Twenty years of vasoplegic syndrome treatment in heart surgery. Methylene blue revised

Objective: This study was conducted to reassess the concepts established over the past 20 years, in particular in the last 5 years, about the use of methylene blue in the treatment of vasoplegic syndrome in cardiac surgery. Methods: A wide literature review was carried out using the data extracted from: MEDLINE, SCOPUS and ISI WEB OF SCIENCE. Results: The reassessed and reaffirmed concepts were 1) MB is safe in the recommended doses (the lethal dose is 40 mg/kg); 2) MB does not cause endothelial dysfunction; 3) The MB effect appears in cases of NO up-regulation; 4) MB is not a vasoconstrictor, by blocking the cGMP pathway it releases the cAMP pathway, facilitating the norepinephrine vasoconstrictor effect; 5) The most used dosage is 2 mg/kg as IV bolus, followed by the same continuous infusion because plasma concentrations sharply decrease in the first 40 minutes; and 6) There is a possible "window of opportunity" for MB's effectiveness. In the last five years, major challenges were: 1) Observations about side effects; 2) The need for prophylactic and therapeutic guidelines, and; 3) The need for the establishment of the MB therapeutic window in humans. Conclusion: MB action to treat vasoplegic syndrome is time-dependent. Therefore, the great challenge is the need, for the establishment the MB therapeutic window in humans. This would be the first step towards a systematic guideline to be followed by possible multicenter studies.