NITRIC-OXIDE SYNTHASE INHIBITION BY L-NAME IN LEUKOCYTOPENIC PATIENTSWITH SEVERE SEPTIC SHOCK

Objectives:To investigate the effects of nitric oxide synthase inhibit ion by N-G-nitro-L-arginine methyl ester (L-NAME) on hemodynamics and outcome in leukocytopenic (<1000/mu l) patients with severe septic sho ck requiring strong vasopressor support. Design: Prospective clinical study. Setting: Medical intensive care unit. Patients: 10 patients wit h hematologic malignancies in chemotherapy-induced leukocytopenia with severe septic shock and high-dose vasopressor requirement. Interventi on: Continuous intravenous infusion of L-NAME (0.3 mg/kg per hour) for a study period of 24 h with prolongation for up to 96 h according to individual requirements. Measurements and results: Compared to baselin e values, an increase in mean arterial pressure (p = 0.0021), systemic vascular resistance (p = 0.0001), and left ventricular stroke work in dex (p = 0.023) with a concomitant decrease in vasopressor requirement (p < 0.05) was observed during the first 24 h of L-NAME treatment. Ca rdiac output data were unchanged during the study period (p = 0.49). L -NAME was tapered off in five patients who again became responsive to vasopressor medication. Two patients survived the episode of septic sh ock and vasoactive medication was stopped. Conclusions: The data demon strate that inhibition of nitric oxide synthase may be beneficial for the treatment of severe septic shock in leukocytopenic patients as ind icated by an increase in systemic vascular resistance, mean arterial p ressure, and left ventricular stroke work index.