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Effect of L-NAME, an Inhibitor of Nitric Oxide Synthesis, on Cardiopulmonary Function in Human Septic Shock

Jurgen A.M. Avontuur; Rudolf P. Tutein Nolthenius; Steven L.C.E. Buijk; Karan J.K. Kanhai; Hajo A. Bruining
Author and Funding Information

From the Department of Surgery and Intensive Care, University Hospital Rotterdam, Rotterdam, the Netherlands


1998 by the American College of Chest Physicians


Chest. 1998;113(6):1640-1646. doi:10.1378/chest.113.6.1640
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Abstract

Study objectives: We tested the effects of continuous infusion of NG-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/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 · 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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