Breaking Down the Barriers in Complicated Pleural Sepsis.

sis within the pleural space. Increased procoagulant and decreased fibrinolytic activity in response to infection is unique to the serosal spaces and although the exact mechanism still needs to be elucidated, its effects are well known: pleural surfaces coated with fibrin and fibrin strands with secondary adhesions and loculations, all complicating pleural fluid drainage [1] . The third and final stage of pleural infection is the organising phase. The mainstay of treatment of complicated parapneumonic effusions remains drainage of the infected pleural fluid with chest tube thoracostomy and appropriate antibiotic cover. This course of management is frequently unsuccessful, which traditionally necessitated referral for surgical interventions (thoracotomy or thoracoscopy). Conservative management tends to fail in elderly or those with multiple comorbidities, which not infrequently preclude them from surgery. The reasons for failing conservative management seem to stem directly from the characteristics of the infected pleural space, with high fluid viscosity and fibrous septations impeding drainage [1] . These characteristics have become the targets of medical management aimed at improving the outcome of pleural infections and avoiding referral for surgery. Tillett and Sherry [2] were responsible for the introduction of intrapleural fibrinolysis as a supplement to antimicrobial therapy as early as 1949. Although the theoretical advantage of fibrinolytics certainly seemed obvious, it took ‘If a pleurisy lasts 20 days then it forms an empyema and if it does not rupture then death will occur.’ Although Hippocrates described the natural course of empyema more than two millenniums ago and despite the fact that our knowledge of medicine has increased exponentially during the last few decades, complicated pleural infections still carry up to a 20% 1-year mortality in the 21st century [1] . The development of a parapneumonic effusion occurs in three clinically relevant stages that represent a continuum. A rapid influx of exudative fluid into the pleural space is observed in up to 40% of patients with pneumonia and heralds the first or exudative stage [1] . The accumulation of fluid is due to increased pulmonary interstitial fluid traversing the pleura to enter the pleural space and an increase in vascular permeability secondary to pro-inflammatory cytokines. Most patients with uncomplicated parapneumonic effusions will respond to antibiotics alone and drainage is generally not required. Untreated exudative effusions may develop into fibrinopurulent effusions. During the fibrinopurulent stage, the pleural space becomes increasingly infected. Loculations may develop and closed or open drainage becomes necessary, the point in time where an effusion is referred to as ‘complicated’ [1] . A critical characteristic of the fibrinopurulent stage of pleural sepsis is the disturbance of the physiological equilibrium between clotting and fibrinolyPublished online: January 27, 2016