361 Medical and Surgical Management of Empyema Mark S. Godfrey, MD1 Kyle T. Bramley, MD1 Frank Detterbeck, MD2 1 Pulmonary, Critical Care and Sleep Medicine, Yale New Haven Address for correspondence Frank Detterbeck, MD, 330 Cedar Street, Hospital, New Haven, Connecticut P.O. Box 208062, New Haven, CT 06520 2 Section of Thoracic Surgery, Yale University School of Medicine, (e-mail: [email protected]). New Haven, Connecticut Semin Respir Crit Care Med 2019;40:361–374. Abstract Infection of the pleural space is an ancient and common clinical problem, the incidence which is on the rise. Advances in therapy now present clinicians of varying disciplines with an array of therapeutic options ranging from thoracentesis and chest tube drainage (with or without intrapleural fibrinolytic therapies) to video-assisted thoracic surgery (VATS) or thoracotomy. A framework is provided to guide decision making, which involves weighing multiple factors (clinical history and presentation, imaging characteristics, comorbidities); Keywords multidisciplinary collaboration and active management are needed as the clinical course ► empyema over a few days determines subsequent refinement. The initial choice of antibiotics depends ► pleural infection on whether the empyema is community-acquired or nosocomial, and clinicians must ► tissue plasminogen recognize that culture results often do not reflect the full disease process. Antibiotics alone activator are rarely successful and can be justified only in specific circumstances. Early drainage with ► deoxyribonuclease or without intrapleural fibrinolytics is usually required. This is successful in most patients; ► thoracoscopy however, when surgical decortication is needed, clear benefit and low physiologic impact ► video-assisted are more likely with early intervention, expeditious escalation of interventions, and care at a thoracic surgery center experienced with VATS. During World War I, the U.S. Army formed an empyema with pleural infection. We refer readers to other literature commission to address an epidemic of empyema among regarding topics not addressed here, such as the clinical and enlisted men in crowded camps and exacerbated by the radiographic presentation of pleural infection,3 management 1918 influenza pandemic.1 Their management recommenda- of postresection pleural space infection and empyema associ- 4,5 tions were (1) early closed pleural drainage (through serial ated with a bronchial or esophageal fistula, nonbacterial Downloaded by: Yale University Library. Copyrighted material. aspiration or closed chest tube), (2) avoidance of early open (mycobacterial, fungal) empyema, and pleural infection in drainage, (3) sterilization and obliteration of the empyema children.6 cavity, and (4) maintenance of the patient’s nutritional status.2 One-hundred years later these remain core principles, despite Incidence and Mortality of Pleural Infection major advances including antibiotic therapy, imaging techni- ques, intrapleural fibrinolytic drugs, and minimally invasive Parapneumonic effusion develops in 14 to 19% of patients with surgical techniques. Despite these advances, the morbidity, community-acquired pneumonia (CAP), and roughly a third of mortality, and burden of pleural infection remain high. Judging these patients will have empyema or complicated parapneu- which interventions are needed to optimally manage an monic effusion (CPE).7,8 However, the notion that empyema individual patient is complex and involves qualitative factors. represents an extension of bacterial pneumonia is currently While clinical studies provide guidance, ambiguity in how to being challenged. Many patients with empyema lack imaging apply the evidence remains. evidence of an underlying pneumonia; in a recent study, chest This review aims to provide practical guidance to the computed tomography (CT) demonstrated evidence of pneu- general or respiratory physician or surgeon managing a patient monia in only 44% (64/164) of community-acquired empyema Issue Theme Pleural Diseases; Guest Copyright © 2019 by Thieme Medical DOI https://doi.org/ Editors: Jonathan Puchalski, MD, and Publishers, Inc., 333 Seventh Avenue, 10.1055/s-0039-1694699. Najib M. Rahman, DPhil, MSc, FRCP New York, NY 10001, USA. ISSN 1069-3424. Tel: +1(212) 584-4662. 362 Medical and Surgical Management of Empyema Godfrey et al. (CAE) cases and 27% (88/324) of health care associated empy- (n ¼ 128) among 1,080 patients with invasive pneumococcal ema (HCAE).9 Retrospective cohorts demonstrate no seasonal infection was the pneumococcal serotype (not any clinical or variation in empyema incidence, in contrast with the season- demographic features).34 Notably, pneumonia-specificand ality of pneumonia. The microbiology of CAP is remarkably generic sepsis scores (such as the pneumonia severity index different from that of CAE (see “Microbiology”). While occa- or CURB-65) on admission do not predict development of CPE sionally pleural infection arises through hematogenous spread, or empyema.8 from subdiaphragmatic infection, trauma, or iatrogenically Because there are no clinical characteristics that identify an from procedures, the mechanism for the development of uncomplicated effusion in patients with pneumonia or sepsis, many empyemas is unclear. thoracentesis should be performed whenever such patients The crude and/or age-adjusted incidence of adult pleural have >10 mm of pleural fluid.4,35,36 A pleural effusion should infection is consistently rising in diverse cohorts and health bespecifically sought for when patients with pneumonia fail to systems (e.g., in Canada,10,11 Denmark,12 Finland,13 and the respond within 48 to 72 hours of antibiotic therapy, or in United States).14,15 The largest incidence ratio increase is in elderly patients (who often lack overtly infectious symptoms the elderly.11,12 Because the 30-day/in-hospital case fatality and present with dyspnea, anemia, or weight loss).37 rate of empyema (7–11%) has remained stable for over 30 Classification schemas for pleural infection differ regarding years,14,15 the rising incidence is not likely due to improved pleural fluid glucose thresholds (6038 vs. 40 mg/dL35,39)and detection of clinically less-significant disease. This would be inclusion35,38 or not39 of pleural fluid lactate dehydrogenase expected to dilute the case fatality rate, in fact one study measurement.40 All classifications include pH measurement, found both an increasing incidence of empyema and inci- but pH can be affected by residual air, heparin, or lidocaine in dence of empyema-specific deaths.16 the sample,41 can significantly vary between individual Long-term outcomes of patients with pleural infection locules,42 or be elevated by urease-producing organisms demonstrate high rates of readmission and repeated inter- such as Proteus.43 Therefore, a pleural effusion should not be ventions. Among 4,095 patients with empyema, 21% were classified and managed as uncomplicated solely by biochemi- readmitted within 90 days and 27% of these readmissions cal features; for borderline laboratory results the clinical were specifically secondary to the empyema.17 Additionally, context of the patient must be considered. Escalating therapy a subsequent procedure within 30 days was required in 51 empirically or resampling the effusion is indicated whenever and 39%, respectively, of patients managed initially with a clinical questions linger. chest tube or with initial surgery.17 Although their baseline status is unclear, 22 to 31% of pleural infection patients are Timely Management of Pleural Infection reportedly discharged to a facility instead of home.11,14 A three-stage classification of parapneumonic effusion (exuda- A substantial late mortality is reported after a pleural tive, fibrinopurulent, and organizing) was proposed in 1962.44 infection. The 1-, 3-, and 5-year mortality was 15, 24, and Early observations suggested that it took 2 to 3 weeks for the 30%, respectively, among 191 patients with empyema or CPE18; early exudate to become frankly purulent.2 However, the time their 3-month mortality of 8% was similar to those of other to progression from one stage to another is highly variable. prospective cohorts.19 The majority (66%) of late mortality in Therefore, interventions should be performed expeditiously, patients with empyema is attributable to causes other than and treatments escalated rapidly when the pleural process did pneumonia or empyema.20 Empyema often stems from under- not improve within a few days. There is no role for protracted lying vulnerability—the high long-term mortality likely reflects “expectant” management of a potentially infected pleural Downloaded by: Yale University Library. Copyrighted material. these patients’ substantial burden of comorbid disease.21 space; delaying diagnostic thoracentesis of a parapneumonic effusion for an anticipated response to antibiotics alone is General Principles of Management associated with increased hospital length of stay (LOS) and costs.45 Similarly, delaying a chest tube >3 days after recogni- Timely Identification of Pleural Infection tion of pleural fluid is associated with increased mortality.46 An empyema is defined as pus in the pleural space or pleural Preclinical models of pleural infection have demonstrated fluid with organisms present on Gram stain or culture. CPE is rapid progression of pleural organization within hours to defined as pleural fluid pH <7.20 or pleural fluid glucose days. In a Pasteurella rabbit model, less pleural rind was <60 mg/dL with clinical evidence of