Alveolar Dead-Space Response to Activated Protein C in Acute Respiratory Distress Syndrome

Abstract

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.