TY - JOUR
T1 - A dose-finding study of methylene blue to inhibit nitric oxide actions in the hemodynamics of human septic shock
AU - Juffermans, Nicole P.
AU - Vervloet, Marc G.
AU - Daemen-Gubbels, Catharina Rg
AU - Binnekade, Jan M.
AU - Jong, Martin de
AU - Groeneveld, Ab Johan
PY - 2010
Y1 - 2010
N2 - Methylene blue increases blood pressure and myocardial function in septic shock mainly by inhibiting nitric oxide (NO) actions. However, a dose-dependency of methylene blue has not been established. Therefore, the compound is currently used as rescue treatment only. To evaluate dose-dependency, a prospective, randomized, double blind, single centre study was performed in 15 consecutive, mechanically ventilated patients with septic shock admitted to the intensive care unit, in whom methylene blue was infused at 1 mg/kg (n = 4), 3 mg/kg (n = 6) or 7 mg/kg (n = 5) over 20 min. Hemodynamic parameters were measured before and after the infusion. Gastric tonometry was performed. Methylene blue treatment increased heart rate, cardiac index, mean arterial, pulmonary artery, pulmonary artery occlusion and central venous pressures, systemic vascular resistance, ventricular stroke work indices and O-2 delivery and uptake, and decreased lactate levels. Methylene blue had a dose-dependent effect on cardiac index, mean arterial, mean pulmonary artery and pulmonary artery occlusion pressures, left ventricular function, O-2 delivery and consumption and lactate levels. The drug dose-dependently increased the gastric-arterial blood PCO2 gap. The data suggest that in human septic shock, methylene blue increases mean arterial blood pressure by an increase in cardiac index and systemic vascular resistance. The rise in cardiac index is caused by an increase in left ventricular filling and function, increasing tissue oxygenation, even at a dose of 1 mg/kg. High doses of methylene blue may compromise splanchnic perfusion, even though further enhancing global hemodynamics, and should therefore, be avoided in future studies. (C) 2010 Elsevier Inc. All rights reserved
AB - Methylene blue increases blood pressure and myocardial function in septic shock mainly by inhibiting nitric oxide (NO) actions. However, a dose-dependency of methylene blue has not been established. Therefore, the compound is currently used as rescue treatment only. To evaluate dose-dependency, a prospective, randomized, double blind, single centre study was performed in 15 consecutive, mechanically ventilated patients with septic shock admitted to the intensive care unit, in whom methylene blue was infused at 1 mg/kg (n = 4), 3 mg/kg (n = 6) or 7 mg/kg (n = 5) over 20 min. Hemodynamic parameters were measured before and after the infusion. Gastric tonometry was performed. Methylene blue treatment increased heart rate, cardiac index, mean arterial, pulmonary artery, pulmonary artery occlusion and central venous pressures, systemic vascular resistance, ventricular stroke work indices and O-2 delivery and uptake, and decreased lactate levels. Methylene blue had a dose-dependent effect on cardiac index, mean arterial, mean pulmonary artery and pulmonary artery occlusion pressures, left ventricular function, O-2 delivery and consumption and lactate levels. The drug dose-dependently increased the gastric-arterial blood PCO2 gap. The data suggest that in human septic shock, methylene blue increases mean arterial blood pressure by an increase in cardiac index and systemic vascular resistance. The rise in cardiac index is caused by an increase in left ventricular filling and function, increasing tissue oxygenation, even at a dose of 1 mg/kg. High doses of methylene blue may compromise splanchnic perfusion, even though further enhancing global hemodynamics, and should therefore, be avoided in future studies. (C) 2010 Elsevier Inc. All rights reserved
U2 - https://doi.org/10.1016/j.niox.2010.01.006
DO - https://doi.org/10.1016/j.niox.2010.01.006
M3 - Article
C2 - 20109575
SN - 1089-8603
VL - 22
SP - 275
EP - 280
JO - Nitric Oxide
JF - Nitric Oxide
IS - 4
ER -