Cyclic 3', 5'-guanosine monophosphate (cGMP) stimulated by increased nitric oxide (NO) is responsible for the hypotension associated with low vascular tone and disturbance of gas exchange in a septic hyperdynamic state. We hypothesized that methylene blue (MB), a soluble guanylate cyclase inhibitor, would improve systemic circulation and gas exchange. In order to achieve this aim, we administered MB to eight septic patients in a hyperdynamic state (cardiac index>3.5L·min.^-1·m^-2).
Hemodynamic data before MB infusion showed low vascular resistance and hypotension despite the administration of catecholamines. A high respiratory index (RI) and intrapulmonary shunt (QVA/QT) were also demonstrated. MB 2mg·Kg^-1 was continuously administered for 30 minutes. Systemic and pulmonary hemodynamics and respiratory parameters were measured and blood cyclic 3', 5'-adenosine monophosphate (cAMP) and cGMP were also assessed before, at the end of, and one hour, two hours and 24 hours after MB infusion.
Mean arterial pressure (mAP) and the systemic vascular resistance index (SVRI) increased significantly, whereas mean pulmonary arterial pressure (mPAP), the pulmonary vascular resistance index (PVRI), Q_VA/Q_t and RI did not change following MB administration. MB significantly incerased mAP and SVRI up to 24 hours with the maximum increase occurring at the end of MB infusion. The blood cGMP levels decreased significantly two hours after MB administration, but the blood cAMP levels showed no significant change.
These results suggest that MB improves systemic circulation but does not alter gas exchange in patients with septic shock.