The lung in sepsis: guilty or innocent?
The mortality rate of severe sepsis is still high (20 to 65%) despite the advances in critical care. The most important determinant of the prognosis in this condition is the occurrence of multiple organ dysfunction syndrome (MODS). The lung is the most frequently identified organ to fail in sepsis and is also the most frequent primary site of infection. The development of acute respiratory distress syndrome (ARDS) is common in those cases. The current understanding of the pathogenesis of ARDS suggests that the degree of inflammatory response and its sustained leukocyte activation may determine the clinical evolution of ARDS. The way that mechanical ventilation is delivered is responsible for the start and/or the perpetuation of a pro-inflammatory cascade activation that, due to the loss of the alveolar compartmentalization in ARDS, can reach the bloodstream and induce MODS. On the other hand, during sepsis, the alveolar compartmentalization is lost, allowing the passage of cytokines, released to the bloodstream by any other organ, to the pulmonary endothelium. These cytokines, especially IL-1, TNF-alpha and IL-8, have important roles in the lung dysfunction. Experimental and clinical studies have been demonstrated that ventilation strategies using low tidal volumes and limitation of airway pressures can block cytokines and reduce mortality of patients with respiratory failure. The studies are still insufficient to determine the role of pharmacological therapies in those patients.
Costa
E L V
EL
Respiratory ICU, Hospital das Clnicas, University of Sao Paulo medical School and Intensive Care Unit, Hospital Sirio Libanes, Sao Paulo, SP, Brazil.
Schettino
I A L
IA
Schettino
G P P
GP
D000818:Animals; D006801:Humans; D008168:Lung / Q000382:microbiology; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000276:immunology / Q000382:microbiology*; D018805:Sepsis / Q000097:blood / Q000276:immunology / Q000382:microbiology*