PULMONARY-HYPERTENSION AND REDUCED CARDIAC-OUTPUT DURING INHIBITION OF NITRIC-OXIDE SYNTHESIS IN HUMAN SEPTIC SHOCK

It has been suggested that inhibitors of nitric oxide synthesis are of value in the treatment of hypotension during sepsis. In this pilot st udy, we examined the effects of inhibition of nitric oxide synthesis b y continuous infusion of N-omega-nitro-L-arginine methyl ester (L-NAME ) at 1.5 mg/kg/h in a patient with severe septic shock. L-NAME produce d a rise in mean arterial blood pressure and systemic vascular resista nce; catecholamine infusion could be reduced. Parallel to these findin gs, there was a 50% reduction in cardiac output and a 5-fold rise in p ulmonary vascular resistance, which resulted in severe pulmonary hyper tension after 3 h of L-NAME infusion, for which the infusion had to be stopped. Following the termination of L-NAME infusion, pulmonary arte ry pressure and blood pressure returned to baseline values, although p ulmonary and systemic vascular resistance remained elevated for severa l hours. We conclude that nitric oxide appears to play a role in the c ardiovascular derangements during human sepsis. Inhibition of nitric o xide synthesis with L-NAME can increase blood pressure and systemic va scular resistance. However, reduced cardiac output and pulmonary hyper tension are possible side effects of continuous NO synthase inhibition . These side effects necessitate careful monitoring and may hinder the clinical application of NO synthase inhibitors.