Acute cholecystitis

Straight to the point of care

Last updated: Jul 23, 2024

 Table of Contents
Overview 3
Summary 3
Definition 3

Theory 5
Epidemiology 5
Risk factors 5
Aetiology 6
Pathophysiology 6
Classification 7
Case history 8

Diagnosis 9
Recommendations 9
History and exam 18
Investigations 22
Differentials 26
Criteria 27

Management 29
Recommendations 29
Treatment algorithm overview 43
Treatment algorithm 44
Emerging 69
Primary prevention 69
Secondary prevention 69

Follow up 70
Monitoring 70
Complications 70
Prognosis 70

Guidelines 72
Diagnostic guidelines 72
Treatment guidelines 73

Online resources 75

References 76

Images 83

Disclaimer 85
Acute cholecystitis Overview

Summary
Acute cholecystitis is a major complication of cholelithiasis (i.e., gallstones); symptomatic gallstones are
common before developing cholecystitis.

OVERVIEW
Patients typically present with pain and localised tenderness, with or without guarding, in the upper right
quadrant.

There may be evidence of a systemic inflammatory response with fever, elevated white cell count, and raised
C-reactive protein.

Ultrasound is the definitive initial test. Magnetic resonance cholangiopancreatography may be required. In
a patient with suspected sepsis, use computed tomography (or magnetic resonance imaging) to identify the
cause.

Treatment is with antibiotics, analgesia, and fluid resuscitation as required, likely to be followed by an early
cholecystectomy.

Definition
Acute cholecystitis is acute gallbladder inflammation, and one of the major complications of cholelithiasis
or gallstones. It develops in up to 10% of patients with symptomatic gallstones.[1] In most cases (90%), it is
caused by complete cystic duct obstruction usually due to an impacted gallstone in the gallbladder neck or
cystic duct, which leads to inflammation within the gallbladder wall.[1] In 5% of cases, bile inspissation (due
to dehydration) or bile stasis (due to trauma or severe systemic illness) can block the cystic duct, causing an
acalculous cholecystitis.[1]

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OVERVIEW Acute cholecystitis Overview

The biliary tree

Created by BMJ Publishing Group

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Acute cholecystitis Theory

Epidemiology
The distribution and incidence of acute cholecystitis follow that of cholelithiasis because of the close
relationship between the two.

THEORY
Cholelithiasis occurs in approximately 15% of adults.[4] In the US, 20 to 25 million people are estimated to
have gallstones, and approximately 750,000 cholecystectomies are performed annually.[5] The prevalence
rates are relatively low in Africa and Asia.[6] Most patients with gallstones do not develop symptoms. About
1% to 2% of people with asymptomatic gallstones become symptomatic each year.[7] [8] [9] [10] Acute
cholecystitis occurs in about 10% of symptomatic patients.[11] It is 3 times more common in women than in
men up to the age of 50 years, and is about 1.5 times more common in women than in men thereafter.[3]

Acute acalculous cholecystitis accounts for 5% to 14% of cases of acute cholecystitis.[3] The incidence is
higher in the intensive-care population, particularly in patients in burn and trauma units.

Risk factors
Strong
gallstones
Gallstones cause 90% of cases, by becoming impacted within the cystic duct, leading to gallbladder
inflammation.[3] Gallstones become more common with age in both genders. Studies have indicated
an increased frequency of gallstone disease in families, twins, and relatives of gallstone patients.[6]

severe illness
Factors leading to biliary tract disease in critically ill patients include gallbladder dysmotility, gallbladder
ischaemia, and total parenteral nutrition.[6] Vascular compromise, especially in critically ill patients who
experience episodes of hypotension, is thought to be a contributing factor.[17] Recent severe illness,
including trauma and burns, puts the patient at risk of acalculous cholecystitis.

total parenteral nutrition (TPN)

Fasting causes gallbladder hypomotility. Prolonged TPN causes gallbladder stasis, biliary sludge,
and gallstones due to decreased gallbladder emptying. Around 60% of patients receiving TPN exhibit
sludge after only 3 weeks.[6] It is thought that bile stasis leads to accumulation of toxic agents in the
gallbladder lumen, causing gallbladder mucosa damage.[17]

diabetes
There is an increased risk of gallbladder disease in people with diabetes.[20]

Weak
physical inactivity
Risk factor for developing gallstones.

low fibre intake

Risk factor for developing gallstones.

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 Acute cholecystitis Theory
trauma
Related to bile stasis, ischaemia, bacterial infection, sepsis, and activation of factor XII.[18]

severe burns
THEORY

Patients with extensive burns commonly have multiple risk factors for developing acalculous
cholecystitis, such as sepsis, dehydration, total parenteral nutrition use, and positive pressure
ventilation.[19]

ceftriaxone
Secreted into bile; can precipitate with calcium, forming biliary sludge and stones.[6]

ciclosporin
Can decrease bile acid secretion, which may predispose to sludge or stone formation.[11]

hepatic arterial embolisation

Ischaemia occurs as a primary event (e.g., small vessel vasculitis) or as a complication of hepatic
chemoembolisation, such as inadvertent embolisation of the cystic artery causing acalculous acute
cholecystitis.[21]

infections
Cytomegalovirus, Cryptosporidium , and Salmonella typhi can infect the biliary system and
produce cholecystitis. Can occur in HIV-positive patients as part of the spectrum of AIDS-related
cholangiopathy due to infections with microsporidia species.

Aetiology
At least 90% of patients have gallstones.[3] [2] [11]

Occasionally, acute cholecystitis occurs in the absence of gallstones.[3] Starvation, total parenteral nutrition,
narcotic analgesics, and immobility are predisposing factors for acute acalculous cholecystitis. It has also
been described as a rare occurrence during the course of acute Epstein-Barr virus (EBV) infection and can
be an atypical clinical presentation of primary EBV infection.[12] Secondary infection with gram-negative flora
occurs in most cases of acute acalculous cholecystitis.

Helminthic infection is one of the major causes of biliary disease in Asia, southern Africa, and Latin America,
but not the US.[13] Infection with Salmonella organisms has been described as a primary event in
cholecystitis secondary to typhoid fever. AIDS-related cholecystitis and cholangiopathy may be secondary
to cytomegalovirus and Cryptosporidium organisms. Various micro-organisms can be identified early
in the onset of disease. These include Escherichia coli , Klebsiella , enterococci, Pseudomonas , and
Bacteroides fragilis .[14] It has been suggested that this bacterial invasion is not a primary perpetrator of
injury, because in >40% of patients no bacterial growth is obtained from surgical specimens.[3] [8] [15] [16]
Generally, bacterial infection is a secondary feature and not an initiating event.

Pathophysiology
Fixed obstruction or passage of gallstones into the gallbladder neck or cystic duct causes acute inflammation
of the gallbladder wall. The impacted gallstone causes bile to become trapped in the gallbladder, which
causes irritation and increases pressure in the gallbladder. Trauma caused by the gallstone stimulates

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Acute cholecystitis Theory
prostaglandin synthesis (PGI2, PGE2), which mediates the inflammatory response. This can result in
secondary bacterial infection leading to necrosis and gallbladder perforation.[3]

The pathophysiology of acalculous cholecystitis is poorly understood, but it is probably multi-factorial.

THEORY
Functional cystic duct obstruction is often present and related to biliary sludge or bile inspissation caused
by dehydration or bile stasis (due to trauma or systemic illness). Occasionally, extrinsic compression may
play a role in the development of bile stasis. Some patients with sepsis may have direct gallbladder wall
inflammation and localised or generalised tissue ischaemia without obstruction.

Jaundice occurs in up to 10% of patients and is caused by inflammation of contiguous biliary ducts (Mirizzi's
syndrome).[1]

Acute cholecystitis may resolve spontaneously 5 to 7 days after symptom onset. The impacted stone
becomes dislodged, with re-establishment of cystic duct patency. If cystic duct patency is not re-established
inflammation and pressure necrosis may develop, leading to mural and mucosal haemorrhagic necrosis.
Untreated acute cholecystitis can lead to suppurative, gangrenous, and emphysematous cholecystitis.

Classification
Types of acute cholecystitis[2]
1. Calculous - 90% to 95%.

2. Acalculous - 3.7% to 14%.

Pathological classification[2]
1. Oedematous

• 2 to 4 days
• Gallbladder tissue is intact histologically, with oedema in the subserosal layer.

2. Necrotising

• 3 to 5 days
• Oedema with areas of haemorrhage and necrosis
• Necrosis does not involve the full thickness of the wall.

3. Suppurative

• 7 to 10 days
• WBCs present within the gallbladder wall, with areas of necrosis and suppuration
• Intra-wall abscesses involving the entire thickness of the wall
• Pericholecystic abscesses present.

4. Chronic

• Occurs after repeated episodes of mild attacks

• Mucosal atrophy and fibrosis of the gallbladder wall.

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 Acute cholecystitis Theory
5. Emphysematous

• Air appears in the gallbladder wall due to infection with gas-forming anaerobes
• Often found in diabetic patients.
THEORY

Case history
Case history #1
A 20-year-old obese woman with a 2-year history of gallstones presents to the emergency department
with severe, constant right upper quadrant (RUQ) pain, nausea, and vomiting after eating fried chicken
for dinner. She denies any chest pain or diarrhoea. Three months ago she developed intermittent,
sharp RUQ pains. On physical examination she has a temperature of 38°C (100.4°F), moderate RUQ
tenderness on palpation, but no evidence of jaundice.

Other presentations
Mild jaundice (serum bilirubin <60 micromol/L) can be the presenting sign in severe acute cholecystitis.
It is caused by inflammation and oedema around the biliary tract, as well as direct pressure from the
distended gallbladder. A serum bilirubin >60 micromol/L suggests choledocholithiasis (gallstone in
the common bile duct) or Mirizzi's syndrome (impaction of a gallstone in Hartmann's pouch causing
obstruction).[3] Sepsis may develop if there is superimposed bacterial infection.[3] Acute cholecystitis can
occur without gallstones (acalculous cholecystitis). This is more common in critically ill patients and those
>65 years of age.

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Acute cholecystitis Diagnosis

Recommendations

Urgent
Urgently refer or admit to hospital anyone with suspected acute cholecystitis.[27]

Think 'Could this be sepsis?' based on acute deterioration in an adult patient in whom there is clinical
evidence or strong suspicion of infection.[28] [29] [30] See Sepsis in adults .

• Use a systematic approach (e.g., National Early Warning Score 2 [NEWS2]), alongside your clinical
judgement, for assessment; urgently consult a senior clinical decision-maker (e.g., ST4 level doctor
in the UK) if you suspect sepsis.[29] [30] [31] [32]
• Refer to local guidelines for the recommended approach at your institution for assessment and
management of the patient with suspected sepsis.
• Having enacted a sepsis management bundle in line with the recommended approach at your
institution, identify the cause. Sepsis, organ failure, or death may be caused by other illnesses or
complications of cholecystitis, such as:

• Acute pancreatitis
• Perforated peptic ulcer
• Emphysematous cholecystitis
• Gangrenous cholecystitis
• Gallbladder perforation.

Measure serum lipase/amylase to exclude acute pancreatitis.[27] [33]

Source control is essential in patients with sepsis.Involve the surgical team early.[30] Consider
immediate surgical treatment for emphysematous or gangrenous cholecystitis. Empyema may need
percutaneous drainage.[3]

Confirm the diagnosis of acute cholecystitis using ultrasound.[3] [27] [34]

DIAGNOSIS
Key Recommendations
Presentation
Patients typically present with pain and localised tenderness, with or without guarding, in the upper
right quadrant.

• There may be evidence of a systemic inflammatory response with fever, elevated white cell count,
and raised C-reactive protein.[3] [27] [34]
• Observe for jaundice.[3] Check for Murphy’s sign (where the examiner's hand rests along the costal
margin and deep inspiration causes pain).

History and examination

Take a detailed history to establish whether there is ongoing pain in the right upper quadrant and to check
for any known risk factors for acute cholecystitis.

• Check for a raised temperature and raised inflammatory markers.[3]

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 Acute cholecystitis Diagnosis
• Palpate for a mass or tenderness.[3] [34]

Imaging
Use ultrasound to confirm diagnosisand to exclude differential diagnoses.[3] [27] [34]

• The followings signs on ultrasound are indicative of acute cholecystitis:[35]

• Pericholecystic fluid
• Distended gallbladder
• Thickened gallbladder wall (>3 mm)
• Gallstones
• Positive sonographic Murphy's sign (may be absent in gangrenous cholecystitis).

Use computed tomography or magnetic resonance imaging to identify infection that may be the
cause of sepsis, if present.

Causes
About 90% of patients with acute cholecystitis have gallstones.[2] [3]

• Acalculous cholecystitis can also occur. The cause for this may be infections, such as Salmonella
infection, or it can appear spontaneously in critically ill patients, particularly those who are fasting
long-term or receiving total parenteral nutrition.

Full Recommendations
Clinical presentation
Patients present with a trio of clinical features:[3] [27] [34]
DIAGNOSIS

• Constant pain in the right upper quadrant

• Tenderness in the right upper quadrant
• Signs and symptoms of inflammation.

Pain and tenderness

Establish whether there is pain and/or tenderness in the right upper quadrant, with or without
guarding. A constant pain present for several hours is consistent with cholecystitis.[3] [27]

• The pain is severe and steady.

• Duration of pain can be shorter if the gallstone returns into the gallbladder lumen or passes into the
duodenum.
• Pain may radiate to the back.
• Nausea may also be present.
• Referred pain from the gallbladder may be felt in the right shoulder or interscapular region.

Examine for tenderness in the right upper quadrant: [3] [27]

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Acute cholecystitis Diagnosis
• With or without Murphy’s sign (the examiner's hand rests along the costal margin and deep
inspiration causes pain)
• With or without a palpable mass.

• Guidelines from the UK National Institute for Health and Care Excellence on recognition of
and referral for suspected cancer recommend:[36]

• Considering an urgent direct access ultrasound scan, to be performed within 2 weeks,

to assess for gallbladder cancer or liver cancer in patients with an abdominal mass
consistent with an enlarged gallbladder or an enlarged liver
• Considering a suspected cancer pathway referral for people with an upper abdominal
mass consistent with stomach cancer.

Inflammation
Test to confirm inflammatory markers. Raised inflammatory markers indicate infection or inflammation of
the gallbladder and are a guide to severity.

• Signs of inflammation include:[34]

• Fever
• Elevated white cell count
• Elevated C-reactive protein
• Elevated erythrocyte sedimentation rate.

History

DIAGNOSIS
Take a detailed history. Ask about the following.

1. Medical

• The pain in detail

• Character – is it unremitting? Does it radiate to the back? Pain is likely to be severe

• Duration – a constant pain present for several hours; can be shorter if the gallstone
returns into the gallbladder lumen or passes into the duodenum

• Current or previous episodes of biliary colic/gallstones

• About 90% of acute cholecystitis patients have gallstones[2] [3]

• About 50% of the patients who have had 1 episode of biliary pain will have another
within 1 year[37]

• Nausea
• Fever
• Chills
• Anorexia

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 Acute cholecystitis Diagnosis
• Obesity or weight loss[38]
• Recent severe illness – gallbladder dysmotility or ischaemia may occur in critically ill patients,
increasing the risk of cholecystitis[6]
• Recent intervention (e.g., endoscopic retrograde cholangiopancreatography/stent)
• History of biliary stricture/malignancy
• Risk factors for acalculous cholecystitis:[3]

• Severe trauma or burns – patients with extensive burns commonly have multiple risk
factors for developing acalculous cholecystitis, such as sepsis, dehydration, total
parenteral nutrition use, and positive pressure ventilation[19]
• Major surgery (such as cardiopulmonary bypass)
• Long-term fasting
• Total parenteral nutrition
• Sepsis arising from any infection (including pneumonia)
• Diabetes mellitus – there is an increased risk of gallbladder disease in people with
diabetes[20]
• Atherosclerotic disease
• Systemic vasculitis
• Acute renal failure
• HIV - cholangiopathy due to infection can occur.

2. Social history

• Physical activity level – being physically active may provide some protection against
gallstone disease generally.[24]

3. Medication

• Ceftriaxone – causes precipitation of calcium salts into bile[39]

• Ciclosporin – can decrease bile acid secretion, which may predispose to sludge or stone
formation[11]
• Hormone replacement therapy.[40]
DIAGNOSIS

Physical examination
Identify any signs of sepsis.

• Think 'Could this be sepsis?' based on acute deterioration in an adult patient in whom there is
clinical evidence or strong suspicion of infection.[28] [29] [30] See Sepsis in adults .

• The patient may present with non-specific or non-localised symptoms (e.g., acutely unwell
with a normal temperature) or there may be severe signs with evidence of multi-organ
dysfunction and shock.[28] [29] [30]
• Remember that sepsis represents the severe, life-threatening end of infection.[41]

• Use a systematic approach (e.g., National Early Warning Score 2 [NEWS2]), alongside your
clinical judgement, to assess the risk of deterioration due to sepsis.[28] [29] [31] [42] Consult local
guidelines for the recommended approach at your institution.
• Arrange urgent review by a senior clinical decision-maker (e.g., ST4 level doctor in the UK) if you
suspect sepsis:[32]

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Acute cholecystitis Diagnosis
• Within 30 minutes for a patient who is critically ill (e.g., NEWS2 score of 7 or more,
evidence of septic shock, or other significant clinical concerns)
• Within 1 hour for a patient who is severely ill (e.g., NEWS2 score of 5 or 6).

• Follow your local protocol for investigation and treatment of all patients with suspected sepsis, or
those at risk. Start treatment promptly. Determine urgency of treatment according to likelihood of
infection and severity of illness, or according to your local protocol.[32] [42]
• In the community: refer for emergency medical care in hospital (usually by blue-light ambulance in
the UK) any patient who is acutely ill with a suspected infection and is:[30]

• Deemed to be at high risk of deterioration due to organ dysfunction (as measured by risk
stratification)
• At risk of neutropenic sepsis.

• Having enacted a sepsis management bundle in line with the recommended approach at your
institution, identify the cause. Sepsis, organ failure, or death may be caused by other illnesses or
complications of cholecystitis, such as:

• Acute pancreatitis
• Perforated peptic ulcer
• Emphysematous cholecystitis
• Gangrenous cholecystitis
• Gallbladder perforation.

Use an Airway, Breathing, Circulation, Disability, Exposure (ABCDE) approach to assess the
patient. [43]

• Remember that the patient’s status can change quickly.

• Involve your senior team when needed.

Examine the patient’s abdomen.Palpate for:

DIAGNOSIS
• Right upper quadrant tenderness
• Right upper quadrant mass - this may indicate localised perforation[3]

• A distended, tender gallbladder may be palpable as a distinct mass in 30% to 40% of

patients[11]

• Presence of Murphy’s sign.

Practical tip

There are limitations to Murphy’s sign (rest your hand along the costal margin and assess if deep
inspiration causes pain). It has a high sensitivity but low specificity.[44] It is particularly unreliable
in older adults. This physical sign must be elicited with gentleness; it relies on causing the patient
pain, which should be minimised.

Check for jaundice. [3]

• Caused by inflammation and oedema around the biliary tract and direct pressure on the biliary tract
from the distended gallbladder.[3]

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 Acute cholecystitis Diagnosis
• Present in about 10% of patients with cholecystitis.[1]

Assess the patient’s overall fitness and desire for surgical intervention.[27]

Monitor the patient using an early warning score, such as the NEWS2 score: [28] [NEWS2]

• Respiration rate
• Oxygen saturation (document the fraction of inspired oxygen [FiO 2 ] or O 2 flow rate of any
supplemental oxygen)
• Temperature
• Systolic blood pressure
• Heart rate
• Level of consciousness or new-onset confusion.

Imaging

Patients with suspected sepsis

Diagnosing and managing sepsis is the priority in patients presenting with symptoms of
cholecystitis.

In a patient with suspected sepsis of cholecystic origin, use computed tomography (CT) or magnetic
resonance imaging (MRI) to identify the cause. Request contrast-enhanced CT or MRI for diagnosing
gangrenous cholecystitis or gallbladder perforation.[3] [34]

• The specific findings indicating cholecystitis include:

• Irregular thickening of the gallbladder wall

• Poor contrast enhancement of the gallbladder wall (interrupted rim sign)
• Increased density of fatty tissue around the gallbladder
• Gas in the gallbladder lumen or wall
• Membranous structures within the lumen (intraluminal flap or intraluminal membrane)
DIAGNOSIS

• Peri‐gallbladder abscess.

• Such signs are often underestimated in ultrasound.

Patients without suspected sepsis

Use abdominal ultrasound to confirm diagnosis of cholecystitis and to exclude differential
diagnoses.[3] [27] [34] The following signs on ultrasound are indicative of acute cholecystitis:[35]

• Pericholecystic fluid
• Distended gallbladder
• Thickened gallbladder wall (>3 mm)
• Gallstones
• Positive sonographic Murphy's sign (may be absent in gangrenous cholecystitis).

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Acute cholecystitis Diagnosis

Ultrasound of acute cholecystitis and presence of gallstones

From the collection of Dr Charles Bellows; used with permission

Use ultrasound as the first investigation to identify the presence of gallstones.

Request magnetic resonance cholangiopancreatography (MRCP) if ultrasound has not detected common
bile duct stones but the bile duct is dilated and/or liver function test results are abnormal.[4]

• The findings of acute cholecystitis on MRI are:[34]

• Thickening of the gallbladder wall (≥4 mm)

• Enlargement of the gallbladder (long axis ≥8 cm, short axis ≥4 cm)
• Gallstones or retained debris
• Fluid accumulation around the gallbladder
• Linear shadows in the fatty tissue around the gallbladder.

• Consider endoscopic ultrasound (EUS) if MRCP does not allow a diagnosis to be made.[4]

Practical tip

DIAGNOSIS
EUS is good at detecting distal common bile duct stones. If MRCP does not show a stone but the
patient has deranged liver function tests, EUS is an excellent test but invasive; therefore, have a
high index of suspicion before requesting this test.

Consider further investigations and appropriate management as required if conditions other than gallstone
disease are suspected.[4]

Use CT for diagnosing emphysematous cholecystitis.[34]

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 Acute cholecystitis Diagnosis

Evidence: Comparison of imaging studies

Evidence shows that several imaging methods accurately rule out cholecystitis, although the
diagnostic accuracy and costs of investigations vary.

Despite evidence that cholescintigraphy is more accurate than ultrasound and MR

imaging at diagnosing acute cholecystitis, other factors such as availability, cost, and the
ability to view an area outside of the biliary tract mean that ultrasound is generally the
preferred initial test.

• A systematic review, including 57 studies, sought to estimate the diagnostic accuracy of:[45]

• Cholescintigraphy
• Ultrasonography
• MRI.

• It found that the sensitivity of cholescintigraphy (96%, 95% CI 94% to 97%) was significantly
higher than the sensitivity of ultrasonography (81%, 95% CI 75% to 87%) and magnetic
resonance imaging (85%, 95% CI 66% to 95%) for diagnosing acute cholecystitis. There were
no significant differences in specificity between cholescintigraphy (90%, 95% CI 86% to 93%),
ultrasonography (83%, 95% CI 74% to 89%), and MR imaging (81%, 95% CI 69% to 90%).[45]
• The 2018 Tokyo guidelines and the UK 2014 National Institute for Health and Care Excellence
(NICE) guidelines both recommend ultrasound as a reasonable initial choice, based on
issues such as low invasiveness, low risk, widespread availability, ease of use, and cost‐
effectiveness.[4] [34]
• The NICE guideline recommends MRCP if abnormalities are present in the bile duct or liver
function tests but ultrasound has not detected common bile duct stones.[4]

• Two health economic studies found that MRCP appeared cost-effective compared with
endoscopic retrograde cholangiopancreatography for diagnosing common bile duct
stones.[4]

• Note that in a patient with sepsis, use CT (or MRI) to identify the cause.
DIAGNOSIS

Investigations

Full blood count

Look for significant deviations from the normal values.

• A significantly raised or lowered white cell count can indicate an infection or inflammation.

C-reactive protein
Look for elevation, which may indicate infection or inflammation of the gallbladder.[27]

Bilirubin
Look for elevation, which may indicate acute focal cholestasis in adjacent liver tissue or be due to
common bile duct stones.[4] [27]

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Acute cholecystitis Diagnosis

Liver function tests

Request liver function tests to indicate whether further imaging is required, such as magnetic resonance
cholangiopancreatography.

• May show elevated bilirubin, alkaline phosphatase, and gamma glutamyl transferase due to acute
focal cholestasis in adjacent liver tissue or due to common bile duct stones.[4] [27]
• Alanine aminotransferase can also be elevated if a stone has passed down the common bile duct,
or if there is focal inflammation of the liver parenchyma in severe cholecystitis.

Serum lipase or amylase

Identify or exclude the presence of acute pancreatitis.[27] [33] Use serum lipase testing (if available) in
preference to serum amylase.[33] [46] [47]

• A result >3 times the upper limit of the normal range confirms the diagnosis of acute
pancreatitis in a patient with acute upper abdominal pain.[33] [48]
• Serum lipase and amylase have similar sensitivity and specificity but lipase levels remain elevated
for longer (up to 14 days after symptom onset versus 5 days for amylase), providing a higher
likelihood of picking up the diagnosis in patients with a delayed presentation.[33] [49] [50]

Blood cultures and/or bile cultures

Request in patients with grade II (moderate) and III (severe) disease in order to identify an infection that
may be the cause of sepsis.[51]

• See Assessing severity below for guidance on how to define grade of cholecystitis.

Practical tip

There are no blood tests that will specifically confirm the diagnosis of cholecystitis, but they help to
build the clinical picture of how unwell the patient is and can help to exclude other diagnoses.

Assessing severity

DIAGNOSIS
Urgently refer or admit to hospitalanyone with suspected acute cholecystitis.[27]

Sepsis and organ failure are of paramount importance in assessing severity.

• During admission, assess severity based on the signs and symptoms of sepsis and the absence/
presence of local complications or organ failure.

Assess the severity in order to determine the optimum treatment strategy.[52]

• The Tokyo guidelines use a grading system of mild, moderate, and severe to classify severity.
Treatment can be based on this classification.[34]

Severe (grade III) acute cholecystitis is associated with dysfunction of any one of the
following organs/systems. [34]

1. Cardiovascular: hypotension requiring treatment with dopamine ≥5 micrograms/kg per minute, or

any dose of noradrenaline (norepinephrine).
2. Neurological: decreased level of consciousness.
3. Respiratory: PaO 2 /fraction of inspired oxygen (FiO 2 ) ratio <300.

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 Acute cholecystitis Diagnosis
4. Renal: oliguria, creatinine >2.0 mg/dL.
5. Hepatic: prothrombin time – international normalised ratio (PT‐INR) >1.5.
6. 3
Haematological: platelet count <100,000/mm .

Moderate (grade II) acute cholecystitis is associated with any one of the following
conditions.

1. 3
Elevated white blood cell count (>18,000/mm ).
2. Palpable tender mass in the right upper abdominal quadrant.
3. Duration of symptoms >72 hours.
4. Marked local inflammation (gangrenous cholecystitis, pericholecystic abscess, hepatic abscess,
biliary peritonitis, emphysematous cholecystitis).

Mild (grade I) acute cholecystitis: [34]

• Acute cholecystitis that does not meet the criteria of grade III or grade II acute cholecystitis. It
can also be defined as acute cholecystitis in a healthy patient with no organ dysfunction and mild
inflammatory changes in the gallbladder, making cholecystectomy a safe and low-risk operative
procedure.

History and exam

Key diagnostic factors
pain in the upper right quadrant (common)
Establish whether there is pain in the right upper quadrant. A constant pain present for several hours is
consistent with cholecystitis.[3] [27] [34]

• The pain is severe and steady.

DIAGNOSIS

• Duration of pain can be shorter if the gallstone returns into the gallbladder lumen or passes into
the duodenum.
• Pain may radiate to the back.

tenderness in the right upper quadrant (common)

Examine for tenderness in the right upper quadrant:[3] [27] [34]

• With or without Murphy’s sign

• With or without a palpable mass.

Practical tip

There are limitations to Murphy’s sign (rest your hand along the costal margin and assess
whether deep inspiration causes pain). It has a high sensitivity but low specificity.[44] It is
particularly unreliable in older adults. This physical sign must be elicited with gentleness; it relies
on causing the patient pain, which should be minimised.

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Acute cholecystitis Diagnosis
signs and symptoms of inflammation (common)
Test to confirm inflammatory markers. Raised inflammatory markers indicate infection or inflammation
of the gallbladder and are a guide to severity.

• Signs of inflammation include:[34]

• Fever
• Elevated white cell count
• Elevated CRP
• Elevated erythrocyte sedimentation rate.

palpable mass (common)

Palpate the abdomen. A distended, tender gallbladder may be palpable as a distinct mass.[11] [34]

Guidelines from the UK National Institute for Health and Care Excellence on recognition of and referral
for suspected cancer recommend:[36]

• Considering an urgent direct access ultrasound scan, to be performed within 2 weeks, to assess
for gallbladder cancer or liver cancer in patients with an abdominal mass consistent with an
enlarged gallbladder or an enlarged liver
• Considering a suspected cancer pathway referral for people with an upper abdominal mass
consistent with stomach cancer.

presence of risk factors (common)

Cover the following risk factors to help assess the likelihood of cholecystitis.

• Gallstones

DIAGNOSIS
• About 90% of acute cholecystitis patients have gallstones.[2] [3]

• Previous episode of biliary pain

• About 50% of patients who have had 1 episode of biliary pain will have another within 1
year.[37]

• Severe illness

• Gallbladder dysmotility or ischaemia may occur in critically ill patients, increasing the risk
of cholecystitis.[6]

• Physical activity level

• Being physically active may provide some protection against gallstone disease
generally.[24]

• Ceftriaxone

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 Acute cholecystitis Diagnosis
• Causes precipitation of calcium salts into bile.[39]

• Ciclosporin

• Can decrease bile acid secretion, which may predispose to sludge or stone formation.[11]

• Risk factors for acalculous cholecystitis:[3]

• Severe trauma or burns – patients with extensive burns commonly have multiple risk
factors for developing acalculous cholecystitis, such as sepsis, dehydration, total
parenteral nutrition use, and positive pressure ventilation[19]
• Major surgery (such as cardiopulmonary bypass)
• Long-term fasting
• Total parenteral nutrition
• Sepsis arising from any infection (including pneumonia)
• Diabetes mellitus – there is an increased risk of gallbladder disease in people with
diabetes[20]
• Atherosclerotic disease
• Systemic vasculitis
• Acute renal failure
• HIV – cholangiopathy due to infection can occur.

Other diagnostic factors

fever/chills (common)
Enquire about fever and chills. These may be present as a symptom of infection.

• Persistent pain and fever may suggest either more complicated disease such as abscess
DIAGNOSIS

formation or perforation, or acalculous cholecystitis.

nausea (common)
Enquire about nausea. It can occur in conjunction with severe pain. It can be a prominent symptom of
a stone in the common bile duct.

right shoulder pain (common)

Ask about shoulder pain. Referred pain from the gallbladder may be felt in the right shoulder or
interscapular region.

anorexia (common)
Ask about food and drink intake. Anorexia is associated with biliary disease. Not specific for
cholecystitis.

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Acute cholecystitis Diagnosis
vomiting (uncommon)
Ask whether the patient has vomited. Sometimes associated with biliary disease. Not specific for
cholecystitis. It can be a prominent symptom of a stone in the common bile duct.

jaundice (uncommon)
Check for jaundice. [3]

• Caused by inflammation and oedema around the biliary tract and direct pressure on the biliary
tract from the distended gallbladder.[3]
• Present in about 10% of patients with cholecystitis.[1]

DIAGNOSIS

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 Acute cholecystitis Diagnosis

Investigations
1st test to order

Test Result
CT or MRI of the abdomen The specific findings
If sepsis is suspected, request contrast-enhanced CT or MRI for indicating cholecystitis
diagnosing gangrenous cholecystitis or gallbladder perforation.[3] [34] include:

Use CT for diagnosing emphysematous cholecystitis. • Irregular thickening of

the gallbladder wall
Evidence: Comparison of imaging studies • Poor contrast
Evidence shows that several imaging methods accurately enhancement of
rule out cholecystitis, although the diagnostic accuracy and the gallbladder wall
costs of investigations vary. (interrupted rim sign)
• Increased density of
Despite evidence that cholescintigraphy is more accurate
than ultrasound and MR imaging at diagnosing acute fatty tissue around the
cholecystitis, other factors such as availability, cost, and gallbladder
the ability to view an area outside of the biliary tract mean • Gas in the gallbladder
that ultrasound is generally the preferred initial test.
lumen or wall
• A systematic review, including 57 studies, sought to • Membranous structures
estimate the diagnostic accuracy of:[45] within the lumen
• Cholescintigraphy (intraluminal flap or
• Ultrasonography intraluminal membrane)
• Peri‐gallbladder
• MRI.
abscess
• It found that the sensitivity of cholescintigraphy (96%, 95%
CI 94% to 97%) was significantly higher than the sensitivity
of ultrasonography (81%, 95% CI 75% to 87%) and
DIAGNOSIS

magnetic resonance imaging (85%, 95% CI 66% to 95%)

for diagnosing acute cholecystitis. There were no significant
differences in specificity between cholescintigraphy (90%,
95% CI 86% to 93%), ultrasonography (83%, 95% CI 74%
to 89%), and MR imaging (81%, 95% CI 69% to 90%).[45]
• The 2018 Tokyo guidelines and the UK 2014 National
Institute for Health and Care Excellence (NICE) guidelines
both recommend ultrasound as a reasonable initial
choice, based on issues such as low invasiveness,
low risk, widespread availability, ease of use, and cost‐
effectiveness.[4] [34]
• The NICE guideline recommends magnetic resonance
cholangiopancreatography (MRCP) if abnormalities are
present in the bile duct or liver function tests but ultrasound
has not detected common bile duct stones.[4]

• Two health economic studies found that MRCP

appeared cost-effective compared with endoscopic
retrograde cholangiopancreatography for diagnosing
common bile duct stones.[4]

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Acute cholecystitis Diagnosis

Test Result
• Note that in a patient with sepsis, use CT (or MRI) to
identify the cause.

abdominal ultrasound The following signs on

ultrasound are indicative of
If sepsis is not suspected, use abdominal ultrasound to confirm
diagnosis of cholecystitis and to exclude differential diagnoses.[3] [27] acute cholecystitis:[35]
[34]
• Pericholecystic fluid
Use ultrasound as the first investigation to identify the presence of • Distended gallbladder
gallstones. • Thickened gallbladder
wall (>3 mm)
• Gallstones
• Positive sonographic
Murphy's sign (may be
absent in gangrenous
cholecystitis)

FBC White cell count may be

Check white cell count for an indication of infection or inflammation. elevated in severe disease

CRP Elevation may indicate

infection or inflammation of
Look for elevation.[27]
the gallbladder[27]

bilirubin Elevation may indicate acute

focal cholestasis in adjacent
Look for elevation.[4] [27]
liver tissue or due to common
bile duct stones[4] [27]

DIAGNOSIS
LFTs May show elevated bilirubin,
alkaline phosphatase, alanine
Request liver function tests to indicate whether further imaging is
aminotransferase, and
required, such as magnetic resonance cholangiopancreatography. gamma glutamyl transferase
due to acute focal liver
inflammation or cholestasis in
adjacent liver tissue or due to
common bile duct stones[4]
[27]

• Alanine
aminotransferase can
also be elevated if
a stone has passed
down the common bile
duct, or if there is focal
inflammation of the

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 Acute cholecystitis Diagnosis

Test Result
liver parenchyma in
severe cholecystitis

serum lipase or amylase A result >3 times the upper

limit of the normal range
Identify or exclude the presence of acute pancreatitis.[27] [33] Use
serum lipase testing (if available) in preference to serum amylase.[33] confirms the diagnosis of
acute pancreatitis in a patient
[46] [47]
with acute upper abdominal
• Serum lipase and amylase have similar sensitivity and pain[33] [48]
specificity but lipase levels remain elevated for longer (up
to 14 days after symptom onset versus 5 days for amylase),
providing a higher likelihood of picking up the diagnosis in
patients with a delayed presentation.[33] [49] [50]

blood cultures and/or bile cultures Will confirm infective

Request in patients with grade II (moderate) and III (severe) disease organism, if present
in order to identify an infection that may be the cause of sepsis.

See Assessing severity in Diagnosis recommendations for guidance

on how to define grade of cholecystitis.

Practical tip

There are no blood tests that will specifically confirm the

diagnosis of cholecystitis, but they help to build the clinical
picture of how unwell the patient is and can help to exclude
other diagnoses.
DIAGNOSIS

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Acute cholecystitis Diagnosis

Other tests to consider

Test Result
magnetic resonance cholangiopancreatography (MRCP) The findings of acute
cholecystitis on MRI are:[34]
Request MRCP if ultrasound has not detected common bile duct
stones but the bile duct is dilated and/or liver function test results are
• Thickening of the
abnormal.[4]
gallbladder wall (≥4
• Consider endoscopic ultrasound if MRCP does not allow a mm)
diagnosis to be made.[4] • Enlargement of the
gallbladder (long axis
≥8 cm, short axis ≥4
cm)
• Gallstones or retained
debris
• Fluid accumulation
around the gallbladder
• Linear shadows in the
fatty tissue around the
gallbladder

endoscopic ultrasound (EUS) May detect stones not

Consider EUS if MRCP does not allow a diagnosis to be made.[4] identified by MRCP or
abdominal ultrasound
Practical tip

EUS is good at detecting distal common bile duct stones. If

MRCP does not show a stone but the patient has deranged
LFTs, EUS is an excellent test but invasive; therefore, have a
high index of suspicion before requesting this test.

DIAGNOSIS

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 Acute cholecystitis Diagnosis

Differentials

Condition Differentiating signs / Differentiating tests

symptoms
Acute cholangitis • Classic findings are fever • Magnetic resonance
and chills, jaundice, and cholangiography or MRI
abdominal pain (Charcot's findings: intra-ductal purulent
triad).[53] About 50% to 70% material with low signal
of patients with cholangitis intensity on heavily T2-
develop all 3 symptoms.[54] weighted images and/or
intermediate signal intensity
on fat-suppressed T1-
weighted images.

Chronic cholecystitis • Repeated bouts of mild • No specific investigations.

attacks or chronic irritation • Mucosal atrophy and fibrosis
by large gallstones.[2] of the gallbladder wall in
postoperative specimens.

Peptic ulcer disease • Burning epigastric pain that • Endoscopy may reveal a
occurs hours after meals or peptic ulcer.
with hunger. Often wakes
the patient at night. Pain
improves with eating.

Acute pancreatitis • Epigastric or periumbilical • Tripling of serum amylase

abdominal pain that radiates and lipase.
to the back. • Pancreatic inflammation on
• Ecchymosis in the CT abdomen.
periumbilical region
(Cullen's sign) or the
flank (Grey Turner's sign)
may be present in severe
pancreatitis.
DIAGNOSIS

Sickle cell crises • Associated with gallstone • Blood film may show sickle
disease. cells.
• Pain can occur anywhere in • Haemoglobin
the body (including the right electrophoresis shows the
upper quadrant), which may presence of haemoglobin S
be unrelated to gallstone or C.
formation.

Appendicitis • Pain is usually located in the • Abdominal CT scan: dilated

right iliac fossa but may start appendix with thickened,
in the periumbilical region. hyperenhancing wall and
mural stratification of
appendix.

Right lower lobe • Productive cough with fever. • Right lower lobe
pneumonia • Examination may reveal consolidation on CXR.
bronchial breath sounds,
crepitations, and dullness to
percussion.

Acute coronary syndrome • Typically central chest • Ischaemic changes on ECG

pain, squeezing in nature, (ST elevation or depression,

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Acute cholecystitis Diagnosis

Condition Differentiating signs / Differentiating tests

symptoms
radiation to jaw or left arm. T-wave inversion, left bundle-
Pain may be felt in the branch block).
epigastrium. • Elevated cardiac enzymes.
• May be a history of angina
and risk factors for coronary
artery disease (e.g.,
smoking, hypertension,
diabetes mellitus, obesity).

GORD • Burning sensation in chest • Therapeutic trial with proton

after meals, worse on pump inhibitors leads to
bending over or lying down. symptom relief.
May be acid reflux and • Oesophagitis may be seen
dysphagia on endoscopy.

Criteria
Sonographic criteria of acute cholecystitis[35]
• Pericholecystic fluid
• Distended gallbladder
• Thickened gallbladder wall (>3 mm)
• Gallstones
• Positive sonographic Murphy 's sign.

TG18/TG13 severity grading for acute cholecystitis[34]

The Tokyo guidelines use a grading system of mild, moderate, and severe to classify severity. Treatment can

DIAGNOSIS
be based on this classification.

Severe (grade III) acute cholecystitis is associated with dysfunction of any one of the following
organs/systems.

1. Cardiovascular: hypotension requiring treatment with dopamine ≥5 micrograms/kg per minute, or any
dose of noradrenaline (norepinephrine).
2. Neurological: decreased level of consciousness.
3. Respiratory: PaO 2 /fraction of inspired oxygen (FiO 2 ) ratio <300.
4. Renal: oliguria, creatinine >2.0 mg/dL.
5. Hepatic: prothrombin time – international normalised ratio (PT‐INR) >1.5.
6. 3
Haematological: platelet count <100,000/mm .

Moderate (grade II) acute cholecystitis is associated with any one of the following conditions.

1. 3
Elevated white blood cell count (>18,000/mm ).
2. Palpable tender mass in the right upper abdominal quadrant.
3. Duration of complaints >72 hours.

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 Acute cholecystitis Diagnosis
4. Marked local inflammation (gangrenous cholecystitis, pericholecystic abscess, hepatic abscess, biliary
peritonitis, emphysematous cholecystitis).

Mild (grade I) acute cholecystitis:

• Acute cholecystitis that does not meet the criteria of grade III or grade II acute cholecystitis. It can also
be defined as acute cholecystitis in a healthy patient with no organ dysfunction and mild inflammatory
changes in the gallbladder, making cholecystectomy a safe and low‐risk operative procedure.
DIAGNOSIS

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Acute cholecystitis Management

Recommendations

Urgent
Manage sepsis and organ failure, if present. Investigate for the cause of sepsis with a view to
source control.

In patients with organ dysfunction, transfer the patient to the intensive care unit to monitor and
treat the organ dysfunction.

Provide fluid resuscitation, along with analgesia and antibiotics (if infection is suspected), prior
to surgery.[27] [34] [52]

Arrange urgent surgery for patients with generalised peritonitis or emphysematous cholecystitis.[3]

Key Recommendations
Initial treatment
In all patients, give analgesia, fluid resuscitation, and antibiotics (if infection is suspected), as
required.[27] [34] [52]

• Assess severity and identify sepsis.

• Assess fluid status and resuscitate with intravenous fluids as appropriate.
• Monitor the patient using an early warning score, such as the National Early Warning Score 2
(NEWS2) score.[28]
• Prior to surgery, identify and treat any correctable comorbidities so that surgery is not delayed and
assess the patient’s bleeding and venous thromboembolism risk.[55]

Surgery
Refer for a laparoscopic cholecystectomy.

• The UK National Institute for Health and Care Excellence (NICE) states that surgery should be
performed within a week of diagnosis where resources allow.[4]
• Other sources state that surgery within 72 hours of onset is preferable.[27] [52]
• If a surgeon with experience of operating on patients with acute cholecystitis is not available locally,
consider transferring the patient to a specialist unit.[27]

Refer for a percutaneous cholecystostomy patients who are unfit for general anaesthesia and surgery,
who do not improve after treatment with antibiotics, analgesia, and fluid resuscitation.[27]

• Gallbladder drainage is not a permanent solution, and where possible a delayed cholecystectomy
MANAGEMENT

(>6 weeks after drainage) is recommended.[56]

Endoscopic ultrasound-guided gallbladder drainage can also be considered when surgery is not an
option - this is a technically challenging procedure and should only be done in specialist centres.[57]
It is important to note that it is not a permanent solution but rather a bridge to surgery, and assessment

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 Acute cholecystitis Management
for future cholecystectomy should resume once the acute episode and any underlying sepsis has been
treated.[56]

Complications
• Offer percutaneous cholecystostomy to manage gallbladder empyema when surgery is
contraindicated at presentation and conservative management is unsuccessful.[4]
• Consider urgent laparoscopic cholecystectomy in patients at high risk of gangrene.[3]
• Perforation occurs in 10% of cases of acute cholecystitis.[3]
• Consider percutaneous drainage of the resulting collection or expedited surgery. Treatment should
be tailored to the individual circumstances of each patient.

Full Recommendations
Treatment goals
The main treatment goals are to:

• Manage sepsis, if suspected

• Provide supportive treatment to reduce the risk of progression to organ failure and/or local
complications
• Treat the underlying cause
• Manage local complications.

Treatment set ting

Treat patients with acute cholecystitis in hospital.[27]

• Transfer patients to a specialist unit with surgeons experienced at performing surgery on this group
of patients if such surgeons are not available locally.[27]
• Patients with severe (Tok yo guideline grade III) cholecystitis should be managed in an
intensive care set ting.[52] See Assessing severity in Diagnosis recommendations for guidance
on how to define grade of cholecystitis.

Initial treatment for all patients

In all patients, give analgesia, fluid resuscitation, and antibiotics (if infection is suspected), as
required.[27] [34] [52] Most patients will require surgery. Patients should be nil by mouth in order to rest
the gallbladder and because of the likelihood of imminent surgery.[3] [52]

In patients with severe acute cholecystitis (grade III according to the Tokyo guideline;
see Assessing severity in Diagnosis recommendations for guidance on how to define grade of
cholecystitis):[52]
MANAGEMENT

• Transfer the patient to the intensive care unit to monitor and treat the organ
dysfunction
• Determine the degree of organ dysfunction and attempt to normalise function through organ
support

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Acute cholecystitis Management
• Consider urgent/early biliary drainage if it is not possible to control the gallbladder inflammation.

Analgesia
Pain is the predominant symptom. Ensure it is treated promptly and effectively.[52]

• Failure to control pain can compromise breathing and contribute to haemodynamic instability.
• Use a pain score to monitor the response to analgesia and adjust the dose and/or type of analgesic
medication in line with local pain management protocols.

Use paracetamol or a non-steroidal anti-inflammatory drug such as diclofenac or indometacin

initially.[27] [58] Move onto opioid analgesia (e.g., morphine) if required.[10]

Fluid resuscitation
Assess fluid status and resuscitate with intravenous fluids as appropriate.

• Administer intravenous fluids, if needed, to all patients who cannot tolerate oral intake
• Give intravenous fluids based on fluid status assessment.[59]
• Use either a balanced crystalloid or normal saline 0.9% initially.

• Check local protocols for specific recommendations on fluid choice. There is debate, based
on conflicting evidence, on whether there is a benefit in using normal saline or balanced
crystalloid in critically ill patients.
• Tailor the intravenous fluid to the patient’s condition and electrolytes.

• Regularly monitor patients receiving intravenous fluids.[59]

• Clinical monitoring should include current status and trends in:

• National Early Warning Score (NEWS2)

• Fluid balance charts
• Weight.

• Laboratory investigations should include current status and trends in:

• Full blood count

• Urea
• Creatinine
• Electrolytes.

Treat the underlying cause as early as possible. Consider local protocols but, in general, escalate patients
with shock to a senior clinician. See our topic Shock.
MANAGEMENT

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 Acute cholecystitis Management
Practical tip

Be aware that large volumes of normal saline as the sole fluid for resuscitation may lead to
hyperchloraemic acidosis.
Also note that use of lactate-containing fluid in a patient with impaired liver metabolism may lead to
a spuriously elevated lactate level, so results need to be interpreted with other markers of volume
status.
MANAGEMENT

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Acute cholecystitis Management

Evidence: Choice of fluids

Evidence from two large randomised controlled trials (RCTs) suggests there is no difference
between normal saline and a balanced crystalloid for critically ill patients in mortality at 90
days, although results from two meta-analyses including these RCTs point to a possible small
benefit of balanced solutions compared with normal saline .

There has been extensive debate over the choice between normal saline (an unbalanced
crystalloid) versus a balanced crystalloid (such as Hartmann’s solution [also known as
Ringer’s lactate], or Plasma-Lyte). Clinical practice varies widely, so you should check
local protocols.

• In 2021 to 2022 two large double blind RCTs were published assessing intravenous fluid
resuscitation in ICU patients with a balanced crystalloid solution (Plasma-Lyte) versus normal
saline. The Plasma-Lyte 148 versus Saline (PLUS) trial (53 intensive care units [ICUs] in
Australia and New Zealand; N=5037) and the Balanced Solutions in Intensive Care Study
(BaSICS) trial (75 ICUs in Brazil; N=11,052).[60] [61]

• In the PLUS study 45.2% of patients were admitted to ICU directly from surgery
(emergency or elective), 42.3% had sepsis and 79.0% were receiving mechanical
ventilation at the time of randomisation.
• In BaSICS almost half the patients (48.4%) were admitted to ICU after elective surgery
and around 68% had some form of fluid resuscitation before being randomised.
• Both found no difference in 90-day mortality overall or in prespecified subgroups for
patients with acute kidney injury (AKI), sepsis or post-surgery. They also found no
difference in the risk of AKI.
• In BaSICS, for patients with traumatic brain injury, there was a small decrease in 90
day mortality with normal saline - however, the overall number of patients was small (<5%
of total included in the study) so there is some uncertainty about this result. Patients with
traumatic brain injury were excluded from PLUS as the authors felt these patients should
be receiving saline or a solution of similar tonicity.

• One meta-analysis of 13 RCTs (including PLUS and BaSICS) confirmed no overall difference,
although the authors did highlight a non-significant trend towards a benefit of balanced solutions
for risk of death.[62]
• A subsequent individual patient data meta-analysis included 6 RCTs of which only PLUS
and BaSICS were assessed as being at low risk of bias. There was no statistically significant
difference in in-hospital mortality (OR 0·96, 95%CI 0·91–1·02). However, the authors argued
that using a Bayesian analysis there was a high probability that balanced solutions reduced in-
hospital mortality, although they acknowledged that the absolute risk reduction was small.[63]

• A prespecified subgroup analysis of patients with traumatic brain injury (N=1961)

found that balanced solutions increased the risk of in-hospital mortality compared with
normal saline (OR 1·42, 95%CI 1·10 to 1·82).
MANAGEMENT

• Previous evidence has been mixed.

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 Acute cholecystitis Management
• One 2015 double-blind, cluster randomised, double-crossover trial conducted in four
ICUs in New Zealand (N=2278), the 0.9% Saline vs Plasma-Lyte for ICU fluid Therapy
(SPLIT) trial, found no difference for in-hospital mortality, AKI, or use of renal-replacement
therapy.[64]
• However, one 2018 US multicentre unblinded cluster-randomised trial - the isotonic
Solutions and Major Adverse Renal events Trial (SMART), among 15,802 critically ill
adults receiving ICU care - found possible small benefits from balanced crystalloid
(Ringer’s lactate or Plasma-Lyte) compared with normal saline. The 30-day outcomes
showed a non-significant reduced mortality in the balanced crystalloid group versus
the normal saline group (10.3% vs 11.1%; OR 0.90, 95% CI 0.80 to 1.01) and a major
adverse kidney event rate of 14.3% versus 15.4% respectively (OR 0.91, 95% CI 0.84 to
0.99).[65]

• One 2019 Cochrane review included 21 RCTs (N=20,213) assessing balanced crystalloids
versus normal saline for resuscitation or maintenance in a critical care setting.[66]

• The three largest RCTs in the Cochrane review (including SMART and SPLIT) all
examined fluid resuscitation in adults and made up 94.2% of participants (N=19,054).
• There was no difference in in‐hospital mortality (OR 0.91, 95% CI 0.83 to 1.01; high
quality evidence as assessed by GRADE), acute renal injury (OR 0.92, 95% CI 0.84 to
1.00; GRADE low), or organ system dysfunction (OR 0.80, 95% CI 0.40 to 1.61; GRADE
very low).

Antibiotics
Follow your local protocol for investigation and treatment of all patients with suspected sepsis, or those
at risk. Start treatment promptly. Determine urgency of treatment according to likelihood of infection and
severity of illness, or according to your local protocol.[32] [42]

For patients with suspected biliary infection, start antibiotics as soon as infection is suspected and before
any procedure is performed.[67] Not all patients will require antibiotics; do not start antimicrobial therapy
unless there is clear evidence of an infection.[68]

• Follow local policy and consider discussing with microbiology/infectious disease colleagues to
determine the most appropriate choice. Avoid inappropriate use of broad-spectrum antibiotics.[68]
• Consider antimicrobial stewardship, such as the ‘start smart – then focus’ principles from Public
Health England.[68]
• Ask about any antibiotic use in the last 6 months. The patient is more likely to be harbouring a
resistant organism if they have a recent (within 6 months) history of antibiotic use.[67]
• Take a thorough drug allergy history when prescribing antibiotics.[67] [68]

Expert opinion suggests that empirical intravenous therapy should be chosen bearing in mind the
MANAGEMENT

following factors:[67]

• Observational studies have demonstrated that Escherichia coli is the organism most frequently
implicated

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Acute cholecystitis Management
• Local susceptibility patterns vary geographically and over time
• The likelihood of resistance of the organism will also vary by whether the infection was hospital- or
community-acquired, although there may be resistant organisms in the community
• More-severe grades of infection require more potent antibiotics (monotherapy or combination
therapy).

Use a definitive therapy once the sensitivities are reported from culture specimens.[67]

• Specific therapy may involve penicillins, cephalosporins, or fluoroquinolones.[67]

Change intravenous therapy to oral antibiotics when the patient is able to eat. Stop the antibiotics when
safe to do so.[67] [68]

The duration of therapy needs to balance benefits (eliminating the infection and reducing the risk of
complications) against risks (resistant organisms, the cost of therapy, and the prolonged length of hospital
stay).[67]

Surgery
The majority of patients should be offered cholecystectomy. Only patients who are not fit for surgery,
or who have localised complications that would make surgery dangerous, should be managed
conservatively (with the option of a delayed cholecystectomy). These decisions will be made by a
specialist.

Presurgical assessment
Prior to surgery, identify and treat any correctable comorbidities so that surgery is not delayed.

• Assess the patient’s bleeding and venous thromboembolism risk prior to surgery.[55]
• Use a validated tool. The UK National Institute for Health and Care Excellence (NICE) states that
a commonly used risk assessment tool for surgical patients is the Department of Health venous
thromboembolism risk assessment tool.[55]
• Arrange a group and save and crossmatch.
• Reassess the risk of bleeding and venous thromboembolism at the point of consultant review or if
the patient’s clinical condition changes.

Use a risk score, such as the American Society of Anesthesiologists (ASA) physical status
classification system to stratify a patient's health status before surgery.[52] [69]

Laparoscopic cholecystectomy
Refer for a laparoscopic cholecystectomy under general anaesthesia in patients fit for surgery.[4]

• NICE states that surgery should be performed within a week of diagnosis where resources
allow.[4]
MANAGEMENT

• Other sources state that surgery within 72 hours of onset is preferable.[27] [52]
• In patients with severe cholecystitis, manage organ dysfunction in an intensive care unit
prior to surgery.

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 Acute cholecystitis Management
• If a surgeon with experience of operating on patients with acute cholecystitis is not available locally,
transfer the patient to a specialist unit.[27]

Severe inflammation of the gallbladder and its surroundings increases the difficulty of a laparoscopic
cholecystectomy and the frequency of postoperative complications.[70]

• The following risk factors are associated with prolonged operative time:[70]

• Gallbladder wall thickening

• Incarcerated stones in the gallbladder neck
• Duration of elevated C-reactive protein
• Non-visualised gallbladder on preoperative cholangiography
• Body temperature
• Abscess formation
• BMI.

• The following risk factors are associated with conversion to open procedure:[70]

• Gallbladder wall >4 to 5 mm on preoperative ultrasound

• Age >60 or 65 years
• Male Acute cholecystitis (Tokyo guidelines grade II/III)
• Contracted gallbladder on ultrasound
• Previous abdominal surgery
• BMI
• ASA score.
MANAGEMENT

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Acute cholecystitis Management

Evidence: Efficacy of laparoscopic cholecystectomy

The NICE interventional procedures guidance on single-incision laparoscopic cholecystectomy

(SILC) found that studies comparing SILC with conventional multiport laparoscopic
cholecystectomy (CMLC) efficacy had mixed results depending on outcomes measured. [71]

In terms of efficacy, the NICE interventional procedures guidance included two

systematic reviews.

• One systematic review included 25 randomised controlled trials (RCTs) involving a total of 1841
patients comparing SILC with CMLC.[72]

• A meta-analysis of these data found significant differences between the groups on six
efficacy measures: two favouring CMLC (operative time and the need for additional
instrumentation) and four favouring SILC (the length of the incision, pain at 3-4 hours,
pain at 6-8 hours, and cosmesis score).
• There was no significant difference in the meta-analysis on conversion to open surgery,
blood loss, time to oral intake, length of stay, time to return to work, or pain at 12 or 24
hours.
• Three of the RCTs in this review reported quality of life: in one, this was worse at 1 month
for the SILC group than for the CMLC group (mean 51.1 vs. 54.1 on the short-form 12
[SF-12] scale, P = 0.03); in one it was better at 1 month for the SILC group (median 40 vs.
35 on the SF-12, P = 0.028); and in the third there was no significant difference between
the groups at 10 days (mean 101.6 vs. 102.5 on the gastrointestinal quality-of-life index, P
= 0.567).[73] [74] [75]

• The other systematic review included 40 studies (16 RCTs and 24 non-randomised comparative
studies) involving a total of 3711 patients, with some overlap of the studies included in this
review and the one above.[76]

• Meta-analysis of these data showed significant differences between the groups on five
efficacy measures: two favouring CMLC (conversions and operative time) and three
favouring SILC (length of incision, length of stay, and cosmesis score at 1 month).
• There was no significant difference in terms of blood loss; analgesia use; time to return
to work; pain at 24 hours, 48 hours, 72 hours, or 1 week; or cosmesis score at 3 or 6
months).
MANAGEMENT

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 Acute cholecystitis Management

Evidence: Safety of laparoscopic cholecystectomy

NICE concludes that current evidence on the safety and efficacy of single#incision
laparoscopic cholecystectomy (SILC) is adequate to support the use of this procedure provided
that normal arrangements are in place for clinical governance, consent, and audit.

In terms of safety, the NICE interventional procedures guidance included two systematic
reviews, a non-systematic review of safety data, and expert opinion. [71]

• One systematic review included 25 randomised controlled trials (RCTs) involving a total of 1841
patients.[72]

• A meta-analysis of these data found no significant difference in bile-duct injuries (odds

ratio [OR] 1.00, 95% CI 0.165 to 6.066, P = 1.0), retained gallstones (OR 2.15, 95%
CI 0.55 to 8.33, P = 0.269), or incisional hernia (OR 1.937; 95% CI 0.658 to 5.706, P =
0.230).
• One of the studies reported the rate of gallbladder perforation was 9/75 (12%) with SILC
versus 6/75 (8%) with conventional multiport laparoscopic cholecystectomy (no P value
reported).[74]
• Another study reported similar rates of erythema (5/119 [4%] vs. 0/81 [0%]) and
ecchymosis (1/119 [1%] vs. 0/81 [0%]).[73]

• The other systematic review included 40 studies (16 RCTs and 24 non-randomised comparative
studies) involving a total of 3711 patients.[76]

• Meta-analysis of these data showed no significant difference between the groups for
wound haematomas (OR 2.07, 95% CI 0.90 to 4.74, P = 0.09), wound infections (OR
1.03, 95% CI 0.53 to 2.0, P = 0.92), or incisional hernias (OR 1.67, 95% CI 0.65 to 4.27,
P = 0.29).

• A non-systematic review of adverse events after SILC (with no comparator) included 38 studies
involving a total of 1180 patients, of whom 17 (1%) reported seroma, 2 (0.17%) had ileus, and 1
(0.08%) had renal failure.[77]
• Experts suggest that other theoretical adverse events (which are not known to have been
reported in the literature) include retained gallstones, incisional hernias, or injuries to the
viscera.[71]
MANAGEMENT

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Acute cholecystitis Management

Evidence: Timing of cholecystectomy

Benefits and complications vary according to when surgery is performed.

A meta#analysis including 15 randomised controlled trials found that early

cholecystectomy (defined as either within 1 week or within 72 hours) was similar to
delayed cholecystectomy in terms of mortality and complication rates. [52]

• There was no difference in length of hospital stay after surgery, but total hospital stays were
shorter for early cholecystectomy.

• Overall cost of treatment was lower with cholecystectomy performed within 72 hours
compared with delayed surgery.

• There was no difference in the incidence of bile duct injury, but authors reported that the total
number of patients was too small to draw conclusions regarding this complication.[52]

Another meta-analysis including 15 randomised controlled trials compared early

laparoscopic cholecystectomy (defined as within 7, 4, or 3 days) with delayed laparoscopic
cholecystectomy. [78]

• There was no difference in bile duct injury and bile leakage, rate of wound infection, total
complications, conversion to open surgery, or operation times, but early laparoscopic
cholecystectomy performed within 7 days was associated with a longer surgery time.
• Early laparoscopic cholecystectomy was found to significantly shorten the duration of total
hospital stay.

A comparison of surgery performed within 24 hours of symptom onset and surgery performed
within 72 hours showed that the outcomes from the 24-hours group were not superior to those in the
latter group.[79]

A systematic review for the 2014 NICE guideline on gallstone disease found six
randomised controlled trials comparing early laparoscopic cholecystectomy (within 1
week of the acute presentation) with delayed laparoscopic cholecystectomy (more than 4
weeks after presentation) for people with acute cholecystitis. [4]

• Readmission rates and length of stay were lower with early versus delayed laparoscopic
cholecystectomy and quality-of-life scores were higher.
• Early laparoscopic cholecystectomy was more cost-effective compared with delayed
laparoscopic cholecystectomy.

Percutaneous cholecystostomy
MANAGEMENT

Refer for a percutaneous cholecystostomy patients who are unfit for general anaesthesia
and surgery, who do not improve after treatment with antibiotics, analgesia, and fluid
resuscitation. [27]

• The aim is to drain fluid from the infected gallbladder in patients at high surgical risk.[4]

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 Acute cholecystitis Management
• The procedure involves inserting a drainage catheter in the gallbladder through a small entry hole
made in the abdominal wall.[57]
• This procedure could relieve the symptoms completely, or at least allow the patient’s condition
to improve sufficiently for a definitive elective procedure (laparoscopic cholecystectomy) to be
undertaken later, rather than in an emergency situation.[4]
• An incomplete or poor response to cholecystostomy within the first 48 hours may indicate causes
of sepsis other than cholecystitis, inadequate antibiotic coverage, possible complications (such as
dislodgement of the drainage tube), or necrosis of the wall of the gallbladder.[3]
• Offer percutaneous cholecystostomy to manage gallbladder empyema when surgery is
contraindicated at presentation and conservative management is unsuccessful.[4]

Evidence: Percutaneous cholecystostomy

Evidence is limited on the balance of risks and benefits of percutaneous cholecystostomy. [80]

NICE guidelines suggest percutaneous cholecystostomy in patients in whom it is safer to avoid

a general anaesthetic but the infection is not resolving with conservative measures (fluids and
antibiotics).[4]

Two small trials included in a Cochrane systematic review suggest that percutaneous cholecystostomy
and early laparoscopic cholecystectomy may reduce length of hospital stay and costs, but the
evidence base is not robust.[80]

• The review found two randomised controlled trials (both at high risk of bias) involving a total of
156 participants.[80]
• One trial involving 70 participants compared percutaneous cholecystostomy (within 8 hours of
referral to the surgeon) followed by early laparoscopic cholecystectomy (within 96 hours when
patient improved) versus delayed laparoscopic cholecystectomy (8 weeks after the symptoms
settled).[81]

• It found a shorter length of stay (mean difference -9.90 days, 95% CI -12.31 to -7.49) and
lower costs (mean difference -1123 US dollars, 95% CI -1336.60 to -909.40 US dollars)
with percutaneous cholecystostomy followed by early laparoscopic cholecystectomy.
There was no significant difference between the groups in terms of the numbers of
participants needing conversion to open cholecystectomy, complications, or mortality.[81]

• The other trial involving 86 participants compared percutaneous cholecystostomy (within

24 hours of referral) versus conservative treatment; either could be followed if necessary
by delayed cholecystectomy (not stated how many were laparoscopic or converted to open
operations).[82]

• It found no significant difference between the groups on the numbers needing delayed
laparoscopic cholecystectomy.[82]
MANAGEMENT

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Acute cholecystitis Management
Endoscopic ultrasound-guided gallbladder drainage
An alternative option for patients with acute cholecystitis where surgery is not an option is
endoscopic ultrasound-guided gallbladder drainage. [57]

• In patients where surgery is unsuitable (either due to the risks involved or the presence of other
conditions which may make surgery unsuitable) NICE recommends that endoscopic ultrasound
(EUS) guided gallbladder drainage can be used as an alternative.[57]

• The procedure is typically carried out under sedation or general anaesthesia using a specialist
endoscope, with an ultrasound probe and fluoroscopic guidance, to insert a stent through an
anastomotic tract created into the gallbladder through the wall of the stomach or duodenum.

• There is good evidence to show that this procedure is effective in treating acute cholecystitis and
the aim is to drain bile from the gallbladder to avoid the need for emergency cholecystectomy,
though it is a technically challenging procedure which should only be done in specialist centres by
clinicians trained and experienced in using this procedure for gallbladder drainage.[57] [83] [84] [85]
[86]

• A disadvantage of the procedure when compared to cholecystectomy is that cholecystitis may

reoccur.[57]

• It is important to note that it is not a permanent solution but rather a bridge to surgery, and
assessment for future cholecystectomy should resume once sepsis has been treated.[56]

Manage complications

Gallbladder empyema
Offer percutaneous cholecystostomy to manage gallbladder empyema when surgery is
contraindicated at presentation and conservative management is unsuccessful.[4]

• Gallbladder empyema can result when cholecystitis is left to progress with concurrent bile stasis
and cystic duct obstruction.
• It is a surgical emergency.
• Gallbladder empyema is the most severe form of acute cholecystitis.
• Reconsider laparoscopic cholecystectomy for people who have had percutaneous cholecystostomy
once they are well enough for surgery.[4]

Gangrenous cholecystitis
Consider urgent laparoscopic cholecystectomy in patients at high risk of gangrene.[3]
MANAGEMENT

• Gangrene occurs most commonly at the fundus due to a compromised vascular supply.[3]
• Have a low threshold for conversion to open cholecystectomy during the procedure.[3]

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 Acute cholecystitis Management
Gallbladder perforation
Perforation may require percutaneous drainage of the resulting collection or expedited surgery. Treatment
should be tailored to the individual circumstances of each patient.[3]

• Perforation occurs in 10% of people with acute cholecystitis.[3]

• This is often when there has been a delay in seeking or receiving medical attention or in patients
who do not respond to conservative management.[3]
• Perforation most commonly occurs at the fundus.[3]
• After the gallbladder has perforated, patients may experience transient relief of their symptoms
because the gallbladder decompresses, but peritonitis then develops.[3]

Acute cholangitis
Mortality risk is high. Treat with antibiotic therapy and reduce the biliary pressure.[87]

• Acute cholangitis occurs when biliary stenosis results in cholestasis and biliary infection.[87]
• The stenosis or blockage may be due to benign causes, such as bile duct stone, or a tumour.
• This elevates pressure within the biliary system and flushes the micro-organisms or endotoxins
from the infected bile into systemic circulation, which causes a systemic inflammatory response.
• See our topic Ascending cholangitis for more information.

Treating the underlying cause

About 90% of patients with acute cholecystitis have gallstones. [2] [3]

• See our topic Gallstones for more on diagnosis and management.

• Manage any precipitating infections.
• Optimise any contributing factors in critically ill patients, such as those fasting or receiving total
parenteral nutrition.

Ongoing management
Provide simple analgesia, such as paracetamol or a non-steroidal anti-inflammatory drug, for
postoperative pain; it is usually minimal.

Advise patients that they do not need to avoid any particular food or drinks after having their gallbladder
or gallstones removed, but to seek further advice from their general practitioner if eating or drinking
causes new symptoms to develop.[4]

Ask about any nausea, vomiting, and abdominal pain. Review the wound for erythema, discharge, or
pain.

• In a survey of patients followed up by a weekly telephone questionnaire for 6 weeks after

MANAGEMENT

laparoscopic cholecystectomy, 22% reported nausea and vomiting continuing after hospital
discharge, 11% said postoperative pain was not controlled by prescribed analgesia after hospital
discharge, and 70% reported wound-related symptoms such as discharge.[88]

Continue to assess for signs of jaundice.

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Acute cholecystitis Management
Liaise with community colleagues to offer a care package post discharge.

Treatment algorithm overview

Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

Acute ( summary )
associated organ dysfunction
(severe; Tok yo guideline grade III)

1st intensive care admission

plus analgesia

consider fluid resuscitation

consider antibiotic therapy

consider percutaneous cholecystostomy

consider endoscopic ultrasound-guided

gallbladder drainage

consider delayed cholecystectomy

plus postoperative management

no associated organ dysfunction

(mild or moderate; Tok yo guideline
grade I or II)

1st analgesia

consider fluid resuscitation

consider antibiotic therapy

plus early laparoscopic cholecystectomy or

percutaneous cholecystostomy

consider endoscopic ultrasound-guided

gallbladder drainage

plus postoperative management

MANAGEMENT

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 Acute cholecystitis Management

Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

Acute
associated organ dysfunction
(severe; Tok yo guideline grade III)

1st intensive care admission

» In patients with severe acute

cholecystitis (grade III according to the Tokyo
guideline; see Assessing severity in Diagnosis
recommendations for guidance on how to define
grade of cholecystitis):[52]

• Transfer the patient to the intensive

care unit to monitor and treat the
organ dysfunction.
• Determine the degree of organ
dysfunction and attempt to normalise
function through organ support.
• Consider urgent/early biliary drainage if it
is not possible to control the gallbladder
inflammation.

plus analgesia
Treatment recommended for ALL patients in
selected patient group
Primary options

» paracetamol: oral: 500-1000 mg orally

every 4-6 hours when required, maximum
4000 mg/day; intravenous (<51 kg body
weight): 15 mg/kg intravenously every 4-6
hours when required, maximum 60 mg/kg/
day; intravenous (≥51 kg body weight): 1000
mg intravenously every 4-6 hours when
required, maximum 4000 mg/day (3000 mg/
day if risk factors for hepatotoxicity)

OR

» diclofenac potassium: 75-150 mg/day orally

(immediate-release) given in 2-3 divided
doses when required
MANAGEMENT

OR

» diclofenac sodium: 75-150 mg/day rectally

given in divided doses when required; 75

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Acute cholecystitis Management

Acute
mg intramuscularly once or twice daily when
required for a maximum of 2 days

OR

» indometacin: 50-200 mg/day orally

(immediate-release) given in 2-3 divided
doses when required; 100 mg rectally twice
daily when required

Secondary options

» morphine sulfate: 5-10 mg orally

(immediate-release)/subcutaneously/
intravenously/intramuscularly every 4 hours
initially, adjust dose according to response

» Pain is the predominant symptom. Ensure it is

treated promptly and effectively.[52]

• Failure to control pain can compromise

breathing and contribute to
haemodynamic instability.
• Use a pain score to monitor the response
to analgesia and adjust the dose and/or
type of analgesic medication in line with
local pain management protocols.

» Use paracetamol or a non-steroidal anti-

inflammatory drug such as diclofenac or
indometacin initially.[27] [58] Move onto opioid
analgesia (e.g., morphine) if required.[10]
consider fluid resuscitation
Treatment recommended for SOME patients in
selected patient group
» Assess fluid status and resuscitate with
intravenous fluids as appropriate.

• Administer intravenous fluids, if needed,

to all patients who cannot tolerate oral
intake.
• Give intravenous fluids based on fluid
status assessment.[59]
• Use either a balanced crystalloid or
normal saline 0.9% initially.

• Check local protocols for specific

MANAGEMENT

recommendations on fluid choice.

There is debate, based on
conflicting evidence, on whether
there is a benefit in using normal

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 Acute cholecystitis Management

Acute
saline or balanced crystalloid in
critically ill patients.

• Tailor the intravenous fluid to the

patient’s condition and electrolytes.

• Regularly monitor patients receiving

intravenous fluids.[59]

• Clinical monitoring should include

current status and trends in:

• National Early Warning Score

(NEWS2)
• Fluid balance charts
• Weight.

• Laboratory investigations should

include current status and trends in

• Full blood count

• Urea
• Creatinine
• Electrolytes.

» Treat the underlying cause as early as

possible. Consider local protocols but, in
general, escalate patients with shock to a senior
clinician. See our topic Shock.

Practical tip

Be aware that large volumes of normal

saline as the sole fluid for resuscitation
may lead to hyperchloraemic acidosis.
Also note that use of lactate-containing
fluid in a patient with impaired liver
metabolism may lead to a spuriously
elevated lactate level, so results need to be
interpreted with other markers of volume
status.
MANAGEMENT

Evidence: Choice of fluid

Evidence from two large randomised

controlled trials (RCTs) suggests there
is no difference between normal saline
and a balanced crystalloid for critically ill

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Acute cholecystitis Management

Acute
patients in mortality at 90 days,#although
results from two meta-analyses including
these RCTs point to a possible small
benefit of balanced solutions compared
with normal saline.

There has been extensive debate

over the choice between normal
saline (an unbalanced crystalloid)
versus a balanced crystalloid (such
as Hartmann’s solution [also known
as Ringer’s lactate], or Plasma-Lyte).
Clinical practice varies widely, so you
should check local protocols.

• In 2021 to 2022 two large double

blind RCTs were published assessing
intravenous fluid resuscitation in ICU
patients with a balanced crystalloid
solution (Plasma-Lyte) versus normal
saline: the Plasma-Lyte 148 versus
Saline (PLUS) trial (53 intensive care
units [ICUs] in Australia and New
Zealand; N= 5037) and the Balanced
Solutions in Intensive Care Study
(BaSICS) trial (75 ICUs in Brazil;
N=11,052).[60] [61]

• In the PLUS study 45.2%

of patients were admitted
to ICU directly from surgery
(emergency or elective), 42.3%
had sepsis and 79.0% were
receiving mechanical ventilation
at the time of randomisation.
• In BaSICS almost half the
patients (48.4%) were admitted
to ICU after elective surgery and
around 68% had some form of
fluid resuscitation before being
randomised.
• Both found no difference in 90-
day mortality overall or in pre-
specified subgroups for patients
with acute kidney injury (AKI),
sepsis or post-surgery. They
also found no difference in the
MANAGEMENT

risk of AKI.
• In BaSICS, for patients with
traumatic brain injury, there
was a small decrease in 90 day
mortality with normal saline -

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47
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 Acute cholecystitis Management

Acute
however, the overall number of
patients was small (<5% of total
included in the study) so there
is some uncertainty about this
result. Patients with traumatic
brain injury were excluded from
PLUS as the authors felt these
patients should be receiving
saline or a solution of similar
tonicity.

• One meta-analysis of 13 RCTs

(including PLUS and BaSICS)
confirmed no overall difference,
although the authors did highlight
a non-significant trend towards a
benefit of balanced solutions for risk of
death.[62]
• A subsequent individual patient data
meta-analysis included 6 RCTs of
which only PLUS and BaSICS were
assessed as being at low risk of bias.
There was no statistically significant
difference in in-hospital mortality (OR
0·96, 95%CI 0·91–1·02). However, the
authors argued that using a Bayesian
analysis there was a high probability
that balanced solutions reduced
in-hospital mortality, although they
acknowledged that the absolute risk
reduction was small.[63]

• A pre-specified subgroup
analysis of patients
with traumatic brain injury
(N=1961) found that balanced
solutions increased the risk of in-
hospital mortality compared with
normal saline (OR 1·42, 95%CI
1·10 to 1·82).

• Previous evidence has been mixed.

• One 2015 double-blind, cluster

randomised, double-crossover
trial conducted in four ICUs in
New Zealand (N=2278), the
0.9% Saline vs Plasma-Lyte
for ICU fluid Therapy (SPLIT)
trial, found no difference for in-
MANAGEMENT

hospital mortality, AKI, or use of

renal-replacement therapy.[64]
• However, one 2018 US
multicentre unblinded cluster-
randomised trial - the isotonic
Solutions and Major Adverse

48 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Jul 23, 2024.
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subject to our disclaimer. © BMJ Publishing Group Ltd 2024. All rights reserved.
Acute cholecystitis Management

Acute
Renal events Trial (SMART),
among 15,802 critically ill
adults receiving ICU care -
found possible small benefits
from balanced crystalloid
(Ringer’s lactate or Plasma-Lyte)
compared with normal saline.
The 30-day outcomes showed a
non-significant reduced mortality
in the balanced crystalloid group
versus the normal saline group
(10.3% vs 11.1%; OR 0.90,
95% CI 0.80 to 1.01) and a
major adverse kidney event
rate of 14.3% versus 15.4%
respectively (OR 0.91, 95% CI
0.84 to 0.99).[65]

• One 2019 Cochrane review included

21 RCTs (N=20,213) assessing
balanced crystalloids versus normal
saline for resuscitation or maintenance
in a critical care setting.[66]

• The three largest RCTs in the

Cochrane review (including
SMART and SPLIT) all
examined fluid resuscitation in
adults and made up 94.2% of
participants (N=19,054).
• There was no difference in in‐
hospital mortality (OR 0.91,
95% CI 0.83 to 1.01; high
quality evidence as assessed
by GRADE), acute renal injury
(OR 0.92, 95% CI 0.84 to 1.00;
GRADE low), or organ system
dysfunction (OR 0.80, 95% CI
0.40 to 1.61; GRADE very low).

consider antibiotic therapy

Treatment recommended for SOME patients in
selected patient group
MANAGEMENT

» Follow your local protocol for investigation

and treatment of all patients with suspected
sepsis, or those at risk. Start treatment promptly.
Determine urgency of treatment according to
likelihood of infection and severity of illness, or
according to your local protocol.[32] [42]

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49
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 Acute cholecystitis Management

Acute
» For patients with suspected biliary infection,
start antibiotics as soon as infection is suspected
and before any procedure is performed.[67]
Not all patients will require antibiotics; do not
start antimicrobial therapy unless there is clear
evidence of an infection.[68]

• Follow local policy and consider

discussing with microbiology/infectious
disease colleagues to determine the most
appropriate choice. Avoid inappropriate
use of broad-spectrum antibiotics.[68]
• Consider antimicrobial stewardship, such
as the ‘start smart – then focus’ principles
from Public Health England.[68]
• Ask about any antibiotic use in the last 6
months. The patient is more likely to be
harbouring a resistant organism if they
have a recent (within 6 months) history of
antibiotic use.[67]
• Take a thorough drug allergy history when
prescribing antibiotics.[67] [68]

» Expert opinion suggests that empirical

intravenous therapy should be chosen bearing in
mind the following factors:[67]

• Observational studies have demonstrated

that Escherichia coli is the organism
most frequently implicated
• Local susceptibility patterns vary
geographically and over time
• The likelihood of resistance of the
organism will also vary by whether the
infection was hospital- or community-
acquired, although there may be resistant
organisms in the community
• More-severe grades of infection require
more potent antibiotics (monotherapy or
combination therapy).

» Use a definitive therapy once the sensitivities

are reported from culture specimens.[67]

• Specific therapy may involve penicillins,

cephalosporins, or fluoroquinolones.[67]

» Change intravenous therapy to oral antibiotics

MANAGEMENT

when the patient is able to eat. Stop the

antibiotics when safe to do so.[67] [68]

» The duration of therapy needs to balance

benefits (eliminating the infection and reducing
the risk of complications) against risks (resistant

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subject to our disclaimer. © BMJ Publishing Group Ltd 2024. All rights reserved.
Acute cholecystitis Management

Acute
organisms, the cost of therapy, and the
prolonged length of hospital stay).[67]
consider percutaneous cholecystostomy
Treatment recommended for SOME patients in
selected patient group
» Refer for a percutaneous
cholecystostomy patients who are unfit for
general anaesthesia and surgery, who do
not improve after treatment with analgesia,
fluid resuscitation, and antibiotics. [27]

• The aim is to drain fluid from the infected

gallbladder in patients at high surgical
risk.[4]
• This procedure could relieve the
symptoms completely, or at least allow the
patient’s condition to improve sufficiently
for a definitive elective procedure
(laparoscopic cholecystectomy) to
be undertaken later, rather than in an
emergency situation.[4]
• An incomplete or poor response to
cholecystostomy within the first 48 hours
may indicate causes of sepsis other
than cholecystitis, inadequate antibiotic
coverage, possible complications (such
as dislodgement of the drainage tube), or
necrosis of the wall of the gallbladder.[3]
• Offer percutaneous cholecystostomy
to manage gallbladder empyema
when surgery is contraindicated
at presentation and conservative
management is unsuccessful.[4]

Evidence: Percutaneous
cholecystostomy

Evidence is limited on the balance of

risks and benefits of percutaneous
cholecystostomy. [80]

UK National Institute for Health and Care

Excellence guidelines suggest percutaneous
cholecystostomy in patients in whom it is
safer to avoid a general anaesthetic but the
infection is not resolving with conservative
measures (fluids and antibiotics).[4]

Two small trials included in a Cochrane

MANAGEMENT

systematic review suggest that percutaneous

cholecystostomy and early laparoscopic
cholecystectomy may reduce length of
hospital stay and costs, but the evidence
base is not robust.[80]

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51
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 Acute cholecystitis Management

Acute
• The review found two randomised
controlled trials (both at high risk
of bias) involving a total of 156
participants.[80]
• One trial involving 70 participants
compared percutaneous
cholecystostomy (within 8 hours of
referral to the surgeon) followed by
early laparoscopic cholecystectomy
(within 96 hours when patient
improved) versus delayed laparoscopic
cholecystectomy (8 weeks after the
symptoms settled).[81]

• It found a shorter length

of stay (mean difference
-9.90 days, 95% CI -12.31
to -7.49) and lower costs
(mean difference -1123 US
dollars, 95% CI -1336.60
to -909.40 US dollars) with
percutaneous cholecystostomy
followed by early laparoscopic
cholecystectomy. There was
no significant difference
between the groups in terms
of the numbers of participants
needing conversion to open
cholecystectomy, complications,
or mortality.[81]

• The other trial involving 86

participants compared percutaneous
cholecystostomy (within 24 hours of
referral) versus conservative treatment;
either could be followed if necessary
by delayed cholecystectomy (not
stated how many were laparoscopic or
converted to open operations).[82]

• It found no significant
difference between the
groups on the numbers
needing delayed laparoscopic
cholecystectomy.[82]

consider endoscopic ultrasound-guided gallbladder

drainage
MANAGEMENT

Treatment recommended for SOME patients in

selected patient group
» Recommended in patients where surgery is
unsuitable (either due to the risks involved or
the presence of other conditions which may

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Acute cholecystitis Management

Acute
make surgery unsuitable).[57] The aim is to
drain bile from the gallbladder to avoid the
need for emergency cholecystectomy, though
it is a technically challenging procedure which
should only be done in specialist centres by
clinicians trained and experienced in using this
procedure for gallbladder drainage.[57] [83]
[84] [85] [86] A disadvantage of the procedure
when compared to cholecystectomy is that
cholecystitis may reoccur.[57] It is important to
note that it is not a permanent solution but rather
a bridge to surgery, and assessment for future
cholecystectomy should resume once sepsis has
been treated.[56]
consider delayed cholecystectomy
Treatment recommended for SOME patients in
selected patient group
» Reconsider a cholecystectomy when the
patient is well enough for the procedure.
plus postoperative management
Treatment recommended for ALL patients in
selected patient group
» Provide simple analgesia, such as
paracetamol or a non-steroidal anti-inflammatory
drug, for postoperative pain; it is usually minimal.

» Ask about any nausea, vomiting, and

abdominal pain. Review the wound for
erythema, discharge, or pain.

• In a survey of patients followed up by

weekly telephone questionnaire for 6
weeks after laparoscopic cholecystectomy,
22% reported nausea and vomiting
continuing after hospital discharge, 11%
said postoperative pain was not controlled
by prescribed analgesia after hospital
discharge, and 70% reported wound-
related symptoms such as discharge.[88]

» Continue to assess for signs of jaundice.

» Plan for discharge. Advise patients that

they do not need to avoid any particular food or
drinks after having their gallbladder or gallstones
removed, but to seek further advice from
their general practitioner if eating or drinking
causes new symptoms to develop.[4] Liaise with
MANAGEMENT

community colleagues to offer a care package

post discharge.
no associated organ dysfunction
(mild or moderate; Tok yo guideline
grade I or II)

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53
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 Acute cholecystitis Management

Acute
1st analgesia
Primary options

» paracetamol: oral: 500-1000 mg orally

every 4-6 hours when required, maximum
4000 mg/day; intravenous (<51 kg body
weight): 15 mg/kg intravenously every 4-6
hours when required, maximum 60 mg/kg/
day; intravenous (≥51 kg body weight): 1000
mg intravenously every 4-6 hours when
required, maximum 4000 mg/day (3000 mg/
day if risk factors for hepatotoxicity)

OR

» diclofenac potassium: 75-150 mg/day orally

(immediate-release) given in 2-3 divided
doses when required

OR

» diclofenac sodium: 75-150 mg/day rectally

given in divided doses when required; 75
mg intramuscularly once or twice daily when
required for a maximum of 2 days

OR

» indometacin: 50-200 mg/day orally

(immediate-release) given in 2-3 divided
doses when required; 100 mg rectally twice
daily when required

Secondary options

» morphine sulfate: 5-10 mg orally

(immediate-release)/subcutaneously/
intravenously/intramuscularly every 4 hours
initially, adjust dose according to response

» Pain is the predominant symptom. Ensure it is

treated promptly and effectively.[52]

• Failure to control pain can compromise

breathing and contribute to
haemodynamic instability.
• Use a pain score to monitor the response
to analgesia and adjust the dose and/or
MANAGEMENT

type of analgesic medication in line with

local pain management protocols.

» Use paracetamol or a non-steroidal anti-

inflammatory drug such as diclofenac or

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Acute cholecystitis Management

Acute
indometacin initially.[27] [58] Move onto opioid
analgesia (e.g., morphine) if required.[10]
consider fluid resuscitation
Treatment recommended for SOME patients in
selected patient group
» Assess fluid status and resuscitate with
intravenous fluids as appropriate.

• Administer intravenous fluids, if needed,

to all patients who cannot tolerate oral
intake.
• Give intravenous fluids based on fluid
status assessment.[59]
• Use either a balanced crystalloid or
normal saline 0.9% initially.

• Check local protocols for specific

recommendations on fluid choice.
There is debate, based on
conflicting evidence, on whether
there is a benefit in using normal
saline or balanced crystalloid in
critically ill patients.
• Tailor the intravenous fluid to the
patient’s condition and electrolytes.

• Regularly monitor patients receiving

intravenous fluids.[59]

• Clinical monitoring should include

current status and trends in:

• National Early Warning Score

(NEWS2)
• Fluid balance charts
• Weight.

• Laboratory investigations should

include current status and trends in:

• Full blood count

• Urea
MANAGEMENT

• Creatinine
• Electrolytes.

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 Acute cholecystitis Management

Acute
» Treat the underlying cause as early as
possible. Consider local protocols but, in
general, escalate patients with shock to a senior
clinician. See our topic Shock.

Practical tip

Be aware that large volumes of normal

saline as the sole fluid for resuscitation
may lead to hyperchloraemic acidosis.
Also note that use of lactate-containing
fluid in a patient with impaired liver
metabolism may lead to a spuriously
elevated lactate level, so results need to be
interpreted with other markers of volume
status.

Evidence: Choice of fluids

Evidence from two large randomised

controlled trials (RCTs) suggests there
is no difference between normal saline
and a balanced crystalloid for critically ill
patients in mortality at 90 days, although
results from two meta-analyses including
these RCTs point to a possible small
benefit of balanced solutions compared
with normal saline.

There has been extensive debate

over the choice between normal
saline (an unbalanced crystalloid)
versus a balanced crystalloid (such
as Hartmann’s solution [also known
as Ringer’s lactate], or Plasma-Lyte).
Clinical practice varies widely, so you
should check local protocols.

• In 2021 to 2022 two large double

blind RCTs were published assessing
intravenous fluid resuscitation in ICU
patients with a balanced crystalloid
solution (Plasma-Lyte) versus normal
saline: the Plasma-Lyte 148 versus
Saline (PLUS) trial (53 intensive care
units [ICUs] in Australia and New
Zealand; N=5037) and the Balanced
Solutions in Intensive Care Study
(BaSICS) trial (75 ICUs in Brazil;
N=11,052).[60] [61]
MANAGEMENT

• In the PLUS study 45.2%

of patients were admitted
to ICU directly from surgery
(emergency or elective), 42.3%
had sepsis and 79.0% were

56 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Jul 23, 2024.
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Acute cholecystitis Management

Acute
receiving mechanical ventilation
at the time of randomisation.
• In BaSICS almost half the
patients (48.4%) were admitted
to ICU after elective surgery and
around 68% had some form of
fluid resuscitation before being
randomised.
• Both found no difference in 90-
day mortality overall or in pre-
specified subgroups for patients
with acute kidney injury (AKI),
sepsis or post-surgery. They
also found no difference in the
risk of AKI.
• In BaSICS, for patients with
traumatic brain injury, there
was a small decrease in 90 day
mortality with normal saline -
however, the overall number of
patients was small (<5% of total
included in the study) so there
is some uncertainty about this
result. Patients with traumatic
brain injury were excluded from
PLUS as the authors felt these
patients should be receiving
saline or a solution of similar
tonicity.

• One meta-analysis of 13 RCTs

(including PLUS and BaSICS)
confirmed no overall difference,
although the authors did highlight
a non-significant trend towards a
benefit of balanced solutions for risk of
death.[62]
• A subsequent individual patient data
meta-analysis included 6 RCTs of
which only PLUS and BaSICS were
assessed as being at low risk of bias.
There was no statistically significant
difference in in-hospital mortality (OR
0·96, 95%CI 0·91–1·02). However, the
authors argued that using a Bayesian
analysis there was a high probability
that balanced solutions reduced
MANAGEMENT

in-hospital mortality, although they

acknowledged that the absolute risk
reduction was small.[63]

• A pre-specified subgroup
analysis of patients

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 Acute cholecystitis Management

Acute
with traumatic brain injury
(N=1961) found that balanced
solutions increased the risk of in-
hospital mortality compared with
normal saline (OR 1·42, 95%CI
1·10 to 1·82).

• Previous evidence has been mixed.

• One 2015 double-blind, cluster

randomised, double-crossover
trial conducted in four ICUs in
New Zealand (N=2278), the
0.9% Saline vs Plasma-Lyte
for ICU fluid Therapy (SPLIT)
trial, found no difference for in-
hospital mortality, AKI, or use of
renal-replacement therapy.[64]
• However, one 2018 US
multicentre unblinded cluster-
randomised trial - the isotonic
Solutions and Major Adverse
Renal events Trial (SMART),
among 15,802 critically ill
adults receiving ICU care -
found possible small benefits
from balanced crystalloid
(Ringer’s lactate or Plasma-Lyte)
compared with normal saline.
The 30-day outcomes showed a
non-significant reduced mortality
in the balanced crystalloid group
versus the normal saline group
(10.3% vs 11.1%; OR 0.90,
95% CI 0.80 to 1.01) and a
major adverse kidney event
rate of 14.3% versus 15.4%
respectively (OR 0.91, 95% CI
0.84 to 0.99).[65]

• One 2019 Cochrane review included

21 RCTs (N=20,213) assessing
balanced crystalloids versus normal
saline for resuscitation or maintenance
in a critical care setting.[66]

• The three largest RCTs in the

Cochrane review (including
SMART and SPLIT) all
examined fluid resuscitation in
MANAGEMENT

adults and made up 94.2% of

participants (N=19,054).
• There was no difference in in‐
hospital mortality (OR 0.91,

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Acute cholecystitis Management

Acute
95% CI 0.83 to 1.01; high
quality evidence as assessed
by GRADE), acute renal injury
(OR 0.92, 95% CI 0.84 to 1.00;
GRADE low), or organ system
dysfunction (OR 0.80, 95% CI
0.40 to 1.61; GRADE very low).

consider antibiotic therapy

Treatment recommended for SOME patients in
selected patient group
» Follow your local protocol for investigation
and treatment of all patients with suspected
sepsis, or those at risk. Start treatment promptly.
Determine urgency of treatment according to
likelihood of infection and severity of illness, or
according to your local protocol.[32] [42]

» For patients with suspected biliary infection,

start antibiotics as soon as infection is suspected
and before any procedure is performed.[67] Not
all patients will require antibiotics; do not start
antimicrobial therapy unless there is clear
evidence of an infection.[68]

• Follow local policy and consider

discussing with microbiology/infectious
disease colleagues to determine the most
appropriate choice. Avoid inappropriate
use of broad-spectrum antibiotics.[68]
• Consider antimicrobial stewardship, such
as the ‘start smart – then focus’ principles
from Public Health England.[68]
• Ask about any antibiotic use in the last 6
months. The patient is more likely to be
harbouring a resistant organism if they
have a recent (within 6 months) history of
antibiotic use.[67]
• Take a thorough drug allergy history when
prescribing antibiotics.[67] [68]

» Expert opinion suggests that empirical

intravenous therapy should be chosen bearing in
mind the following factors:[67]

• Observational studies have demonstrated

MANAGEMENT

that Escherichia coli is the organism

most frequently implicated
• Local susceptibility patterns vary
geographically and over time

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 Acute cholecystitis Management

Acute
• The likelihood of resistance of the
organism will also vary by whether the
infection was hospital- or community-
acquired, although there may be resistant
organisms in the community
• More-severe grades of infection require
more potent antibiotics (monotherapy or
combination therapy).

» Use a definitive therapy once the sensitivities

are reported from culture specimens.[67]

• Specific therapy may involve penicillins,

cephalosporins, or fluoroquinolones.[67]

» Change intravenous therapy to oral antibiotics

when the patient is able to eat. Stop the
antibiotics when safe to do so.[67] [68]

» The duration of therapy needs to balance

benefits (eliminating the infection and reducing
the risk of complications) against risks (resistant
organisms, the cost of therapy and the
prolonged length of hospital stay).[67]
plus early laparoscopic cholecystectomy or
percutaneous cholecystostomy
Treatment recommended for ALL patients in
selected patient group
» The choice between an early laparoscopic
cholecystectomy or percutaneous
cholecystostomy is based on whether the patient
is fit for surgery.

» Refer for a laparoscopic

cholecystectomy under general anaesthesia in
patients fit for surgery.[4]

• The UK National Institute for Health

and Care Excellence (NICE) states that
surgery should be performed within a
week of diagnosis where resources
allow.[4]
• Other sources state that surgery within
72 hours of onset is preferable.[27]
[52]
• In patients with severe cholecystitis,
manage organ dysfunction in an
MANAGEMENT

intensive care unit prior to surgery.

• If a surgeon with experience of operating
on patients with acute cholecystitis is not
available locally, transfer the patient to a
specialist unit.[27]

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Acute cholecystitis Management

Acute
» Severe inflammation of the gallbladder and
its surroundings increases the difficulty of a
laparoscopic cholecystectomy and the frequency
of postoperative complications.[70]

» The following risk factors are associated with

prolonged operative time:[70]

• Gallbladder wall thickening

• Incarcerated stones in the gallbladder
neck
• Duration of elevated CRP
• Non-visualised gallbladder on
preoperative cholangiography
• Body temperature
• Abscess formation
• BMI.

» The following risk factors are associated with

conversion to open procedure:[70]

• Gallbladder wall >4 to 5 mm on

preoperative ultrasound
• Age >60 or 65 years
• Male
• Acute cholecystitis (Tokyo guidelines
grade II/III)
• Contracted gallbladder on ultrasound
• Previous abdominal surgery
• BMI
• American Society of Anesthesiologists
(ASA) score.

Evidence: Efficacy of laparoscopic

cholecystectomy

The NICE interventional procedures

guidance on single-incision laparoscopic
cholecystectomy (SILC) found that
studies comparing SILC with conventional
multiport laparoscopic cholecystectomy
(CMLC) efficacy had mixed results
depending on outcomes measured. [71]

In terms of efficacy, the NICE

interventional procedures guidance
MANAGEMENT

included two systematic reviews.

• One systematic review included 25

randomised controlled trials (RCTs)
involving a total of 1841 patients
comparing SILC with CMLC.[72]

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 Acute cholecystitis Management

Acute
• A meta-analysis of these data
found significant differences
between the groups on six
efficacy measures: two
favouring CMLC (operative
time and the need for additional
instrumentation) and four
favouring SILC (the length of
the incision, pain at 3-4 hours,
pain at 6-8 hours, and cosmesis
score).
• There was no significant
difference in the meta-analysis
on conversion to open surgery,
blood loss, time to oral intake,
length of stay, time to return to
work, or pain at 12 or 24 hours.
• Three of the RCTs in this review
reported quality of life: in one,
this was worse at 1 month
for the SILC group than for
the CMLC group (mean 51.1
vs. 54.1 on the short-form 12
[SF-12] scale, P = 0.03); in one
it was better at 1 month for the
SILC group (median 40 vs. 35
on the SF-12, P = 0.028); and in
the third there was no significant
difference between the groups at
10 days (mean 101.6 vs. 102.5
on the gastrointestinal quality-
of-life index, P = 0.567).[73] [74]
[75]

• The other systematic review included

40 studies (16 RCTs and 24 non-
randomised comparative studies)
involving a total of 3711 patients, with
some overlap of the studies included in
this review and the one above.[76]

• Meta-analysis of these data

showed significant differences
between the groups on five
efficacy measures: two favouring
MANAGEMENT

CMLC (conversions and

operative time) and three
favouring SILC (length of

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Acute cholecystitis Management

Acute
incision, length of stay, and
cosmesis score at 1 month).
• There was no significant
difference in terms of blood loss;
analgesia use; time to return
to work; pain at 24 hours, 48
hours, 72 hours, or 1 week;
or cosmesis score at 3 or 6
months).

Evidence: Safety of laparoscopic

cholecystectomy

NICE concludes that current evidence

on the safety and efficacy of single-
incision laparoscopic cholecystectomy
(SILC) is adequate to support the use
of this procedure provided that normal
arrangements are in place for clinical
governance, consent, and audit.

In terms of safety, the NICE

interventional procedures guidance
included two systematic reviews, a non-
systematic review of safety data, and
expert opinion. [71]

• One systematic review included 25

randomised controlled trials (RCTs)
involving a total of 1841 patients.[72]

• A meta-analysis of these data

found no significant difference in
bile-duct injuries (odds ratio [OR]
1.00, 95% CI 0.165 to 6.066, P
= 1.0), retained gallstones (OR
2.15, 95% CI 0.55 to 8.33, P =
0.269), or incisional hernia (OR
1.937; 95% CI 0.658 to 5.706, P
= 0.230).
• One of the studies reported
the rate of gallbladder
perforation was 9/75 (12%)
with SILC versus 6/75 (8%)
MANAGEMENT

with conventional multiport

laparoscopic cholecystectomy
(no P value reported).[74]
• Another study reported similar
rates of erythema (5/119 [4%]

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 Acute cholecystitis Management

Acute
vs. 0/81 [0%]) and ecchymosis
(1/119 [1%] vs. 0/81 [0%]).[73]

• The other systematic review included

40 studies (16 RCTs and 24 non-
randomised comparative studies)
involving a total of 3711 patients.[76]

• Meta-analysis of these data

showed no significant difference
between the groups for wound
haematomas (OR 2.07, 95%
CI 0.90 to 4.74, P = 0.09),
wound infections (OR 1.03, 95%
CI 0.53 to 2.0, P = 0.92), or
incisional hernias (OR 1.67, 95%
CI 0.65 to 4.27, P = 0.29).

• A non-systematic review of adverse

events after SILC (with no comparator)
included 38 studies involving a total
of 1180 patients, of whom 17 (1%)
reported seroma, 2 (0.17%) had ileus,
and 1 (0.08%) had renal failure.[77]
• Experts suggest that other theoretical
adverse events (which are not known
to have been reported in the literature)
include retained gallstones, incisional
hernias, or injuries to the viscera.[71]

Evidence: Timing of cholecystectomy

Benefits and complications vary

according to when surgery is performed.

A meta#analysis including 15
randomised controlled trials found that
early cholecystectomy (defined as either
within 1 week or within 72 hours) was
similar to delayed cholecystectomy in
terms of mortality and complication
rates. [52]

• There was no difference in length of

hospital stay after surgery, but total
hospital stays were shorter for early
MANAGEMENT

cholecystectomy.

• Overall cost of treatment was

lower with cholecystectomy

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Acute cholecystitis Management

Acute
performed within 72 hours
compared with delayed surgery.

• There was no difference in the

incidence of bile duct injury, but
authors reported that the total
number of patients was too small
to draw conclusions regarding this
complication.[52]

Another meta-analysis including 15

randomised controlled trials compared
early laparoscopic cholecystectomy
(defined as within 7, 4, or 3 days) with
delayed laparoscopic cholecystectomy.
[78]

• There was no difference in bile

duct injury and bile leakage, rate of
wound infection, total complications,
conversion to open surgery, or
operation times, but early laparoscopic
cholecystectomy performed within 7
days was associated with a longer
surgery time.
• Early laparoscopic cholecystectomy
was found to significantly shorten the
duration of total hospital stay.

A comparison of surgery performed within

24 hours of symptom onset and surgery
performed within 72 hours showed that the
outcomes from the 24-hours group were not
superior to those in the latter group.[79]

A systematic review for the 2014

NICE guideline on gallstone disease
found six randomised controlled
trials comparing early laparoscopic
cholecystectomy (within 1 week of
the acute presentation) with delayed
laparoscopic cholecystectomy (more
than 4 weeks after presentation) for
people with acute cholecystitis. [4]

• Readmission rates and length of stay

were lower with early versus delayed
MANAGEMENT

laparoscopic cholecystectomy and

quality-of-life scores were higher.

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 Acute cholecystitis Management

Acute
• Early laparoscopic cholecystectomy
was more cost-effective compared with
delayed laparoscopic cholecystectomy.

» Refer for a percutaneous

cholecystostomy patients who are unfit
for general anaesthesia and surgery,
who do not improve after treatment
with antibiotics, analgesia, and fluid
resuscitation. [27]

• The aim is to drain fluid from the infected

gallbladder in patients at high surgical
risk.[4]
• This procedure could relieve the
symptoms completely, or at least allow the
patient’s condition to improve sufficiently
for a definitive elective procedure
(laparoscopic cholecystectomy) to
be undertaken later, rather than in an
emergency situation.[4]
• An incomplete or poor response to
cholecystostomy within the first 48 hours
may indicate causes of sepsis other
than cholecystitis, inadequate antibiotic
coverage, possible complications (such
as dislodgement of the drainage tube), or
necrosis of the wall of the gallbladder.[3]
• Offer percutaneous cholecystostomy
to manage gallbladder empyema
when surgery is contraindicated
at presentation and conservative
management is unsuccessful.[4]

Evidence: Percutaneous
cholecystostomy

Evidence is limited on the balance of

risks and benefits of percutaneous
cholecystostomy. [80]

NICE guidelines suggest percutaneous

cholecystostomy in patients in whom it is
safer to avoid a general anaesthetic but the
infection is not resolving with conservative
measures (fluids and antibiotics).[4]

Two small trials included in a Cochrane

systematic review suggest that percutaneous
MANAGEMENT

cholecystostomy and early laparoscopic

cholecystectomy may reduce length of
hospital stay and costs, but the evidence
base is not robust.[80]

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Acute cholecystitis Management

Acute
• The review found two randomised
controlled trials (both at high risk
of bias) involving a total of 156
participants.[80]
• One trial involving 70 participants
compared percutaneous
cholecystostomy (within 8 hours of
referral to the surgeon) followed by
early laparoscopic cholecystectomy
(within 96 hours when patient
improved) versus delayed laparoscopic
cholecystectomy (8 weeks after the
symptoms settled).[81]

• It found a shorter length

of stay (mean difference
-9.90 days, 95% CI -12.31
to -7.49) and lower costs
(mean difference -1123 US
dollars, 95% CI -1336.60
to -909.40 US dollars) with
percutaneous cholecystostomy
followed by early laparoscopic
cholecystectomy. There was
no significant difference
between the groups in terms
of the numbers of participants
needing conversion to open
cholecystectomy, complications,
or mortality.[81]

• The other trial involving 86

participants compared percutaneous
cholecystostomy (within 24 hours of
referral) versus conservative treatment;
either could be followed if necessary
by delayed cholecystectomy (not
stated how many were laparoscopic or
converted to open operations).[82]

• It found no significant
difference between the
groups on the numbers
needing delayed laparoscopic
cholecystectomy.[82]

consider endoscopic ultrasound-guided gallbladder

drainage
MANAGEMENT

Treatment recommended for SOME patients in

selected patient group
» Recommended in patients where surgery is
unsuitable(either due to the risks involved or the

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 Acute cholecystitis Management

Acute
presence of other conditions which may make
surgery unsuitable).[57]

• The aim is to drain bile from the

gallbladder to avoid the need for
emergency cholecystectomy, though it is
a technically challenging procedure which
should only be done in specialist centres
by clinicians trained and experienced
in using this procedure for gallbladder
drainage.[57] [83] [84] [85] [86] A
disadvantage of the procedure when
compared to cholecystectomy is that
cholecystitis may reoccur.[57]

plus postoperative management

Treatment recommended for ALL patients in
selected patient group
» Provide simple analgesia, such as
paracetamol or a non-steroidal anti-inflammatory
drug, for postoperative pain; it is usually minimal.

» Ask about any nausea, vomiting, and

abdominal pain. Review the wound for
erythema, discharge, or pain.

• In a survey of patients followed up by

weekly telephone questionnaire for 6
weeks after laparoscopic cholecystectomy,
22% reported nausea and vomiting
continuing after hospital discharge, 11%
said postoperative pain was not controlled
by prescribed analgesia after hospital
discharge, and 70% reported wound-
related symptoms such as discharge.[88]

» Continue to assess for signs of jaundice.

» Plan for discharge. Advise patients that

they do not need to avoid any particular food or
drinks after having their gallbladder or gallstones
removed, but to seek further advice from
their general practitioner if eating or drinking
causes new symptoms to develop.[4] Liaise with
community colleagues to offer a care package
post discharge.
MANAGEMENT

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Acute cholecystitis Management

Emerging
Robotic cholecystectomy
There is some evidence that robotic cholecystectomy may decrease minor biliary injuries, open conversion
rates, and mean blood loss compared with laparoscopic cholecystectomy.[89] However, other studies have
not found any benefit in surgical outcomes with the robotic approach.[90]

Primary prevention
People at high risk of gallstones include:

• Patients (with a gallbladder in situ) who have undergone bariatric surgery and are experiencing rapid
weight loss[22]
• Those receiving parenteral nutrition
• Those using somatostatin long-term.

Primary prevention starts with preventing gallstones, which entails lifestyle modification: a diet high in
fibre and low in saturated fat, and maintenance of a normal body weight, coupled with moderate physical
activity.[23] [24] The evidence for a preventative effect of healthy lifestyle, diet, regular physical activity, and
maintenance of an ideal body weight, however, is weak.[25]

Preventative medical therapy employs ursodeoxycholic acid (UDCA) to lower cholesterol saturation in bile
and so lessen the short-term risk of stone formation in obese individuals undergoing rapid weight loss
through dietary caloric restriction or bariatric surgery.[22] UDCA has limited value for dissolving established
gallstones.[26] This agent is best reserved for the occasional non-surgical candidate with small gallstones
who is truly symptomatic.

Secondary prevention
Patients with symptomatic gallstones should be offered elective cholecystectomy to prevent development of
acute cholecystitis.

MANAGEMENT

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 Acute cholecystitis Follow up

Monitoring
Monitoring
FOLLOW UP

Patients who undergo cholecystectomy should be seen within 2 weeks after discharge from hospital.
Patients should be asked about presence or absence of nausea, vomiting, and abdominal pain, as well
as their ability to tolerate oral intake. The wound should be reviewed for erythema, discharge, or pain. In
addition any signs of jaundice should be noted; if such signs are present, the direct and indirect bilirubin
level should be determined and an abdominal ultrasound ordered.

In patients who have undergone percutaneous cholecystostomy, if no gallstones are present and
cholangiogram showed a patent cystic duct, the tube should be removed in 6 to 8 weeks.

Complications

Complications Timeframe Likelihood

suppurative cholecystitis short term medium

Thickened gallbladder wall with white cell infiltration, intra-wall abscesses, and necrosis. This may result in
perforation of the gallbladder and a pericholecystic abscess formation.[2]

bile duct injury due to surgery short term low

A rare complication of cholecystectomy. Therapy involves endoscopic stenting, percutaneous transhepatic

dilation, and surgical reconstruction. Early recognition and adequate multidisciplinary approach involving
specialists is the cornerstone for an optimal final outcome.

gallstone ileus short term low

Caused by a gallstone passing from the biliary tract into the intestinal tract (through a fistula), leading
to small-intestinal obstruction.[3] The gallstone grows during its passage. Treatment is with enterotomy
(proximal to the obstruction site because of the risk of closing compromised bowel) and stone extraction.
This is followed by cholecystectomy in an inflammatory-free interval 4 to 6 weeks later.

cholecystoenteric fistulas short term low

The most common sites for fistulas are the duodenum and the hepatic flexure of the colon.

Decompression of the gallbladder because of a fistula may cause resolution of the acute cholecystitis.[3]
[91]

Prognosis

Removing the gallbladder and the contained gallstones when biliary pain starts will prevent further biliary
attacks and reduce the risk of developing cholecystitis. If the gallbladder perforates, mortality is 30%.

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Acute cholecystitis Follow up
Untreated acute acalculous cholecystitis is life-threatening and is associated with up to 50% mortality.[3]

FOLLOW UP

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 Acute cholecystitis Guidelines

Diagnostic guidelines

United Kingdom

Gallstone disease: diagnosis and management

Published by: National Institute for Health and Care Excellence Last published: 2014

Europe

Surgeon-performed point-of-care ultrasound for acute cholecystitis:

indications and limitations
Published by: European Society for Trauma and Emergency Surgery Last published: 2020

North America
GUIDELINES

ACR appropriateness criteria: right upper quadrant pain

Published by: American College of Radiology Last published: 2022

ACR appropriateness criteria: jaundice

Published by: American College of Radiology Last published: 2018

ACR appropriateness criteria: acute (nonlocalized) abdominal pain

Published by: American College of Radiology Last published: 2018

ACR-SPR practice parameter for the performance of hepatobiliary

scintigraphy
Published by: American College of Radiology and Society for Pediatric Last published: 2021
Radiology

Asia

Tok yo guidelines 2018: diagnostic criteria and severity grading of acute

cholecystitis (with videos)
Published by: Tokyo Guidelines Revision Committee Last published: 2018

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Acute cholecystitis Guidelines

Treatment guidelines

United Kingdom

Pathway for the management of acute gallstone diseases

Published by: Association of Upper Gastrointestinal Surgery of Great Last published: 2015
Britain and Ireland

Gallstone disease: diagnosis and management

Published by: National Institute for Health and Care Excellence Last published: 2014

International

2020 World Society of Emergency Surgery updated guidelines for the

diagnosis and treatment of acute calculus cholecystitis

GUIDELINES
Published by: World Society of Emergency Surgery Last published: 2020

2017 WSES and SICG guidelines on acute calculous cholecystitis in elderly

population
Published by: World Society of Emergency Surgery; Italian Surgical Last published: 2017
Society for Elderly

North America

SAGES guidelines for the clinical application of laparoscopic biliary tract

surgery
Published by: Society of American Gastrointestinal and Endoscopic Last published: 2010
Surgeons

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 Acute cholecystitis Guidelines

Asia

Tok yo guidelines 2018: flowchart for the management of acute cholecystitis

Published by: Tokyo Guidelines Revision Committee Last published: 2018

Tok yo guidelines 2018: surgical management of acute cholecystitis: safe

steps in laparoscopic cholecystectomy for acute cholecystitis (with videos)
Published by: Tokyo Guidelines Revision Committee Last published: 2018

Tok yo guidelines 2018: management bundles for acute cholangitis and

cholecystitis
Published by: Tokyo Guidelines Revision Committee Last published: 2018

Tok yo Guidelines 2018: management strategies for gallbladder drainage in

patients with acute cholecystitis (with videos)
GUIDELINES

Published by: Tokyo Guidelines Revision Committee Last published: 2018

Tok yo guidelines 2018: antimicrobial therapy for acute cholangitis and

cholecystitis
Published by: Tokyo Guidelines Revision Committee Last published: 2018

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Acute cholecystitis Online resources

Online resources
1. NEWS2 (external link)

ONLINE RESOURCES

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 Acute cholecystitis References

Key articles
• Indar AA, Beckingham IJ. Acute cholecystitis. BMJ. 2002 Sep 21;325(7365):639-43. Full text
REFERENCES

Abstract

• National Institute for Health and Care Excellence. Gallstone disease: diagnosis and management.
October 2014 [internet publication]. Full text

• Association of Upper Gastrointestinal Surgeons. Pathway for the management of acute gallstone
diseases. September 2015 [internet publication]. Full text

• Yokoe M, Hata J, Takada T, et al. Tokyo guidelines 2018: diagnostic criteria and severity grading
of acute cholecystitis (with videos). J Hepatobiliary Pancreat Sci. 2018 Jan;25(1):41-54. Full text
Abstract

• Okamoto K, Suzuki K, Takada T, et al. Tokyo guidelines 2018: flowchart for the management of acute
cholecystitis. J Hepatobiliary Pancreat Sci. 2018 Jan;25(1):55-72. Full text Abstract

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3. Indar AA, Beckingham IJ. Acute cholecystitis. BMJ. 2002 Sep 21;325(7365):639-43. Full text
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Acute cholecystitis References
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 Acute cholecystitis References
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82 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Jul 23, 2024.
BMJ Best Practice topics are regularly updated and the most recent version
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Acute cholecystitis Images

Images

IMAGES
Figure 1: The biliary tree
Created by BMJ Publishing Group

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 Acute cholecystitis Images

Figure 2: Ultrasound of acute cholecystitis and presence of gallstones

From the collection of Dr Charles Bellows; used with permission
IMAGES

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Contributors:

// Expert Advisers:

John Abercrombie, FRCS

General and Colorectal Surgeon
Queen's Medical Centre, Nottingham, UK
DISCLOSURES: JA is a member of the Council of The Royal College of Surgeons of England and Clinical
Lead for General Surgery, Getting It Right First Time. JA provides expert advice regarding suitability of
surgical treatments for Spire Healthcare.

Acknowledgements,
BMJ Best Practice would like to gratefully acknowledge the previous expert contributor, whose work has
been retained in parts of the content:
Charles Bellows MD, Professor of Surgery, University of New Mexico School of Medicine, Albuquerque, NM
DISCLOSURES: CB is an author of one study referenced in this topic. CB declares that he has no other
competing interests.

// Peer Reviewers:

Christian Macutkiewicz, MD, FHEA, FRCS

Consultant General and Hepato-Pancreato-Biliary Surgeon
Clinical Lead for Emergency General Surgery, Gastrointestinal Medicine, and Surgery CSU, Manchester
Royal Infirmary, Manchester, Director of Scientific Programme, Association of Surgeons of Great Britain and
Ireland, UK
DISCLOSURES: CM declares that he has no competing interests.

// Editors:

Emma Quigley,
Section Editor, BMJ Best Practice
DISCLOSURES: EQ declares that she has no competing interests.

Sue#Mayor,
Lead Section Editor, BMJ Best Practice
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the company name under which she provides medical writing and communications services.
Tanna z Aliabadi-Oglesby,
Lead Section Editor, BMJ Best Practice
DISCLOSURES: TAO declares that she has no competing interests.

Julie Costello,
Comorbidities Editor, BMJ Best Practice
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Adam Mitchell,
Drug Editor, BMJ Best Practice
DISCLOSURES: AM declares that he has no competing interests.