Infusion of methylene blue in human septic shock: a pilot, randomized, controlled study.
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.


METHODS
Prospective, randomized, controlled, open-label, pilot study.


METHODS
Multidisciplinary intensive care unit of a university hospital.


METHODS
Twenty patients with septic shock diagnosed <24 hrs before randomization.


METHODS
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.


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.
Kirov
M Y
MY
Department of Anesthesiology, Northern State Medical University, Arkhangelsk, Russia.
Evgenov
O V
OV
Evgenov
N V
NV
Egorina
E M
EM
Sovershaev
M A
MA
Sveinbjørnsson
B
B
Nedashkovsky
E V
EV
Bjertnaes
L J
LJ
D000328:Adult; D000368:Aged; D001774:Blood Chemical Analysis; D017024:Chemotherapy, Adjuvant; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D006785:Hospitals, University; D006801:Humans; D007262:Infusions, Intravenous; D007362:Intensive Care Units; D008297:Male; D008751:Methylene Blue / Q000008:administration & dosage*; D008875:Middle Aged; D010865:Pilot Projects; D011336:Probability; D011446:Prospective Studies; D012016:Reference Values; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate; D016896:Treatment Outcome
D008751:Methylene Blue