eMedicine Specialties > Gastroenterology > Biliary

Empyema, Gallbladder

Benjamin Pace, MD, Director of Surgery, Chief of Breast Service, Queens Hospital Center
Bruce Morel, MD, FACS, Clinical Assistant Professor, Department of Surgery, Mount Sinai School of Medicine; Sita Chokhavatia, MD, MBBS, Associate Fellowship Director, Associate Professor, Department of Internal Medicine, Division of Gastroenterology, Mount Sinai School of Medicine

Updated: Jun 17, 2008

Introduction

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, in 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

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

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.

Differential Diagnoses

Cholecystitis
Cholelithiasis

Workup

Laboratory 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

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.

The conversion-to-open and complication rates reported in the literature for laparoscopic treatment of empyema vary widely. However, they are all significantly higher than the comparative rates reported in the same studies for laparoscopic treatment of uncomplicated acute cholecystitis. Laparoscopic subtotal cholecystectomy is acceptable only if the encountered pericholecystic inflammation is so severe as to preclude safe dissection via either a laparoscopic procedure or an open procedure.¹

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

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

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.

Gentamicin (Garamycin)

Aminoglycoside antibiotic for gram-negative coverage bacteria, including Pseudomonas species. Synergistic with beta-lactamase against enterococci. Interferes with bacterial protein synthesis by binding to 30S and 50S ribosomal subunits.
Dosing regimens are numerous and are adjusted based on CrCl and changes in volume of distribution, as well as body space into which agent needs to distribute. Dose of gentamicin may be given IV/IM. Each regimen must be followed by at least a trough level drawn on the third or fourth dose, 0.5 h before dosing; may draw peak level 0.5 h after 30-min infusion.

Dosing

Adult

Loading dose and maintenance dose: 1-2.5 mg/kg IV and 1-1.5 mg/kg IV, respectively, q8h
Serious life-threatening infections and normal renal function: 3 mg/kg/dose IV q8h
Follow each regimen by at least a trough level drawn on the third or fourth dose (0.5 h before dosing); may draw a peak level 0.5 h after 30-min infusion

Pediatric

Not established

Interactions

Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; because aminoglycosides enhance effects of neuromuscular blocking agents, 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)

Contraindications

Documented hypersensitivity; non-dialysis dependent renal insufficiency

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

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

Ampicillin (Omnipen, Polycillin)

Indicated as single-agent therapy in early empyema of the gallbladder. Bactericidal activity against susceptible organisms. Dosing depends on severity of infection.

Dosing

Adult

1-2 g IV q4-6h; not to exceed 14 g/d

Pediatric

100-200 mg/kg/d IV divided q4-6h; not to exceed 2-3 g/d

Interactions

Probenecid and disulfiram elevate levels; allopurinol decreases effects and has additive effects on ampicillin rash; may decrease effects of oral contraceptives

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal failure; evaluate rash, and differentiate from hypersensitivity reaction

Cefazolin (Ancef, Kefzol)

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.

Dosing

Adult

1-2 g IV/IM q6-12h; not to exceed 12 g/d

Pediatric

25-100 mg/kg/d IV divided q8h

Interactions

Probenecid prolongs effects; coadministration with aminoglycosides may increase renal toxicity; may yield false-positive urine-dip test results for glucose

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

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

Metronidazole (Flagyl)

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.

Dosing

Adult

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

30 mg/kg/d IV divided q6h; not to exceed 4 g/d

Interactions

May increase toxicity of anticoagulants, lithium, and phenytoin; cimetidine may increase toxicity of metronidazole; disulfiram reaction may occur with orally ingested ethanol

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy

Follow-up

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, in those who are immunocompromised, or in 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

Medicolegal 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

1. Philips JA, Lawes DA, Cook AJ, Arulampalam TH, Zaborsky A, Menzies D, et al. The use of laparoscopic subtotal cholecystectomy for complicated cholelithiasis. Surg Endosc. Jul 2008;22(7):1697-700. [Medline].

2. Cox MR, Wilson TG, Luck AJ, Jeans PL, Padbury RT, Toouli J. Laparoscopic cholecystectomy for acute inflammation of the gallbladder. Ann Surg. Nov 1993;218(5):630-4. [Medline].

3. Eldar S, Eitan A, Bickel A, Sabo E, Cohen A, Abrahamson J, 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].

4. Empyema of the gallbladder - a forgotten disease. Lancet. Mar 17 1984;1(8377):606. [Medline].

5. Fabre JM, Fagot H, Domergue J, Guillon F, Balmes M, Zaragosa C, et al. Laparoscopic cholecystectomy in complicated cholelithiasis. Surg Endosc. Oct 1994;8(10):1198-201. [Medline].

6. 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].

7. Hemmer PH, Zeebregts CJ, Roelofsen E, Klaase JM. Gallbladder carcinoma presenting as an empyema with Staphylococcus aureus. ANZ J Surg. Apr 2004;74(4):289. [Medline].

8. Kato T, Yamagami T, Iida S. Percutaneous drainage under real-time computed tomography-fluoroscopy guidance. Hepatogastroenterology. Jul-Aug 2005;52(64):1048-52. [Medline].

9. Kiviluoto T, Sirén J, Luukkonen P, Kivilaakso E. Randomised trial of laparoscopic versus open cholecystectomy for acute and gangrenous cholecystitis. Lancet. Jan 31 1998;351(9099):321-5. [Medline].

10. Koperna T, Kisser M, Schulz F. Laparoscopic versus open treatment of patients with acute cholecystitis. Hepatogastroenterology. Mar-Apr 1999;46(26):753-7. [Medline].

11. Lee KT, Wong SR, Cheng JS, Ker CG, Sheen PC, Liu YE. Ultrasound-guided percutaneous cholecystostomy as an initial treatment for acute cholecystitis in elderly patients. Dig Surg. 1998;15(4):328-32. [Medline].

12. 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. [Medline].

13. 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].

14. Thornton JR, Heaton KW, Espiner HJ, Eltringham WK. Empyema of the gall bladder - reappraisal of a neglected disease. Gut. Dec 1983;24(12):1183-5. [Medline].

15. 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].

16. Van Steenbergen W, Rigauts H, Ponette E, Peetermans W, Pelemans W, Fevery J. Percutaneous transhepatic cholecystostomy for acute complicated calculous cholecystitis in elderly patients. J Am Geriatr Soc. Feb 1993;41(2):157-62. [Medline].

17. 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. Apr 2001;154(1-2):45-53. [Medline].

Keywords

empyema of the gallbladder, acute cholecystitis, calculous cholecystitis, acalculous cholecystitis, gangrenous cholecystitis, cholelithiasis, chololithiasis, sepsis, Escherichia coli, E coli, Klebsiella pneumoniae, K pneumoniae, Streptococcus faecalis, S faecalis, Bacteroides, Clostridia

Contributor Information and Disclosures

Author

Benjamin Pace, MD, Director of Surgery, Chief of Breast Service, Queens Hospital Center
Benjamin Pace, MD is a member of the following medical societies: American College of Surgeons, American Medical Association, Association for Academic Surgery, Association for Surgical Education, and Medical Society of the State of New York
Disclosure: no financial interest  None None

Coauthor(s)

Bruce Morel, MD, FACS, Clinical Assistant Professor, Department of Surgery, Mount Sinai School of Medicine
Bruce Morel, MD, FACS is a member of the following medical societies: American College of Surgeons, American Medical Association, and Medical Society of the State of New York
Disclosure: Nothing to disclose.

Sita Chokhavatia, MD, MBBS, Associate Fellowship Director, Associate Professor, Department of Internal Medicine, Division of Gastroenterology, Mount Sinai School of Medicine
Sita Chokhavatia, MD, MBBS is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.

Medical Editor

Maurice A Cerulli, MD, FACG, Chief, Division of Gastroenterology and Hepatology, Associate Professor of Clinical Medicine, Department of Internal Medicine, Division of Gastroenterology, New York Methodist Hospital, Cornell University
Maurice A Cerulli, MD, FACG is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, American Medical Association, and American Society for Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Simmy Bank, MD, Chair, Professor, Department of Internal Medicine, Division of Gastroenterology, Long Island Jewish Hospital, Albert Einstein College of Medicine
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Assistant Dean for Medical Curriculum, Associate Professor of Medicine, Division of General Internal Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania
Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law Medicine and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

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