Lack of alteration of endogenous nitric oxide pathway during prolonged nitric oxide inhalation in intensive care unit patients.
OBJECTIVE
To compare hemodynamic and gasometric variables and the plasma concentrations of nitric oxide metabolites (cyclic guanosine monophosphate and nitrate and nitrite), endothelin-1, and renin-angiotensin metabolites before and after the start of nitric oxide inhalation, after prolonged nitric oxide inhalation, and before and after nitric oxide withdrawal.


METHODS
Prospective study.


METHODS
Surgical intensive care unit, university hospital.


METHODS
Patients with acute lung injury and right ventricular failure.


METHODS
Nitric oxide inhalation (10-12 ppm) during a median of 2.9 days (12 hrs to 6.5 days).


RESULTS
The pulmonary vasodilator effects of inhaled nitric oxide improved arterial oxygenation in patients with acute lung injury (p < .05) and reduced right atrial pressure in patients with right ventricular dysfunction (p < .01). These beneficial effects lasted the whole period of prolonged inhaled nitric oxide therapy up to 6.5 days. However, when inhaled nitric oxide was withdrawn, pulmonary vasodilator effects rapidly disappeared, and Pao2/Fio2 ratio markedly deteriorated in all studied patients to return to pre-inhaled nitric oxide levels. Changes in plasma cyclic guanosine monophosphate and nitrate and nitrite paralleled those of pulmonary vasodilatory effects. An immediate increase in plasma cyclic guanosine monophosphate with a slightly delayed increase in plasma nitrate and nitrite was observed at inhaled nitric oxide start with no attenuation during the prolonged inhaled nitric oxide therapy. A marked decrease toward pre-inhaled nitric oxide levels was seen within hours of inhaled nitric oxide withdrawal. In addition, no alteration of plasma endothelin-1 or renin-angiotensin mediators was observed during or after inhaled nitric oxide therapy.


CONCLUSIONS
Our study showed a lack of attenuation in the beneficial effects of inhaled nitric oxide and a lack of alteration of endogenous nitric oxide, endothelin-1, and renin-angiotensin pathways during prolonged nitric oxide inhalation.
Lukaszewicz
Anne-Claire
AC
Department of Anesthesiology and Critical Care Medicine, Hospital Lariboisière, University Paris 7, Paris, France.
Mebazaa
Alexandre
A
Callebert
Jacques
J
Matéo
Joaquim
J
Gatecel
Claire
C
Kechiche
Hakim
H
Maistre
Geneviève
G
Carayon
Alain
A
Baudin
Bruno
B
Payen
Didier
D
D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D009320:Atrial Natriuretic Factor / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D019332:Endothelin-1 / Q000097:blood; D045462:Endothelium-Dependent Relaxing Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D018497:Ventricular Dysfunction, Right / Q000097:blood / Q000628:therapy*
D019332:Endothelin-1; D045462:Endothelium-Dependent Relaxing Factors; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP