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 x s x cm(-5)/m2. Parallel to this, cardiac index (CI) decreased from 4.8+/-0.4 to 3.9+/-0.4 L/min/m2 and myocardial stroke volume (SV) was reduced from 43+/-3 to 34+/-3 mL/m2. Left ventricular stroke work was increased in the first hour of L-NAME infusion from 31+/-3 to 43+/-4 g x m/m2 (all 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 PO2 to the fraction of inspired O2 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 (DO2) 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 CI 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 DO2.
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 illpatients 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 x s x cm(-5)/m2. Parallel to this, cardiac index (CI) decreased from 4.8+/-0.4 to 3.9+/-0.4 L/min/m2 and myocardial stroke volume (SV) was reduced from 43+/-3 to 34+/-3 mL/m2. Left ventricular stroke work was increased in the first hour of L-NAME infusion from 31+/-3 to 43+/-4 g x m/m2 (all 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 PO2 to the fraction of inspired O2 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 (DO2) 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 CI 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 DO2.
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Authors: Maryam Alfalasi; Sarah Alzaabi; Linda Östlundh; Rami H Al-Rifai; Suhail Al-Salam; Paul Michel Mertes; Seth L Alper; Elhadi H Aburawi; Abdelouahab Bellou Journal: Biology (Basel) Date: 2022-06-16
Authors: Auguste Dargent; Abderrahmane Bourredjem; Laurent Argaud; Bruno Levy; Isabelle Fournel; Amélie Cransac; Julio Badie; Luc Quintin; Jean-Pierre Quenot Journal: Front Med (Lausanne) Date: 2022-08-09
Authors: Ary Serpa Neto; Antônio P Nassar; Sérgio O Cardoso; José A Manetta; Victor G M Pereira; Daniel C Espósito; Maria C T Damasceno; James A Russell Journal: Crit Care Date: 2012-08-14 Impact factor: 9.097