title: Methylene blue increases systemic vascular resistance in human septic shock. Preliminary observations.
abstract: We report the hemodynamic improvements induced by intravenous methylene blue (MB), a guanylate cyclase inhibitor, in 2 patients with hyperdynamic septic shock treated with norepinephrine (NE) infusion, mechanical ventilation and hemodialysis. MB injection augmented the low vascular resistance, mean arterial pressure and induced a slight decrease of cardiac index, without any change of heart rate and pulmonary artery wedge pressure. Plasma cyclic GMP levels decreased without a significant change of atrial natriuretic factor levels. MB (2 mg.kg-1) induced a longer lasting improvement of circulatory failure without deleterious side effects, but did not prevent the occurrence of delayed multiorgan failure or subsequent death. These data suggest that in patients, severe sepsis-induced loss of vascular responsiveness to NE involves activation of soluble guanylate cyclase, possibly stimulated by enhanced nitric oxide production. Furthermore, these observations support the concept that pharmacological blockade of guanylate cyclase may improve hemodynamics but not survival rates.
authors.affiliation: Service de Réanimation Médicale, Hôpital de Hautepierre, Strasbourg, France.
authors.forename: F
authors.initials: F
authors.lastname: Schneider
authors.forename: P
authors.initials: P
authors.lastname: Lutun
authors.forename: M
authors.initials: M
authors.lastname: Hasselmann
authors.forename: J C
authors.initials: JC
authors.lastname: Stoclet
authors.forename: J D
authors.initials: JD
authors.lastname: Tempé
mesh_terms: D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008751:Methylene Blue / Q000627:therapeutic use*; D009638:Norepinephrine / Q000627:therapeutic use; D012121:Respiration, Artificial; D012772:Shock, Septic / Q000503:physiopathology* / Q000628:therapy; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D008751:Methylene Blue; D009638:Norepinephrine