AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

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Background

Emphysematous cholecystitis is an acute infection of the gallbladder wall caused by gas-forming organisms. First described by Stoltz in 1901, it was thought to be a rare disorder. However, as a result of improved imaging techniques, it is now being described with increasing frequency.

Pathophysiology

Four pathogenetic factors are proposed in the development of emphysematous cholecystitis.

Vascular compromise of the gallbladder

In most cases, the cystic artery is the sole arterial supply of the gallbladder. Occlusion or stenosis results in compromised viability of the gallbladder. Arteriosclerosis is the usual causative abnormality, although the condition has been described after an embolic event. The evidence that vascular insufficiency is a root cause of emphysematous cholecystitis is circumstantial, that is, association with diabetes mellitus, greater incidence in males, high frequency of gangrene, and occurrence in older patients. However, exceptions exist for each of these.

Gallstones

Gallstones are observed in 28-80% of patients with emphysematous cholecystitis. Impaction of stones in the cystic duct leads to localized edema of the wall, which contributes to the vascular compromise of the gallbladder. Nevertheless, emphysematous cholecystitis in the presence of acalculous cholecystitis is well established. Indeed, the proportion of patients with acalculous cholecystitis in association with emphysematous cholecystitis exceeds that of patients with ordinary acute calculous cholecystitis. These observations raise doubt about the role of gallstones in the pathogenesis of emphysematous cholecystitis.^{1, 2}

Impaired immune protection

Diabetes mellitus is detected in 38-55% patients with emphysematous cholecystitis, and the mean age of patients is 59 years. Both metabolic abnormality and older age probably contribute to the increased risk of infection.

Infection with gas-forming organisms

Microorganisms commonly isolated are clostridial species, Escherichia coli, and Klebsiella species. Less frequently, enterococci and anaerobic streptococci are among the other organisms detected. While the intramural gas observed in patients with emphysematous cholecystitis seems to result from gas-forming bacteria, whether these bacteria represent the primary cause of the disorder or are secondary invaders remains unclear. Concomitant emphysematous cholecystitis and emphysematous pyelonephritis raise the possibility of septic seeding of the gallbladder wall.

Rare associations

Cases have been reported following endoscopic retrograde cholangiopancreatography (ERCP) and following the use of sunitinib in the treatment of gastrointestinal stromal tumor (GIST).

See related CME at New Guidelines Address Management of Common Bile Duct Stones.

Frequency

United States

Emphysematous cholecystitis occurs infrequently. Reports in the surgical literature indicate that emphysematous cholecystitis develops in approximately 1% of all cases of acute cholecystitis. 

An estimated 500,000 cholecystectomies are performed per year in the United States. Assuming all patients with emphysematous cholecystitis come to surgery, this would indicate that 5000 cholecystectomies are performed per year for emphysematous cholecystitis. While the number of patients who are treated successfully without surgery is certainly small, the number of patients who die without surgery is unknown.

Mortality/Morbidity

Overall mortality rates vary from 15-25%. These rates are 5 times the operative mortality rates for nonemphysematous cholecystitis. In addition to the septic character of the disease, comorbidities attendant to advanced age and diabetes mellitus also add to the risk of mortality.²

Race

No racial predilection has been described.

Sex

Unlike other biliary tract disorders, emphysematous cholecystitis occurs more frequently in men; men comprise 65-70% of all patients with emphysematous cholecystitis.^{3, 2}

Age

The disease occurs more commonly in older patients. In one study, the mean age of 20 patients was 59 years, and, in another study, 59% of patients were aged 60 years or older.

CLINICAL

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History

The typical patient is a man older than 60 years, often with type II diabetes mellitus. Otherwise, the clinical scenario does not differ significantly from that observed in acute calculous cholecystitis.

• Pain is localized to the right upper quadrant and often radiates to the back. It is unrelated to position or physical activity.
• An antecedent history of self-limited episodes of pain may be present. However, the clinician must be aware that elderly patients may develop acute intra-abdominal disorders with little or no localizing symptoms or signs.

Physical

• Physical examination usually reveals an elderly patient with fever and tachycardia.
• Abdominal examination shows tenderness in the right upper quadrant.
• An enlarged tense gallbladder may be noted, best demonstrated by light palpation.
• Bowel sounds are diminished or absent, especially if peritonitis has supervened.
• Jaundice is unusual unless a concomitant common duct obstruction and/or intrahepatic disease is present.
• Transient relief of right upper quadrant pain followed by the appearance of peritoneal signs is the hallmark of perforation.

Causes

See Pathophysiology.

DIFFERENTIALS

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Other Problems to be Considered

Two levels of differential diagnosis should be considered: clinical and radiologic.

The clinical differential diagnosis is that of acute cholecystitis (nonemphysematous), both calculous and acalculous.

The radiologic differential is that of finding gas in the biliary tree, which may be due to a biliary-enteric fistula (spontaneous or surgical); may occur after an endoscopic retrograde cholangiopancreatography, especially following a sphincterotomy; or may be due to cholangitis caused by gas-forming organisms.^{4, 5}

WORKUP

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Lab Studies

• Patients have leukocytosis that is, at times, strikingly high.
• Liver tests results are usually normal or slightly elevated (eg, aspartate aminotransferase [AST], alanine aminotransferase [ALT]), reflecting the patient's febrile state. Very abnormal liver test results, especially alkaline phosphatase, bilirubin, or gamma-glutamyl transpeptidase (GGTP), suggest a common duct obstruction or intrahepatic disease.
• Urinalysis, chest radiograph, and electrocardiogram add little to establish a diagnosis but should be obtained as part of the preoperative assessment of the patient.

Imaging Studies

• Imaging studies are the key diagnostic maneuvers.
• Abdominal radiographs
• • Abdominal radiographs show the classic picture of a gallbladder wall containing gas. The gallbladder is often fluid-filled, and gas that has leaked into its lumen collects in the least dependent portion. The absence of a gas-filled gallbladder wall on an abdominal radiograph does not exclude a diagnosis of emphysematous cholecystitis.^{5, 6}
  • Inflammation and gas formation may extend to the pericholecystic tissues and extrahepatic ducts. This picture has been regarded as specific for emphysematous cholecystitis, but the sensitivity is unknown. 
  • With the advent of other imaging techniques, especially CT scan, the importance of plain radiographs of the abdomen has declined; further, the presence of abnormal findings on a plain film of the abdomen may indicate advanced disease.¹
  • Changes noted on CT scan and ultrasound of the abdomen can be observed before the classic abnormalities are visible on plain abdominal radiograph.¹
  • The classic picture observed on abdominal radiographs is believed to represent a late phase in the evolution of emphysematous cholecystitis and may presage a poorer outcome.
  • Further abdominal radiographs may be negative in up to 60% of cases. This consideration has altered both the diagnostic workup and the surgical options; early diagnosis requires CT scanning, and the presence or absence of gas outside the gallbladder will influence the choice of the surgical approach.¹
• Abdominal ultrasound
• • Obfuscation of the gallbladder by high-level echoes occurs when gas accumulates in the wall and the lumen of the gallbladder and renders differentiation from intestinal gas difficult. This finding is not diagnostic of emphysematous cholecystitis. The alert physician questions the paradoxical absence (ie, sonographic nonvisualization) of a gallbladder in the clinical setting of a patient who likely has gallbladder disease.^{1, 7}
  • Curvilinear gaseous artifacts in the gallbladder, the "ring-down effect" or "comet tail," are diagnostic of emphysematous cholecystitis, but the frequency with which these are observed is not clear.⁸
  • As the gas leaks out from the wall of the gallbladder into the bile, a picture described as "effervescent bile" can be observed.^{8, 9}
• Computerized tomography scan of the abdomen
• • CT scan demonstrates emphysematous changes in the gallbladder wall that are diagnostic of this condition. CT scan may also demonstrate extension into the pericholecystic tissues and the hepatic ducts. Gas in the peritoneum indicates perforation.¹⁰
  • CT scan is emerging as the most sensitive and specific diagnostic study. It should be performed early in the evaluation when the clinical picture warrants. It should certainly be performed if ultrasound and abdominal radiograph findings are not diagnostic.
• Magnetic resonance imaging of the abdomen
• • Experience remains limited with MRI, and no large series has been described. In one report, a gas-fluid level was shown by a signal void in the nondependent portion of the gallbladder contrasted against an intermediate signal intensity in the dependent portion. Gas within the wall was demonstrated by a rim of low signal intensity. Extraluminal gas, suggesting perforation, may cause small magnetic field inhomogeneous collections referred to as "blooming" artifacts.¹¹
  • These findings are preliminary. No data as to sensitivity or specificity are available. Further experience should resolve these questions.
  • MRI will likely prove to be as diagnostic as CT scan and would be of particular value in pregnant women.

Histologic Findings

Following the invasion of the wall by gas-forming bacteria, the different layers of the gallbladder wall become separated, leading to the characteristic tissue crepitus. Histologically, colonies of bacteria can be observed forming intramural abscesses. Gallbladder contents are often purulent. Even with prompt intervention, necrosis and gangrene are observed in 75% of gallbladders at surgery, and nearly 20% of the gallbladders perforate.²

Staging

Staging is image based. Diagnostic visualization on plain radiographs of the abdomen is thought to represent late-stage disease. CT imaging differentiates pre-perforation disease from post-perforation disease.¹

TREATMENT

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Medical Care

Although sporadic cases of presumed emphysematous cholecystitis treated only with antibiotics and supportive measures are described, it should be emphasized that definitive management requires surgical intervention.^{1, 12}

• Intravenous antibiotics of choice are those that have beta-lactamase inhibitor activity or combinations that provide coverage for anaerobic and gram-negative organisms.
• Fluid replacement and correction of electrolyte deficits and metabolic imbalances should be initiated in preparation for surgery. The authors emphasize that these temporary and preparatory maneuvers are not intended to reverse the basic disease process.

Surgical Care

Management of emphysematous cholecystitis is surgical. Antibiotics and fluid replacement are started immediately to stabilize the patient, but because of the risk of perforation and its impact on survival, clinicians tend to proceed to surgery with deliberate speed. Overall, surgical mortality rates vary from 15-25%.

• Interventional radiology
• • Interventional radiologic techniques allow drainage and decompression followed by interval excision of the gallbladder. These techniques are particularly useful for patients with complications, such as perforation, and for those with high surgical risk.¹³
  • With increasing experience with percutaneous drainage, surgical survival appears improved. However, the following important issues remain unresolved:
  • • With improving diagnostic techniques, specifically ultrasound and CT scan, the disease process is likely at an early stage of its evolution. For this reason, it may have been amenable to a combination of radiologic drainage, concomitant antibiotic therapy, and interval cholecystectomy in a well-prepared, stable patient.
    • The case descriptions do not clarify the appropriate interval between interventional drainage and surgical excision of the gallbladder.
  • At the very least, current experience suggests that interventional radiological drainage can be performed without increasing the overall mortality rate and appears to be a reasonable temporizing option in a seriously ill patient.
  • Hopefully, the favorable impact of interventional radiology will be confirmed. It does not yet obviate the need for ultimate surgical removal of the gallbladder. Further experience is required to determine the role of percutaneous transhepatic gallbladder drainage. The final management algorithm for emphysematous cholecystitis has yet to been written.
• Experience with laparoscopic cholecystectomy continues to increase. While laparoscopic cholecystectomy is feasible, the number of cases does not allow valid comparisons to open cholecystectomy for mortality and complications. A preoperative diagnosis of perforation would likely preclude a laparoscopic approach, thereby requiring a preoperative CT scan or MRI of the abdomen.^{15, 14}

Consultations

• Consultation with surgical and internal medicine specialists is indicated in all cases.
• If available, the services of an interventional radiologist is indicated when percutaneous gallbladder drainage is considered an option. This would be especially true in a patient who is seriously ill and/or has multiple comorbidities.
• Consultation with specialists in infectious diseases is indicated for optimal selection of antibiotics.
• Consultation with other medical subspecialists depends on the array of comorbid conditions present.

Diet

• The patient should not be given anything by mouth until a decision has been made regarding surgery.
• Postoperative feedings are dictated by surgical considerations.
• Upon discharge, dietary recommendations reflect the presence of active comorbid diseases.
• The episode of emphysematous cholecystitis itself should not impose any dietary requirements.

Activity

• Early postoperative activity is dictated by surgical considerations.
• Upon discharge after the operation, the patients should experience no limitation of activity that was not present before the episode.

MEDICATION

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Medications reflect the need to control infection and to manage comorbidities. The 3 most common organisms isolated in patients with emphysematous cholecystitis are E coli, Klebsiella species, and clostridial species. Antibiotic regimens are suggested with the following caveats: (1) antibiotics are not definitive therapy for this condition, and (2) antibiotic regimens should be evaluated in light of changing bacterial sensitivities, changing antibiotic options, and changing patient characteristics.

Drug Category: Antibiotics

Therapy must be comprehensive and cover all likely pathogens in the context of the clinical setting. In the absence of sensitivity data, antibiotic selection is based on empirical considerations including the most likely organisms present and contraindications reflecting the patient's comorbidities and history of sensitivity.

The use of a single effective broad-spectrum fixed antibiotic combination offers simplicity of administration, relative safety, and limited drug interactions.

The use of multiple antibiotics increases the range of therapeutic options in the event of hypersensitivity to one or more single agents or in the event of a loss of sensitivity of one or more organisms to the range of a single agent.

Suggested drug combinations are gentamicin plus metronidazole and levofloxacin plus ceftriaxone.

Cultures obtained as a result of intervention should be used to focus the selection of antibiotics.

FOLLOW-UP

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Further Inpatient Care

• Patients should be observed for the development of pseudomembranous enterocolitis manifested by diarrhea. This diagnosis is established by demonstrating Clostridium difficile toxin in the stool. Treatment is usually started with metronidazole and switched to vancomycin if metronidazole fails to elicit a response.
• Patients should be observed for the development of early postoperative complications, such as leak from the cystic duct stump and retained common duct stone.

Further Outpatient Care

• Patients should be observed for the development of common duct stricture and/or postcholecystectomy diarrhea.

In/Out Patient Meds

• Antibiotics should be continued until optimal control of infections is obtained.

Complications

• Early and late complications are those associated with the interventional procedure.

Prognosis

• The mortality rate approaches 15%. In a recent report of 18 patients, there were no deaths in the immediate postoperative period; 13 of the 18 patients had laparoscopic cholecystectomy.^{2, 14}

Patient Education

• Patients should be educated to watch for features of bile duct obstruction, including changes in the color of the skin, eyes, urine, and stool, which may indicate a retained common duct stone or stricture.

MISCELLANEOUS

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Medical/Legal Pitfalls

• Although most patients have the typical clinical presentation as described, the clinician must be aware of the following:
• • Older patients may not present with significant abdominal pain or fever, even in the presence of frank peritonitis.
  • A plain film of the abdomen may not be diagnostic. A normal finding on a plain film does not exclude the diagnosis of emphysematous cholecystitis.^{1, 5, 6}
  • The gallbladder may not be readily observed on ultrasound examination. Indeed, the apparent absence of a visualized gallbladder on ultrasound in a patient with biliary tract features should prompt the clinician to proceed to an abdominal CT scan.^{7, 1}
  • Ultimately, a CT scan is the most reliable diagnostic test.

MULTIMEDIA

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Media file 1:  Emphysematous cholecystitis. A 47-year-old man with diabetes who experienced abdominal pain. Computerized tomography scan shows gas within the wall of the gallbladder (horizontal arrow) as well as within the lumen of the gallbladder (vertical arrow). Radiograph courtesy of Helen Morehouse, MD.
	View Full Size Image
Media type:  CT

Media file 2:  Emphysematous cholecystitis. A 61-year-old nondiabetic man with right upper quadrant abdominal pain, fever, and leukocytosis. Film shows the gallbladder with multiple stones. The wall of fundus is delineated by intramural gas. Extramural gas also appears to be present in the soft tissues over the superior aspect of the gallbladder.
	View Full Size Image
Media type:  X-RAY

Media file 3:  Emphysematous cholecystitis. A 78-year-old man with diabetes with minimal abdominal distress. The film shows an enlarged gallbladder with multiple stones. The wall of the gallbladder is outlined by intramural gas.
	View Full Size Image
Media type:  X-RAY

REFERENCES

Section 11 of 11

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1. Gill KS, Chapman AH, Weston MJ. The changing face of emphysematous cholecystitis. Br J Radiol. Oct 1997;70(838):986-91. [Medline].
2. Mentzer RM Jr, Golden GT, Chandler JG, et al. A comparative appraisal of emphysematous cholecystitis. Am J Surg. Jan 1975;129(1):10-5. [Medline].
3. May RE, Strong R. Acute emphysematous cholecystitis. Br J Surg. Jun 1971;58(6):453-8. [Medline].
4. Bloom RA, Libson E, Lebensart PD, et al. The ultrasound spectrum of emphysematous cholecystitis. J Clin Ultrasound. May 1989;17(4):251-6. [Medline].
5. Lorenz RW, Steffen HM. Emphysematous cholecystitis: diagnostic problems and differential diagnosis of gallbladder gas accumulations. Hepatogastroenterology. Dec 1990;37 Suppl 2:103-6. [Medline].
6. Chuang C, Hsieh H, Wu H, et al. Management of emphysematous cholecystitis. Chir Gastroenterol. 2007;23:75-78.
7. Mammen L, Watkins GE. Emphysematous cholecystitis. Applied Radiology Online [serial online]. 10 October 2000;Accessed 12/27/2000. Available at http://appliedradiology.com/case/case,asp?Id=11&IssueId=11.
8. Parulekar SG. Sonographic findings in acute emphysematous cholecystitis. Radiology. Oct 1982;145(1):117-9. [Medline].
9. Wu CS, Yao WJ, Hsiao CH. Effervescent gallbladder: sonographic findings in emphysematous cholecystitis. J Clin Ultrasound. Jun 1998;26(5):272-5. [Medline].
10. Safioleas M, Stamatakos M, Kanakis M, et al. Soft tissue gas gangrene: a severe complication of emphysematous cholecystitis. Tohoku J Exp Med. Dec 2007;213(4):323-8. [Medline].
11. Koenig T, Tamm EP, Kawashima A. Magnetic resonance imaging findings in emphysematous cholecystitis. Clin Radiol. May 2004;59(5):455-8. [Medline].
12. Chiu HH, Chen CM, Mo LR. Emphysematous cholecystitis. Am J Surg. Sep 2004;188(3):325-6. [Medline].
13. Slot WB, Ooms HW, Van der Werf SD, et al. Percutaneous gallbladder drainage in emphysematous cholecystitis. Neth J Med. Feb 1995;46(2):86-9. [Medline].
14. Hazey JW, Brody FJ, Rosenblatt SM, et al. Laparoscopic management and clinical outcome of emphysematous cholecystitis. Surg Endosc. Oct 2001;15(10):1217-20. [Medline].
15. Banwell PE, Hill AD, Menzies-Gow N, et al. Laparoscopic cholecystectomy: safe and feasible in emphysematous cholecystitis. Surg Laparosc Endosc. Jun 1994;4(3):189-91. [Medline].
16. Lee HM, Jeffrey RB. Emphysematous pyelonephritis with resultant emphysematous cholecystitis secondary to hematogenous dissemination. Abdom Imaging. Mar-Apr 1995;20(2):169-72. [Medline].

Article Last Updated: Jul 11, 2008