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

Crit Care Med. 2006 Jul;34(7):1918-24. doi: 10.1097/01.CCM.0000220498.48773.3C.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Infective Agents / administration & dosage
  • Anti-Infective Agents / pharmacology*
  • Anti-Infective Agents / therapeutic use
  • Female
  • Humans
  • Male
  • Microcirculation / drug effects*
  • Middle Aged
  • Mouth Floor / blood supply*
  • Prospective Studies
  • Protein C / administration & dosage
  • Protein C / pharmacology*
  • Protein C / therapeutic use
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • Sepsis / drug therapy
  • Sepsis / physiopathology*
  • Treatment Outcome


  • Anti-Infective Agents
  • Protein C
  • Recombinant Proteins
  • drotrecogin alfa activated