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Hemodynamic and Gas Exchange Effects of Sildenafil in Patients with Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension

¹ Department of Pulmonary Medicine, Hospital Clínic–Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona; and ² Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Spain

Correspondence and requests for reprints should be addressed to Joan A. Barberà, M.D., Servei de Pneumologia, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain. E-mail: jbarbera{at}clinic.ub.es

Rationale: Sildenafil, a phosphodiesterase-5 inhibitor, could be useful for treating pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD). However, vasodilators may inhibit hypoxic pulmonary vasoconstriction and impair gas exchange in this condition.

Objectives: To assess the acute hemodynamic and gas exchange effects of sildenafil in patients with COPD-associated PH.

Methods: We conducted a randomized, dose comparison trial in 20 patients with COPD-associated PH. Eleven patients were assigned to 20 mg, and 9 patients to 40 mg, of sildenafil. Pulmonary hemodynamics and gas exchange, including ventilation–perfusion () relationships, were assessed at rest and during constant-work rate exercise, before and 1 hour after sildenafil administration.

Measurements and Main Results: Both sildenafil doses reduced the mean pulmonary arterial pressure (PAP) at rest and during exercise, without differences between them. Overall, PAP decreased –6 mm Hg (95% confidence interval [95% CI], –7 to –4) at rest and –11 mm Hg (95% CI, –14 to –8) during exercise. After sildenafil, Pa_O2 decreased –6 mm Hg (95% CI, –8 to –4) at rest because of increased perfusion in units with low ratio, without differences between doses. No change in Pa_O2 (95% CI, –3 to 0.2 mm Hg) or relationships occurred during exercise after sildenafil. Changes induced by sildenafil in Pa_O2 and distributions at rest correlated with their respective values at baseline.

Conclusions: In patients with COPD-associated PH, sildenafil improves pulmonary hemodynamics at rest and during exercise. This effect is accompanied by the inhibition of hypoxic vasoconstriction, which impairs arterial oxygenation at rest. The use of sildenafil in COPD should be done cautiously and under close monitoring of blood gases.

Clinical trial registered with www.clinicaltrials.gov (NCT00491803).

Key Words: vasodilator agents • pulmonary circulation • arterial oxygen pressure • ventilation–perfusion relationships • phosphodiesterase-5 inhibitors

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Sildenafil, a phosphodiesterase-5 inhibitor, is currently used to treat pulmonary arterial hypertension. It could be also useful to treat pulmonary hypertension associated with chronic obstructive pulmonary disease (COPD). However, vasodilators may inhibit hypoxic pulmonary vasoconstriction and impair gas exchange in this condition. What This Study Adds to the Field In patients with COPD-associated pulmonary hypertension, sildenafil improves pulmonary hemodynamics at rest and during exercise, but it also entails the risk of worsening arterial oxygenation due the inhibition of hypoxic pulmonary vasoconstriction, especially at rest. Accordingly, assessment of the long-term effects of this type of drugs in this condition should be done with caution and under close monitoring of arterial oxygenation, to detect patients that would require supplementary oxygen to counteract its potential detrimental effect on gas exchange.

 

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Vasodilators in Patients with Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension: Not Ready for Prime Time!

Marc Humbert and Gérald Simonneau
AJRCCM 2010 181: 202-203. [Full Text]  

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				M. Humbert and G. Simonneau Vasodilators in Patients with Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension: Not Ready for Prime Time! Am. J. Respir. Crit. Care Med., February 1, 2010; 181(3): 202 - 203. [Full Text] [PDF]