Comparative study between high and low dose methylene blue infusion in septic cancer patients. A randomized, blinded, controlled study

Abstract

Purpose: septic shock is a common threat, and is the primary cause of death in almost all critical care units. Management protocols and guidelines are continuously updated. The early use of methylene blue in different doses as adjunctive to vasopressors has promising results. Methods: This double-blind, randomized, controlled trial comprised 90 patients equally divided into 3 groups: Group A received a 100ml 0.9% Nacl placebo over a 20-minute period; Group B received Methylene blue (MB) bolus of 1 mg/kg in 100ml 0.9% Nacl; and Group C received MB bolus of 4 mg/kg in 100ml 0.9% Nacl during the same period. Groups B and C were given a 0.25 mg/kg/hour infusion of MB for 72 hours after the bolus dose. All patients were started on noradrenaline at an infusion rate of 0.1-0.2 microgram/kg/min and were adjusted accordingly to maintain MAP ≥ 65 mmHg. Time of vasopressor discontinuation was the primary outcome while total doses of vasopressors, ventilation days, vasopressors free days, total ICU stay, total hospital stay and mortality rate were the secondary outcomes. Results: Groups B and C had significantly lower noradrenaline dosages compared to Group A (P value <0.05), however no significant difference between Group B and Group C was found. Groups B and C exhibited significantly decreased time to vasopressor termination, mechanical ventilation days, vasopressor free days at 28 days, ICU duration of stay, and hospital stay in comparison to Group A (P value <0.05). However, there was no significant difference between Groups B and C. No discernible difference in the mortality rates between groups was found. Conclusion: In septic shock, early adjunctive low dose MB delivery decreased the need for noradrenaline. Time to vasopressor stop, number of days without vasopressors (28 days), days of mechanical ventilation, duration of intensive care unit & hospital stay were all decreased. No significance between either high or low MB doses while no significant adverse effects were noted. Ethics: After approval of the ethical committee at National Cancer Institute (NCI) - Cairo University [Institutional Review Board Number AP2307-501-058] and prospectively registered at clinicaltrials.gov [NCT 06005558].