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

Abstract

Pulmonary hypertension (PH) is a characteristic feature of the acute respiratory distress syndrome (ARDS). The magnitude of PH has been shown to correlate with the severity of lung injury in patients with ARDS independently of the severity of associated hypoxaemia and has an adverse prognostic significance.Early in the histopathological evolution of ARDS, pulmonary vasoconstriction, thromboembolism and interstitial oedema contribute to the development of PH, although pulmonary vascular remodelling probably occurs eventually. Intravenous vasodilator agents lead to an increase in intrapulmonary shunting and systemic hypotension, which can limit their therapeutic use, and have not been shown to improve survival. By contrast, rapidly metabolised vasodilators administered by inhalation induce selective pulmonary vasodilatation and decrease shunting, but again do not appear to confer a survival benefit.Research aimed at further understanding the mechanisms that underlie pulmonary hypertension, a characteristic feature of the acute respiratory distress syndrome, are expected to provide improvements in pharmacological interventions for the treatment of pulmonary hypertension in the acute respiratory distress syndrome.

Sildenafil for pulmonary hypertension in ARDS: a new pleasant effect?

“…Inhaled NO not only reduced pulmonary hypertension, thus decreasing the RV load, but also improved matching of ventilation and perfusion, thus ameliorating hypoxemia [5,7,8]. Similar findings were reported in physiologic investigations using aerosolized prostacyclin [7].…”

“…Acute cor pulmonale, described as RV dilation with septal dyskinesia, impairment of left ventricle diastolic filling, and compensatory tachycardia to preserve cardiac output, occurs in 25% of patients with ALI/ARDS receiving protective mechanical ventilation [6]. In this scenario, systemic vasodilators are not usually recommended because their benefit on pulmonary circulation is achieved at the cost of further aggravation of ventilation/perfusion mismatch due to increases in intrapulmonary shunt and hypoxemia induced by the simultaneous dilation of systemic and pulmonary vessels, and might favor systemic hypotension [5,7].Selective modulation of pulmonary perfusion in ARDS became feasible with the introduction of nitric oxide (NO). Inhaled NO not only reduced pulmonary hypertension, thus decreasing the RV load, but also improved matching of ventilation and perfusion, thus ameliorating hypoxemia [5,7, 8].…”

“…In this scenario, systemic vasodilators are not usually recommended because their benefit on pulmonary circulation is achieved at the cost of further aggravation of ventilation/perfusion mismatch due to increases in intrapulmonary shunt and hypoxemia induced by the simultaneous dilation of systemic and pulmonary vessels, and might favor systemic hypotension [5,7].…”

“…In patients with ARDS, all the aforementioned pathophysiologic events are associated with an increased risk of death [2][3][4]. Pulmonary hypertension might be further aggravated because of hypoxic pulmonary vasoconstriction, which preserves gas exchange, and/ or protective mechanical ventilation with low tidal volume and moderate/high positive end-expiratory pressure (PEEP), which causes a variable degree of hypercapnia and subsequently vasoconstriction of the pulmonary vascular bed [5,6]. The negative effect of pulmonary hypertension is particularly important in the performance of the right ventricle (RV).…”

“…Moreover, most of the patients had sepsis requiring treatment with vasoactive drugs. In sepsis, NO-induced vasodilation probably increases the effect of sildenafil in the systemic circulation [5]. Second, patients initially presenting with bilateral infiltrates suggestive of bilateral pneumonia were excluded from the study.…”