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


METHODS
Prospective clinical study.


METHODS
ICU of a university hospital.


METHODS
Eleven critically ill patients with severe refractory septic shock.


METHODS
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.


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.
Avontuur
J A
JA
Department of Surgery and Intensive Care, University Hospital Rotterdam, The Netherlands.
Tutein Nolthenius
R P
RP
Buijk
S L
SL
Kanhai
K J
KJ
Bruining
H A
HA
D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011446:Prospective Studies; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D012772:Shock, Septic / Q000503:physiopathology*
D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester