Opening the microcirculation: can vasodilators be useful in sepsis?

Objective: A prominent feature of sepsis is dysfunction of the microcirculation, with impaired perfusion and regional tissue oxygenation causing a deficit in oxygen extraction. If shunting of oxygen transport past closed hypoxic microcirculatory beds is responsible for this, vasodilator therapy, which raises the driving pressure of the microcirculation and thereby promotes flow, could recruit such shunted microcirculatory units and improve tissue oxygenation. Design: A literature search was conducted in Medline for evidence of this expected benefit of vasodilators in sepsis. Methods: Studies were searched using the keyword for vasodilating drugs in combination with sepsis, septic, multiple organ failure, or critically ill patients. The search included animal and clinical investigations but only where the effects of vasodilator therapy were demonstrated by regional measures of oxygen transport variables (e.g., oxygen extraction variables, regional ischemia, microcirculatory flow or tissue oxygenation measurements). The vasodilating drugs investigated included prostacyclin, pentoxifylline, N-acetyl-cysteine, and nitric oxide donors used in animal and human sepsis. Results: Prostacyclin and nitric oxide donors are the best studied vasodilating agents in experimental sepsis and have shown improved tissue perfusion and oxygen extraction. In several clinical studies prostacyclin has also been shown to have such beneficial effects. Recent studies using orthogonal polarization spectral imaging have shown microcirculatory recruitment by nitric oxide donors in hemodynamically resuscitated septic patients. Whether such therapeutic modalities aimed at recruitment of the microcirculation improve outcome, however, still has to be determined.