Safety guidelines for use of nitric oxide

Foubert, L.; Fleming, Bruce L.; Latimer, R.D.; Jonas, Max; Oduro, A.; Borland, Colin; Higenbottam, Tim

doi:10.1016/0140-6736(92)91886-d

Cited by 160 publications

(48 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[5][6][7][8] Unfortunately, NO is a toxic molecule and requires specialized delivery systems and monitoring due to the production of methemoglobin and higher oxides of nitrogen. 9 Because of its short half-life, NO has to be administered continuously, and even brief interruptions may cause a dangerous rebound of PH. 10 The advantages of inhaled PGI 2 and iloprost include a lack of toxic reactions and ease of administration.…”

Section: Objectifmentioning

confidence: 99%

Selective pulmonary vasodilation with inhaled aerosolized milrinone in heart transplant candidates

Sablotzki¹,

Starzmann²,

Scheubel

et al. 2005

Can J Anesth/J Can Anesth

View full text Add to dashboard Cite

Purpose: Selective pulmonary vasodilation is an advantageous method for testing the responsiveness of the pulmonary vasculature of heart transplant candidates. A pilot study was undertaken to test the hypothesis that inhaled aerosolized milrinone may cause selective pulmonary vasodilation.Methods: 18 consecutive male heart transplant candidates with either dilated or ischemic cardiomyopathy were included in this open clinical study. Nine of the patients had significant pulmonary hypertension with a mean pulmonary arterial pressure > 30 mmHg. After baseline measurements, 2 mg of milrinone was administered by ultrasonic nebulization. Pulmonary and systemic hemodynamics were measured ten, 30, and 60 min after inhalation. Results:After inhalation for ten minutes, milrinone induced a significant reduction of mean pulmonary arterial pressure (32.7 ± 9.1 vs 37.7 ± 7.5 mmHg, P = 0.01), pulmonary vascular resistance index (296 ± 150 vs 396 ± 151 dyn·sec -1 ·cm -5 · · m 2 , P = 0.02) and transpulmonary gradient (10.6 ± 5.5 vs 15 ± 4.9, P = 0.01) only in patients with significant pulmonary hypertension. There was no significant effect on mean arterial pressure or systemic vascular resistance at any time after inhalation in either group. Furthermore, there was no influence on extravascular lung water or intrathoracic blood volume. Conclusions:We conclude that inhaled aerosolized milrinone for a short period selectively dilates the pulmonary vasculature in heart transplant candidates with elevated pulmonary arterial pressure, without producing systemic side effects. Further comparative studies are necessary to evaluate possible advantages of milrinone compared to other inhaled vasodilators. Résultats : Après avoir été inhalée pendant 10 min, la milrinone a réduit significativement la tension artérielle pulmonaire moyenne (32,7 ± 9,1 vs 37,7 ± 7,5 mmHg, P = 0,01), l'index de résistance vasculaire pulmonaire (296 ± 15 vs 396 ± 151 dyn·s -1 ·cm -5 ·m 2 , P = 0,02) et le gradient transpulmonaire (10,6 ± 5,5 vs 15 ± 4,9, P = 0,01) Objectif

show abstract

Section: Objectifmentioning

confidence: 99%

Selective pulmonary vasodilation with inhaled aerosolized milrinone in heart transplant candidates

Sablotzki¹,

Starzmann²,

Scheubel

et al. 2005

Can J Anesth/J Can Anesth

View full text Add to dashboard Cite

show abstract

“…NO is stable in air for the conditions described (Foubert, et al 1992;E. Demoncheaux, personal communication) while the fan at the front of the horse rapidly removed residual exhaled air.…”

mentioning

confidence: 99%

Nitric oxide and exercise in the horse.

Mills

Marlin

Demoncheaux

et al. 1996

The Journal of Physiology

View full text Add to dashboard Cite

1. The effects of exercise on the production rate of nitric oxide (NO) in exhaled air (VNO) and 20 1 min-', respectively, and induced cyclical changes in the breathing pattern.4. Exercise induced a linear increase in VNO with work intensity to a maximum (428 1 + 31'6 pmol min-' kg-) which coincided with the maximal oxygen uptake for the horses (138 3 + 11 7 ml min-' kg-), although a further increase in VNO (779 3 + 38-4 pmol min-' kg-') occurred immediately after exercise. The changes in VNo correlated well with the tidal volume (r = 0-968; P < 0-01) and the haematocrit (r = 0-855; P < 0-01). 5. In the first 2 min of high intensity exercise, inhaled NO (80 p.p.m.) significantly (P < 0 05) reduced the pulmonary artery pressure: during the first minute, pulmonary artery pressure was 83-1 + 7-6 mmHg compared with a control value of 94 4 + 6-3 mmHg, and during the second minute, 84-2 + 7-1 mmHg compared with a control value of 98-4 + 4-7 mmHg.There were no other significant changes in cardiovascular or respiratory indices, including cardiac output, measured during exercise between control and inhaled NO tests. 6. The results show that exhaled NO is released from the airways of the horse and may contribute to the regulation of pulmonary vascular tone during exercise.

show abstract

“…In clinical practice, this might allow the use of much lower doses of inhaled NO, thereby reducing the potential toxicity related to NO inhalation, such as methemoglobinemia (24), oxidation of NO to NO 2 (25), and NO 2 -related bronchospasm in humans (20). Furthermore, very little is known about the oxidant stress from the production of peroxynitrite (21) in patients with lung inflammation and in immature babies likely to have decreased antioxidant defenses (10).…”

Section: Discussionmentioning

confidence: 99%

Intravenous Dipyridamole Enhances the Effects of Inhaled Nitric Oxide and Prevents Rebound Pulmonary Hypertension in Piglets

et al. 2002

Self Cite

View full text Add to dashboard Cite

Inhaled nitric oxide (NO) is increasingly used in the treatment of pulmonary hypertension, despite its potential toxicity and the risk of life-threatening rebound pulmonary hypertension upon its discontinuation. We investigated whether i.v. dipyridamole, a cGMP phosphodiesterase inhibitor, increased the effects of inhaled NO and prevented rebound pulmonary hypertension. In 14 anesthetized and mechanically ventilated piglets, pulmonary hypertension was induced with U-46619, a thromboxane A 2 analogue. Response to NO and rebound pulmonary hypertension were evaluated without and with i.v. dipyridamole. Low-dose dipyridamole (10 g/kg/min) increased cardiac output and augmented the effects of inhaled NO on pulmonary vascular resistance, with marginal additive effect on mean pulmonary artery pressure. Pulmonary vascular resistance decreased from 904 to 511 (20 parts per million NO) (p Ͻ 0.0005) and 358 dyne s cm Ϫ5 (20 parts per million NO ϩ dipyridamole) (p Ͻ 0.001 versus NO alone), and mean pulmonary artery pressure decreased from 29.0 to 20.5 (p Ͻ 0.0001) and 19.3 mm Hg (NS versus NO), respectively. Mean arterial pressure decreased from 85 to 74 mm Hg (dipyridamole ϩ NO) (p Ͻ 0.01). High-dose dipyridamole (100 g/kg/min) with inhaled NO reduced pulmonary vascular resistance to 334 dyne s cm Ϫ5 but also decreased mean arterial pressure to 57 mm Hg. Eight piglets developed rebound pulmonary hypertension. Two died of acute right ventricular failure and, in five, rebound pulmonary hypertension was prevented by low-dose dipyridamole. NO is a potent endothelium-derived relaxing factor that exerts its vasodilating action through stimulation of soluble guanylyl cyclase and subsequent increase in cGMP in the vascular smooth muscle cell (1-3), where it is rapidly hydrolyzed by cGMP-specific phosphodiesterases (PDE 5) (4, 5). Since its introduction as a selective pulmonary vasodilator, inhaled NO (5, 6) has been used in a variety of pathologies associated with PHT, including adult respiratory distress syndrome, persistent PHT of the newborn, and in adult and neonatal cardiac surgery (7-10). Despite these beneficial effects, two major problems are a cause for concern. First, the safety of long-term inhalation of NO has not been fully elucidated. The maximal exposure limit of 25 ppm NO for 8 h a day, set by the Occupational Safety and Health Administration (11), may not be safe in patients with PHT who are receiving NO continuously for a prolonged period and who, additionally, are likely to have an abnormal pulmonary circulation. Second, severe rebound PHT on sudden withdrawal of inhaled NO has been described previously (12,13).Because cGMP phosphodiesterase (PDE 5) inhibitors induce pulmonary vasodilation (14 -16), we investigated whether dipyridamole, a clinically available cGMP phosphodiesterase inhibitor, could enhance the effects of inhaled NO in experi-

show abstract

Safety guidelines for use of nitric oxide

Cited by 160 publications

References 2 publications

Selective pulmonary vasodilation with inhaled aerosolized milrinone in heart transplant candidates

Selective pulmonary vasodilation with inhaled aerosolized milrinone in heart transplant candidates

Nitric oxide and exercise in the horse.

Intravenous Dipyridamole Enhances the Effects of Inhaled Nitric Oxide and Prevents Rebound Pulmonary Hypertension in Piglets

Contact Info

Product

Resources

About