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NCT 02168751; EudraCT 2011-002294-29.

Ventilation-perfusion (VA/Q) relationships and gas exchange were studied by the multiple inert gas technique in 19 patients admitted to hospital with acute severe asthma (FEV, 41 % predicted) before and during the administration of intravenous salbutamol, inhaled salbutamol, or 100% oxygen. Eight patients received a continuous intravenous infusion of salbutamol (4 jig/min, total dose 360 ,ug) and were studied before treatment, after 60 and 90 minutes of treatment, and one hour after treatment had been discontinued. Six patients had measurements before and 15 minutes after inhaling 300 jg salbutamol from a metered dose inhaler on two occasions (total dose 600 jug) and one hour after the last dose. Measurements were also made in five patients before and while they breathed 100% oxygen for 20 minutes. At baseline (fractional inspired oxygen (Fio2) 21%) all patients showed a broad unimodal (n = 10) or bimodal (n = 9) distribution of blood flow with respect to VA/Q. A mean of 10-5% of the blood flow was associated with low VA/) units without any appreciable shunt. One of the best descriptors of VA/) inequality, the second moment of the perfusion distribution on a log scale (log SD Q), was moderately high with a mean of 1 18 (SEM 0 08) (normal < 0-6). Measures of VA/( inequality correlated poorly with spirometric findings. After salbutamol the increase in airflow rates was similar regardless of the route of administration. Intravenous salbutamol, however, caused a significant increase in heart rate, cardiac output, and oxygen consumption (Vo2); in addition, both perfusion to low VA/4 areas and log SD 0 increased significantly. Inhaled salbutamol caused only minor changes in heart rate, cardiac output, Vo2, and VA/Q inequality. Arterial oxygen tension (Pao2) remained unchanged during salbutamol administration, irrespecive of the route of administration. During 100% oxygen breathing there was a significant increase in log SD 0 (from 1 11 to 1 44). It is concluded that patients with acute severe asthma show considerable VA/Q inequality with a high level of pulmonary vascular reactivity. Despite similar bronchodilator effects from inhaled and intravenous salbutamol, VA/0 relationships worsened only during intravenous infusion. Pao2 remained unchanged, however, because the change in VA/Q relationships was associated with an increase in metabolic rate and cardiac output.

Almitrine improves ventilation/perfusion relationships (VA/Q) in COPD, but its effects in ARDS, in which VA/Q mismatching is the cause of severe hypoxemia, are not known. The effects of almitrine on pulmonary gas exchange and circulation were assessed in 9 patients with ARDS who were sedated, paralyzed, and mechanically ventilated at constant FlO2 (range, 0.48 to 0.74). Systemic and pulmonary hemodynamics, conventional gas exchange, and the VA/Q distribution by the multiple inert gas elimination technique (MIGT) were measured before (baseline), during (ALM 15), at the end of (ALM 30), and at 30-min intervals after (POSTALM 30, 60, and 90) the intravenous infusion of 0.5 mg/kg body weight of almitrine over 30 min. Almitrine significantly increased PaO2 from 78 +/- 15 mm Hg to 140 +/- 49 at ALM 15 and 138 +/- 52 at ALM 30. AaPO2 and QS/QT decreased during the administration of the drug. The MIGT showed that almitrine redistributed pulmonary blood flow from shunt areas (reduction from 29 +/- 11 to 17 +/- 11% of QT) to lung units with normal VA/Q ratios (increase from 63 +/- 9 to 73 +/- 6% of QT). The Ppa increased from 26 +/- 5 to 30 +/- 5 mm Hg without changes in QT. Changes were transient, returning toward baseline 30 min after stopping the infusion of the drug. Almitrine significantly reduced the VA/Q inequalities present in ARDS and may be useful in the management of those patients.

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