Effects of methylene blue infusion on gastrointestinal perfusion and gut mucosal damage in septic shock patients

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Patients with severe sepsis (infection) frequently die. Sepsis interferes with the clotting and inflammatory systems and affects the heart, blood pressure as well as tissue oxygenation of the body. The pathogenesis of vasodilation and organ dysfunction in septic shock involves the excessive production of nitric oxide (NO) by activated inducible NO synthase (iNOS). NO stimulates the soluble intracellular enzyme guanylate cyclase (sGC), increasing the generation of cyclic guanosine monophosphate (cGMP). Ultimately, this pathway leads to vasodilation, myocardial depression, increased vascular permeability, loss of gut barrier function, and organ dysfunction. Methylene blue (MB) is a chemical dye that has been shown to scavenge NO, inhibit iNOS, and to inhibit sGC. In septic patients, small trials of MB have consistently demonstrated an increase in blood pressure. MB has been shown to be safe in humans, and has been used for treatment of cyanide poisoning, methemoglobimemia, and malaria. In this study we administered MB to 10 Intensive Care patients with septic shock. A variety of invasive and non-invasive measurements and blood tests were taken over a 24 hour period. Demographic data and illness severity scores were recorded as well as usual haemodynamic measures and recordings for seriously ill patients. Statistical analysis using standard techniques, was done on SPSS version 14.0.

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