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

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