Vardenafil and Weaning from Inhaled Nitric Oxide: Effect on Pulmonary Hypertension in ARDS

Abstract

During severe acute respiratory distress syndrome (ARDS), pulmonary hypertension occurs due to obliteration of the pulmonary capillary bed and together with microvascular vasoconstriction, may lead to right ventricular failure 1 . This is a relatively frequent complication of the disease 2 . Inhaled nitric oxide (iNO) may improve oxygenation, reduce pulmonary artery pressure and improve right heart performance 3 . phosphodiesterase (PDE-1) has recently been reported to enhance iNO pulmonary vasodilation effect for a short period in infants after cardiac surgery 4 and in ARDS 5 . No data are available on the prolonged use of PDE inhibitors in adult critically ill patients, although ample literature is now available on chronically ill subjects with pulmonary hypertension 6 . by the FDA for erectile dysfunction. It did not show 7 and the onset and the duration of the two drugs are in patients with prolonged Q-T, although no severe adverse effects have been reported so far. Subsequent studies focused on its potential use in pulmonary PDE-1 8 .There is little data supporting the enteral use of any kind of PDE-1 for the treatment of refractory pulmonary hypertension in the critical care setting. We report a case of right ventricular failure in ARDS due to pulmonary hypertension, in which weaning from iNO and from mechanical ventilation was possible CASE HISTORYAfter seven days of bilateral pnemococcal pneumonia, a 66-year-old woman with septic shock was admitted to our intensive care unit (ICU). She was a heavy smoker with a clinical history of recurrent bronchitis. A CT scan showed bilateral lung consolidation. The P a O 2 /FiO 2 ratio was 97 with 12 cmH 2 O positive end expiratory pressure and the total static lung compliance was 37 ml/cmH 2 O. Fluids and inotropic support (dobutamine and noradrenaline) resulted in cardiac index (CI) 2.9 l/min/m 2 , global end-diastolic volume 859 ml/m 2 and intrathoracic blood volume 1363 ml/m 2 , measured using continuous cardiac output with the PiCCO system SUMMARY We report a 66-year-old patient with refractory pulmonary hypertension secondary to ARDS who was being treated with inhaled nitric oxide. Enteral vardenafil (phosphodiesterase-5 inhibitor) was tried at two different doses (10 mg and 5 mg), in order to wean the patient from nitric oxide. The higher dose decreased pulmonary pressure but caused systemic hypotension and the drug was discontinued. Subsequently, a 5 mg dose of vardenafil decreased pulmonary pressure without hypotension. Pulmonary hypertension was controlled using vardenafil 10-15 mg divided in 2-3 daily doses. This therapy allowed nitric oxide withdrawal, weaning from mechanical ventilation and discharge from ICU.Vardenafil acted in synergy with inhaled nitric oxide, permitted nitric oxide reduction and discontinuation and proved to be effective as a single, long-term treatment for pulmonary hypertension.

Pulmonary vascular and right ventricular dysfunction in adult critical care: current and emerging options for management: a systematic literature review

“…Limitations include accumulation of toxic metabolites, although this is not usually a clinically significant problem [206]. Rebound PH with RV dysfunction may occur after weaning from NO [262-264], which may be reduced with PDE5 inhibitors [265-270]. …”

Erectile Function Rehabilitation in the Radical Prostatectomy Patient

“…On the other hand, there exists a randomized, controlled trial comparing all three PDE5i in the pulmonary hypertension literature demonstrating superiority of sildenafil over vardenafil in a number of end points (primarily pulmonary artery oxygenation) [37]; (iii) The vardenafil was not dosed correctly for rehabilitation. Of note, doses of vardenafil used in pulmonary hypertension are 10–15 mgs 2–3 times per day [38,39]; (iv) Confounders existed unrelated to lack of efficacy of vardenafil, including surgeon and nerve sparing quality variability related to the large number of centers and surgeons included in the trial; (v) It is also possible that the complexity of the trial design obscured any therapeutic effect.…”

Oral Phosphodiesterase Type 5 Inhibitors: Nonerectogenic Beneficial Uses

“…Giacomini et al. [14] indicated that vardenafil acted in synergy with inhaled NO, permitted NO reduction and discontinuation and proved to be effective as a single, long‐term treatment for PH.…”

“…Aizawa et al [13] showed that long-term oral vardenafil was a safe and effective treatment for PH patients. Giacomini et al [14] indicated that vardenafil acted in synergy with inhaled NO, permitted NO reduction and discontinuation and proved to be effective as a single, long-term treatment for PH.…”