone, bile leak, or infection.

Evidence

• Two prospective, randomized studies showed overall complication rates of 13% (75) and 9% (76)

in patients having early laparoscopic cholecystectomy for acute cholecystitis.

• A retrospective literature review showed that the overall risk for biliary injury during laparoscopic

cholecystectomy (for any indication) is 2.58%; major bleeding occurred in 1.38% of cases, wound

infection in 0.6%, bile leak in 0.4%, biliary injury in 0.2%, and bowel injury in 0.16% (81). A

retrospective, single-center study showed bile-duct injury occurring in 0.59% of patients having

laparoscopic cholecystectomy for any indication (82).

Rationale

• Laparoscopic cholecystectomy carries risk for postoperative complications; these risks are higher in

patients having the procedure for acute cholecystitis.

• The surgeon should watch for signs and symptoms of biliary-tract complications and wound

infections.

Comments

• The surgeon should determine the postoperative follow-up schedule.

7.2 Re-evaluate patients who have had cholecystostomy or medical management.

Recommendations

• In consultation with a surgeon, re-evaluate patients with acute cholecystitis who have had:

Cholecystostomy or medical therapy alone for subsequent cholecystectomy

Medical therapy with UDCA to dissolve remaining symptomatic gallstones

ERCP with or without sphincterotomy to remove a retained bile-duct stone

• Ask about recurrent symptoms of right upper quadrant pain and biliary colic, fever, and jaundice.

Evidence





• A retrospective study showed that 61.5% of patients with acute calculous cholecystitis who were

temporized with a cholecystostomy tube were able to have subsequent elective cholecystectomy.

Surgical morbidity was 12.5% with no mortalities (83).

Rationale

• Many patients treated conservatively for acute calculous cholecystitis will have recurrent significant

complications.

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• Cholecystectomy provides definitive therapy.

Comments

• Extremely poor-risk surgical candidates can be maintained with a permanent cholecystostomy

drainage tube.

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68. Byrne MF, Suhocki P, Mitchell RM, Pappas TN, Stiffler HL, Jowell PS, et al. Percutaneous cholecystostomy in patients with acute cholecystitis: experience of 45 patients at a US referral center. J Am Coll Surg. 2003;197:206-11. (PMID: 12892798)

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Glossary Top

ALT alanine aminotransferase

AST aspartate aminotransferase

CBC complete blood count

CDCA chenodeoxycholic acid

CI

confidence interval

CT

computed tomography

DISIDA diisopropyl phenyl carboxymethyl iminodiacetic acid

ERCP endoscopic retrograde cholangiopancreatography

GI

gastrointestinal

HIDA hepato-iminodiacetic acid

ICU intensive care unit

IgG immunoglobulin G

IgM immunoglobulin M

iv intravenous

LFT liver function test

MRC

magnetic resonance cholangiography

MRCP magnetic resonance cholangiopancreatography

NSAID nonsteroidal anti-inflammatory drug

RR

risk ratio

SD standard deviation

TPN total parenteral nutrition

UDCA ursodeoxycholic acid

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Tables Top

Laboratory and Other Studies for Acute Cholecystitis

Test Notes

Complete blood count Look for leukocytosis

Liver function tests Can be elevated in acute cholecystitis

Serum bilirubin If >4 mg/dL, consider common bile-duct stones or Mirizzi's syndrome

Serum amylase If significant increases (more than three times the upper limit of normal), consider pancreatitis or

common bile-duct stones (33)

Serum alkaline phosphatase Elevation significantly predicts acute cholecystitis (25)

Right upper quadrant ultrasound scan Sensitivity 81-98%

Specificity 70-98%

Portable, inexpensive.

Sonographic Murphy's sign (showing maximal tenderness directly over the visualized gallbladder) is

over 90% predictive of acute cholecystitis

HIDA scan Sensitivity 85-97%

Specificity 90%

CT scan Expensive; most useful to diagnose such complications as perforation

MRI scan or MRCP scan Sensitivity 100% for cystic-duct obstruction; 69 for gallbladder-wall thickening

Specificity 93% for cystic-duct obstruction; 83% for gallbladder-wall thickening

Commonly used to diagnose ductal obstruction caused by stones or a malignant lesion

CT = computed tomography; HIDA = hepato-iminodiacetic acid; MRCP = magnetic resonance cholangiopancreatography; MRI = magnetic resonance imaging.

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Differential Diagnosis of Acute Cholecystitis

Disease Characteristics

Acute cholecystitis Mid-epigastric pain progressing to right upper quadrant. Pain may also radiate to right scapula, right

shoulder, back, or lower abdomen. Murphy's sign is highly specific and predictive

Bilirubin >4 mg/dL is not a feature of uncomplicated acute cholecystitis

Acute cholangitis Charcot triad (right upper quadrant pain, fever, jaundice)

or

Reynold pentad (Charcot triad and shock and mental-status changes)

Bilirubin generally >4 mg/dL.

AST and ALT levels may exceed 1000 U/L

Acute appendicitis Mid-epigastric pain radiating to right lower quadrant

Can mimic acute cholecystitis, especially with a high-lying cecum

Acute pancreatitis Mid-epigastric pain radiating to the back, nausea, vomiting, elevated amylase and lipase

Vomiting and hyperamylasemia are generally more pronounced than in acute cholecystitis

Pyelonephritis (right) Costovertebral angle tenderness, evidence of urinary infection

Urinalysis helps establish the diagnosis

Peptic ulcer disease Right upper quadrant or mid-epigastric pain

Perforated ulcer can mimic acute cholecystitis

Pulmonary/pleural disease Cough, shortness of breath, chest or upper abdominal pain

Pleuritic pain component much less common in acute cholecystitis

Acute viral hepatitis Prodromal syndrome, jaundice, AST and ALT levels generally >1000 U/L

LFT and bilirubin level usually much higher than in acute cholecystitis

Acute alcoholic hepatitis Right upper quadrant pain, fever, jaundice, coagulopathy, leukocytosis, AST level usually two to three

times greater than ALT level

Bilirubin level generally >4 mg/dL

Recent significant alcohol intake

Inferior myocardial infarction Chest/mid-epigastric pain, diaphoresis, shortness of breath, elevated cardiac enzymes, acutely

abnormal electrocardiogram

Presence of cardiac risk factors.

Pain characteristics generally different than acute cholecystitis

Mesenteric ischemia Periumbilical or mid-epigastric pain out of proportion to tenderness

Fitz-Hugh-Curtis syndrome (gonococcal perihepatitis) Right upper quadrant pain, adnexal tenderness, leukocytosis

Cervical smear shows gonococci

Hepatic abscess or tumor Right upper quadrant pain, fever

Probably requires imaging studies to differentiate

Pre- and post-herpetic neuralgia Right upper quadrant pain, fever, and malaise followed by vesicular rash on the thoracic dermatome






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Varicella IgM and IgG antibody assays helpful

Bleeding or infection of hepatic hydatid cysts Right upper quadrant pain and fever

Ultrasound or CT scans confirm the diagnosis (34)

Gall bladder ascariasis Right upper quadrant pain and fever

Ultrasound or MRC confirms the diagnosis (35)

Benign liver adenomas Right upper quadrant pain

Ultrasound, CT scans, and biopsy confirm the diagnosis (36)

Torsion of the gallbladder Right upper quadrant pain and fever


Bleeding within the gallbladder Right upper quadrant pain


ALT = alanine aminotransferase; AST = aspartate aminotransferase; CT = computed tomography; IgG = immunoglobulin G; IgM = immunoglobulin M; LFT = liver function test; MRC = magnetic resonance

cholangiography.

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Drug Treatment for Acute Cholecystitis

Drug or Drug Class Dosing Side Effects Precautions Clinical Use

Penicillins Hypersensitivity reactions, hematologic

toxicity, vomiting, diarrhea

Seizures can occur when large doses

given with renal impairment

Piperacillin/tazobactam (Zosyn) 3.375 g iv q6hr Constipation, hypokalemia, headache If CrCl<40, decrease dose to 2.25 g iv

q6-8hr

Ampicillin/sulbactam (Unasyn) 3 g iv q6hr If CrCl<30, extend dosing interval

Ticarcillin/clavulanate (Timentin) 3.1 g iv q6hr Nephrotoxicity If <60 kg or CrCl<60, decrease dose.

Monitor electrolytes

Ampicillin 2 g iv q6hr If CrCl<50, extend dosing interval Combine with gentamicin and

metronidazole

Other antibiotics

Ceftazidime (Fortaz, Tazicef) 1 g iv q8hr Hypersensitivity reactions, hematologic

toxicity, hepatotoxicity, vomiting,

diarrhea

If CrCl<50, decrease dose Combine with metronidazole

Metronidazole (Flagyl, Metro) 500 mg iv q6hr Vomiting, diarrhea, anorexia,

headache, dizziness

Carcinogenicity. Avoid with

pregnancy. Avoid alcohol. Decrease

dose by 50% with severe hepatic

disease. Caution with: CKD, warfarin

Used in combination therapy

Gentamicin 3-5 mg/kg total daily dose, dosed q8hr Vomiting, hepatotoxicity Neurotoxicity, ototoxicity,

nephrotoxicity, neuromuscular

blockade, respiratory paralysis. Use serum levels to guide dosing. Avoid

with pregnancy. Caution with severe

hepatic disease. Decrease dose with

CKD

Used in combination therapy

Meropenem (Merrem) 1 g iv q8hr Vomiting diarrhea, constipation,

headache

Caution with seizure disorder. If

CrCl<50, decrease dose

= black box warning; bid = twice daily; CKD = chronic kidney disease; CNS = central nervous system; CrCl = creatinine clearance; GI = gastrointestinal; IM = intramuscular; iv = intravenous; PO = oral;

q6hr = every 6 hours; qd = once daily; qid = four times daily; SC = subcutaneous; tid = three times daily.

PIER provides key prescribing information for practitioners but is not intended to be a source of comprehensive drug information.

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Figures Top

Gallbladder Ultrasound Showing Gallstones

On ultrasonography, gallstones appear as an echogenic focus that casts an acoustic shadow.

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Acalculous Cholecystitis

Gallbladder ultrasound consistent with acalculous cholecystitis showing an absence of gallstones or sludge, thickened gallbladder wall, and pericholecystic fluid.

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Normal Gallbladder Ultrasound

An ultrasound of a normal gallbladder. The gallbladder wall is denoted by a thin white line. The gallbladder is filled with fluid and appears black.

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Gallstone Ileus

Plain film of the abdomen showing air in the hepatic biliary tree (arrow) and dilated loops of bowel. Air in the biliary tree and signs of bowel obstruction support the diagnosis of fistula between the biliary tree and bowel, most likely created by a gallstone that obstructed the cystic duct, eroded through the wall, and is now obstructing the small bowel.

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