Short-term effects of methylene blue on hemodynamics and gas exchange in humans with septic shock

Objective. The aim of this study was to investigate the acute effects of methylene blue (MB), an inhibitor of the L-arginine nitric oxide pathway, in patients with septic shock. Design: A prospective, open, single-dose study. Setting: The medical ICU of a university hospital. Patients. Six patients with severe septic shock. interventions: Complete hemodynamic values were recorded before and 20 min after the infusion of intravenous MB (3 mg kg(-1)). Arterial pressure was then monitored during the next 24 h or until death. Measurements and results: Methylene blue increased the mean arterial pressure from 69.7 +/- 4.5 to 83.7 +/- 15.1 mmHg (p = 0.028) and the mean pulmonary artery pressure, from 34.3 +/- 7.2 to 38.7 +/- 8.0 mmHg (p = 0.023). Systemic vascular resistance index was increased from 703.1 +/- 120.6 to 903.7 +/- 152.2 dyne.s.cm(-5).m(-2) (p = 0.028) and pulmonary vascular resistance index, from 254.6 +/- 96.9 to 342.2 +/- 118.9 dyne.s.cm(-5).m(-2) (p = 0.027). The PaO2/FIO2 decreased from 229.2 +/- 54.4 to 162.2 +/- 44.1 mmHg (p = 0.028), without significant modification of intrapulmonary shunting. Heart rate, cardiac index, right atrial pressure, DO2, VO2, oxygen extraction and arterial lactate were essentially unchanged. Sequential measurements of arterial pressure demonstrated a return to baseline level in 2-3 h. All but one patients died, three in shock and two in multiple organ failure. Conclusions: MB induces systemic and pulmonary vasoconstriction in patients with septic shock, without significant decrease in cardiac index. The worsening of arterial oxygenation following MB injection may limit its use in patients with the adult respiratory distress syndrome. Larger studies are required to determine whether MB improves the outcome of patients with septic shock.