Acalculous cholecystitis

INTRODUCTION — 

Acute acalculous cholecystitis is an acute necroinflammatory disease of the gallbladder with a multifactorial pathogenesis, occurring in the absence of gallstones. It accounts for approximately 10 percent of all cases of acute cholecystitis and is associated with high morbidity and mortality rates.

This topic will review the pathophysiology, clinical manifestations, diagnosis, and management of acute acalculous cholecystitis. Acute calculous cholecystitis is discussed separately. (See "Acute calculous cholecystitis: Clinical features and diagnosis" and "Treatment of acute calculous cholecystitis".)

“Chronic acalculous cholecystitis,” a previously used term for chronic, recurrent biliary colic in the absence of gallstones, is more accurately classified as pain related to gallbladder dysmotility and is discussed separately. (See "Functional gallbladder disorder in adults".)

PATHOGENESIS — 

The pathogenesis of acalculous cholecystitis is multifactorial and likely results from ischemia and cholestasis. The cystic artery, which supplies blood to the gallbladder, is a terminal artery and susceptible to ischemia. Ischemia and necrosis of the gallbladder wall can occur with hypoperfusion in cases of hypotension, vasoactive drug use, or major surgery and trauma [1]. Cholestasis may be seen in prolonged fasting states, usage of total parental nutrition, and ileus or bowel obstruction. Cholestasis results in increased pressure within the gallbladder and distension, further decreasing perfusion to the gallbladder wall. Pathologically, ischemia and cholestasis result in local inflammatory response in the gallbladder wall, epithelial injury, and eventually necrosis of the gallbladder tissue [1,2]. Once acalculous cholecystitis is established, secondary infection with enteric pathogens, including Escherichia coli, Enterococcus faecalis, Klebsiella spp, Pseudomonas spp, Proteus spp, and Bacteroides fragilis and related strains, is common [3]. Perforation occurs in severe cases [4,5]. (See 'Complications' below.)

The majority of patients with acalculous cholecystitis have multiple risk factors (table 1) [6-12]. In some cases, specific primary infections with non-enteric organisms predispose to acalculous cholecystitis (table 2). As an example, acalculous cholecystitis occurring in patients with acquired immunodeficiency syndrome (AIDS) and other immunosuppressed patients may be due to opportunistic infections such as microsporidia, Cryptosporidium, or cytomegalovirus [13]. More often, however, these infections cause a cholangiopathy without cholecystitis (see "AIDS cholangiopathy"). There is also association of acalculous cholecystitis with COVID-19, though it is unclear whether disease results from primary infection of the biliary system or critical illness [14]. (See "COVID-19: Gastrointestinal symptoms and complications", section on 'Acute cholecystitis'.)

EPIDEMIOLOGY — 

Acalculous cholecystitis is classically described in patients who are hospitalized and critically ill, though it has also been reported in outpatients with risk factors [15,16] (table 1). There is a male predominance, ranging from 64 to 82 percent [15,17,18].

Acalculous cholecystitis has been reported in 0.7 to 0.9 percent of patients following open abdominal aortic reconstruction, in 0.5 percent of patients following cardiac surgery, and in as many as 4 percent of patients who have undergone bone marrow transplantation [9,17,19-21].

While acalculous cholecystitis is classically associated with critical illness, it is also seen in outpatients [16,22]. In one of the largest single center reports, 36 of 47 patients (77 percent) diagnosed with acalculous cholecystitis identified over a seven-year period developed symptoms at home, without evidence of acute illness or trauma [16]. Significant vascular disease was observed in 72 percent of these patients.

CLINICAL MANIFESTATIONS

Clinical presentation — The clinical presentation of acalculous cholecystitis varies based on the severity of illness and underlying predisposing conditions (table 1). In general, symptoms and signs can be similar to those seen in calculous cholecystitis. (See "Acute calculous cholecystitis: Clinical features and diagnosis", section on 'Clinical manifestations'.)

Symptoms — Common symptoms include fever and right upper quadrant pain [2]. Less common symptoms include epigastric and diffuse abdominal pain as well as nausea and vomiting [16]. In the critically ill population, the appearance of unexplained fever may be the only symptom.

Signs — Physical examination may reveal tenderness to palpation in the right upper quadrant, positive Murphy's sign (pain and inspiratory arrest during inspiratory effort, while pressure is applied to the gallbladder fossa) or palpable right upper quadrant mass. Rarely, jaundice may be present [16,22,23].

Because the presentation may be insidious, patients may also have sepsis, shock, and peritonitis at presentation due to complications including gallbladder necrosis, emphysematous cholecystitis, or gallbladder perforation. Patients with emphysematous cholecystitis may have crepitus of the right upper quadrant. (See 'Complications' below.)

Laboratory findings — Laboratory findings are neither sensitive nor specific, and thus cannot be used in isolation to rule out or rule in the diagnosis. Findings include leukocytosis, which is present in 70 to 96 percent of patients, and elevations in serum aminotransferases, alkaline phosphatase, and direct bilirubin [2,16,24,25]. The elevation of alkaline phosphatase and direct bilirubin may be nonspecific and related to critical illness. (See "Acute calculous cholecystitis: Clinical features and diagnosis", section on 'Laboratory findings' and "Approach to the patient with abnormal liver tests".)

Complications — Similar to patients with acute calculous cholecystitis, complications of acalculous cholecystitis include gallbladder necrosis, emphysematous cholecystitis (image 1), and gallbladder perforation [6,23]. Gallbladder necrosis develops in approximately 50 percent of patients with acalculous cholecystitis and can result in gallbladder perforation [25]. Emphysematous cholecystitis, in particular, puts patients at risk for perforation. Overall, perforation occurs in approximately 10 percent of patients with acalculous cholecystitis [20].

Perforation may result in a cholecystoenteric fistula, abscess formation, or free perforation with generalized peritonitis. In patients with necrosis without perforation, complications may include acute pancreatitis and obstruction of the common hepatic duct. Extrinsic compression of the common bile duct by a phlegmon (Mirizzi-type syndrome) can also occur [26]. These complications are discussed in detail separately. (See "Acute calculous cholecystitis: Clinical features and diagnosis", section on 'Complications' and "Mirizzi syndrome".)

Patients with complicated cholecystitis can only be treated with cholecystectomy, as a gallbladder drainage procedure relies on an intact gallbladder wall enclosure, which a threatened or compromised gallbladder does not provide. (See 'Procedural/surgical management' below.)

DIAGNOSTIC APPROACH

Clinical suspicion — Acalculous cholecystitis should be suspected in critically ill patients with sepsis or jaundice without a clear source, and in patients with unexplained postoperative jaundice. It may also be considered in outpatients with right upper quadrant pain or fever in the absence of gallstone-related disease or other explanatory diagnoses.

A diagnosis of acalculous cholecystitis can be challenging to make due to lack of sensitive or specific laboratory and imaging findings, and the diagnosis rests on overall clinical gestalt with suggestive imaging findings [24]. It is important to maintain a high index of suspicion and judiciously order imaging in at-risk patients with suggestive clinical features. (See 'Diagnosis' below and "Classification and causes of jaundice or asymptomatic hyperbilirubinemia", section on 'Disorders associated with conjugated hyperbilirubinemia' and "Approach to the patient with postoperative jaundice", section on 'Acalculous cholecystitis'.)

Laboratory evaluation — A complete blood count, basic metabolic panel, hepatic function panel, and lipase should be obtained. In addition, we perform a urine analysis to look for evidence of urinary tract infection, and a chest radiograph to evaluate for pneumonia. Blood cultures should be obtained in all patients with suspected acalculous cholecystitis. Culture results can guide narrowing of empiric antibiotics. (See 'Antibiotics' below and "Antimicrobial approach to intra-abdominal infections in adults", section on 'Assessment of culture data'.)

Imaging — Imaging in acalculous cholecystitis is not specific enough to make the diagnosis alone. Imaging findings must be interpreted in the context of the clinical presentation. (See 'Diagnosis' below.)

Ultrasonography — We perform abdominal imaging with an ultrasonography as a first-line test in patients with suspected acalculous cholecystitis (algorithm 1) [3,23,27,28]. Ultrasonography is rapid, noninvasive, and can be performed at the bedside in critically ill patients. Radiologic features suggestive of acalculous cholecystitis include:

●3.5- to 4-mm (or more) thick wall (if the gallbladder is distended to at least 5-cm longitudinally and the patient has no ascites or hypoalbuminemia)

●Sonographic Murphy's sign, defined as the presence of maximal tenderness elicited over a sonographically localized gallbladder (may be absent in the setting of analgesic administration)

●Pericholecystic fluid

●Gallbladder wall edema  

●Absence of gallstones or sludge (echogenic bile, which is the equivalent of gallstone disease)

Other imaging findings in patients with acalculous cholecystitis include (image 2):

●Intramural gas

●Sloughed wall membranes

●Distended gallbladder (distension greater than 8 cm longitudinally or 5 cm transversely, with anechoic fluid)

The reported sensitivity of ultrasound for acalculous cholecystitis is variable and ranges from 30 to 92 percent [2,25,29]. The specificity of ultrasound for acalculous cholecystitis ranges from 89 to 100 percent. The variance in sensitivity and specificity measurements are due to overall rarity of the condition and use of different criteria for sonographic diagnosis from small, mostly retrospective studies. In one prospective study, an ultrasound with abnormal findings, in addition to clinical suspicion for acalculous cholecystitis, had 100 percent specificity for the diagnosis [30]. Thickening of the gallbladder wall has been regarded as an important feature in the diagnosis of acalculous cholecystitis, with a sensitivity of 80 percent and specificity of 98.5 percent at 3.5 mm thickness in some reports [25]. Sonographic Murphy's sign is operator-dependent and requires an alert and cooperative patient, but, when present, is indicative of gallbladder inflammation.

However, gallbladder abnormalities can be seen in a significant number of critically ill patients, in the absence of acalculous cholecystitis. In one study of 44 critically ill patients, at least one sonographic abnormality suggestive of the diagnosis was detected in 37 patients (84 percent) and up to three sonographic abnormalities were detected in 25 (57 percent). However, only two patients had acalculous cholecystitis [31]. The low specificity observed may be explained by the study cohort, which had a relatively low pretest probability. False-positive ultrasound results may be due to hypoalbuminemia, ascites, sludge, non-shadowing stones, or cholesterolosis, which can mimic a thickened gallbladder wall.

In equivocal cases in critically ill patients, we find that serial ultrasounds can be helpful to evaluate for stability or worsening findings [2,32].    

Computed tomography — In patients in whom the diagnosis remains uncertain after ultrasonography or with concern for other abdominopelvic pathology in the setting of acute illness, we obtain a contrast-enhanced abdominal/pelvic computed tomography (CT) scan for evidence of acute acalculous cholecystitis or alternate diagnoses. CT scan has greater sensitivity than ultrasound in cases of calculous cholecystitis, though specificity appears to be similar in acalculous cholecystitis [33-35]. CT scan findings are similar to ultrasound and include (image 3) [25]:

●Gallbladder wall thickening (>3 mm) and hyperenhancement

●Subserosal edema

●Pericholecystic fluid (in the absence of ascites or hypoalbuminemia) and stranding

●Intramural gas

●Wall sloughing

●Mucosal hyperenhancement

●Absence of gallstones or sludge (equivalent to gallstone disease); however, 25 to 35 percent of gallstones are isodense to bile, precluding their visualization, and CT cannot confirm the absence of gallstones [36]

●Gallbladder distention (>5 cm)

●Hyperemia in the adjacent liver

As with ultrasound, CT gallbladder abnormalities are highly prevalent in general critically ill patients, and in one retrospective study of 127 medical and surgical intensive care unit patients, presence of any abnormal finding of the gallbladder was present in 96 percent of all patients [37]. Thus, imaging findings must be interpreted in the context of the clinical presentation. CT exceeds in its negative predictive value, as the absence of CT findings will help rule out acalculous cholecystitis.      

CT findings of gangrenous cholecystitis include focal transmural defects in the wall, sloughing of wall into the lumen, and perforation of the wall with adjacent collections [36]. Emphysematous cholecystitis, another complication, presents with air in the gallbladder wall [38].

Cholescintigraphy — In hemodynamically stable patients in whom the diagnosis is unclear after ultrasonography and abdominal CT scan, but clinical suspicion remains high, we perform cholescintigraphy with a hepatic iminodiacetic acid (HIDA) scan [39]. However, in critically ill patients, HIDA is almost never performed and not recommended, due to the length of time required (hours), which may delay therapy and interfere with continuous monitoring.

Technetium labeled (Tc^99m) HIDA is injected intravenously and is then taken up selectively by hepatocytes and excreted into bile. In a normal gallbladder, the cystic duct is patent, allowing the tracer to enter the gallbladder. Visualization of contrast within the common bile duct, gallbladder, and small bowel typically occurs within 30 to 60 minutes. Failure to opacify the gallbladder at one hour is abnormal and a positive test. While the cystic duct is not obstructed by stones in acalculous cholecystitis, duct mucosal edema and biliary stasis, ischemia, and low cholecystokinin levels lead to improper gallbladder emptying, and inability to fill with the radiotracer [2,40].  

The sensitivity of cholescintigraphy for acalculous cholecystitis ranges from 67 to 100 percent, while specificity ranges from 38 to 88 percent [2,41]. False negatives include cases of patent cystic ducts despite gallbladder inflammation or misidentification of a bowel loop (or bile leak) as normal gallbladder. False positives can be seen in severe hepatic dysfunction decreasing radiotracer uptake and excretion, severe illness limiting gallbladder function, use of total parenteral nutrition limiting gallbladder stimulation, or the presence of biliary sphincterotomy resulting in low resistance outflow into bowel.

Diagnosis — The diagnosis of acalculous cholecystitis is based upon a constellation of symptoms and signs (eg, critically ill patients with jaundice and/or sepsis without a clear source) in the setting of supportive imaging findings and the exclusion of alternative diagnoses. Imaging findings alone do not make the diagnosis and must be interpreted in the context of the clinical presentation.

While there are no formal diagnostic criteria, the diagnosis of acalculous cholecystitis is often made in patients with all of the following:

●Fever, abdominal pain, leukocytosis and/or elevated liver tests (see 'Clinical manifestations' above)

●Risk factors for acalculous cholecystitis (table 1)

●Radiologic features suggestive of acalculous cholecystitis (eg, gallbladder wall thickening, sonographic Murphy’s sign, pericholecystic fluid) (see 'Imaging' above)

●No evidence of other conditions that could elicit the clinical and radiographic findings

DIFFERENTIAL DIAGNOSIS — 

The differential diagnosis of acalculous cholecystitis includes other causes of sepsis (eg, calculous cholecystitis, cholangitis, urinary tract infection) or conditions presenting with right upper quadrant pain and/or jaundice. These include:

●Acute calculous cholecystitis

●Ascending cholangitis

●Acute pancreatitis

●Hepatic or subphrenic abscess

●Right-sided pyelonephritis

These conditions can be ruled out by clinical examination, laboratory tests, and imaging (eg, abdominal CT scan) performed as part of the evaluation in patients with suspected acalculous cholecystitis. (See 'Clinical suspicion' above and 'Diagnostic approach' above.)

The clinical features and diagnosis of these conditions are discussed separately:

●(See "Acute calculous cholecystitis: Clinical features and diagnosis".)

●(See "Acute cholangitis: Clinical manifestations, diagnosis, and management".)

●(See "Clinical manifestations, diagnosis, and natural history of acute pancreatitis".)

●(See "Acute complicated urinary tract infection (including pyelonephritis) in adults".)

●(See "Pyogenic liver abscess".)

MANAGEMENT — 

The management of acute acalculous cholecystitis starts with resuscitation and general supportive care (as patients are typically medically ill), as well as broad-spectrum intravenous antibiotics. Patients with complicated cholecystitis require urgent cholecystectomy as soon as they are adequately resuscitated. Patients with uncomplicated cholecystitis can be monitored for 24 to 48 hours. Those who do not improve clinically require procedural/surgical management. Suitable surgical candidates can choose between cholecystectomy and gallbladder drainage. Non-surgical candidates can only undergo gallbladder drainage. Patients who undergo gallbladder drainage also require follow-up care to determine the necessity of cholecystectomy before the drainage catheter is removed (algorithm 2).

Supportive care — Patients diagnosed with acalculous cholecystitis require inpatient management, and based on their hemodynamic status, may need monitored or intensive care unit support. Supportive care includes:

●Close monitoring of hemodynamic status.

●Intravenous hydration and correction of any associated electrolyte disorders. (See "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Intravenous fluids (first three hours)'.)

●Patients should be kept fasting until clinical stability is ensured and definitive plan for management is created. Those with nausea and vomiting should have placement of a nasogastric tube.

●Pain control in patients can usually be achieved with nonsteroidal anti-inflammatory drugs or opioids. Progression of pain during treatment for acute cholecystitis, despite adequate analgesia, is an indicator of a clinical progression.

Antibiotics — After blood cultures are obtained, intravenous broad-spectrum antibiotics should be started. Acute cholecystitis is primarily an inflammatory process, but secondary infection of the gallbladder commonly occurs as a result of cystic duct obstruction and bile stasis.

The choice of antibiotics should take into consideration whether the infection is community-acquired versus healthcare-associated and individual risk factors for adverse outcomes and infection with antibiotic-resistant bacteria (table 3). We recommend the following antibiotic regimens for patients with acute cholecystitis based on their individual risk category [42]:

●For patients with healthcare-associated acute cholecystitis (table 4).

●For patients with high-risk community-acquired acute cholecystitis (table 5).

●For patients with low-risk community-acquired acute cholecystitis (table 6).

Given that acalculous cholecystitis tends to occur in hospitalized patients who are acutely ill [43-45], many will have healthcare-associated acute cholecystitis.

The chosen antimicrobial agents should subsequently be tailored to culture and susceptibility results when they become available. The duration of antibiotics depends on the adequacy of infection source control and the clinical stability of the patient. Antibiotic therapy for intra-abdominal infections, including acute cholecystitis and the duration of therapy, are discussed in detail elsewhere. (See "Antimicrobial approach to intra-abdominal infections in adults", section on 'Empiric antimicrobial therapy'.)

Procedural/surgical management — Procedural or surgical gallbladder treatment consists of either gallbladder drainage (percutaneous or endoscopic) or cholecystectomy (open or laparoscopic), one of which is required in patients with either complicated cholecystitis or uncomplicated cholecystitis refractory to antibiotic therapy (algorithm 2):

●Patients with complicated cholecystitis, in which the integrity of the gallbladder is compromised or threatened, can only be treated with cholecystectomy. Whether open or laparoscopic surgery is performed will depend on whether the patient’s hemodynamics can tolerate pneumoperitoneum. Complications that would require an emergency cholecystectomy include:

•Gallbladder necrosis

•Emphysematous cholecystitis

•Gallbladder perforation

●Patients with uncomplicated cholecystitis may or may not require procedural/surgical gallbladder treatment as some studies have reported treating acalculous cholecystitis with antibiotics alone [46]. Patients who respond to antibiotics generally improve within 24 to 48 hours. In nonresponders, we then pursue procedural/surgical management.  

•Patients who cannot tolerate surgery (eg, critically ill) should be treated with gallbladder drainage. For such patients, gallbladder drainage is the only available option. In multiple retrospective series of acalculous cholecystitis, gallbladder drainage is safer and associated with better outcomes than open cholecystectomy [47-50].

•Patients who are stable enough to tolerate surgery can be treated with either laparoscopic cholecystectomy or gallbladder drainage. The decision should be made based on available local expertise and patient preference. Existing literature on this subject consists of either single-institution retrospective series [47,48] or large administrative database reviews [49,51], neither of which can be relied upon to make a definitive recommendation [52].

Although laparoscopic cholecystectomy is generally preferred over gallbladder drainage for patients with acute calculous cholecystitis, it assumes that all patients will eventually require cholecystectomy for gallstones. However, due to the low recurrence rate in true acalculous cholecystitis, gallbladder drainage can be a definitive treatment. Therefore, it is a reasonable option for patients who prefer to avoid surgery, even if they are suitable candidates for laparoscopic cholecystectomy.

Drainage of the gallbladder can be performed under radiologic guidance via a percutaneous cholecystostomy tube. Endoscopic gallbladder drainage is reserved for patients in whom percutaneous approaches are contraindicated, or are not anatomically feasible (ie, advanced liver disease, ascites, or coagulopathy). (See "Treatment of acute calculous cholecystitis", section on 'Gallbladder drainage'.)

Patients with acalculous cholecystitis treated with cholecystostomy should improve rapidly (within 24 hours). Failure to improve (defined as persistent fever, signs of sepsis, or evidence of new multiorgan dysfunction) may be due to gangrenous cholecystitis, catheter dislodgement, bile leakage resulting in peritonitis, or an incorrect diagnosis of acalculous cholecystitis. If patient deterioration is attributed to refractory cholecystitis, rescue cholecystectomy is required or else the prognosis is dismal.

Follow-up care — Once the episode of acalculous cholecystitis has resolved, patients treated by gallbladder drainage should undergo a tube study to evaluate for cystic duct patency before drain removal (algorithm 2).

●If the cystic duct is occluded, elective cholecystectomy should be performed in suitable surgical candidates. The cholecystostomy tube should be left in place until the cholecystectomy. Nonsurgical candidates with an occluded cystic duct are treated with either long-term tube drainage of the gallbladder or medical therapy for any recurrent cholecystitis after the tube is removed.  

●If the cystic duct is patent, the cholecystostomy tube can be removed when there is minimal drainage (less than 10 cc per day). This is typically four to six weeks after cholecystostomy tube placement. Following that, because the recurrence rate is low (1.8 to 7 percent [46,47,53-55]), and patients are generally high-risk, interval cholecystectomy is typically not required [46,56,57].

PROGNOSIS — 

Acalculous cholecystitis is associated with a high mortality rate due to sepsis and multiorgan system failure. Mortality in patients with acalculous cholecystitis depends upon coexistent medical or surgical conditions and the timeliness of diagnosis and management.

Gallbladder necrosis, or perforation are frequently present at the time of diagnosis, particularly in the critically ill, and are associated with poor outcomes [6,23]. The mortality rate can be as high as 90 percent in critically ill patients or as low as 10 percent in community-acquired cases [23,58]. Overall, the mortality rate is approximately 30 percent, which in part reflects the fact that acalculous cholecystitis typically develops in patients who are already critically ill [25]. If treatment is delayed, mortality rates may be as high as 75 percent [59,60]. The cause of death in most patients with acalculous cholecystitis is sepsis with multiorgan failure [61].

Success rates for cholecystostomy range from 56 to 100 percent [47,56,57,62-71]. Complications include hemorrhage, sepsis, bile peritonitis, pneumothorax, intestinal perforation, secondary infection of the gallbladder, and catheter dislodgement [25,66,67,72,73].

Timely cholecystectomy has been associated with survival rates of greater than 90 percent in patients with acute acalculous cholecystitis related to trauma, although lower survival rates would be expected in patients who develop acalculous cholecystitis in the setting of a critical illness [59].

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cholecystitis and other gallbladder disorders".)

SUMMARY AND RECOMMENDATIONS

●Pathogenesis and epidemiology – Acalculous cholecystitis is an acute necroinflammatory disease of the gallbladder with a multifactorial pathogenesis related to ischemia and cholestasis. It accounts for approximately 10 percent of all acute cholecystitis cases and is associated with high morbidity and mortality. Acalculous cholecystitis is classically described in critically ill patients, but has also been reported in outpatients with risk factors (table 1). (See 'Pathogenesis' above and 'Epidemiology' above.)

●Clinical manifestations – Symptoms include fever, right upper quadrant pain, and nausea and vomiting. Physical examination signs include right upper quadrant tenderness, positive Murphy’s sign, or jaundice. Laboratory findings include leukocytosis and elevations in serum aminotransferases, alkaline phosphatase, and direct bilirubin. (See 'Clinical manifestations' above.)

●Clinical suspicion – Acalculous cholecystitis should be suspected in critically ill patients with sepsis or jaundice without a clear source, and in patients with unexplained postoperative jaundice. It may also be considered in outpatients with right upper quadrant pain or fever in the absence of gallstone-related disease or other explanatory diagnoses. (See 'Clinical suspicion' above.)

●Approach to imaging – We perform abdominal imaging with ultrasonography as a first-line test in patients with suspected acalculous cholecystitis. In patients in whom the diagnosis remains uncertain after ultrasonography or with concern for other abdominopelvic pathology in the setting of acute illness, we obtain a contrast-enhanced abdominal/pelvic computed tomography (CT) scan. In hemodynamically stable patients in whom we still have high clinical suspicion for acalculous cholecystitis, after nondiagnostic ultrasonography and abdominal CT scan, we perform a hepatic iminodiacetic acid (HIDA) scan. (See 'Imaging' above.)

●Diagnosis – The diagnosis of acute acalculous cholecystitis is based on a constellation of symptoms and signs in the setting of supportive imaging findings and the exclusion of alternative diagnoses. The diagnosis of acute acalculous cholecystitis is often made in patients with all of the following (see 'Diagnosis' above):

•Fever, abdominal pain, leukocytosis, and/or elevated liver tests

•Risk factors for acute acalculous cholecystitis (table 1)

•Radiologic features suggestive of acalculous cholecystitis

•No evidence of other conditions that could explain the clinical and radiographic findings

●Management – The management of acute acalculous cholecystitis starts with resuscitation, supportive care (as patients are typically medically ill), and broad-spectrum intravenous antibiotics. Patients with either complicated cholecystitis or uncomplicated cholecystitis refractory to antibiotic therapy require procedural or surgical management (algorithm 2).

•Supportive care – Patients with acalculous cholecystitis require supportive care with intravenous fluids, correction of electrolyte abnormalities, bowel rest, and pain control. (See 'Supportive care' above.)

•Antibiotics – For most patients with acute acalculous cholecystitis, we recommend antibiotics (Grade 1B). Secondary infections are common and carry a high mortality rate due to sepsis and multiorgan system failure. Antibiotic therapy should be initiated as soon as blood cultures have been drawn, and the choice of agents should take into consideration whether the infection is healthcare-associated versus community-acquired, individual risk factors for infection with resistant bacteria, and risk for adverse outcomes (see 'Antibiotics' above):

-For patients with healthcare-associated acute cholecystitis (table 4).

-For patients with high-risk community-acquired acute cholecystitis (table 5).

-For patients with low-risk community-acquired acute cholecystitis (table 6).

•Procedural or surgical management – Procedural or surgical gallbladder treatment consists of either gallbladder drainage (percutaneous or endoscopic) or cholecystectomy (open or laparoscopic), one of which is required in patients with either complicated cholecystitis or uncomplicated cholecystitis refractory to antibiotic therapy (see 'Procedural/surgical management' above):

-Patients with complicated cholecystitis – Patients with complicated cholecystitis (eg, gallbladder necrosis, emphysematous cholecystitis, gallbladder perforation), in which the integrity of the gallbladder is compromised or threatened, can only be treated with cholecystectomy.

-Patients with uncomplicated cholecystitis – Patients with uncomplicated acalculous cholecystitis who do not improve clinically after 24 to 48 hours of supportive care and antibiotics require procedural/surgical management. Nonsurgical candidates (eg, critically ill patients) should be treated with gallbladder drainage, whereas surgical candidates can choose between gallbladder drainage and laparoscopic cholecystectomy.

•Follow-up care after gallbladder drainage – Once the episode of acalculous cholecystitis has resolved, patients treated by gallbladder drainage should undergo a tube study to evaluate for cystic duct patency. If the cystic duct is occluded, elective cholecystectomy should be performed in suitable surgical candidates. If the cystic duct is patent, interval cholecystectomy is typically not required, and the cholecystostomy tube can be removed when there is minimal drainage. (See 'Follow-up care' above.)

●Prognosis – Acalculous cholecystitis is associated with a high mortality rate due to sepsis and multiorgan system failure. Mortality in patients with acalculous cholecystitis depends upon coexistent medical or surgical conditions and the rapidity of diagnosis. The risk of recurrent cholecystitis appears to be low among those treated with cholecystostomy drainage. (See 'Prognosis' above.)