Effects of drotrecogin alfa activated on microcirculatory... : Critical Care Medicine (original) (raw)

Clinical Investigations

Effects of drotrecogin alfa activated on microcirculatory alterations in patients with severe sepsis

De Backer, Daniel MD, PhD; Verdant, Colin MD; Chierego, Marialuisa MD; Koch, Marc MD; Gullo, Antonino MD; Vincent, Jean-Louis MD, PhD, FCCM

From the Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Brussels, Belgium (DDB, CV, MC, MK, JLV); and Department of Aenesthesia and Intensive Care, Trieste University Medical School, Trieste, Italy (MC, AG).

Supported by an unrestricted grant from Eli Lilly Company.

Dr. De Backer has received honoraria and grant support from Eli Lilly. Dr. Vincent has consulted for Eli Lilly and received honoraria and grant support from the company. The remaining authors do not have any financial interests to declare.

Abstract

Objective:

Microvascular 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.

Design:

Prospective, nonrandomized study.

Setting:

A 31-bed, medico-surgical intensive care unit of a university hospital.

Patients:

Forty adult patients with severe sepsis who met the EU criteria for DAA administration.

Interventions:

Twenty patients received the drug (DAA) and 20 had a contraindication to DAA administration (control).

Measurements and Main Results:

An 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.

Conclusions:

DAA administration rapidly improves sepsis-induced microvascular alterations, whereas its cessation is associated with a transient deterioration.