A best evidence topic was written according to a structured protocol described in ICVTS. The question addressed was ‘In patients with vasoplegic syndrome following cardiac surgery with cardiopulmonary bypass, does adjunctive methylene blue improve outcomes including reduced mortality, morbidity and vasopressor requirements?’

Ovid Medline was searched using a reported search algorithm. Articles that represented the best evidence to answer the clinical question were selected, tabulated and discussed.

Seven articles were selected: 4 randomized controlled trials and 3 observational studies. Studies were single centre with sample sizes ranging from 30 to 120 patients. Two studies reported a significant reduction in mortality among patients who received adjunctive methylene blue for post-cardiopulmonary bypass (CPB) vasoplegic syndrome compared with placebo or standard therapy. Four studies reported improved haemodynamic stability and reduced vasopressor requirements following methylene blue. No studies reported methylene blue-related adverse events or worse outcomes compared to controls or standard therapy. There was significant heterogeneity among the included studies in terms of the timing and dosage of methylene blue therapy as well as the definition of vasoplegic syndrome.

The summation of the best available evidence, which was limited to small clinical trials and observational studies, suggests that the adjunctive administration of methylene blue for refractory post-CPB vasoplegic syndrome is safe and may provide benefits in terms of improved haemodynamic stability, reduction in vasopressor requirements and reduced mortality. Questions surrounding the optimal timing of methylene blue administration, as prophylactic, adjunctive, or rescue therapy for vasoplegic syndrome, require further investigation.