1-s2.0-S2211594315000131 Clinicas de Norteamerica Colecistitis

Acute Cholecystitis,
Choledocholithiasis,
a nd A c ut e C h o l an g i t i s
Adam Littich, MD*, Cheryl R. McDonough, MD
KEYWORDS
Gallstone Cholelithiasis Biliary colic Acute cholecystitis Choledocholithiasis
Acute cholangitis Cholecystectomy Cholecystostomy
HOSPITAL MEDICINE CLINICS CHECKLIST
1. Cholelithiasis is common, but often asymptomatic. When symptomatic, the

usual presentation is biliary colic.
2. Gallstone disease most commonly affects women (especially if pregnant),
older patients, the obese, and those of Hispanic heritage.
3. The most common complication of gallstone disease is acute cholecystitis,
which presents similarly to biliary colic, but with fever and more severe symp-
toms that do not spontaneously resolve. Physical examination may show a
positive Murphy sign.
4. Acalculous cholecystitis is usually seen in critically ill or postoperative patients.
5. Choledocholithiasis, or gallstones in the common bile duct, presents with
biliary colic and jaundice, or with complications such as cholangitis or gall-
stone pancreatitis. Serum bilirubin level is typically greater than 4 mg/dL
with a marked increase in alkaline phosphatase.
6. Acute cholangitis caused by bacterial infection in an occluded bile duct pre-
sents with the Charcot triad of right upper quadrant pain, jaundice, and fever.
Blood and bile cultures are often positive.
7. Ultrasonography is the imaging method of choice in suspected gallstone dis-
ease. HIDA (99mTc-hepatic iminodiacetic acid) scan is second-line imaging
CONTINUED
Disclosure: The authors have no financial or commercial disclosures to declare.

Division of Hospital Medicine, Department of Internal Medicine, Washington University School
of Medicine, 660 South Euclid Ave, Campus Box 8048, Saint Louis, MO 63110, USA
* Corresponding author.
E-mail address: alittich@dom.wustl.edu
Hosp Med Clin 4 (2015) 342357

http://dx.doi.org/10.1016/j.ehmc.2015.03.004
2211-5943/15/$ see front matter 2015 Elsevier Inc. All rights reserved.
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Cholecystitis, Choledocholithiasis, Cholangitis 343
CONTINUED
for diagnosis of acute cholecystitis. Magnetic resonance cholangiopancrea-
tography, endoscopic ultrasonography, and endoscopic retrograde cholan-
giopancreatography (ERCP) are of equal accuracy for diagnosis of
choledocholithiasis.
8. Hospitalization for intravenous antibiotics and early laparoscopic cholecystec-
tomy is recommended for acute cholecystitis.
9. Antibiotics for acute cholecystitis and cholangitis should be targeted against
enteric bacteria per Infectious Diseases Society of America guidelines.
10. If medical instability or comorbidities preclude early laparoscopic cholecys-
tectomy, acute cholecystitis can be managed with antibiotics and percuta-
neous cholecystostomy followed by elective cholecystectomy in 2 to
3 months.
11. Current evidence suggests that early surgical intervention for acute cholecys-
titis yields improved morbidity, shorter hospital stay, and reduced symptom
recurrence.
12. Choledocholithiasis generally warrants intervention for stone removal; typi-
cally ERCP with biliary sphincterotomy. Afterward, early cholecystectomy is
recommended to prevent recurrent biliary events.
13. Gallstone disease is often complicated by pancreatitis. Early ERCP is only
required for concurrent cholangitis and biliary obstruction. Cholecystectomy
should be performed before hospital discharge unless the pancreatitis was
severe or necrotizing.
14. Acute cholangitis is managed with antibiotic treatment and decompression,
either endoscopically or with percutaneous cholecystostomy.
DEFINITIONS
What is cholelithiasis?
Cholelithiasis refers to the development of stones in the gallbladder because of crys-
tallization of cholesterol (80%) or pigment (20%).1 Cholelithiasis may result in biliary
colic or complications such as acute cholecystitis, choledocholithiasis, gallstone
pancreatitis, or cholangitis. The risk of developing these complications in a patient
with asymptomatic gallstones is low at 1% to 2% per year.1
What is biliary colic?
Approximately 20% of those with asymptomatic stones develop symptoms over

15-year follow up.2 Symptoms are usually caused by transient inflammation or
obstruction when gallstones migrate into the cystic duct or common bile duct. The
characteristic presentation is biliary colic, a severe constant ache or fullness in the
right upper quadrant (RUQ) or epigastrium, with frequent radiation to the right shoul-
der. Nausea and vomiting are often associated. Episodes are frequently precipitated
by a meal and spontaneously remit after 15 minutes to 5 hours.
What is acute cholecystitis?
Acute cholecystitis is caused by inflammation of the gallbladder wall. The usual trigger
is cystic duct obstruction with resultant inflammation, although other inflammatory
344 Littich & McDonough
factors, such as chemical irritation or infection, are also frequently present. Table 1
outlines diagnostic criteria for acute cholecystitis.3 Acute cholecystitis is the most
common complication of gallstone disease.2,4 Mortality for acute cholecystitis is
currently less than 1%.3
Table 1
Data from Tokyo Guidelines 2013 diagnostic criteria for acute cholecystitis
A. Local signs of B. Systemic signs of C. Imaging

inflammation inflammation 1. Imaging findings characteristic
1. Murphy sign 1. Fever of acute cholecystitis
2. RUQ pain/mass/ 2. Increased CRP level
tenderness 3. Increased WBC count
Suspected diagnosis: 1 item in A plus 1 item in B
Definite diagnosis: 1 item in each A plus B plus C
Abbreviations: CRP, C-reactive protein; WBC, white blood cell.

Adapted from Yokoe M, Takada T, Strasberg SM, et al. TG13 diagnostic criteria and severity
grading of acute cholecystitis (with videos). J Hepatobiliary Pancreat Sci 2013;20:38; with
permission.
What is acalculous cholecystitis?

Approximately 10% to 15% of acute cholecystitis cases are caused by acalculous
cholecystitis, usually in critically ill or postoperative patients.5 Acalculous cholecystitis
is inflammation or necrosis of the gallbladder in the absence of gallstones, with gall-
bladder epithelial injury thought to be secondary to chemical insult caused by stasis
of concentrated bile or ischemic injury from hemodynamic instability. Acalculous
cholecystitis has a worse prognosis, with a mortality of w30%, as well as a greater
number of complications, including gallbladder gangrene, perforation, abscess, and
sepsis.6 Cholecystectomy or percutaneous cholecystostomy is performed depending
on the surgical candidacy of the patient.1 In patients who undergo percutaneous
drainage, interval cholecystectomy is not necessarily required, because recurrence
of cholecystitis is rare in the absence of gallstones.79
What is choledocholithiasis?
Choledocholithiasis is the occurrence of gallstones in the common bile duct (CBD).
Passage of gallstones from the gallbladder into the CBD occurs in 10% to 15% of
patients with gallstones or gallstones may form de novo in the bile ducts.1 Like stones
in the gallbladder, those in the CBD may remain asymptomatic; however, unlike
gallbladder stones, which tend to present with benign symptoms, choledocholithiasis
often manifests with serious complications such as cholangitis or gallstone
pancreatitis.
What is acute cholangitis?

Acute cholangitis is defined by the additional presence of bacterial infection of the
biliary tract in a patient with biliary obstruction, and is the most serious complication
of gallstones, with a mortality of 10%.10 Approximately 85% of cases are caused by
an obstructing gallstone.11 Other less common causes are neoplasms, biliary stric-
tures, parasitic infections, and congenital abnormalities.11 Table 2 shows diagnostic
criteria for acute cholangitis.10
Table 2
Data from Tokyo Guidelines 2013 diagnostic criteria for acute cholangitis
A. Systemic inflammation B. Cholestasis C. Imaging

1. Fever and/or shaking 1. Jaundice 1. Biliary dilatation
chills 2. Laboratory data: 2. Evidence of the cause
2. Laboratory data: evidence abnormal liver on imaging
of inflammatory response function tests
Suspected diagnosis: 1 item in A plus 1 item in either B or C
Definite diagnosis: 1 item in each A plus B plus C
Adapted from Kiriyama S, Takada T, Strasberg SM, et al. TG13 guidelines for diagnosis and severity
grading of acute cholangitis (with videos). J Hepatobiliary Pancreat Sci 2013;20(1):32; with
permission.
EPIDEMIOLOGY
Who gets gallstone disease?

According to the third National Health and Nutrition Examination Survey, which
reviewed ultrasonography (US) data on more than 14,000 people in the Unites States,
the overall prevalence of gallstones is 7.9% in men and 16.6% in women, with prev-
alence highest in Hispanic people (8.9% men, 26.7% women), moderate in white
people (8.6% men, 16.6% women), and lowest in African Americans (5.3% men,
13.9% women).12 Risk factors for cholesterol gallstones, by far the most common
type, include the following1,12:
Female sex
Pregnancy
Obesity
Metabolic syndrome
Rapid weight loss
Increasing age
Prolonged fasting or total parenteral nutrition
Gallbladder hypomotility
Genetic factors
Hispanic ethnicity
Pigment stones are most common in patients with the following1,12:
Increased bilirubin states, such as liver disease or chronic hemolysis
Chronic infection of the gallbladder or biliary tract
Abnormal enterohepatic recycling of bilirubin caused by ileal resection, bypass,
or malabsorption seen in Crohn disease
Asian ethnicity
Biliary colic develops in 1% to 4% of patients with gallstones annually. Of those
symptomatic patients, 10% to 20% eventually develop acute cholecystitis.4,11
About 60% to 70% of patients with acute cholecystitis have an antecedent history
of biliary colic.1 Most CBD stones are cholesterol stones that are passed from the
gallbladder, with choledocholithiasis developing in 10% to 15% of patients with
cholelithiasis.1
Less than 5% of patients are thought to have undetected bile duct stones left after
cholecystectomy.1 De novo stones arising in the bile ducts are generally pigment
stones.1 Cholangitis is common in those with choledocholithiasis because it is more

likely to develop in a bile duct that already contains bacteria and becomes obstructed.
PATIENT HISTORY
How do patients with acute cholecystitis present?

Acute cholecystitis often begins as an episode of biliary colic that does not resolve
spontaneously. As with biliary colic, RUQ pain often radiates to the right scapular
area, may commonly be postprandial or nocturnal, and may be associated with
anorexia and nausea/vomiting. Subjective fever is often noted, usually without rigors
or sweats.
How do patients with choledocholithiasis present?
CBD stones may remain asymptomatic or may pass spontaneously into the duo-
denum. When symptomatic, choledocholithiasis can manifest with biliary colic and
jaundice but often presents with serious sequelae such as cholangitis or gallstone
pancreatitis.11 Presentation is largely determined by the rate of onset of biliary
obstruction and by the amount of bacterial infection. Acute obstruction presents
with biliary pain and jaundice, whereas gradual obstruction may present as pruritus
or isolated jaundice, as is common in cases of malignant biliary obstruction. Nausea
and vomiting are more prominent if pancreatitis has developed.
How do patients with cholangitis present?

If bacteria proliferate in the obstructed bile duct, cholangitis develops. The hallmark of
cholangitis is the Charcot triad, consisting of RUQ pain, jaundice, and fever, with the
full triad present in 70% of patients.11 Chills and rigors are common. However, elderly
patients may have a vague presentation of only lethargy or delirium. The addition of
altered mental status and hypotension to Charcot triad is known as the Reynold
pentad, and occurs in severe suppurative cholangitis.
PHYSICAL EXAMINATION
What are the physical examination findings in acute cholecystitis?
Vital signs often reveal a low-grade fever. Examination shows tenderness to palpation
in the RUQ. Guarding and localized rebound tenderness in the RUQ are usually pre-
sent as well; however, generalized peritoneal signs are usually absent. A positive
Murphy sign may be elicited (discussed later). In one-third of patients, the distended
gallbladder may be felt as a palpable mass in the RUQ.11 Although jaundice is more
typical of choledocholithiasis, mild jaundice may be seen in 20% of patients, and in
up to 40% of the elderly.11
What constitutes a positive Murphy sign?
Evaluate for Murphy sign by deeply palpating the RUQ during inspiration. The test is
positive when the patient ceases inspiration because of pain, theoretically caused
by the gallbladder descending toward the examiners hand during inspiration. Murphy
sign is reported to have a sensitivity of 97% and a specificity of 48%.13 A sonographic
Murphy sign is more accurate and is discussed further later.
What physical examination findings are seen in choledocholithiasis?
The physical examination may be normal in patients with intermittent obstruction.

Jaundice develops when the obstruction is persistent. Jaundice associated with
RUQ tenderness is suggestive of a CBD stone. Choledocholithiasis is often associated
with chronic calculous cholecystitis and a stiff gallbladder that does not distend, and is
therefore not palpable. Painless severe jaundice, especially in the presence of a
palpable gallbladder (Courvoisier sign), favors a malignant cause of obstruction.11
What physical examination findings are seen in cholangitis?

Fever is almost universal, RUQ tenderness is present in 90% of patients, and jaundice
is seen in 80%. Peritoneal signs are only present in 15% of patients.11 Hypotension
and delirium indicate septicemia.
IMAGING AND ADDITIONAL TESTING
What laboratory evaluation should be ordered in suspected gallbladder disease?
Laboratory evaluation should include the following:

Complete blood count
Basic metabolic panel
Hepatic function panel
C-reactive protein
Prothrombin time and International Normalized Ratio (International Normalized
Ratio [INR])
Partial thromboplastin time
Lipase
Other common causes of abdominal pain, such as acute pancreatitis and acute
hepatitis, can be quickly ruled out with this laboratory evaluation.
What are the laboratory findings in acute cholecystitis?

In acute cholecystitis serum bilirubin level may increase to 2 to 4 mg/dL; transami-
nases, alkaline phosphatase, amylase, and lipase levels may be mildly increased.11
The severity of acute cholecystitis is highly dependent on laboratory findings such
as leukocytosis, thrombocytopenia, renal dysfunction, and coagulopathy, as shown
in Table 4.3
What laboratory differences would be expected in choledocholithiasis?

If serum bilirubin level is greater than 4 mg/dL or there is marked increase of amylase or
lipase levels, choledocholithiasis should be suspected. Increasing more rapidly than
bilirubin, increase of serum alkaline phosphatase level often precedes jaundice. Serum
bilirubin level greater than 10 mg/dL suggests malignant obstruction. A transient spike
of transaminases or pancreatic enzymes suggests the passage of a stone.11
What laboratory findings are seen with cholangitis?
Serum bilirubin level is greater than 2 mg/dL and leukocytosis is noted in 80% of
patients.11 Alkaline phosphatase level is usually increased. In most cases, blood
cultures are positive, whereas bacteria are present on bile culture in 75% of
patients.1,14 Commonly cultured species include11:
Escherichia coli
Enterococcus spp
Klebsiella spp
Pseudomonas aeruginosa
Proteus mirabilis
Bacteroides fragilis
Clostridium perfringens
As shown in Table 5, severity assessment criteria for acute cholangitis are similar to
those for acute cholecystitis.10
What imaging should be ordered in suspected acute cholecystitis?

US of the RUQ is the initial test of choice. Diagnostic findings include the following:
Cholelithiasis
Gallbladder wall thickening greater than or equal to 5 mm
Pericholecystic fluid
Distension of the gallbladder lumen
Direct tenderness or inspiratory cessation when the probe is pushed against the
gallbladder (sonographic Murphy sign)
The sensitivity of US is 81%, with specificity of 83%, according to a 2012 meta-
analysis.15 If sonographic Murphy sign is present, sensitivity is increased to
92%.16 In the presence of gallstones, a sonographic Murphy sign has a positive pre-
dictive value of greater than 90% for acute cholecystitis.11 The benefits of US include
its widespread availability, speed, portability, lack of radiation exposure, and low
cost. However, patient characteristics such as obesity or bowel gas overlying the
gallbladder may limit the examination. Because of this, some patients have false-
negative results. Therefore, negative or equivocal US should not deter clinicians; if
there is strong clinical evidence of acute cholecystitis, further evaluation should be
pursued.
What if initial imaging is equivocal?

If the initial US is nondiagnostic or negative in the setting of high clinical suspicion, the
next test should be cholescintigraphy, commonly referred to as HIDA (99mTc-hepatic
iminodiacetic acid) scan. HIDA scan is performed by injecting a radiolabeled tracer
that is taken up by hepatocytes and excreted into the bile. Images evaluate whether
or not bile is taken up into the gallbladder. A positive test is reported when the
gallbladder is not visualized, presumably because of cystic duct obstruction. HIDA
allows definitive diagnosis in most cases, with a sensitivity of 96% and specificity
of 90%, which is the highest diagnostic accuracy of imaging modalities for acute
cholecystitis.15 Its drawbacks include higher cost, limited availability, need for nil-
by-mouth status, exposure to radiation, and length of time for procedure (30 minutes
to 6 hours). False-negatives can occur because of cystic duct obstruction from other
causes (malignancy), severe liver disease or serum hyperbilirubinemia, prior biliary
sphincterotomy, and prolonged fasting (>24 hours), commonly seen in patients on
total parenteral nutrition.
What is the utility of computed tomography (CT) in diagnosis of acute cholecystitis?
The utility of CT imaging is unclear, because studies properly evaluating CT for diag-
nosis of acute cholecystitis are lacking. However, many patients, especially those
with vague abdominal complaints or atypical histories, have CT of the abdomen
and pelvis as the initial imaging test in the emergency department. If there are clear
CT findings such as emphysematous or gangrenous cholecystitis, wall thickening, or
obvious gallstones, further imaging may be unnecessary. However, caution is
advised because gallstones can have the same radiodensity as bile, and thus can
be difficult to visualize on CT. No real-time testing, such as the sonographic Murphy
sign, can be done. Furthermore, CT also entails radiation exposure, and cannot
be recommended as initial imaging of choice in patients with suspected acute
cholecystitis.
What imaging best evaluates for choledocholithiasis?

Often the entire length of the bile duct cannot be examined via US secondary to
luminal bowel gas. Therefore, US is significantly less sensitive for detection of CBD
stones than for gallbladder stones, with only about 50% of CBD stones visible on
US.11 A dilated bile duct on US can hint at the presence of an obstructing stone,
but has a sensitivity of only 75%.11 Endoscopic retrograde cholangiopancreatography
(ERCP) can detect CBD stones with a sensitivity and specificity of 95%,11 but because
of risks such as pancreatitis and postsphincterotomy bleeding, is recommended only
when the clinical probability for choledocholithiasis is high. If the pretest probability is
low to intermediate, endoscopic US and magnetic resonance cholangiopancreatogra-
phy (MRCP) are of equal accuracy to ERCP for the diagnosis of choledocholithiasis,
and would be appropriate to exclude CBD stones.
What imaging findings are seen in acute cholangitis?

No direct imaging findings can show bile infection, but US, CT, or MRCP can support a
diagnosis of acute cholangitis by showing biliary dilatation and evidence of its cause,
such as the presence of stones, tumors, or strictures. Extension of the peripheral bile
duct inflammatory process into the periportal areas causes decreased portal blood
flow and increased arterial blood flow. Therefore, contrast-enhanced dynamic CT
may show inhomogeneous hepatic parenchymal enhancement on the arterial phase,
which disappears in the portal and equilibrium phases in patients with acute cholan-
gitis and may help make a prompt diagnosis.10 CT is generally the most effective
imaging to diagnose the cause of cholangitis and any potential complications. How-
ever, noncalcified biliary stones are not detected by CT, so MRI and/or US can often
be useful as well.
MEDICAL TREATMENT OPTIONS
What can hospitalists do for acute cholecystitis?
Hospitalization for bowel rest, intravenous hydration, pain control, and correction of
electrolyte abnormalities is recommended. Nasogastric suction may be required if
vomiting is prominent. Intravenous antibiotics are recommended (discussed later).
Early laparoscopic cholecystectomy should be the goal for most patients, but critically
ill patients or patients with severe medical comorbidities may need percutaneous
transhepatic cholecystostomy instead. Recurrent biliary symptoms occur in half of

patients managed with cholecystostomy,11 so operative cholecystectomy is still
recommended if the patients condition permits after the acute episode has resolved.
However, residual gallstones can be removed via the cholecystostomy tube and the
patient can be managed expectantly if no better option is available.
Can choledocholithiasis be managed noninvasively?

Because of its tendency toward serious complications such as cholangitis and acute
pancreatitis, choledocholithiasis almost always warrants an intervention to remove the
stones.11
Can cholangitis be managed noninvasively?
Biliary drainage is the mainstay of treatment of cholangitis, but antibiotics may enable
the procedure to be delayed until the patient is more physiologically stable (discussed
later).17
How should antibiotics be managed in acute cholecystitis and cholangitis?

Patients with suspected infection caused by acute cholecystitis or cholangitis should
be treated with empiric antibiotics. Table 3 outlines recommended agents based on
2010 Infectious Diseases Society of America (IDSA) guidelines.18
Table 3
Infectious Diseases Society of America recommendations for empiric antibiotics in biliary
infection
Infection Regimen
Community-acquired acute cholecystitis Cefazolin, cefuroxime, or ceftriaxone
Mild-moderate severity
Community-acquired acute cholecystitis Imipenem-cilastatin, meropenem, doripenem,
Severe physiologic disturbance piperacillin-tazobactam, ciprofloxacin,a
Advanced age levofloxacin,a or cefepime
Immunocompromised state Each in combination with metronidazoleb
Acute cholangitis following bilioenteric Imipenem-cilastatin, meropenem, doripenem,
anastomosis of any severity piperacillin-tazobactam, ciprofloxacin,a
levofloxacin,a or cefepime
Each in combination with metronidazoleb
Health careassociated biliary infection Imipenem-cilastatin, meropenem, doripenem,
of any severity piperacillin-tazobactam, ciprofloxacin,a
levofloxacin,a or cefepime
Each in combination with metronidazoleb
Vancomycinc added to each regimen
a
Local E coli susceptibility to fluoroquinolones should be reviewed.
b
Anaerobic coverage is not recommended unless the patient has a biliary-enteric anastomosis.
c
If rates of vancomycin-resistant Enterococcus (VRE) are high or the patient is known to be
colonized with VRE, linezolid or daptomycin should be used.
From Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-
abdominal infection in adults and children: guidelines by the Surgical Infection Society and the
Infectious Diseases Society of America. Clin Infect Dis 2010;50:135; with permission.
What is the appropriate duration for antibiotic therapy?
Antimicrobials can be discontinued within 24 hours after cholecystectomy is per-

formed for acute cholecystitis, unless there is evidence for infection outside the gall-
bladder wall. Antimicrobial treatment of complicated acute cholecystitis (perforation,
emphysematous changes, or necrosis of the gallbladder) is recommended for 4 to
7 days, although, when bacteremia with Enterococcus or Streptococcus species is
present, 2 weeks of treatment is recommended because of the risk of endocarditis.17
Antibiotic treatment in cholangitis is recommended for 4 to 7 more days after biliary
decompression is achieved. Intravenous antibiotics can be transitioned to oral once
a patient is tolerating oral feeding.
SURGICAL TREATMENT OPTIONS
What are the surgical treatment options for acute cholecystitis?
Open or laparoscopic cholecystectomy is extremely common; approximately 700,000

are performed for gallstone disease in the United States annually.11 Although no
randomized prospective trials compare laparoscopic and open operations in the
United States, available data support the superiority of the laparoscopic approach,
with benefits including shortened hospital stay, decreased pain, reduced disability,
and reduced costs. These benefits apply not only to patients with biliary pain
but also to patients with acute cholecystitis. Early concerns about high rates of
bile duct injury with the laparoscopic approach have largely resolved, because
complication rates are now similar to those with an open operation (0.5% or
less).11 Laparoscopic cholecystectomy is often performed with intraoperative chol-
angiography, which serves to detect common bile stones and to confirm the sur-
geons impression of the bile duct anatomy (particularly useful in patients with
acute cholecystitis). Occasionally, conversion to an open approach may be required.
Percutaneous cholecystostomy, often performed by interventional radiologists, is a
less invasive option that should be reserved for patients who are not candidates
for early surgery.
When should surgery be considered?

Cholecystectomy should be regarded as the optimal treatment of most patients, and
surgical consultation on admission should be sought. The timing of surgical interven-
tion can vary depending on the clinical scenario:
Emergency surgery is performed immediately, usually for cases of gallbladder
perforation, necrosis, or emphysematous changes.
Early surgery is performed within 24 hours to 7 days after presentation.
Delayed surgery is performed 2 to 3 months after the episode of acute cholecys-
titis has resolved.
Tokyo Guidelines recommend stratifying patients into mild, moderate, and severe
categories (see Table 4), with different treatment options for each.3 Early laparoscopic
cholecystectomy is recommended for mild cases, although early is not consistently
defined in the literature, and ranges from 24 hours to 7 days.
Moderate cases are probably also best served by early laparoscopic cholecystec-
tomy, with the caveat that this should be done by experienced surgeons with prompt
conversion to open cholecystectomy if difficulty is encountered.4,19
Because of concerns about increased perioperative morbidity and mortality, many

centers treat severe cases with early percutaneous cholecystostomy and antibiotics. If
a patient does not improve after percutaneous cholecystostomy, laparoscopic chole-
cystectomy is required urgently, but in most cases follows electively after 2 to
3 months.1921 There are limited data regarding the efficacy of this approach. Astute
hospitalists will note the important opportunity to coordinate with both the primary
care physician and the surgeon to arrange for elective cholecystectomy in 2 to
3 months, because the risk of repeat acute cholecystitis is up to 24% if definitive sur-
gery is not performed.21 The risk of other complications of gallstone disease is also
increased. However, less than half of these patients undergo cholecystectomy,
many because of ongoing contraindications.22
Table 4
Data from Tokyo Guidelines 2013 severity grading for acute cholecystitis
Grade III (Severe)

Associated With Dysfunction of Any 1 of the Following Organs/Systems
1. Cardiovascular dysfunction Hypotension requiring dopamine 5 mg/kg/min
or any dose of norepinephrine
2. Neurologic dysfunction Decreased level of consciousness
3. Respiratory dysfunction PaO2/FiO2 ratio <300
4. Renal dysfunction Oliguria, creatinine level >2.0 mg/dL
5. Hepatic dysfunction INR>1.5
6. Hematological dysfunction Platelet count <100,000/mm3
Grade II (Moderate)
Associated With Any 1 of the Following Conditions
1. Increased WBC count (>18,000/mm3)
2. Palpable tender mass in the RUQ
3. Duration of complaints >72 h
4. Marked local inflammation (gangrenous cholecystitis, pericholecystic abscess, hepatic
abscess, biliary peritonitis, emphysematous cholecystitis)
Grade I (Mild)
Does not meet criteria of grade III or grade II
Can also be defined as acute cholecystitis in a healthy patient with no organ dysfunction and
mild inflammatory changes in the gallbladder
Abbreviation: FiO2, fraction of inspired oxygen.

Adapted from Yokoe M, Takada T, Strasberg SM, et al. TG13 diagnostic criteria and severity
grading of acute cholecystitis (with videos). J Hepatobiliary Pancreat Sci 2013;20:43; with
permission.
Is surgery more effective early or later?

Evidence is mounting that early laparoscopic cholecystectomy is the treatment of
choice for most patients with acute cholecystitis. At the least, early surgical consulta-
tion is warranted for every patient admitted with acute cholecystitis. Several meta-
analyses of small trials of early surgery, as well as a large 2013 German multicenter
randomized trial,23 have shown improved morbidity (mediated by fewer episodes of
recurrent cholecystitis, choledocholithiasis, pancreatitis, and so forth while waiting
for delayed surgery), an average 4-day shorter hospital stay, significant cost savings,
and quicker return to work compared with delayed surgery.2328 Complication rates,
conversion to open surgeries, and overall mortality were unchanged.
How does concurrent choledocholithiasis change management?
Up to 15% of patients undergoing cholecystectomy prove to have CBD stones.11 If a

patient is suspected to have CBD stones, a preoperative ERCP is generally performed.
Alternatively, a 1-step laparoscopic cholecystectomy with simultaneous intraopera-
tive bile duct exploration can be performed and results in a shorter hospital stay
compared with 2-step ERCP followed by cholecystectomy; however, morbidity and
mortality are not significantly different between the two approaches.29,30 This 1-step
approach is technically demanding and is highly dependent on the experience and
skill of the surgeon. If choledocholithiasis is identified unexpectedly by intraoperative
cholangiogram, management options include laparoscopic bile duct exploration, con-
version to an open approach with bile duct exploration, or completion of the laparo-
scopic cholecystectomy followed by a postoperative ERCP. This decision is
influenced by the number and location of the CBD stones, any associated ductal dis-
order, and the skill and experience of the surgeon and endoscopist.11 A postoperative
ERCP preserves the minimally invasive approach, but runs the risk of failing and
requiring a second attempt, either endoscopically or surgically.
How is choledocholithiasis managed?

The mainstay of choledocholithiasis management is removal of the stone. More
than 80% of CBD stones can be removed endoscopically by biliary sphincterotomy,
which allows enlargement of the papilla and extraction of stones with a balloon or
basket.11 Large stones (>1.5 cm in diameter) may require mechanical or intraductal
lithotripsy before removal. If large stones cannot be removed, a biliary stent can be
placed for decompression followed by additional elective procedures to remove the
stones. Although more commonly used for pancreatic duct stones, extracorporeal
shock-wave lithotripsy can be considered for large CBD stones impacted in the
bile duct that cannot be removed endoscopically. Successful treatment is seen in
70% to 90% of cases.11 Most patients require endoscopic removal of the stone
fragments.11
An alternative to biliary sphincterotomy is balloon dilation of the papilla (sphincter-
oplasty). This technique has advantages of preserving sphincter of Oddi function and
may have a lower risk of bleeding; disadvantages include a higher rate of pancreatitis
and need for mechanical lithotripsy.31 Balloon sphincteroplasty is not well studied in
the United States, but remains an alternative approach in patients with coagulopathy,
poorly compensated cirrhosis, and altered anatomy making sphincterotomy difficult.
Should cholecystectomy be performed after a diagnosis of choledocholithiasis?
Recurrent gallstone-related disease occurs in a significant number of patients after

sphincterotomy or endoscopic papillary balloon dilation without subsequent chole-
cystectomy. In a 2007 Cochrane Review of patients who underwent cholecystectomy
versus a wait-and-see policy after clearance of CBD stones by ERCP, relative mortal-
ity was increased by 78% in the wait-and-see group.32 In addition, patients in the wait-
and-see group had higher rates of recurrent biliary pain, jaundice, or cholangitis, and
repeat ERCP or other forms of cholangiography. Therefore, if the patient is a surgical
candidate, cholecystectomy is generally offered after biliary sphincterotomy to
eliminate the source of most of the recurrent stones. Earlier rather than delayed sur-
gery seems more favorable; studies have shown an increased risk of recurrent biliary
events during the waiting period in early (within 72 hours) compared with delayed cho-
lecystectomy (68 weeks after sphincterotomy).33,34 This finding represents another
key transition from inpatient to outpatient care in which communication between hos-
pitalists and primary care providers is vital to ensure proper continuity of care.
How is gallstone pancreatitis managed?

Gallstone disease accounts for approximately 50% of acute pancreatitis in Western
countries.35 Early ERCP (within 2472 hours after admission) is recommended if there
is concurrent cholangitis and biliary obstruction, a stone in the CBD on imaging, or
in patients who have clinical deterioration and increasing liver function tests. If
subsequent elective cholecystectomy is not performed there is an increase in
biliary-related events.35 Unless the patient has severe or necrotizing pancreatitis,
cholecystectomy should ideally be performed during the same hospitalization when
clinical signs of pancreatitis have resolved. If residual bile duct stones have not already
been excluded, intraoperative cholangiography is recommended.11
How is acute cholangitis managed?
As noted in Table 5, acute cholangitis is classified as mild (grade I), moderate

(grade II), or severe (grade III).10 For mild disease, antibiotics (see Table 3) are first-
line treatment, with biliary drainage for nonresponders.18 Early biliary drainage along
Table 5
Data from Tokyo Guidelines 2013 severity grading for acute cholangitis
Grade III (Severe)

Associated With Dysfunction of Any 1 of the Following Organs/Systems
1. Cardiovascular dysfunction Hypotension requiring dopamine 5 mg/kg/min
or any dose of norepinephrine
2. Neurologic dysfunction Disturbance of consciousness
3. Respiratory dysfunction PaO2/FiO2 ratio <300
4. Renal dysfunction Oliguria, creatinine level >2.0 mg/dL
5. Hepatic dysfunction INR>1.5
6. Hematological dysfunction Platelet count <100,000/mm3
Grade II (Moderate)
Associated With Any 2 of the Following Conditions
1. Abnormal WBC count (>12,000/mm3 or <4000/mm3)
2. High fever (39 C)
3. Age (75 y)
4. Hyperbilirubinemia (total bilirubin level 5 mg/dL)
5. Hypoalbuminemia (<0.7 lower limit of normal)
Grade I (Mild)
Does not meet criteria of grade III or grade II
Adapted from Kiriyama S, Takada T, Strasberg SM, et al. TG13 guidelines for diagnosis and severity
grading of acute cholangitis (with videos). J Hepatobiliary Pancreat Sci 2013;20(1):32; with
permission.
with antibiotics is required in moderate disease to avert the risk of increased severity.
The presence of organ dysfunction defines severe disease, which requires appropriate
organ support with urgent endoscopic or percutaneous transhepatic biliary drainage
after hemodynamic stability has been achieved. Patients with moderate or severe
cholangitis should undergo endoscopic, percutaneous, or surgical treatment of the
underlying cause of the cholangitis after they have been stabilized.36 Those with
mild cholangitis may be able to undergo simultaneous drainage and treatment of
the underlying cause.36
CLINICAL GUIDELINES
Tokyo Guidelines 20133,10,17,19,36
IDSA 200918
PERFORMANCE IMPROVEMENT
Further studies are needed to evaluate the proper role of CT in diagnosis of gall-
bladder disease.
More research is needed to define the optimal treatment strategy for high-risk pa-
tients or those with moderate or severe acute cholecystitis. Most current studies
exclude ASA (American Society of Anesthesiologists) class IV and V, as well as pa-
tients with severe acute cholecystitis. The CHOCOLATE study is currently ongoing
and aims to address this deficiency.37
A large prospective randomized controlled trial is needed to address the question
of whether surgical complication rates or mortality differ between early and
delayed surgical intervention for acute cholecystitis. Present studies are under-
powered to address these rare events.
Most studies of early laparoscopic cholecystectomy are done at specialized ter-
tiary care facilities with experienced surgeons. It remains to be seen whether
these findings will generalize to all hospital settings.
Higher risk patients tend not to be offered interval cholecystectomy after endo-
scopic clearance of CBD stones or after percutaneous cholecystostomy for
treatment of acute cholecystitis, although some data suggest that they reap
similar benefits as lower risk patients. This growing population would benefit
from further study.
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15. Kiewiet JJ, Leeuwenburgh MM, Bipat S, et al. A systematic review and meta-
analysis of diagnostic performance of imaging in acute cholecystitis. Radiology
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16. Ralls PW, Colletti PM, Lapin SA, et al. Real-time sonography in suspected acute
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17. Gomi H, Solomkin JS, Takada T, et al. TG13 antimicrobial therapy for acute chol-
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18. Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of
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33. Schiphorst AH, Besselink MG, Boerma D, et al. Timing of cholecystectomy after
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Acute Cholecystitis,

HOSPITAL MEDICINE CLINICS CHECKLIST

1. Cholelithiasis is common, but often asymptomatic. When symptomatic, the

Disclosure: The authors have no financial or commercial disclosures to declare.

Hosp Med Clin 4 (2015) 342357

What is biliary colic?

Approximately 20% of those with asymptomatic stones develop symptoms over

What is acute cholecystitis?

A. Local signs of B. Systemic signs of C. Imaging

Abbreviations: CRP, C-reactive protein; WBC, white blood cell.

What is acalculous cholecystitis?

What is acute cholangitis?

A. Systemic inflammation B. Cholestasis C. Imaging

Who gets gallstone disease?

stones.1 Cholangitis is common in those with choledocholithiasis because it is more

How do patients with acute cholecystitis present?

How do patients with choledocholithiasis present?

How do patients with cholangitis present?

What are the physical examination findings in acute cholecystitis?

What constitutes a positive Murphy sign?

What physical examination findings are seen in choledocholithiasis?

The physical examination may be normal in patients with intermittent obstruction.

What physical examination findings are seen in cholangitis?

IMAGING AND ADDITIONAL TESTING

What laboratory evaluation should be ordered in suspected gallbladder disease?

Laboratory evaluation should include the following:

What are the laboratory findings in acute cholecystitis?

What laboratory differences would be expected in choledocholithiasis?

What laboratory findings are seen with cholangitis?

What imaging should be ordered in suspected acute cholecystitis?

What if initial imaging is equivocal?

What is the utility of computed tomography (CT) in diagnosis of acute cholecystitis?

What imaging best evaluates for choledocholithiasis?

What imaging findings are seen in acute cholangitis?

MEDICAL TREATMENT OPTIONS

What can hospitalists do for acute cholecystitis?

transhepatic cholecystostomy instead. Recurrent biliary symptoms occur in half of

Can choledocholithiasis be managed noninvasively?

Can cholangitis be managed noninvasively?

How should antibiotics be managed in acute cholecystitis and cholangitis?

What is the appropriate duration for antibiotic therapy?

Antimicrobials can be discontinued within 24 hours after cholecystectomy is per-

SURGICAL TREATMENT OPTIONS

What are the surgical treatment options for acute cholecystitis?

Open or laparoscopic cholecystectomy is extremely common; approximately 700,000

When should surgery be considered?

Because of concerns about increased perioperative morbidity and mortality, many

Grade III (Severe)

Abbreviation: FiO2, fraction of inspired oxygen.

Is surgery more effective early or later?

How does concurrent choledocholithiasis change management?

Up to 15% of patients undergoing cholecystectomy prove to have CBD stones.11 If a

How is choledocholithiasis managed?

Should cholecystectomy be performed after a diagnosis of choledocholithiasis?

Recurrent gallstone-related disease occurs in a significant number of patients after

How is gallstone pancreatitis managed?

How is acute cholangitis managed?

As noted in Table 5, acute cholangitis is classified as mild (grade I), moderate

Grade III (Severe)

1. Greenberger NJ, Paumgartner G. Diseases of the gallbladder and bile ducts.

26. Gurusamy K, Samraj K, Gluud C, et al. Meta-analysis of randomized controlled

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