Gallbladder Empyema

Back

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.

Etiology

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.

Epidemiology

International

The 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%.

Race-related demographics

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 black persons).

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.[1]

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.

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:

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 Examination

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 in the disease process, 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.

Laboratory Studies

Laboratory tests for presumed empyema of the gallbladder include complete blood cell (CBC) count with differential, liver function tests, 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

Ultrasonography 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. Although 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.

Although ultrasonography is the preferred examination for probable cases of empyema, the condition is frequently discovered on computed tomography (CT) scans performed with other conditions on the differential diagnosis in mind.

On diffusion-weighted (DWI) magnetic resonance imaging (MRI), diffusion restriction in non-neoplastic lesions sometimes provides additional information that can help to establish a correct diagnosis in patients for whom conventional images have yielded equivocal findings. DWI may help to differentiate gallbladder empyema from dense bile or sludge in the gallbladder.[2]

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 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.

Medical Care

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

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 Etiology). Early in the course of the disease, good results are achieved with the adjuvant administration of a second-generation cephalosporin. In more advanced cases associated with perforation and/or generalized sepsis, broader spectrum coverage with piperacillin tazobactam is advised.

Antibiotic coverage is modified by culture results (as soon as available) and the known 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. Although rapid and marked improvement in the patient's condition usually follows, complete resolution without further septic complication (mandating further intervention) is unpredictable.[3]

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.[4] 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.[5]

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.

Following surgical decompression and resection of the gallbladder with empyema, intravenous antibiotic therapy is maintained until fever resolves and the 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 patient specific and, therefore, individualized.

Medication Summary

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

Class Summary

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.

Cefuroxime (Ceftin, Zinacef)

Clinical Context:  Binds to penicillin-binding proteins and inhibits final transpeptidation step of peptidoglycan synthesis, resulting in cell-wall death; resists degradation by beta-lactamase; proper dosing and appropriate route of administration are determined by condition of patient, severity of infection, and susceptibility of microorganism.

Class Summary

Second-generation cephalosporins have extended coverage against anaerobes and gram-negative bacilli.

Piperacillin/tazobactam (Zosyn)

Clinical Context:  Antipseudomonal penicillin plus beta-lactamase inhibitor; inhibits biosynthesis of cell wall mucopeptide synthesis by binding to 1 or more of the penicillin-binding proteins and is effective during active-multiplication stage.

Class Summary

Extended-spectrum penicillins are semi-synthetic penicillin analogs used in the treatment of moderate to severe urinary, respiratory, gastrointestinal tract, skin, bone and joint infections. These agents extended activity against garm-negative bacteria and particular activity against Escherichia coli, Hemophilis  influenzae, Listeria monocytogenesis, Neisseria gonorrhoeae, Proteus mirabilis, Salmonella, Shigella, Staphylococcus aureus (non-penicillinase producing), Staphylococcus epidermidis, and Streptococcus pneumoniae.

Author

Benjamin Pace, MD, FACS, Chief, Division of Breast Surgery, Department of Surgery, Queens Hospital Center; Associate Professor of Surgery, Icahn School of Medicine at Mount Sinai

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Praveen K Roy, MD, AGAF, Chief of Gastroenterology, Presbyterian Hospital; Medical Director of Endoscopy, Presbyterian Medical Group; Adjunct Associate Research Scientist, Lovelace Respiratory Research Institute

Disclosure: Nothing to disclose.

Additional Contributors

Maurice A Cerulli, MD, FACP, FACG, FASGE, AGAF, Associate Professor of Clinical Medicine, Albert Einstein College of Medicine of Yeshiva University; Associate Professor of Clinical Medicine, Hofstra Medical School

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

Disclosure: Nothing to disclose.

Acknowledgements

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.

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.

References

  1. Cull JD, Velasco JM, Czubak A, Rice D, Brown EC. Management of acute cholecystitis: prevalence of percutaneous cholecystostomy and delayed cholecystectomy in the elderly. J Gastrointest Surg. 2014 Feb. 18 (2):328-33. [View Abstract]
  2. Lee NK, Kim S, Kim DU, et al. Diffusion-weighted magnetic resonance imaging for non-neoplastic conditions in the hepatobiliary and pancreatic regions: pearls and potential pitfalls in imaging interpretation. Abdom Imaging. 2015 Mar. 40 (3):643-62. [View Abstract]
  3. Nigri GR, Aurello P, Ramacciato G. An abdominal mass. J Gastrointest Surg. 2011 Oct. 15(10):1902-3. [View Abstract]
  4. Kwon YJ, Ahn BK, Park HK, Lee KS, Lee KG. What is the optimal time for laparoscopic cholecystectomy in gallbladder empyema?. Surg Endosc. 2013 Oct. 27(10):3776-80. [View Abstract]
  5. Philips JA, Lawes DA, Cook AJ, et al. The use of laparoscopic subtotal cholecystectomy for complicated cholelithiasis. Surg Endosc. 2008 Jul. 22 (7):1697-700. [View Abstract]
  6. Cox MR, Wilson TG, Luck AJ, Jeans PL, Padbury RT, Toouli J. Laparoscopic cholecystectomy for acute inflammation of the gallbladder. Ann Surg. 1993 Nov. 218(5):630-4. [View Abstract]
  7. 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. 1999 Oct. 178 (4):303-7. [View Abstract]
  8. Empyema of the gallbladder - a forgotten disease. Lancet. 1984 Mar 17. 1 (8377):606. [View Abstract]
  9. Fabre JM, Fagot H, Domergue J, et al. Laparoscopic cholecystectomy in complicated cholelithiasis. Surg Endosc. 1994 Oct. 8 (10):1198-201. [View Abstract]
  10. 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. 2002 Jun. 12(3):193-8. [View Abstract]
  11. Hemmer PH, Zeebregts CJ, Roelofsen E, Klaase JM. Gallbladder carcinoma presenting as an empyema with Staphylococcus aureus. ANZ J Surg. 2004 Apr. 74(4):289. [View Abstract]
  12. Kato T, Yamagami T, Iida S. Percutaneous drainage under real-time computed tomography-fluoroscopy guidance. Hepatogastroenterology. 2005 Jul-Aug. 52(64):1048-52. [View Abstract]
  13. Kiviluoto T, Sirén J, Luukkonen P, Kivilaakso E. Randomised trial of laparoscopic versus open cholecystectomy for acute and gangrenous cholecystitis. Lancet. 1998 Jan 31. 351(9099):321-5. [View Abstract]
  14. Koperna T, Kisser M, Schulz F. Laparoscopic versus open treatment of patients with acute cholecystitis. Hepatogastroenterology. 1999 Mar-Apr. 46(26):753-7. [View Abstract]
  15. 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. [View Abstract]
  16. Lim MS, Davaraj B, Kandasami P. Endoscopic drainage of empyema of the gallbladder through a concurrent cholecystoduodenal fistula. Asian J Surg. 2006 Jan. 29(1):55-7. [View Abstract]
  17. 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. 1997 Jun. 173(6):513-7. [View Abstract]
  18. Thornton JR, Heaton KW, Espiner HJ, Eltringham WK. Empyema of the gall bladder - reappraisal of a neglected disease. Gut. 1983 Dec. 24(12):1183-5. [View Abstract]
  19. Tseng LJ, Tsai CC, Mo LR, et al. Palliative percutaneous transhepatic gallbladder drainage of gallbladder empyema before laparoscopic cholecystectomy. Hepatogastroenterology. 2000 Jul-Aug. 47(34):932-6. [View Abstract]
  20. 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. 1993 Feb. 41(2):157-62. [View Abstract]
  21. 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 Apr. 154(1-2):45-53. [View Abstract]
  22. Abraham S, Rivero HG, Erlikh IV, Griffith LF, Kondamudi VK. Surgical and nonsurgical management of gallstones. Am Fam Physician. 2014 May 15. 89 (10):795-802. [View Abstract]
  23. Warttig S, Ward S, Rogers G, Guideline Development Group. Diagnosis and management of gallstone disease: summary of NICE guidance. BMJ. 2014 Oct 30. 349:g6241. [View Abstract]
  24. Demehri FR, Alam HB. Evidence-based management of common gallstone-related emergencies. J Intensive Care Med. 2016 Jan. 31 (1):3-13. [View Abstract]
  25. Chathadi KV, Chandrasekhara V, Acosta RD, et al, for the ASGE Standards of Practice Committee. The role of ERCP in benign diseases of the biliary tract. Gastrointest Endosc. 2015 Apr. 81 (4):795-803. [View Abstract]