METHYLENE-BLUE ADMINISTRATION IN SEPTIC SHOCK - A CLINICAL-TRIAL

Objective: A release of nitric oxide has been incriminated in the card iovascular alterations of septic shock, Since guanylate cyclase is the target enzyme in the endothelium-dependent relaxation mediated by nit ric oxide, we studied the acute effects of methylene blue, a potent in hibitor of guanylate cyclase in patients with septic shock, Design: Pr ospective clinical trial, Setting: Medical-surgical intensive care uni t in a university hospital. Patients: Fourteen patients with severe se ptic shock requiring adrenergic therapy, Interventions: Short-term int ravenous infusion of methylene blue, Measurements and Main Results: He modynamic measurements were obtained at baseline, and 30, 60, and 90 m ins after the infusion of 2 mg/kg of methylene blue. Methylene blue ad ministration was followed by a progressive increase in mean arterial p ressure (from 61.1 +/- 7.6 to 71.7 +/- 12.0 mm Hg at 60 mins, p < .01) , Pulmonary arterial pressure, cardiac filling pressures, cardiac outp ut, oxygen delivery, and oxygen consumption were not significantly aff ected. Left ventricular stroke work increased from 42.5 +/- 17.9 to 48 .9 +/- 14.5 g.m after 60 mins (p < .05), Arterial lactate concentratio n decreased from 3.4 +/- 1.4 to 2.7 +/- 1.3 mmol/L (p < .05), Since th ese effects were transient, a second dose of methylene blue was admini stered 90 mins later to six patients and was followed by a similar res ponse. No adverse effect was observed. Conclusions: In septic shock pa tients, the administration of methylene blue results in a transient an d reproducible increase in arterial pressure, associated with an impro vement in cardiac function, but does not increase cellular oxygen avai lability, The significant reduction in blood lactate concentration is probably related to the reductor effect of methylene blue, rather than to an improvement in tissue oxygenation.