Methylene blue dosing strategies in critically ill adults with shock—A retrospective cohort study

Abstract

BackgroundShock increases mortality in the critically ill and the mainstay of therapy is the administration of vasopressor agents to achieve hemodynamic targets. In the past, studies have found that the NO-pathway antagonist methylene blue improves hemodynamics. However, the optimal dosing strategy remains elusive. Therefore, we investigated the hemodynamic and ICU outcome parameters of three different dosing strategies for methylene blue.MethodsWe performed a retrospective cohort study of patients in shock treated with methylene blue. Shock was defined as norepinephrine dose >0.1 μg/kg/min and serum lactate level >2 mmol/l at the start of methylene blue administration. Different demographic variables, ICU treatment, and outcome parameters were evaluated. To compare the differences in the administration of vasopressors or inotropes, the vasoactive inotropic score (VIS) was calculated at different time points after starting the administration of methylene blue. Response to methylene blue or mortality at 28 days were assessed.Results262 patients from July 2014 to October 2019 received methylene blue. 209 patients met the inclusion criteria. Three different dosing strategies were identified: bolus injection followed by continuous infusion (n = 111), bolus injection only (no continuous infusion; n = 59) or continuous infusion only (no bolus prior; n = 39). The groups did not differ in demographics, ICU scoring system, or comorbidities. In all groups, VIS decreased over time, indicating improved hemodynamics. Cardiogenic shock and higher doses of norepinephrine increased the chance of responding to methylene blue, while bolus only decreased the chance of responding to methylene blue treatment. 28-day mortality increased with higher SAPSII scores and higher serum lactate levels, while bolus injection followed by continuous infusion decreased 28-day mortality. No severe side effects were noted.ConclusionIn this cohort, methylene blue as a bolus injection followed by continuous infusion was associated with a reduced 28-day mortality in patients with shock. Prospective studies are needed to systematically evaluate the role of methylene blue in the treatment of shock.

Methylene blue therapy versus standard treatment for acute-phase septic shock: a pilot randomized controlled trial

“…Due to its safety pro le, greater availability and lower cost than other catecholamine-sparing agents [35], MB could emerge as a viable therapy within a multimodal strategy to maintain MAP and improve tissue perfusion. Furthermore, MB contributes to reducing the use of highdose vasopressors [21,23,24,[29][30][31][36][37][38][39], which was also found in our study.…”

“…A retrospective cohort study [29] also showed the bene t of MB in different types of circulatory shock (septic, cardiogenic and vasoplegic), with a reduced need for noradrenaline and reduced mortality after 28 days of observation; however, these ndings highlight the importance of performing a prospective and randomized study.…”

Early adjunctive methylene blue in patients with septic shock: a randomized controlled trial

“…2), we believe our positive findings were in part due to this approach, which provided a longer timeframe of iNOS and sGC inhibition. Data from a recent large retrospective study support this assumption; Sari-Yavuz et al studied different modes of administration of MB in critically-ill patients with shock, and they reported that the length of inhibition of the NO pathway could influence the response to MB, rather than the cumulative dose [41].…”

Medical therapy of cardiogenic shock: Contemporary use of inotropes and vasopressors

“…[130][131][132] In a recent retrospective cohort study including 262 patients with shock despite norepinephrine dose >0.1 μg/kg/min, CS increased the chance of responding to MB (adjusted OR 2.21, 95% CI 1.11-4.36). 133 MB could therefore be considered in patients with CS and concomitant distributive shock who do not respond to standard treatment. The dosing regimen for MB seems to be 1-2 mg/kg.…”

“…Beyond NO synthase inhibition, its positive effects in refractory shock may also be due to an improvement in mitochondrial respiration 130–132 . In a recent retrospective cohort study including 262 patients with shock despite norepinephrine dose >0.1 μg/kg/min, CS increased the chance of responding to MB (adjusted OR 2.21, 95% CI 1.11–4.36) 133 . MB could therefore be considered in patients with CS and concomitant distributive shock who do not respond to standard treatment.…”