Dose-Response Curves of Inhaled Nitric Oxide with and without Intravenous Almitrine in Nitric Oxide-responding Patients with Acute Respiratory Distress Syndrome

Lü, Qin; Mourgeon, Eric; Law-Koune, J.D.; Roche, S.; Vézinet, Corinne; Abdennour, Lamine; Vicaut, Éric; Puybasset, Louis; Diaby, M.; Coriat, Pierre; Rouby, Jean-Jacques

doi:10.1097/00000542-199511000-00005

Cited by 107 publications

(56 citation statements)

References 31 publications

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“…Similar findings have been reported in studies by PUYBASSET et al [12] and ADATIA et al [22]. NO doses of as little as 1-2 ppm have been shown to be sufficient for optimal treatment of pulmonary hypertension in ARDS patients [9][10][11]. In contrast with these, as well as with the present study, the optimal NO dose in terms of pulmonary vasodilation was found to be as high as 100 ppm by GERLACH et al [13].…”

Section: Discussionsupporting

confidence: 92%

“…The present study further confirms that low NO doses, i.e. in the 0.5-5 ppm range, progressively improve Pa,O 2 in ARDS patients [8][9][10][11][12]. In addition, the results indicate that the Pa,O 2 response to NO doses >5 ppm varies between patients.…”

Section: Discussionsupporting

confidence: 87%

“…The various patterns in Pa,O 2 response observed in the present study support previous discordant findings on the doseresponse curves of NO for Pa,O 2 in ARDS patients. Some studies indicate that the effect of NO on Pa,O 2 reaches a plateau at 5 ppm or even lower doses [9][10][11][12]. Other data show that high NO doses can even deteriorate the Pa,O 2 response [13].…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that very low NO doses (<1 parts per million (ppm)) may have a measurable effect both on pulmonary circulation and on arterial oxygenation in ARDS patients [8][9][10]. Published data indicate that low NO doses, between 1-5 ppm, achieve maximal haemodynamic and oxygenation responses [9][10][11][12]. However, other studies in ARDS patients indicate that higher NO doses may induce an additional reduction in pulmonary hypertension and hypoxaemia.…”

mentioning

confidence: 99%

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Acute effects of inhaled nitric oxide in adult respiratory distress syndrome

Iotti¹,

Olivei²,

Palo³

et al. 1998

Eur Respir J

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In patients with adult respiratory distress syndrome (ARDS), inhaled nitric oxide (NO) may both reduce pulmonary hypertension and improve arterial oxygenation [1,2]. The NO-induced decrease in pulmonary artery pressure depends on the selective pulmonary vasodilating effect of inhaled NO [3], while the NO-induced increase in arterial oxygenation is related to the redistribution of pulmonary blood flow to well-ventilated lung areas, which results in improved ventilation to perfusion matching [1,4]. Although potentially beneficial, inhaled NO is a toxic compound, and its toxicity is increased by the oxidation of NO to NO 2 , which occurs during administration of inhaled NO, especially when the inhaled oxygen concentration is high [5]. In order to minimize the risks of toxicity, inhaled NO should be administered at the lowest effective concentration to achieve maximal therapeutic effects [6,7].There is conflicting information on the NO dose for optimal treatment of pulmonary hypertension and hypoxaemia in ARDS. It has been shown that very low NO doses (<1 parts per million (ppm)) may have a measurable effect both on pulmonary circulation and on arterial oxygenation in ARDS patients [8][9][10]. Published data indicate that low NO doses, between 1-5 ppm, achieve maximal haemodynamic and oxygenation responses [9][10][11][12]. However, other studies in ARDS patients indicate that higher NO doses may induce an additional reduction in pulmonary hypertension and hypoxaemia. In a study by GERLACH et al. [13], a dose of NO as high as 100 ppm was required to achieve maximal pulmonary vasodilation, while the impro-vement in arterial oxygen tension (Pa,O 2 ) was maximal at 1 ppm. In contrast, a study on septic ARDS patients rep-orted a dose-dependent increase in Pa,O 2 in the range 0.1-150 ppm and a plateau effect in pulmonary pressure at 5 ppm [14]. A recent study showed that the optimum NO dose to improve Pa,O 2 may vary widely between individuals, ranging 0.1-100 ppm [15]. In that same study, however, the effect on pulmonary haemodynamics was negligible.The aim of this study was to evaluate the dose-response effect of inhaled NO (0.5-100 ppm) on gas exchange and haemodynamics in ARDS patients treated with conventional mechanical ventilation. Materials and methods PatientsDuring a 10-month period, 19 consecutive patients who were mechanically ventilated for severe ARDS were screen- Olivei, A. Palo, C. Galbusera, R. Veronesi, A. Braschi. ©ERS Journals Ltd 1998. ABSTRACT: This study evaluated the dose-response effect of inhaled nitric oxide (NO) on gas exchange, haemodynamics, and respiratory mechanics in patients with adult respiratory distress syndrome (ARDS). Acute effects of inhaled nitric oxide in adult respiratory distress syndrome. G.A. Iotti, M.C.Of 19 consecutive ARDS patients on mechanical ventilation, eight (42%) responded to a test of 10 parts per million (ppm) NO inhalation with a 25% increase in arterial oxygen tension (Pa,O 2 ) over the baseline value. The eight NO-responders were extensively studied during admin...

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Acute effects of inhaled nitric oxide in adult respiratory distress syndrome

Iotti¹,

Olivei²,

Palo³

et al. 1998

Eur Respir J

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“…However, the observation that shunt flow further increased with the U-46619 infusion contrasts with the common belief that increases in pulmonary artery pressure are usually associated with an improvement in V'/Q' matching. In patients with ARDS, it was recently shown that combining the inhaled vasodilator NO with the intravenously applied vasoconstrictor, almitrine, potentiated an improvement in gas exchange and reduction of shunt flow, as with either NO or almitrine applications [35]. Because almitrine selectively constricts pulmonary arteries and not pulmonary veins [36], it is unlikely that almitrine increases the hydrostatic capillary pressure, but this might be responsible for the U-46619-induced shunt flow, probably as a result of a greater proportion of the lungs in zone 3.…”

Section: Discussionmentioning

confidence: 99%

Effects of inhaled versus intravenous vasodilators in experimental pulmonary hypertension

Walmrath

Schermuly²,

Pilch³

et al. 1997

Eur Respir J

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Inhaled nitric oxide (NO) causes selective pulmonary vasodilation and improves gas exchange in acute lung failure. In experimental pulmonary hypertension, we compared the influence of the aerosolized vasodilatory prostaglandins (PG) PGI 2 and PGE 1 on vascular tone and gas exchange to that of infused prostanoids (PGI 2 , PGE 1 ) and inhaled NO.An increase of pulmonary artery pressure (Ppa) from 8 to ~34 mmHg was provoked by continuous infusion of U-46619 (thromboxane A 2 (TxA 2 ) analogue) in blood-free perfused rabbit lungs. This was accompanied by formation of moderate lung oedema and severe ventilation-perfusion (V'/Q') mismatch, with predominance of shunt flow (>50%, assessed by the multiple inert gas elimination technique).When standardized to reduce the Ppa by ~10 mmHg, inhaled NO (200 ppm), aerosolized PGI 2 (4 ng·kg -1 ·min -1 ) and nebulized PGE 1 (8 ng·kg -1 ·min -1 ) all reduced both pre-and postcapillary vascular resistance, but did not affect formation of lung oedema. All inhalative agents improved the V '/Q ' mismatch and reduced shunt flow, the rank order of this capacity being NO > PGI 2 > PGE 1 . In contrast, lowering of Ppa by intravascular administration of PGI 2 and PGE 1 did not improve gas exchange. "Supratherapeutic" doses of inhaled vasodilators in control lungs (400 ppm NO, 30 ng·kg -1 ·min -1 of PGI 2 or PGE 1 ) did not provoke vascular leakage or affect the physiological V'/Q' matching.We conclude that aerosolization of prostaglandins I 2 and E 1 is as effective as inhalation of nitric oxide in relieving pulmonary hypertension. When administered via this route instead of being infused intravascularly, the prostanoids are capable of improving ventilation-perfusion matching, suggesting selective vasodilation in well-ventilated lung areas. Eur Respir J 1997; 10: 1084- Inhalation of nitric oxide (NO) has been shown to cause "selective" pulmonary vasodilation, in the absence of vasodilatory effects in the systemic circulation [1][2][3][4]. The different response of gas exchange to NO might be related to the underlying mechanism of ventilation perfusion (V '/Q ') imbalance. In patients with chronic obstructive pulmonary disease (COPD) with broad V '/Q ' heterogeneity, caused by low V '/Q ' ratios but negligible intrapulmonary shunt, NO may worsen gas exchange because of increased perfusion of poorly-ventilated areas [5]. By contrast, in patients with severe adult respiratory distress syndrome (ARDS), in whom shunt flow predominates, the pulmonary vasodilatory effect of inhaled NO was accompanied by an acute improvement of gas exchange [6][7][8]. Due to the transbronchial route, the vasodilatory property of this agent is apparently restricted to well-ventilated lung areas, effecting a redistribution of blood flow from nonventilated regions to these areas. This is considered a substantial progress compared to the intravenous use of vasodilators, such as prostaglandin (PG) I 2 and PGE 1 . These prostanoids provoke nonselective vasodilation both in pulmonary and systemic vessels, and w...

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Mechanical Ventilation and Pharmacologic Strategies for Acute Respiratory Distress Syndrome

Cawley,

Skaar,

Anderson

et al. 1998

Pharmacotherapy

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Acute or adult respiratory distress syndrome (ARDS) contributes to mortality and morbidity in the intensive care environment. Appropriate application of microprocessor‐controlled mechanical ventilatory support, pathophysiology of the disease, and new pharmacologic modalities are currently being investigated. Mechanical ventilation is usually begun when respiratory failure is caused by alveolar hypoventilation or hypoxia. Primary choices for this therapy are control‐mode ventilation, assist‐control ventilation, pressure‐control ventilation, intermittent mandatory ventilation, and synchronized intermittent mandatory ventilation with the addition of positive end‐expiratory pressure. Patients who deteriorate despite these interventions may require alternative modes of ventilation. Pharmacologic agents in ARDS is important due to the multifactorial pathophysiologic and pharmacodynamic processes that are part of the disease. Clinical studies will continue to determine advantageous agents. Unfortunately, no convincing data exist that any pharmacologic or nonpharmacologic strategy is superior for the support of these patients or results in a better outcome than others.

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Dose-Response Curves of Inhaled Nitric Oxide with and without Intravenous Almitrine in Nitric Oxide-responding Patients with Acute Respiratory Distress Syndrome

Cited by 107 publications

References 31 publications

Acute effects of inhaled nitric oxide in adult respiratory distress syndrome

Acute effects of inhaled nitric oxide in adult respiratory distress syndrome

Effects of inhaled versus intravenous vasodilators in experimental pulmonary hypertension

Mechanical Ventilation and Pharmacologic Strategies for Acute Respiratory Distress Syndrome

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