AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Acute cholecystitis in the presence of bacteria-containing bile may progress to suppurative infection in which the gallbladder fills with purulent material, a condition referred to as empyema of the gallbladder. (The underlying cause of cholecystitis involves obstruction of the cystic duct, which causes the buildup of infected fluid.) Systemic antibiotics and urgent drainage or resection are required to reduce the incidence of complications and to avoid or treat associated sepsis.

Pathophysiology

In the bacterially contaminated gallbladder, the stagnation and marked inflammation associated with acute cholecystitis fills the gallbladder lumen with exudative material principally comprised of frank pus. This process may be associated with calculous cholecystitis, acalculous cholecystitis, or carcinoma of the gallbladder. Left untreated, generalized sepsis ensues, with progression in the gallbladder to patchy gangrene, microperforation, macroperforation, or, rarely, cholecystoduodenal fistula. Patients at increased risk for cholecystitis include those with diabetes, immunosuppression, obesity, or hemoglobinopathies.

Frequency

International

True incidence of empyema of the gallbladder associated with acute cholecystitis is difficult to assess, although findings from limited series indicate a range of 5-15%.

Mortality/Morbidity

The rate of laparoscopic cholecystectomy procedures converted to an open procedure is significantly higher in patients with empyema of the gallbladder. The postoperative complication rate (regardless of approach) for empyema of the gallbladder is 10-20% and includes wound infection, bleeding, subhepatic abscess, cystic stump leak, common bile duct injury, and systemic complications, including acute renal failure and/or respiratory insufficiency associated with sepsis.

Progression to death is unusual in otherwise healthy individuals but may occur in patients of advanced age, patients with compromised immunity, or in individuals with significant comorbid conditions.

Race

American Indians and Central American Indians have an increased risk of cholelithiasis/cholecystitis, as do patients with hemoglobinopathies, such as sickle cell anemia (more likely in blacks).

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

The clinical history of a patient with empyema of the gallbladder is similar to that of a patient with acute cholecystitis (from which the empyema derives). As the disease progresses, severe pain and associated high fever, chills, and even rigors may be reported. Patients with diabetes or immunosuppression may exhibit few signs and symptoms.

Physical

• Patients with an early empyema of the gallbladder often present no differently than any patient with acute cholecystitis, with symptoms that include fever (temperature, >101°F), stable blood pressure, and mild tachycardia.
• However, if localized or free perforation has occurred and/or the patient has generalized sepsis, fevers (temperature, 103°F), chills and/or rigors, and confusion may be observed in association with hypotension and severe tachycardia.
• Early on, abdominal examination findings are similar to those of patients with acute cholecystitis, with mild-to-moderate tenderness in the right upper abdomen and a positive Murphy sign (ie, arrest of inspiration as the gallbladder descends to touch a hand previously placed deep in the mid right abdomen).
• As the disease progresses, empyema of the gallbladder may be associated with a palpable distended gallbladder that is markedly tender on even superficial palpation.

Causes

The most frequent etiology of empyema of the gallbladder is unresolved acute calculous cholecystitis in the face of contaminated bile. The most frequently isolated organisms include Escherichia coli, Klebsiella pneumoniae, Streptococcus faecalis, and anaerobes, including Bacteroides and Clostridia species. Suppurative inflammation ensues, tightly filling the gallbladder with purulent debris. Localized or free perforation occurs if drainage or resection is not performed at this juncture. Generalized sepsis frequently accompanies this progression.

A similar pattern is infrequently observed in association with acute acalculous cholecystitis. Rarely, obstruction of the distal common bile duct may result in pus formation within the extrahepatic biliary tree, which can then decompress into the gallbladder. This distends and infects that organ, with ensuing empyema.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Laboratory tests for presumed empyema of the gallbladder include CBC with differential, liver chemistries, prothrombin time (PT), and activated partial thromboplastin time (aPTT).
• Persistent and even increasing leukocytosis at levels greater than 15,000/dL (with a left shift on differential) despite appropriate antibiotic therapy is characteristic of empyema of the gallbladder. However, this scenario may occur in association with gangrenous cholecystitis and with several other differential diagnoses.
• When arising from complicated acute cholecystitis, liver chemistry findings associated with empyema of the gallbladder are usually within reference ranges, which helps differentiate this condition from empyema of the gallbladder and/or cholangitis secondary to distal biliary tract obstruction. One exception is empyema of the gallbladder in which the enlarged "penile" gallbladder compresses the common/hepatic bile ducts (Mirizzi syndrome), giving rise to mildly elevated alkaline phosphatase and bilirubin levels.
• Serial blood cultures are beneficial in patients with bacteremia; positive results help direct antibiotic therapy.

Imaging Studies

• Ultrasound of the gallbladder is indicated in presumed empyema of the gallbladder. The finding of an enlarged, distended gallbladder and associated pericholecystic fluid points to an acute inflammatory process involving the gallbladder. Though suggestive, this does not adequately differentiate uncomplicated acute cholecystitis from the complication with empyema and/or gangrene. Most importantly, it contraindicates further conservative management and signals the need for prompt intervention.
• While ultrasound is the preferred examination for probable cases of empyema, the condition is frequently discovered on CT scans performed with other differential diagnoses in mind.

Procedures

• Endoscopic retrograde cholangiopancreatography (ERCP) is not indicated if empyema of the gallbladder is thought likely because it may delay definitive diagnosis and operative treatment.

Histologic Findings

Findings include a pus-filled gallbladder, with or without calculi, and an acute suppuration of the gallbladder wall, with or without areas of gangrene and perforation.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Intravenous antibiotic therapy is an adjunct to urgent decompression and/or resection of the gallbladder when empyema is likely. The choice of antibiotic is based on the organisms presumed to be involved (see Causes). Early in the course of the disease, good results are achieved with the adjuvant administration of ampicillin or a first- or second-generation cephalosporin. In more advanced cases associated with perforation and/or generalized sepsis, triple antibiotic therapy that includes an aminoglycoside (usually gentamicin), ampicillin or a cephalosporin, and metronidazole (anaerobic coverage) is advised.

Antibiotic coverage is modified by culture results and the bacterial resistance encountered in the local hospital setting.

Urgent decompression is the goal of therapy for empyema of the gallbladder. In patients who are hemodynamically unstable or in individuals in whom surgery is contraindicated because of significant comorbid conditions, transhepatic drainage of the gallbladder under radiologic guidance may serve as a temporizing or final procedure. Though rapid and marked improvement in the patient's condition usually follows, complete resolution without further septic complication (mandating further intervention) is unpredictable.

Surgical Care

Surgical decompression and resection of the affected gallbladder is the criterion standard of therapy. An advanced laparoscopic surgeon may treat empyema of the gallbladder (without significant gangrenous changes or perforation) with a laparoscopic procedure. Initial decompression may be accomplished under radiographic guidance immediately before the procedure or via intraoperative, laparoscopically guided needle drainage, which allows for more facile manipulation of the gallbladder during the cholecystectomy portion of the procedure.

Though the conversion-to-open and complication rates reported in the literature for laparoscopic treatment of empyema vary widely, they are all significantly higher than the comparative rates reported in the same studies for laparoscopic treatment in cases of uncomplicated acute cholecystitis.

Importantly, the complications are related to the advanced disease process and not to the approach. In skilled hands, no increase is observed in the incidence of laparoscopic surgical misadventure with empyema of the gallbladder. Thus, despite the higher incidence of conversion to an open procedure (40-80%), it is quite reasonable to initially proceed with a laparoscopic procedure.

Consultations

When empyema of the gallbladder is considered, urgent consultation with gastroenterologists and surgeons is essential.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Antibiotics

Therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting. Base selection of antibiotics on blood culture sensitivity whenever feasible. Indicated as an adjunct to decompression/resection of the gallbladder with empyema.

Drug Name	Cefazolin (Ancef, Kefzol)
Description	Indicated as single-agent therapy in early empyema of the gallbladder. First-generation semisynthetic cephalosporin that arrests bacterial cell wall synthesis, thus inhibiting bacterial growth. Dosing depends on severity of infection.
Adult Dose	1-2 g IV/IM q6-12h; not to exceed 12 g/d
Pediatric Dose	25-100 mg/kg/d IV divided q8h
Contraindications	Documented hypersensitivity
Interactions	Probenecid prolongs effects; coadministration with aminoglycosides may increase renal toxicity; may yield false-positive urine-dip test results for glucose
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in severe renal insufficiency (high doses may cause CNS toxicity); superinfections and promotion of nonsusceptible organisms may occur with prolonged or repeated use

Drug Name	Gentamicin (Garamycin)
Description	Aminoglycoside antibiotic for gram-negative coverage, indicated in severe infection in combination with ampicillin and metronidazole, providing coverage of gram-positive organisms and anaerobes. Dosing regimens are numerous; adjust dose based on CrCl rate and changes in volume of distribution.
Adult Dose	Serious infections and normal renal function: 3 mg/kg/d IV q8h Loading dose and maintenance dose: 1-2.5 mg/kg IV q8h and 1-1.5 mg/kg IV q8h, respectively Extended dosing regimen for life-threatening infections: 5 mg/kg/d IV/IM q6-8h Follow each regimen by at least a trough level drawn on third or fourth dose (0.5 h before dosing); may draw a peak level 0.5 h after 30-min infusion
Pediatric Dose	<5 years: 2.5 mg/kg/d IV divided q8h >5 years: 1.5-2.5 mg/kg/d IV divided q8h
Contraindications	Documented hypersensitivity; non-dialysis-dependent renal insufficiency
Interactions	Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents, thus prolonged respiratory depression may occur; coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment

Drug Name	Metronidazole (Flagyl)
Description	Indicated in severe infection in combination with aminoglycoside and ampicillin. Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. Used in combination with other antimicrobial agents.
Adult Dose	Loading dose: 15 mg/kg or 1 g IV over 1 h for 70-kg patient Maintenance dose: 6 h following IV loading dose, infuse 7.5 mg/kg or 500 mg IV q6-8h over 1 h for 70-kg patient; not to exceed 4 g/d
Pediatric Dose	30 mg/kg/d IV divided q6h; not to exceed 4 g/d
Contraindications	Documented hypersensitivity
Interactions	May increase toxicity of anticoagulants, lithium, and phenytoin; cimetidine may increase toxicity of metronidazole; disulfiram reaction may occur with orally ingested ethanol
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Following surgical decompression and resection of the gallbladder with empyema, intravenous antibiotic therapy is maintained until fever resolves and white blood cell count returns to normal. Discharge home, on oral antibiotic therapy, is guided by the results of intraoperative bile cultures.
• For patients with complications (eg, intra-abdominal infections, wound infections, sepsis), therapy and follow-up care are clearly patient specific.

Complications

• The major complications associated with empyema of the gallbladder are localized or free perforation and/or generalized sepsis. Possible surgical complications include the following:
• • Wound infection
  • Bleeding
  • Subhepatic abscess
  • Cystic stump leak
  • Common bile duct injury

Prognosis

• If treated early, otherwise healthy patients have a full recovery and return to normal activity.
• In patients of advanced age, those who are immunocompromised, or those with significant comorbid conditions (including patients with advanced diabetes mellitus, in whom the condition is more prevalent), the development of empyema of the gallbladder and the resultant sepsis constitute a serious life-threatening event.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Initial therapy for all stable patients with presumed acute cholecystitis is expectant with the administration of intravenous antibiotics, as outlined in Medication. In patients for whom the disease either fails to improve or worsens on this therapy (first 12 h), assume progression to gangrene and/or empyema. These patients should receive decompression and, unless contraindicated, timely surgical resection.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Cox MR, Wilson TG, Luck AJ, et al. Laparoscopic cholecystectomy for acute inflammation of the gallbladder. Ann Surg. Nov 1993;218(5):630-4. [Medline].
• Editorial. Empyema of the gallbladder - a forgotten disease. Lancet. 1984;1:606.
• Eldar S, Eitan A, Bickel A, et al. The impact of patient delay and physician delay on the outcome of laparoscopic cholecystectomy for acute cholecystitis. Am J Surg. Oct 1999;178(4):303-7. [Medline].
• Fabre JM, Fagot H, Domergue J, et al. Laparoscopic cholecystectomy in complicated cholelithiasis. Surg Endosc. Oct 1994;8(10):1198-201. [Medline].
• Gharaibeh KI, Qasaimeh GR, Al-Heiss H. Effect of timing of surgery, type of inflammation, and sex on outcome of laparoscopic cholecystectomy for acute cholecystitis. J Laparoendosc Adv Surg Tech A. Jun 2002;12(3):193-8. [Medline].
• Hemmer PH, Zeebregts CJ, Roelofsen E. Gallbladder carcinoma presenting as an empyema with Staphylococcus aureus. ANZ J Surg. Apr 2004;74(4):289. [Medline].
• Kato T, Yamagami T, Iida S. Percutaneous drainage under real-time computed tomography-fluoroscopy guidance. Hepatogastroenterology. Jul-Aug 2005;52(64):1048-52. [Medline].
• Kiviluoto T, Siren J, Luukkonen P. Randomised trial of laparoscopic versus open cholecystectomy for acute and gangrenous cholecystitis. Lancet. Jan 31 1998;351(9099):321-5. [Medline].
• Koperna T, Kisser M, Schulz F. Laparoscopic versus open treatment of patients with acute cholecystitis. Hepatogastroenterology. Mar-Apr 1999;46(26):753-7. [Medline].
• Lee KT, Wong SR, Cheng JS, et al. Ultrasound-guided percutaneous cholecystostomy as an initial treatment for acute cholecystitis in elderly patients. Dig Surg. 1998;15(4):328-32. [Medline].
• Lim MS, Davaraj B, Kandasami P. Endoscopic drainage of empyema of the gallbladder through a concurrent cholecystoduodenal fistula. Asian J Surg. Jan 2006;29(1):55-7.
• Lo CM, Fan ST, Liu CL, et al. Early decision for conversion of laparoscopic to open cholecystectomy for treatment of acute cholecystitis. Am J Surg. Jun 1997;173(6):513-7. [Medline].
• Thornton JR, Heaton KW, Espiner HJ. Empyema of the gall bladder - reappraisal of a neglected disease. Gut. Dec 1983;24(12):1183-5. [Medline].
• Tseng LJ, Tsai CC, Mo LR, et al. Palliative percutaneous transhepatic gallbladder drainage of gallbladder empyema before laparoscopic cholecystectomy. Hepatogastroenterology. Jul-Aug 2000;47(34):932-6. [Medline].
• Van Steenbergen W, Rigauts H, Ponette E, et al. Percutaneous transhepatic cholecystostomy for acute complicated calculous cholecystitis in elderly patients. J Am Geriatr Soc. Feb 1993;41(2):157-62. [Medline].
• Zheng QY, Johnson KR: Hearing loss associated with the modifier of deaf waddler (mdfw) locus corresponds with age-related hearing loss in 12 inbred strains of mice. Hear Res 2001 April; 154(1-2): 45-53.

Article Last Updated: Feb 8, 2007