Long-term Inhaled Nitric Oxide Plus Phosphodiesterase 5 Inhibitors for Severe Pulmonary Hypertension
Received 2 May 2008; received in revised form 30 July 2008; accepted 21 August 2008. published online 27 October 2008.
Background
Inhaled nitric oxide (iNO) is a potent pulmonary vasodilator, but therapeutic experience in patients with severe pulmonary hypertension is scarce.
Methods
Eleven patients with severe pulmonary hypertension, 6 due to pulmonary arterial hypertension and 4 due to chronic thromboembolic disease, were selected for iNO therapy. A phosphodiesterase type 5 inhibitor (PDE5i) was added in cases of clinical worsening. In this study we evaluate the clinical effectiveness and safety of long-term treatment with iNO either alone or combined with a PDE5i.
Results
After 1 month of iNO administration, improvements were observed in World Health Organization functional class, Borg scale (p = 0.003), brain natriuretic peptide levels (p = 0.002) and 6-minute walk test (p = 0.003). After 6 months of treatment, 7 patients had clinical deterioration that was reversed upon adding a PDE5i. One of these patients died in Month 8 and another underwent pulmonary transplantation in Month 9. The clinical condition of the remaining 9 patients was unchanged after 1 year. A second right catheterization showed improvement in mean pulmonary arterial pressure (66 ± 15 mm Hg to 56 ± 18 mm Hg; p = 0.01), pulmonary vascular resistance (1,234 ± 380 dyn/s/cm5 to 911 ± 410 dyn/s/cm5; p = 0.008) and cardiac index (2.0 ± 0.4 liters/min/m2 to 2.5 ± 0.4 liters/min/m2; p = 0.04). There was no significant increase in methemoglobin, no worsening of pulmonary function and no sudden withdrawal syndrome.
Conclusions
We suggest that iNO therapy alone or in combination with a PDE5i could be a therapeutic alternative for severe pulmonary hypertension.
aPneumology Unit, Hospital General de Gran Canaria “Dr Negrín,” Gran Canaria, Spain
bAnesthesiology Unit, Hospital General de Gran Canaria “Dr Negrín,” Gran Canaria, Spain
cVascular Radiology Unit, Hospital General de Gran Canaria “Dr Negrín,” Gran Canaria, Spain
dCardiology Unit, Hospital General de Gran Canaria “Dr Negrín,” Gran Canaria, Spain
eCardiology Unit, Hospital 12 de Octubre, Madrid, Spain
Reprint requests: Gregorio Miguel Pérez-Peñate, MD, Pneumology Unit, Hospital General de Gran Canaria “Dr Negrín,” Barranco de la Ballena s/n, Las Palmas de Gran Canaria 35010, Spain. Telephone: 34-928-450563. Fax: 34-928-450085
ABSTRACT