Prostaglandin E₁in the Adult Respiratory Distress Syndrome: Benefit for Pulmonary Hypertension and Cost for Pulmonary Gas Exchange

Abstract

Prostaglandin E1 (PGE1) has been reported to improve survival in patients with the adult respiratory distress syndrome (ARDS). However, the effects of this pulmonary vasodilating compound on gas exchange have been little documented. We therefore measured hemodynamics, blood gases, and the distributions of ventilation-perfusion ratios (VA/Q), using the multiple inert gas elimination technique, at baseline and during infusion of PGE1 0.02 to 0.04 microgram.kg-1.min-1 in six patients with pulmonary hypertension secondary to ARDS ventilated with 10 cm H2O positive end-expiratory pressure. PGE1 decreased systemic arterial mean pressure (-16%) and pulmonary arterial mean pressure (-15%) and increased cardiac index (+20%) and heart rate (+11%). Arterial PO2 decreased from 99 +/- 6 to 77 +/- 8 mm Hg (p less than 0.01, mean +/- SEM) with no change in mixed venous PO2 and in O2 consumption. PGE1 increased true shunt from 21 +/- 4 to 32 +/- 5% of total blood flow (p less than 0.01) with no significant modification in the pattern of VA/Q distribution. Thus, in ARDS, pulmonary hypertension is reduced by PGE1 at the price of a deterioration in pulmonary gas exchange. The clinical relevance of these findings remains to be evaluated.

Protective role of prostaglandin E1 analog in indomethacin-induced deterioration in acute respiratory distress syndrome in rats

“…PG is one of them but its role in ARDS is not clear. [12][13][14][15] In the present study also, inhibition of PG synthesis by indomethacin pretreatment killed the animals within 15 min of OA administration as reported earlier indicating a beneficial role of PG in ARDS. Further, improvement in the RF, HR, MAP, and lung injury when PGE1 analog (misoprostol) was given as pretreatment along with indomethacin, indicates that PGs play a protective role in ARDS.…”

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

“…In one large-scale, randomised, controlled trial, PGE 1 reduced Ppa and increased cardiac output in patients with ARDS, indicating unequivocal pulmonary vasodilation. However, Pa,O 2 decreased by 22% as the result of an increase in true shunt from 21% to 35% [60]. Further, PGE 1 has not been shown to afford a survival benefit in ARDS, despite significantly reducing PVR [6].…”

“…NO was inhaled for 3-53 days without loss of beneficial haemodynamic effect or evidence of toxicity [64]. In subsequent studies, NO was shown to increase the Pa,O 2 /FI,O 2 ratio, decrease the pulmonary shunt fraction and reduce PVR [60,66]. Doses that improved gas exchange (0.06-0.25 ppm), were found to be lower than the doses that reduced Ppa (5-20 ppm).…”

“…Furthermore, it is difficult to predict which patients will respond to inhaled NO or not [69]. Methaemoglobinaemia decreased platelet aggregation and, when abruptly discontinued, rebound deterioration in arterial oxygenation and elevation of PH were also significant possible side-effects [60,66]. Finally, it has been demonstrated that any benefit in oxygenation does not last longer than 24 h (table 4) [80,81].…”

Effects of inhaled versus intravenous vasodilators in experimental pulmonary hypertension

“…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 within the lung vasculature in ventilated and nonventilated areas, with an increase in shunt flow [9,10].In order to circumvent these disadvantages, we employed aerosolization technology to use the transbronchial route of application for the vasodilatory prostanoid PGI 2 also. We demonstrated an improvement of arterial oxygenation due to decreased shunt flow and a selective pulmonary vasodilation in patients with severe ARDS and severe pneumonia [11,12].…”