Effect of L-NAME, an inhibitor of nitric oxide synthesis, on cardiopulmonary function in human septic shock

Study objectives: We tested the effects of continuous infusion of N-G-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, on cardiovascular performance and pulmonary gas exchange in patients with hyperdynamic septic shock. Design: Prospective clinical study. Setting: ICU of a university hospital, Patients: Eleven critically ill patients with severe refractory septic shock. Interventions: Standard hemodynamic measurements were made and blood samples taken before, during, and after 12 h of continuous infusion of 1 mg/kg/h of L-NAME. Measurements and results: Continuous infusion of L-NAME increased mean arterial pressure (MAP) from 65+/-3 (SEM) to 93+/-4 mm Hg and systemic vascular resistance (SVR) from 962+/-121 to 1,563+/-173 dyne . s . cm(-5)/m(2). Parallel to this, cardiac index (CI) decreased from 4.8+/-0.4 to 3.9+/-0.4 L/min/m(2) and myocardial stroke volume (SV) was reduced from 43+/-3 to 34+/-3 mL/m(2), Left ventricular stroke work was increased in the first hour of L-NAME infusion from 31+/-3 to 43+/-4 g . m/m(2) tall p<0.01 compared with baseline), Heart rate, cardiac filling pressures, and right ventricular stroke work did not change significantly (p>0.05). L-NAME increased the ratio of arterial Po-2 to the fraction of inspired O-2 from 167+/-23 to 212+/-27 mm Hg (p<0.05), Venous admixture (QVA/QT) was reduced from 19.4+/-2.6% to 14.2+/-2.1% (p<0.05) and oxygen extraction ratio increased from 21.1+/-2.4% to 25.3+/-2.7% (p<0.05), Oxygen delivery (Do(2)) was reduced following L-NAME, whereas oxygen uptake and arterial lactate and pH were unchanged. Conclusions: Prolonged inhibition of NO synthesis with L-NAME can restore MAP and SVR in patients with severe septic shock. Myocardial SV and CT decrease, probably as a result of increased afterload, since heart rate and stroke work were not reduced. L-NAME can improve pulmonary gas exchange with a concomitant reduction in QVA/QT. L-NAME did not promote anaerobe metabolism despite a reduction in Do(2).