Meta-Analysis of Clinical Efficacy of Sildenafil, a Phosphodiesterase Type-5 Inhibitor on High Altitude Hypoxia and Its Complications

Abstract

High altitude illness can be life-threatening if left untreated. Acute mountain sickness and high altitude pulmonary hypertension are two syndromes of high altitude illness. Recent clinical studies showed the beneficial effects of phosphodiesterase type 5 (PDE-5) inhibitors on the treatment of pulmonary hypertension. In this report, we performed a meta-analysis to evaluate the clinical efficacy of PDE-5 inhibitors on high altitude hypoxia and its complications. Randomized controlled trials evaluating the efficacy of PDE-5 inhibitor in the setting of high altitude were identified by searching Cochrane Central Register of Controlled Trials (September 2013), PubMed (from 1990 to September 2013), and EMBASE (from 1990 to September 2013). Extracted outcomes from selected studies for meta-analysis included arterial oxygen saturation, pulmonary artery systolic pressure, heart rate, and Lake Louise Consensus AMS symptom score. Weighted mean differences with 95% confidence intervals were presented for the continuous outcomes. Five clinical trials that met the selection criteria were identified for the meta-analysis. All of these studies used sildenafil as the PDE-5 inhibitor. A total of 60 subjects received sildenafil, and 72 subjects were given placebo. In accordance with previous report, short-term treatment with sildenafil (1-2 days) significantly reduced pulmonary artery systolic pressure at rest (MD -4.53; 95% CI -6.72, -2.34; p<0.0001). However, treatment with sildenafil (1-2 days) did not improve oxygen saturation after exposure to high altitude (MD 0.07; 95% CI -1.26, 1.41; p=0.91). Moreover, no significant difference was observed in heart rate between sildenafil and placebo-treated group (MD 6.95; 95% CI -3.53, 17.43; p=0.19). AMS score did not improve after treatment at different time points. Short-term treatment with sildenafil can attenuate the altitude-induced high pulmonary systolic arterial pressure, but has no significant beneficial effects on arterial oxygen saturation, heart rate, and acute mountain sickness.