Inhaled nitric oxide for the adult respiratory distress syndrome.

BACKGROUND The adult respiratory distress syndrome is characterized by pulmonary hypertension and right-to-left shunting of venous blood. We investigated whether inhaling nitric oxide gas would cause selective vasodilation of ventilated lung regions, thereby reducing pulmonary hypertension and improving gas exchange. METHODS Nine of 10 consecutive patients with severe adult respiratory distress syndrome inhaled nitric oxide in two concentrations for 40 minutes each. Hemodynamic variables, gas exchange, and ventilation-perfusion distributions were measured by means of multiple inert-gas-elimination techniques during nitric oxide inhalation; the results were compared with those obtained during intravenous infusion of prostacyclin. Seven patients were treated with continuous inhalation of nitric oxide in a concentration of 5 to 20 parts per million (ppm) for 3 to 53 days. RESULTS Inhalation of nitric oxide in a concentration of 18 ppm reduced the mean (+/- SE) pulmonary-artery pressure from 37 +/- 3 mm Hg to 30 +/- 2 mm Hg (P = 0.008) and decreased intrapulmonary shunting from 36 +/- 5 percent to 31 +/- 5 percent (P = 0.028). The ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2), an index of the efficiency of arterial oxygenation, increased during nitric oxide administration from 152 +/- 15 mm Hg to 199 +/- 23 mm Hg (P = 0.008), although the mean arterial pressure and cardiac output were unchanged. Infusion of prostacyclin reduced pulmonary-artery pressure but increased intrapulmonary shunting and reduced the PaO2/FiO2 and systemic arterial pressure. Continuous nitric oxide inhalation consistently lowered the pulmonary-artery pressure and augmented the PaO2/FiO2 for 3 to 53 days. CONCLUSIONS Inhalation of nitric oxide by patients with severe adult respiratory distress syndrome reduces the pulmonary-artery pressure and increases arterial oxygenation by improving the matching of ventilation with perfusion, without producing systemic vasodilation. Randomized, blinded trials will be required to determine whether inhaled nitric oxide will improve outcome.

[1]  L. Smith,et al.  Potentiation of butylated hydroxytoluene-induced acute lung damage by oxygen. Cell kinetics and collagen metabolism. , 2015, The American review of respiratory disease.

[2]  J. Drazen,et al.  Bronchodilator action of inhaled nitric oxide in guinea pigs. , 1992, The Journal of clinical investigation.

[3]  J. Wain,et al.  Inhaled Nitric Oxide: A Selective Pulmonary Vasodilator Reversing Hypoxic Pulmonary Vasoconstriction , 1992 .

[4]  R. Rossaint,et al.  Extracorporeal Lung Assist with Heparin-Coated Systems , 1992, The International journal of artificial organs.

[5]  J. Wain,et al.  Inhaled nitric oxide. A selective pulmonary vasodilator of heparin-protamine vasoconstriction in sheep. , 1991, Anesthesiology.

[6]  T. Higenbottam,et al.  Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension , 1991, The Lancet.

[7]  S. Moncada,et al.  Nitric oxide: physiology, pathophysiology, and pharmacology. , 1991, Pharmacological reviews.

[8]  P. Kubes,et al.  Nitric oxide: an endogenous modulator of leukocyte adhesion. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[9]  P. Radermacher,et al.  Prostacyclin for the treatment of pulmonary hypertension in the adult respiratory distress syndrome: effects on pulmonary capillary pressure and ventilation-perfusion distributions. , 1990, Anesthesiology.

[10]  L. Ignarro,et al.  Biological Actions and Properties of Endothelium-Derived Nitric Oxide Formed and Released From Artery and Vein , 1989, Circulation research.

[11]  H. Becker,et al.  Prostaglandin E1 and nitroglycerin reduce pulmonary capillary pressure but worsen ventilation-perfusion distributions in patients with adult respiratory distress syndrome. , 1989, Anesthesiology.

[12]  J F Murray,et al.  An expanded definition of the adult respiratory distress syndrome. , 1988, The American review of respiratory disease.

[13]  S. Moncada,et al.  Vascular endothelial cells synthesize nitric oxide from L-arginine , 1988, Nature.

[14]  L. Ignarro,et al.  Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[15]  S. Allen,et al.  Lowered pulmonary arterial pressure prevents edema after endotoxin in sheep. , 1987, Journal of applied physiology.

[16]  S. Gottlieb,et al.  The Effect of Nitroprusside on Pulmonary Edema, Oxygen Exchange, and Blood Flow in Hydrochloric Acid Aspiration , 1987, Anesthesiology.

[17]  S. Moncada,et al.  Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor , 1987, Nature.

[18]  R. Goris,et al.  Multiple-organ failure. Generalized autodestructive inflammation? , 1985, Archives of surgery.

[19]  L. Wood,et al.  Independent influence of blood flow rate and mixed venous PO2 on shunt fraction. , 1983, Journal of applied physiology: respiratory, environmental and exercise physiology.

[20]  W. Sibbald,et al.  Biventricular function in the adult respiratory distress syndrome. , 1983, Chest.

[21]  J. Tomashefski,et al.  The pulmonary vascular lesions of the adult respiratory distress syndrome. , 1983, The American journal of pathology.

[22]  F. Murad,et al.  Agonist‐Induced Endothelium‐Dependent Relaxation in Rat Thoracic Aorta May Be Mediated through cGMP , 1983, Circulation research.

[23]  J. Caldwell.  The magnetic field due to a number of toroidal conductors , 1982 .

[24]  L. Ignarro,et al.  Relationship between cyclic guanosine 3':5'-monophosphate formation and relaxation of coronary arterial smooth muscle by glyceryl trinitrate, nitroprusside, nitrite and nitric oxide: effects of methylene blue and methemoglobin. , 1981, The Journal of pharmacology and experimental therapeutics.

[25]  J. Bogaard,et al.  Thermodilution technique for measurement of cardiac output during artificial ventilation. , 1981, Journal of applied physiology: respiratory, environmental and exercise physiology.

[26]  F. Kuma.  Properties of methemoglobin reductase and kinetic study of methemoglobin reduction. , 1981, The Journal of biological chemistry.

[27]  G. Vlahakes,et al.  The Pathophysiology of Failure in Acute Right Ventricular Hypertension: Hemodynamic and Biochemical Correlations , 1981, Circulation.

[28]  F. Lewis,et al.  Bedside measurement of lung water. , 1979, The Journal of surgical research.

[29]  J. Lynch,et al.  Influence of cardiac output on intrapulmonary shunt. , 1979, Journal of applied physiology: respiratory, environmental and exercise physiology.

[30]  C. Hugod.  Effect of exposure to 43 ppm nitric oxide and 3.6 ppm nitrogen dioxide on rabbit lung , 1979, International archives of occupational and environmental health.

[31]  J. W. Evans,et al.  Limits on VA/Q distributions from analysis of experimental inert gas elimination. , 1977, Journal of applied physiology: respiratory, environmental and exercise physiology.

[32]  W. Zapol,et al.  Pulmonary hypertension in severe acute respiratory failure. , 1977, The New England journal of medicine.

[33]  K. Brigham,et al.  Effect of Increased Vascular Pressure on Lung Fluid Balance in Unanesthetized Sheep , 1975, Circulation research.

[34]  K. Brigham,et al.  Increased sheep lung vascular permeability caused by pseudomonas bacteremia. , 1974, The Journal of clinical investigation.

[35]  J B West,et al.  Measurement of continuous distributions of ventilation-perfusion ratios: theory. , 1974, Journal of applied physiology.

[36]  T L Petty,et al.  Acute respiratory distress in adults. , 1967, Lancet.

[37]  J. Clutton-Brock.  Two cases of poisoning by contamination of nitrous oxide with higher oxides of nitrogen during anaesthesia. , 1967, British journal of anaesthesia.

[38]  F. Roughton,et al.  The kinetics and equilibria of the reactions of nitric oxide with sheep haemoglobin , 1957, The Journal of physiology.

[39]  C. Mélot,et al.  Prostaglandin E1 in the adult respiratory distress syndrome. Benefit for pulmonary hypertension and cost for pulmonary gas exchange. , 1989, The American review of respiratory disease.

[40]  F. Lemaire,et al.  Comparison of ketanserin and sodium nitroprusside in patients with severe ARDS. , 1988, Anesthesiology.

[41]  W. Zapol,et al.  Pulmonary circulation during adult respiratory distress syndrome , 1985 .