An interesting context to end-organ dysfunction in sepsis stems from microcirculatory dysfunction, secondary to endothelial activation and vascular disruption as part of the inflammatory cascade. Even though abnormal vasoconstriction in sepsis may be pharmacologically ameliorated, microcirculatory perfusion remains impaired.
This interesting trial attempted to modulate microcirculation through the use of inhaled nitric oxide. Authors enrolled patients whose macrocirculation had been optimized, using objective targets consistent with contemporary care in septic shock, and randomized them to inhaled nitric oxide or sham. Using a custom device for 40 ppm nitric oxide inhalation – for which authors all deny COI – an enrollment of 138 patients was planned.
However, after 49 patients, the trial was stopped due to futility. The device was a success – as measured by circulating nitrite levels. Unfortunately, from a microcirculation perfusion endpoint, there was no difference. Likewise, there were no obvious differences or trends in secondary clinical outcomes. There were, at least no obvious harms related to therapy.
Next steps in evaluation of this therapy – if any – are as of yet unclear.
“Randomized Controlled Trial of Inhaled Nitric Oxide for the Treatment of Microcirculatory Dysfunction in Patients With Sepsis”
http://www.ncbi.nlm.nih.gov/pubmed/25080051