Nitric oxide synthase inhibition by L-NAME in leukocytopenic patients with severe septic shock

Abstract

Objectives: To investigate the effects of nitric oxide synthase inhibition by N^G-nitro-l-arginine methyl ester (l-NAME) on hemodynamics and outcome in leukocytopenic ( < 1000/μl) patients with severe septic shock requiring strong vasopressor support. Design: Prospective clinical study. Setting: Medical intensive care unit. Patients: 10 patients with hematologic malignancies in chemotherapy-induced leukocytopenia with severe septic shock and high-dose vasopressor requirement. Intervention: 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 baseline values, an increase in mean arterial pressure (p = 0.0021), systemic vascular resistance (p = 0.0001), and left ventricular stroke work index (p = 0.023) with a concomitant decrease in vasopressor requirement (p < 0.05) was observed during the first 24 h of l-NAME treatment. Cardiac 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 shock and vasoactive medication was stopped. Conclusions: The data demonstrate that inhibition of nitric oxide synthase may be beneficial for the treatment of severe septic shock in leukocytopenic patients as indicated by an increase in systemic vascular resistance, mean arterial pressure, and left ventricular stroke work index.