Cholecystitis (Acute, Acalculous, Suspected)

Acute acalculous cholecystitis (AAC) is a life-threatening disease that typically affects the critical ill 1, 2

It accounts for approximately 10% of cases of acute cholecystitis but has a higher morbidity and mortality than cholecystitis caused by gallstones. Mortality rates have been estimated to be 30-50% 1-4

AAC is thought to result from bile stasis and/or gallbladder ischaemia-reperfusion.  Pathological subtypes include simple cholecystitis acute suppurative cholecystitis, gangrenous cholecystitis and GB perforation 5, Hypomotility and increased bile viscosity may lead to increased intraluminal pressures in the gallbladder wall causing ischaemia, inflammation and necrosis. Hypotension, microvascular disease, and hypoperfusion leading to gallbladder ischaemia have been implicated as other contributing factors in critically ill patients. Bacterial colonisation and gallbladder infection can ensue 1, 2, 4, 6, 7

AAC is more frequently seen in patients following: 3, 4, 7, 8

A number of comorbidities also place patients at higher risk, including: 1

Although typically seen in hospitalised and critically ill patients, AAC is sometimes also seen in patients from home without evidence of acute illness or trauma 2

A high index of suspicion is needed for early recognition of AAC to reduce the risk of gallbladder gangrene, perforation, empyema and sepsis 1-4, 7, 10, 11

However, diagnosis is often difficult because clinical and investigation findings are non-specific, and the majority of patients are critically ill and unable to communicate their symptoms 1-4, 11-13

Ultrasound, CT, and cholescintigraphy can aid in the diagnosis, however, controversy exists as to which imaging modality is best and in which order they should be performed 4, 7

Although imaging can aid in diagnosis, critically ill patients frequently have gallbladder abnormalities seen on imaging in the absence of cholecystitis. This is thought to be a manifestation of systemic illness associated with multi-organ dysfunction. 14 Differentiating patients with true AAC requiring treatment from those with abnormal gallbladder findings without AAC remains an ongoing diagnostic and management dilemma 14

Treatment involves antibiotics and source control – either with percutaneous cholecystostomy and/or cholecystectomy 1

AAC carries a high risk of complications such as gangrenous cholecystitis, GB perforation and GB empyema 15

AAC has a high mortality especially with delayed diagnosis 15

Ultrasound (US) is generally considered the best initial imaging modality, partly because it is relatively quick, non-invasive, and can be performed at the bedside 10, 11, 14, 16

Reported sensitivity and specificity of US for diagnosis of AAC ranges between 30-92% and 89-100% respectively 4, 11, 12

Sonographic findings in AAC include: 1, 4, 11

However, critically ill patients will often have abnormal US findings in the absence of AAC. This is sometimes due to hypoalbuminaemia or ascites 1, 11, 13

Boland et al. performed US in 44 ICU patients and found that 84% had at least one sonographic abnormality, and 57% of patients had up to three abnormalities. Of the patients studied, only two patients were confirmed to have AAC 13

Typically involves administration of intravenous antibiotics and source control with percutaneous cholecystostomy (PC) and/or cholecystectomy 1, 3, 20, 21

Although a cholecystectomy would be the treatment of choice, PC is often used because patients are in a critical condition and may be considered too unstable to undergo surgery with a general anaesthesia 1-3, 22

PC is less invasive and can be performed under local anaesthetic at the bedside. It is associated with lower complication rates than urgent cholecystectomy. It is also possible to perform diagnostic cholangiography to assess the biliary tree, and can act as an access for biliary tree intervention 8

Deciding between PC or surgery depends on the patient’s health status, disease stage, and the availability of equipment and expertise 23

Generally it is recommended that: 3, 20, 21, 24, 25

One study of 1,725 cases found that in very ill patients, PC is associated with lower morbidity, fewer ICU admissions, decreased length of hospital stay and lower costs compared with open cholecystectomy 24

Traditionally, PC has been used as a bridging treatment, delaying the need for cholecystectomy until the patient is more stable. However, there is now significant evidence supporting PC as a definitive treatment, and several studies have demonstrated that the majority of patients with AAC do not require subsequent cholecystectomy. This is particularly useful because many patients with AAC will remain high risk surgical candidates 1, 22, 26-30

A study by Noh et al. who examined outcomes in 271 patients who had a PC for AAC found that PC had a good outcome in 86.7% of patients within four days. Only two patients (2.3%) who did not undergo planned interval cholecystectomy experienced a recurrence of cholecystitis within 8 years. 27 They concluded that, given the good outcomes and low recurrence rate, PC can be a definitive treatment option in the majority of patients with AAC 27

A systematic review by Soria-Aledo et al. recommended PC as the first line treatment for patients with AAC, except in cases with perforation or gangrene. In patients with low surgical risk, both cholecystectomy and cholecystostomy are effective treatment options. Based on the reviewed studies, they found that PC can be a definitive therapy with no need for subsequent elective cholecystectomy 23

Alternatives to PC are: Endoscopic Transpapillary GB drainage (performed at Endoscopic Retrograde Cholangiography) and Endoscopic Ultrasound-guided GB drainage 5.

CT has similar diagnostic accuracy to US but may be preferred when other thoracic or abdominal diagnoses are being considered 11, 14, 16

CT may show a higher frequency of gallbladder abnormalities in critically ill patients compared to US  but is frequently non-specific 1, 16, 17.

CT findings suggestive of AAC are similar to US and include: 4

In addition, CT with IV contrast may show liver hyperaemia adjacent to the gallbladder 17

In one retrospective study, 95% of critically ill patients had one or more abnormal gallbladder finding(s) on CT. 9 out of 43 cases with presumed AAC had a necrotic gallbladder on post-cholecystectomy pathology 1, 14

Absence of abnormal gallbladder findings on CT, however, has a very good negative predictive value 1, 14

Cholescintigraphy is a relatively sensitive imaging modality for detecting AAC, however, it is generally not as readily available as US or CT, and has a relatively long acquisition time; making it inappropriate for the majority of patients 11, 14

It is generally reserved for patients in whom screening ultrasound is equivocal but there is still high clinical suspicion for AAC 11. However, it is often not suitable for critically ill patients because of the duration of the examination.

Cholescintigraphy involves injecting radiolabelled technetium which is attached to hepatic iminodiacetic acid (HIDA). This is taken up by the liver and excreted in bile. In a normal gallbladder, high tracer activity is detected in the gallbladder 60 minutes from the time of administration 18.

HIDA scan criteria for cholecystitis includes: 4

Reported sensitivity and specificity for the detection of AAC ranges between 67-100% and 58-88% respectively 1, 12, 19

False negatives can occur from: 11, 18

False positives can occur from: 11

Some centres use cholecystokinin (CCK) to aid in diagnosis, particularly in patients with chronic acalculous cholecystitis or functional gallbladder disease. The radiolabelled technetium is given followed by CCK one hour later. CCK causes the gallbladder to contract and the percentage of gallbladder emptying can be calculated (the amount of radioactivity in the gallbladder is directly proportional to the volume of the gallbladder) 1, 18

An ejection fraction of less than 35% is indicative of gallbladder dysfunction and can be seen in AAC 1

HIDA-CCK can take hours to perform, however, and is therefore only appropriate in some patients 1

A comparison study by Mariat et al. compared US to morphine cholescintigraphy (MC) and found that MC was superior to US for confirming AAC in critically ill patients. However they concluded that, given that US is relatively easy and non-invasive, it is an effective method of bedside screening. If required, the combination of both imaging modalities can improve diagnostic accuracy 19

Percutaneous cholecystostomy has been used as a “diagnostic challenge” or therapeutic trial in patients in whom the diagnosis of AAC remains difficult after non-invasive tests.15, 31

MRCP is rarely feasible in critically ill patients with suspected AAC due to the severity of their condition and co-morbidities.

However, MRCP may be useful in investigating patients in whom US is negative or non-specific , and in those with cholestatic liver function tests; it may show stones in the GB neck, cholecystic duct or common duct 17.