METHYLENE-BLUE INCREASES MYOCARDIAL-FUNCTION IN SEPTIC SHOCK

Objective: To study whether the circulatory changes of human septic sh ock are mediated in part by nitric oxide. Design: Open-label, nonrando mized clinical trial on the effects of methylene blue, an inhibitor of nitric oxide action. Setting: Intensive care unit of a teaching hospi tal. Patients: Nine consecutive patients with documented septic shock and a pulmonary artery catheter in place, after initial resuscitation with fluids, sympathomimetics, and mechanical ventilation, Interventio ns: 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 hy perdynamic circulation, and methylene blue increased (p < .01) mean ar terial pressure from 84 +/- 18 to 109 +/- 31 mm Hg and cardiac index f rom 4.7 +/- 0.9 to 5.6 +/- 1.2 L/min/ m(2), before and 30 mins after s tarting the methylene blue infusion, respectively. Cardiac filling pre ssures did not change. In the same time interval, the subnormal system ic vascular resistance index increased (p = .09) and arterial complian ce decreased (p < .05). Oxygen delivery and oxygen uptake increased (p < .05) from 714 +/- 188 to 865 +/- 250 mL/min/m(2) and from 160 +/- 3 9 to 186 +/- 44 mL/min/m(2), respectively, Except for heart rate, whic h increased by 11 +/- 8 beats/min (p < .01), variables returned to bas eline values at time = 120 mins.Conclusions: After initial resuscitati on from human septic shock, a single dose of methylene blue transientl y 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 cir culatory changes of human septic shock.