OBJECTIVE: To evaluate the effects of continuous infusion of methylene blue (MB), an inhibitor of the nitric oxide pathway, on hemodynamics and organ functions in human septic shock. DESIGN: Prospective, randomized, controlled, open-label, pilot study. SETTING:Multidisciplinary intensive care unit of a university hospital. PATIENTS: Twenty patients with septic shock diagnosed <24 hrs before randomization. INTERVENTIONS: Patients were randomized 1:1 to receive either MB (MB group, n = 10) or isotonic saline (control group, n = 10), adjunctive to conventional treatment. MB was administered as an intravenous bolus injection (2 mg/kg), followed 2 hrs later by infusion at stepwise increasing rates of 0.25, 0.5, 1, and 2 mg/kg/hr that were maintained for 1 hr each. During infusion, mean arterial pressure was maintained between 70 and 90 mm Hg, while attempting to reduce concurrent adrenergic support. MEASUREMENTS AND MAIN RESULTS:Hemodynamics and organ function variables were assessed over a 24-hr period, and the survival rate at day 28 was noted. Infusion of MB prevented the stroke volume and the left-ventricular stroke work indexes from falling and increased mean arterial pressure. Compared with the control group, MB reduced the requirement for norepinephrine, epinephrine, and dopamine by as much as 87%, 81%, and 40%, respectively. Oxygen delivery remained unchanged in the MB group and decreased in the control group. MB also reduced the body temperature and the plasma concentration of nitrates/nitrites. Leukocytes and organ function variables such as bilirubin, alanine aminotransferase, urea, and creatinine were not significantly affected. Platelet count decreased in both groups. Five patients treated with MB survived vs. three patients receiving conventional treatment. CONCLUSIONS: In human septic shock, continuously infused MB counteracts myocardial depression, maintains oxygen transport, and reduces concurrent adrenergic support. Infusion of MB appears to have no significant adverse effects on the selected organ function variables.
RCT Entities:
OBJECTIVE: To evaluate the effects of continuous infusion of methylene blue (MB), an inhibitor of the nitric oxide pathway, on hemodynamics and organ functions in humanseptic shock. DESIGN: Prospective, randomized, controlled, open-label, pilot study. SETTING: Multidisciplinary intensive care unit of a university hospital. PATIENTS: Twenty patients with septic shock diagnosed <24 hrs before randomization. INTERVENTIONS:Patients were randomized 1:1 to receive either MB (MB group, n = 10) or isotonic saline (control group, n = 10), adjunctive to conventional treatment. MB was administered as an intravenous bolus injection (2 mg/kg), followed 2 hrs later by infusion at stepwise increasing rates of 0.25, 0.5, 1, and 2 mg/kg/hr that were maintained for 1 hr each. During infusion, mean arterial pressure was maintained between 70 and 90 mm Hg, while attempting to reduce concurrent adrenergic support. MEASUREMENTS AND MAIN RESULTS: Hemodynamics and organ function variables were assessed over a 24-hr period, and the survival rate at day 28 was noted. Infusion of MB prevented the stroke volume and the left-ventricular stroke work indexes from falling and increased mean arterial pressure. Compared with the control group, MB reduced the requirement for norepinephrine, epinephrine, and dopamine by as much as 87%, 81%, and 40%, respectively. Oxygen delivery remained unchanged in the MB group and decreased in the control group. MB also reduced the body temperature and the plasma concentration of nitrates/nitrites. Leukocytes and organ function variables such as bilirubin, alanine aminotransferase, urea, and creatinine were not significantly affected. Platelet count decreased in both groups. Five patients treated with MB survived vs. three patients receiving conventional treatment. CONCLUSIONS: In humanseptic shock, continuously infused MB counteracts myocardial depression, maintains oxygen transport, and reduces concurrent adrenergic support. Infusion of MB appears to have no significant adverse effects on the selected organ function variables.
Authors: Hendrik Bracht; Enrico Calzia; Michael Georgieff; Joel Singer; Peter Radermacher; James A Russell Journal: Br J Pharmacol Date: 2012-04 Impact factor: 8.739
Authors: Daniel De Backer; Maurizio Cecconi; Jeffrey Lipman; Flavia Machado; Sheila Nainan Myatra; Marlies Ostermann; Anders Perner; Jean-Louis Teboul; Jean-Louis Vincent; Keith R Walley Journal: Intensive Care Med Date: 2019-02-11 Impact factor: 17.440
Authors: Anders Perner; Anthony C Gordon; Daniel De Backer; George Dimopoulos; James A Russell; Jeffrey Lipman; Jens-Ulrik Jensen; John Myburgh; Mervyn Singer; Rinaldo Bellomo; Timothy Walsh Journal: Intensive Care Med Date: 2016-10-01 Impact factor: 17.440