Inhaled nitric oxide: clinical applications, indications, and toxicology

Abstract

Purpose: Although the analogy of nitric oxide (NO) to Endothelium-derived Relaxing Factor remains controversial, medical use of exogenous NO gas by inhalation has grown exponentially. This review presents the mechanisms of action of inhaled NO in pulmonary hypertension, hypoxaemia, inflammation and oE~iema, as well as its therapeutic and diagnostic indications wi~ emphasis on acute respiratory distress syndrome (ARDS) and toxicology, Source: Two medical databases (Current Contents, Medline) were searched for citations containing the abovementionned key words to December 1996. Moreover, many presentations in congresses such as 4th International Meeting of Biology of Nitric Oxide, 52nd and 53rd Annual Meeting of Canadian Ana~-thetists' Society or 10th Annual Meeting of European Association of Cardiothoradc Anaesthesiologists were used. Principal findings: Inhaled NO is now recognized as an invaluable tool in neonatal and paediatric critical care, and for heart/lung surgery. Other clinical applications in adults, such as chronic obstructive pulmonary disease and ARDS, require a cautious approach, The inhaled NO therapy is fairly inexpensive, but it would seem that it is not indicated for everybody with regards to the paradigm of its efficiency and potential toxicity. The recent discovery of its anti-inflammatory and extrapulmonary effects open new horizons for future applications. Conclusion: Clinical use of inhaled NO was mostly reported in case series, properly designed clinical trials must now be performed to establish its real therapeutic role. These trials would permit adequate selection of the cardiopulmonary disorders, and subsequently the patients that would maximally benefr from inhaled NO therapy.Objectif : M~me si la relation entre le monoxyde d'azote (NO) et I'EDRF (endothelium-derived relaxing factor) n'est pas 6tablie de fa~on absolue, rutilisation m~icale du NO exog~ne ,~ I'~t gazeux a cru de fa~on exponentielle. Ce survol de la litt&ature rappelle les m6canismes d'action du NO inhale dam rhypertension pulmonalre, rhypox~mie, I'inflammation et I'oed~me et jette un regard sur ses indications diagnostiques et ~rapeutiques principalement en rapport avec le syndrome de d(~tresse respirato/re de radulte (SDRA) et la toxicologie du NO. Sources : Deux bases de donn(~es (Current Contents, Medline) induant d~cembre 1996, ont ~ consult~s en faisant appel aux mots-d& mentionn& plus haut. En outre, on a n_avis~ les travaux prL, sent~ ~ des congrc~ comme le 4th International Meeting of Biolo~/ of Nitrous Oxide, les 52" et 53 e congr~s annuels de La Soci&~ canadienne des anestl~sistes et le I 0 ~ congr~s annuel de I'Assoc/at/on europ~nne des anestha_siolo~stes cardiothoraciques. Principales constatations : l'inhalation de NO est maintenant reconnue comme faisant pattie de l'arsenal th&apeutique n~natalogique, p~diatrique et chirurgical cardiopulmonaire. Chez les adultes, les autres indications comme la maladie pulmonalre obstructive chronique et le SDRA sont moins ~videntes. I'inhalation th6rapeutique de NO ne cof...

Nitric oxide and high frequency jet ventilation in a patient with bilateral bronchopleural fistulae and ARDS

“…> 40 ppm) is associated with lung injury and thus close monitoring is essential. 6 The ability to monitor respiratory gases accurately while using HFJV is problematic. Rapid response chemiluminescence analysis was not available but would be preferable, particularly during jet ventilation, in which wide swings in inspiratory flow may entrain dangerously high peak NO levels.…”

Uso do óxido nítrico em pediatria

“…To date, three isoforms of NOS have been described and denominated, depending on cell type or the conditions under which they were identified, constitutive forms (endothelial and neuronal) and inducible or macrophagic, 2,4 in that macrophages appear to be the main source of inducible NOS. 5 All three isoforms of NOS have been identified within the airways of human beings.…”

“…The NO that is liberated by the nerves can control bronchomotor tone, while that liberated by the bronchial epithelium may reduce submucosal edema. 2 Once inhaled, NO easily disperses across the alveolarcapillary membrane reaching pulmonary circulation and vascular smooth muscle, increasing intracellular concentrations of Cyclic GMP and provoking vascular relaxation. 6 Consequentially, PAP and pulmonary vascular resistance (PVR) reduce and gas exchange is improved resulting in an improved ventilation/perfusion ratio (V/Q).…”

“…Later it was demonstrated that endothelial liberation of nitric oxide (NO) was responsible for the biological activity of the endothelium-derived relaxing factor, stimulating intense research into the biological effects of the gas. 2 Nitric oxide is a 1:1 combination of two of the most abundant gasses in the atmosphere. It is highly soluble and exercises paracrine effects over many tissues, regulating a number of different functions, such as vasomotor tone, neurotransmission, immunoresponse and the adhesion of inflammatory cells to the vessel walls.…”

“…Such was the interest generated by the first studies that Science awarded NO the title of "molecule of the year", in 1992. 2 …”