Methylene blue for vasodilatory shock in the intensive care unit: a retrospective, observational study

Refractory vasodilatory shock is a state of uncontrolled vasodilation associated with underlying inflammation and endothelial dysregulation. Rescue therapy for vasoplegia refractory to catecholamines includes methylene blue (MB) which restores vascular tone. We hypothesized that (1) at least 40% of critically ill patients would respond positively to MB administration and (2) that those who responded to MB would have a survival benefit.

This study was a retrospective review that included all adult patients admitted to an intensive care unit treated with MB for the indication of refractory vasodilatory shock. Responders to MB were identified as those with a ≥ 10% increase in mean arterial pressure (MAP) within the first 1-2 hours after administration. We examined the association of mortality to the groups of responders versus non-responders to MB. A subgroup analysis in patients undergoing continuous renal replacement therapy (CRRT) was also performed. Statistical calculations were performed in Microsoft Excel® (Redmond, WA, USA). Where appropriate, the comparison of averages and standard deviations of demographics, dosing, MAP, and reductions in vasopressor dosing were performed via Chi squared, Fisher's exact test, or two-tailed t-test with a p-value < 0.05 being considered as statistically significant. After using the F-test to assess for differences in variance, the proper two tailed t-test was used to compare SOFA scores among responders versus non-responders.

A total of 223 patients were included in the responder analysis; 88 (39.5%) had a ≥ 10% increase in MAP post-MB administration that was not associated with a significant change in norepinephrine requirements between responders versus non-responders (p=0.41). There was a non-statistically significant trend (21.6% vs 14.8%, p=0.19) toward improved survival to hospital discharge in the MB responder group compared to the non-responder group. In 70 patients undergoing CRRT, there were 33 responders who were more likely to survive than those who were not (p = 0.0111).

In patients with refractory shock receiving MB, there is a non-statistically significant trend toward improved outcomes in responders based on a MAP increase >10%. Patients supported with CRRT who were identified as responders had decreased ICU mortality compared to non-responders.