Comparison of the effects of intravenous almitrine and positive end-expiratory pressure on pulmonary gas exchange in adult respiratory distress syndrome

Abstract

The effects of almitrine on pulmonary gas exchange and haemodynamics were compared to those of positive end-expiratory pressure (PEEP) in 10 patients with a severe adult respiratory distress syndrome (ARDS) who required continuous mechanical ventilation. Haemodynamic and gas exchange measurements were made before and after 30 min of PEEP at a level of 10 cmH2O, then 30 min later, before and at the end of the intravenous infusion of almitrine at a dose of 0.25 mg.kg-1 in 30 min. There was no significant difference between baseline gas exchange and haemodynamic parameters. PEEP and almitrine increased Pao (p = 0.001) from 10.9 to 12.6 kPa and from 10.6 to 12.6 kPa (1 kPa = 7.5 mmHg), respectively, and ratio of venous admixture to total blood flow (Qs/Qt) decreased (p less than 0.001) from 34 to 29% and from 33 to 29%, respectively, the effects of PEEP and almitrine being not significantly different. Neither PEEP nor almitrine caused a significant change in arterial carbon dioxide tension (PaCO2). The haemodynamic parameters did not change significantly with almitrine, whereas mean systemic arterial pressure decreased from 85.4 to 81.1 mmHg (p less than 0.05) with PEEP. These results are consistent with the hypothesis that both treatments improve ventilation/perfusion (VA/Q) distributions, by an increase in functional residual capacity in the case of PEEP and a redistribution of pulmonary perfusion in the case of almitrine.

Dose-dependent effects of almitrine on hemodynamics and gas exchange in an animal model of acute lung injury

“…On the other hand, active vasoconstriction as an expression of HPV or enhancement of HPV may be associated with in-creases in PAP and PVR. Significant additional elevations of PAP and PVR by almitrine have been shown in oleic acid induced lung injury [20,21] and in ARDS [1,2,4,6], but has not been observed by other investigators [9,10,15]. In our study, induction of lung injury caused an increase in mean PAP of about 75 % and more than doubled pulmonary vascular resistance in both groups compared to prelavage levels.…”

“…Reyes et al [1] reported an increase in PaO 2 and a decrease in Q s /Q t in seven patients with ALI using high-dose almitrine (16 mg ´kg ±1 ´min ±1 ). In a study by Prost and co-workers [15] high-dose almitrine (8.0 mg ´kg ±1 ´min ±1 ) increased PaO 2 in ten patients with severe ARDS to the same extent as a PEEP of 10 cm H 2 O. Several clinical studies combining intravenous almitrine with inhalation of nitric oxide had achieved improvements in pulmonary gas exchange when using high doses of almitrine (³ 8 mg ´kg ±1 ´min ±1 ) [3,5,6,7,9].…”

“…However, in experimental protocols restoration or enhancement of hypoxic pulmonary vasoconstriction by infusion of almitrine has only been demonstrated for low doses of almitrine (£ 4 mg ´kg ±1 ´min ±1 ) [11,12,13], whereas higher rates of infusion (³ 8 mg ´kg ±1 ´min ±1 ) seem to inhibit HPV with deleterious effects on pulmonary gas exchange [14]. Nevertheless, most of the clinical studies describing the effects of almitrine with or without combined application of inhaled nitric oxide in ARDS, has demonstrated an increase in arterial oxygenation using high doses (³ 8 mg ´kg ±1 ´min ±1 ) of almitrine [1,2,3,5,7,9,15].…”