Alveolar dead-space response to activated protein C in acute respiratory distress syndrome.

We report a complicated case of acute respiratory distress syndrome (ARDS) from severe sepsis, in which we measured the ratio of physiologic dead space to tidal volume (V(D)/V(T)) with volumetric capnography prior to, during, and after therapy with human recombinant activated protein C. Previous studies hypothesized that early in ARDS, elevated V(D)/V(T) primarily reflects increased alveolar V(D), probably caused by pronounced thrombi formation in the pulmonary microvasculature. This may be particularly true when severe sepsis is the cause of ARDS. We repeatedly measured V(D)/V(T) in a 29-year-old man with sepsis-induced ARDS over the course of activated protein C therapy. Treatment with activated protein C resulted in a pronounced reduction in V(D)/V(T), from 0.55 to 0.27. Alveolar V(D) decreased from 165 mL to 11 mL (93% reduction). Activated protein C was terminated at 41 h because of gastrointestinal bleeding. When the measurement was repeated 29 h after therapy was discontinued, V(D)/V(T) had increased modestly, to 0.34, whereas alveolar V(D) had increased to 71 mL, or 43% of the pre-activated-protein-C baseline measurement. Alveolar V(T) rose from 260 mL to 369 mL and decreased slightly after termination of activated protein C (336 mL). Over the course of activated protein C therapy there was a persistent decrease in alveolar V(D) and increase in alveolar V(T), even while positive end-expiratory pressure was reduced and respiratory-system compliance decreased. Thus, improved alveolar perfusion persisted despite signs of alveolar de-recruitment. This suggests that activated protein C may have reduced microvascular obstruction. This report provides indirect evidence that microvascular obstruction may play an important role in elevated V(D)/V(T) in early ARDS caused by severe sepsis.