Inhaled Nitric Oxide and Vasoconstrictors in Acute Respiratory Distress Syndrome

Abstract

It has been suggested that the increase in PO(2) observed with nitric oxide (NO) should be enhanced by the addition of a vasoconstrictor agent. The vasoconstrictor used in combination with NO should mimic or enhance hypoxic vasoconstriction. The aim of this study was to evaluate the respiratory and hemodynamic effects of norepinephrine (a nonspecific vasoconstrictor), almitrine bismesylate (a specific pulmonary vasoconstrictor), and inhaled NO, alone or together. During a 6-mo period, 16 patients presenting with ARDS were prospectively investigated. On inclusion, no patient was receiving cardiovasoactive drugs. The protocol consisted of seven consecutive phases: baseline, norepinephrine (in order to obtain a 3 mm Hg rise in mean pulmonary arterial pressure [Ppa]), almitrine bismesylate (16 micrograms/kg/min), inhaled NO (20 ppm delivered during inspiration), norepinephrine + inhaled NO, almitrine bismesylate + inhaled NO, almitrine bismesylate + norepinephrine + inhaled NO. General factorial analysis of variance showed that inhaled NO and almitrine bismesylate increased oxygenation (p < 0.0001). Norepinephrine had no effect on oxygenation. A synergistic effect between inhaled NO and almitrine bismesylate was found (p < 0.05), whereas norepinephrine did not affect the response to inhaled NO. Nitric oxide produced a significant decrease in Ppa and pulmonary vascular resistances (PVRI) (p < 0.0001). Both almitrine bismesylate and norepinephrine induced an increase in Ppa (p < 0.0001). Norepinephrine increased PVRI (p < 0.002), whereas almitrine bismesylate had no effect on PVRI. The present results support the hypothesis that a selective pulmonary vasoconstrictor enhances the increase in oxygenation induced by inhaled NO, whereas norepinephrine attenuates this effect.

Pathophysiology and pharmacological treatment of pulmonary hypertension in acute respiratory distress syndrome

“…However, they are superficially unattractive because of their negative effect on Ppa and right ventricular function. In these circumstances, constricting the shunting vascular bed whilst simultaneously vasodilating well-ventilated areas would be therapeutically attractive [86][87][88]. Almitrine, a peripheral chemoreceptor agonist, improves V9/Q9 matching in patients with chronic obstructive pulmonary disease, presumably through an enhancement of HPV [89].…”

Phosphodiesterases in the Vascular System.

“…Inhalation of gaseous NO (Troncy et al, 1998;Papazian et al, 1999) and nebulization of PGI2 (Walmrath et al, 1993;Olschewski et al, 1996;Walmrath et al, 1996;Zwissler et al, 1996) have been noted both to improve ventilationperfusion matching and to lower pulmonary arterial pressure in patients suffering from acute respiratory distress syndrome or chronic pulmonary hypertension. The prostanoid PGI2 doses, however, possess a very short biological half-life (2-3 min) at a physiological pH, and after inhalation of aerosolized PGI2 the pulmonary vasodilator effect is lost within <30 min both under experimental conditions and when tested in patients Schermuly et al, 1999).…”

The Initial Response to Inhaled Nitric Oxide Treatment for Intensive Care Unit Patients with Acute Respiratory Distress Syndrome

“…Patients who fail to respond to INO may benefit from an optimal PEEP trial [31]. Selective vasoconstrictors, such as almitrine, have also been shown to improve oxygenation [32], but nonselective vasoconstrictors, such as norepinephrine, have not been shown to improve oxygenation [33]. …”