Inhaled nitric oxide and prevention of pulmonary hypertension after congenital heart surgery: a randomised double-blind study

Miller, Owen; Tang, Swee Fong; Keech, Anthony; Pigott, Nicholas B; Beller, Elaine; Celermajer, David S.

doi:10.1016/s0140-6736(00)02869-5

Cited by 215 publications

(131 citation statements)

References 30 publications

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“…46 Inhaled NO has been reported to ameliorate the postoperative pulmonary hypertension of congenital heart disease 47 and to decrease the need for postoperative ECMO. 48 In a randomized double-blind study, Miller and colleagues 49 examined the effects of the prophylactic use of inhaled NO in high-risk infants undergoing congenital heart surgery. They reported that compared with placebo, infants who after surgery inhaled 10 ppm NO continuously until just before extubation had fewer pulmonary hypertensive crises and shorter times to eligibility for extubation.…”

Section: Treatment Of Perioperative Pulmonary Hypertension With Inhalmentioning

confidence: 99%

Inhaled Nitric Oxide

2004

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Since the recognition of nitric oxide (NO) as a key endothelial-derived vasodilator molecule in 1987, the field of NO research has expanded to encompass many areas of biomedical research. It is now well established that NO is an important signaling molecule throughout the body. The therapeutic potential of inhaled NO as a selective pulmonary vasodilator was suggested in a lamb model of pulmonary hypertension and in patients with pulmonary hypertension in 1991. 1,2 Because NO is scavenged by hemoglobin (Hb) on diffusing into the blood and is thereby rapidly inactivated, the vasodilatory effect of inhaled NO is limited largely to the lung. This is in contrast to intravenously infused vasodilators that can cause systemic vasodilation and severe systemic arterial hypotension.Recent data indicate that inhaled NO can be applied in various diseases. For example, studies suggest that inhaled NO is a safe and effective agent to determine the vasodilatory capacity of the pulmonary vascular bed. This article summarizes the pharmacology and physiology of inhaled NO and reviews the current uses of inhaled NO for the treatment, evaluation, and prevention of cardiovascular and respiratory diseases. Pharmacology and Physiology of Inhaled NO Chemistry of NO GasNO is a colorless, odorless gas that is only slightly soluble in water. 3 NO and its oxidative byproducts (eg, NO 2 and N 2 O 4 ) are produced by the partial oxidation of atmospheric nitrogen in internal combustion engines, in the burning cinder cones of cigarettes, and in lightning storms. Medical-grade NO gas is produced under carefully controlled conditions, diluted with pure nitrogen, and stored in the absence of oxygen. The recent article by Williams 4 provides a review of the chemistry of NO. Therapeutic Versus Endogenous NO Concentrations in the AirwayAlthough early studies of inhaled NO in the treatment of pulmonary hypertension used concentrations of 5 to 80 ppm, it has since been realized that concentrations Ͼ20 ppm provide little additional hemodynamic benefit in most patients. In some adults with acute respiratory failure, the effective concentrations of inhaled NO required to improve oxygenation can be as low as 10 ppb. 5,6 Of note, NO has been detected in exhaled human breath. The majority of exhaled NO in normal humans appears to be derived from nasal bacterial flora (25 to 64 ppb), with lower concentrations measured in the mouth, trachea, and distal airway (1 to 6 ppb). 5,7 Mechanism of ActionAfter inhalation, NO diffuses rapidly across the alveolarcapillary membrane into the subjacent smooth muscle of pulmonary vessels to activate soluble guanylate cyclase (Figure 1). This enzyme mediates many of the biological effects of NO and is responsible for the conversion of GTP to cGMP. Increased intracellular concentrations of cGMP relax smooth muscle via several mechanisms. The physiological actions of cGMP are limited to its area of synthesis by its hydrolysis to GMP by cyclic nucleotide phosphodiesterases (PDE) or by its export from the cell. Of the 11 reported...

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Section: Treatment Of Perioperative Pulmonary Hypertension With Inhalmentioning

confidence: 99%

Inhaled Nitric Oxide

2004

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“…iNO therapy in pediatric patients after surgery for congenital heart disease has been reported in a variety of clinical trials, including case reports, pilot studies, prospective and retrospective investigations, randomized controlled clinical studies, and crossover studies. 3,[7][8][9][10][11][12][13][14][15][16][17][18] The recommended dose of iNO is 20 ppm for the approved indication of hypoxic respiratory failure associated with pulmonary hypertension in term and near-term neonates. 3,19 iNO may also be beneficial in patients with right ventricular dysfunction because it selectively decreases right ventricular afterload and improves right ventricular function.…”

Section: Discussionmentioning

confidence: 99%

Reducing Variation in the Use of Inhaled Nitric Oxide

Simsic¹,

Harrison

Evans

et al. 2014

Pediatrics

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BACKGROUND AND OBJECTIVE: Decreasing practice variation and following clinical guidelines improve patient outcomes and reduce costs. Inhaled nitric oxide (iNO) is an effective but expensive treatment of pulmonary hypertension and right heart failure in patients with congenital or acquired heart disease. Our objective was to implement standardized initiation and weaning guidelines for iNO usage in the cardiothoracic ICU (CTICU) to reduce variation in use while maintaining quality patient care. METHODS: All CTICU patients who received iNO from January 2011 to December 2012 were retrospectively reviewed. Standardized iNO initiation and weaning guidelines were implemented in January 2012. Variables before and after guideline implementation were compared. RESULTS: From January to December 2011, there were 36 separate iNO events (6% of CTICU admissions; n = 547). Mean ± SD iNO usage per event was 159 ± 177 hours (median: 63 hours; range: 27–661 hours). From January to December 2012, there were 47 separate iNO events (8% of CTICU admissions; n = 554). Mean iNO usage per event was 125 ± 134 hours (median: 72 hours; range: 2–557 hours). Initiation guideline compliance improved from 83% to 86% (P = .9); weaning guideline compliance improved from 17% to 79% (P < .001). Although mean iNO usage per event decreased, there was no significant reduction in utilization of iNO (P = .09). CONCLUSIONS: Implementation of standardized iNO initiation and weaning guidelines in the CTICU was successful in reducing practice variation supported by increasing guideline compliance. However, decreasing practice variation did not significantly reduce iNO utilization and does not necessarily reduce cost.

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“…52 Inhaled NO reduces myocardial dysfunction in endotoxemic rats 53 and can prevent pulmonary hypertension after congenital heart defect repair in humans. 54 If these observations are confirmed by clinical trials, prophylactic iNO at non-toxic concentrations could be an excellent medication to reduce excessive inflammatory responses that follow medical or surgical pathologies.…”

Section: Effects On Inflammationmentioning

confidence: 98%

Inhaled nitric oxide in 2003: a review of its mechanisms of action

Wang

Kebir

Blaise

2003

Can J Anesth/J Can Anesth

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P Pu ur rp po os se e: : To review the pulmonary and systemic effects of endogenous nitric oxide and inhaled nitric oxide administered to patients.S So ou ur rc ce e: : A systematic search for experimental data, human case reports, and randomized clinical trials since 1980, the year of discovery of endothelium-derived relaxing factor. P Pr ri in nc ci ip pa al l f fi in nd di in ng gs s: : Nitric oxide has pulmonary and systemic effects. Inhaled nitric oxide not only causes selective pulmonary vasodilation but also results in pulmonary vasoconstriction of the vessels perfusing non-ventilated alveolae. The systemic effects of inhaled nitric oxide, which include modulation of the distribution of systemic blood flow, increase in renal output, interaction with coagulation, fibrinolysis and platelet functions, alteration of the inflammatory response, are described and the mechanisms of nitric oxide transport are explained. The possible toxicity of inhaled nitric oxide is also discussed.C Co on nc cl lu us si io on n: : The multiple effects of inhaled nitric oxide support its role as a pulmonary and extra-pulmonary medication.

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Inhaled nitric oxide and prevention of pulmonary hypertension after congenital heart surgery: a randomised double-blind study

Cited by 215 publications

References 30 publications

Inhaled Nitric Oxide

Inhaled Nitric Oxide

Reducing Variation in the Use of Inhaled Nitric Oxide

Inhaled nitric oxide in 2003: a review of its mechanisms of action

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