• Daniel De Backer, Colin Verdant, Marialuisa Chierego, Marc Koch, Antonino Gullo, and Jean-Louis Vincent.
• Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Brussels, Belgium.
• Crit. Care Med. 2006 Jul 1;34(7):1918-24.

ObjectiveMicrovascular alterations may play an important role in the development of sepsis-induced organ dysfunction. Drotrecogin alfa activated (DAA) improves outcome in patients with severe sepsis, but its precise mechanism of action is not entirely defined. We investigated whether DAA can influence microcirculatory alterations in patients with severe sepsis.DesignProspective, nonrandomized study.SettingA 31-bed, medico-surgical intensive care unit of a university hospital.PatientsForty adult patients with severe sepsis who met the EU criteria for DAA administration.InterventionsTwenty patients received the drug (DAA) and 20 had a contraindication to DAA administration (control).Measurements And Main ResultsAn orthogonal polarization spectral imaging technique was used to visualize the sublingual microcirculation. In all patients, measurements were obtained at baseline, 4 hrs later, and then every 24 hrs for up to 7 days. In patients receiving DAA, measurements were also obtained just before and 4 hrs after the end of DAA infusion. The two groups were well matched for severity of disease, number of failing organs, and the degree of microvascular alterations at baseline. The proportion of perfused capillaries increased in the DAA treated patients already at 4 hrs (from 64% [51-80%] to 84% [71-88%], p < .01) but not in the control group (from 67% [59-76%] to 68% [61-71%], p = not significant). Microvascular perfusion decreased transiently at the end of DAA infusion. The improvement in microvascular blood flow was associated with a more rapid resolution of hyperlactatemia.ConclusionsDAA administration rapidly improves sepsis-induced microvascular alterations, whereas its cessation is associated with a transient deterioration.

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