Tissue oxygenation and hemodynamic response to no synthase inhibition in septic shock

The objective of the study was to evaluate the tissue oxygenation and hemod ynamic effects of NOS inhibition in clinical severe septic shock. Eight pat ients with septic shock refractory to volume loading and high level of adre nergic support were prospectively enrolled in the study. Increasing doses o f NOS inhibitors [N-G-nitro-L-arginine-methyl ester (L-NAME) or N-G-monomet hyl-L-arginine (L-NMMA)] were administered as i.v. bolus until a peak effec t = 10 mmHg on mean blood pressure was obtained or until side effects occur red. If deemed clinically appropriate, a continuous infusion of L-NAME was instituted and adrenergic support weaning attempted. The bolus administrati on of NOS inhibitors transiently increased mean blood pressure by 10 mm Hg in all patients. Seven out of eight patients received an L-NAME infusion, a ssociated over 24 h with a progressive decline in cardiac index (P < 0.001) and an increase in systemic vascular resistance (P < 0.01). Partial or tot al adrenergic support weaning was rapidly possible in 6/8 patients. Oxygen transport decreased (P < 0.001), but oxygen consumption remained unchanged in those patients in whom it could be measured by indirect calorimetry (5/8 ). Blood lactate and the difference between tonometric gastric and arterial PCO2 remained unchanged. There were 4/8 ICU survivors. We conclude that ni tric oxide synthase inhibition in severe septic shock was followed with a p rogressive correction of the vasoplegic hemodynamic disturbances with final ly normalization of cardiac output and systemic vascular resistances withou t any demonstrable deterioration in tissue oxygenation.