Septic Shock Clinical Trial
Official title:
The Effect of Methylene Blue on Microcirculation in Patients With Septic Shock: a Randomized Controlled Trial
This trial aims to identify the effects of methylene blue infusion on the the micro-circulation in patients with septic shock. The investigators will evaluate various indices of micro-circulation such as: microvascular flow index, the flow heterogeneity index, the total vessel density, the perfused vessel density, and the proportion of perfused vessels.
The mortality rate of patients with septic shock remains very high. Arterial hypotension,
related to arteriolar vasodilation and myocardial depression are the mainstays of septic
shock pathology.
At the level of the micro-circulation, there is insufficient delivery of oxygen to organs and
tissues which results in organ dysfunction and potential organ necrosis.One key factor
leading to vascular dysfunction is the inappropriately increased production of nitric oxide
within the blood vessel endothelium. Elevated levels of nitric oxide results in the blood
vessel endothelium receiving direct vasodilator input, as well as the inability to respond to
norepinephrine-mediated vasoconstriction. Nitric oxide activates the soluble isoform of the
enzyme guanylatecyclase, which in turn increases production of cyclic guanosine
monophosphate. Nitric oxide has other beneficial effects which are mediated via other
pathways than guanylatecyclase; therefore, administration of a guanylate cyclase inhibitor
such as methylene blue could be a safer therapeutic option than the inhibition of nitric
oxide production.
These effects of methylene blue could be related to vasoconstriction and positive inotropic
effects as well to an increase in blood volume, itself related to a decrease in vascular
permeability. The use of methylene blue has been recently advocated as a potential adjunct in
the treatment of shock states. However, the effect of MB at the level of the capillary bed,
where vital exchange of oxygen and nutrients occurs, is unknown. Thus in this study, the
investigators will investigate the effect of methylene blue in combination with NE at the
microvascular level in septic shock.
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