Evaluating in Cirrhotics With Refractory Vasoplegia the Effect of Methylene Blue
Status:
Completed
Trial end date:
2018-01-10
Target enrollment:
Participant gender:
Summary
Mortality rates associated septic shock remains unacceptably high, around 20-50%, with
refractory hypotension in half of these patients. Widespread vasodilatation involves the
activation of the soluble intracellular enzyme guanylate cyclase (GC) by nitric oxide (NO),
resulting in the production of cyclic guanosine monophosphate (cGMP). Initially discovered as
an endothelium-derived relaxing factor in blood vessels, NO is made by the enzyme nitric
oxide synthase (NOS). It has been suggested that the inhibition of NO generation might be a
treatment option for sepsis and septic shock. Methylene blue (MB) is a dye that easily
crosses cell membranes, inhibits iNOS, and is capable of inhibiting the GC enzyme in vascular
smooth muscle cells.Early use of MB can block the progressive decrease in systemic vascular
resistance of patients unresponsive to noradrenaline and mitigate the need for prolonged
vasoconstrictor use. The investigators propose to study the effect of methylene blue on
cirrhotic adults with sepsis, with refractory vasoplegia unresponsive to maximum doses of
noradrenaline and vasopressin.