Methylene blue increases myocardial function in septic shock.

OBJECTIVE: To study whether the circulatory changes of human septic shock are mediated in part by nitric oxide.
DESIGN: Open-label, nonrandomized clinical trial on the effects of methylene blue, an inhibitor of nitric oxide action.
SETTING: Intensive care unit of a teaching hospital. PATIENTS: Nine consecutive patients with documented septic shock and a pulmonary artery catheter in place, after initial resuscitation with fluids, sympathomimetics, and mechanical ventilation.
INTERVENTIONS: Hemodynamic and metabolic variables were measured before and then 15, 30, 60, and 120 mins after the start of a 20-min infusion of 2 mg/kg of methylene blue.
MEASUREMENTS AND MAIN RESULTS: Patients had a hyperdynamic circulation, and methylene blue increased (p < .01) mean arterial pressure from 84 +/- 18 to 109 +/- 31 mm Hg and cardiac index from 4.7 +/- 0.9 to 5.6 +/- 1.2 L/min/m2, before and 30 mins after starting the methylene blue infusion, respectively. Cardiac filling pressures did not change. In the same time interval, the subnormal systemic vascular resistance index increased (p = .09) and arterial compliance decreased (p < .05). Oxygen delivery and oxygen uptake increased (p < .05) from 714 +/- 188 to 865 +/- 250 mL/min/m2 and from 160 +/- 39 to 186 +/- 44 mL/min/m2, respectively. Except for heart rate, which increased by 11 +/- 8 beats/min (p < .01), variables returned to baseline values at time = 120 mins.
CONCLUSIONS: After initial resuscitation from human septic shock, a single dose of methylene blue transiently increases mean arterial pressure and oxygen uptake, associated with a decrease in arterial compliance and increases in myocardial function and oxygen delivery. Hence, nitric oxide may be a mediator of the circulatory changes of human septic shock.