Study suggests sildenafil may relieve severe form of edema in swimmers

Swimmers and divers who are prone to pulmonary edema in cold water (which can be deadly), could benefit from a dose of sildenafil, which is more commonly known by its brand name, Viagra®.

We all know that sildenafil can be used to treat erectile dysfunction in men, but it is also used to treat pulmonary arterial hypertension.  It works by dilating blood vessels.  In cold water swimmers and divers, their blood vessels rapidly constrict; this can lead to pooling of blood in the heart and lungs.

Athletes and swimmers with SIPE (swiming-induced pulmonary edema) cough up blood, have trouble breathing, and have low blood oxygen.  The symptoms may go away over 24 hours, but the condition can be fatal.

Researchers put 10 SIPE-susceptible athletes into a pool that mimicked the conditions that trigger SIPE.  They then compared those 10 athletes to 20 other athletes who had no history of SIPE.  The SIPE-susceptible athletes had higher pulmonary arterial pressure and pulmonary artery wedge pressure during the underwater exercise.

When the SIPE susceptible athletes were given sildenafil and performed the same exercises, their pressures were no longer as elevated.

In the words of Moon, one of the researchers, the conclusion of the study is that “It appears that the drug, which dilates the blood vessels, could be creating more capacity in the blood vessels in the arms and legs, reducing the tendency for blood to redistribute to the thorax, and therefore reducing the high pressure in the pulmonary vessels.”

This can be a promising lead on a drug that can make swimming/diving possible for people who are prone to SIPE.

The question I will pose is:  Is it better to take drugs as a preventative measure, or to take them after symptoms have developed?

 

 

Richard E. Moon, Stefanie D. Martina, Dionne F. Peacher, Jennifer F. Potter, Tracy E. Wester, Anne D. Cherry, Michael J. Natoli, Claire E. Otteni, Dawn N. Kernagis, William D. White, and John J. Freiberger. Swimming-Induced Pulmonary Edema: Pathophysiology and Risk Reduction With Sildenafil. Circulation: Journal of the American Heart Association, February 2016 DOI:10.1161/CIRCULATIONAHA.115.019464

Use of Sildenafil in term and premature infants for pulmonary hypertension

Sildenafil is more commonly being used to treat pulmonary hypertension in term and premature infants. However, the FDA has only approved this use in adults. Controlled trials that studied the efficacy of sildenafil use in term and premature infants with hypertension as well as premature infants at risk for developing bronchopulmonary dysplasia (BPD) were reviewed in a review article.

The researchers from the review article designed their study to answer two main questions: Does sildenafil use improve in-hospital mortality in term infants with pulmonary hypertension or premature infants with BPD-associated pulmonary hypertension compared with placebo or inhaled nitric oxide? Does sildenafil use in premature infants prevent or treat BPD as defined by oxygen requirement at 36 weeks’ corrected gestational age (GA)? Primary studies were found using a literature search of MEDLINE, PubMed, EMBASE, Cochrane Library, and International Pharmaceutical Abstracts databases. Studies with a focus on these questions were selected if they included term or near-term infants with pulmonary hypertension and previous exposure to sildenafil or premature infants at risk for BPD or who had BPD-associate pulmonary hypertension. Also, studies that compared efficacy of sildenafil to a placebo or inhaled nitric oxide, but not other therapies, were analyzed. The selected studies were reviewed by two people who assessed the quality of the study, research design, analysis, and results.

Of 4 articles and 1abstract reviewed, 3 articles and the abstract looked at the use of sildenafil for term or near-term infants. The other article studied sildenafil use in premature infants. Sildenafil was dosed in a range of 1mg/kg every 8 hours to 3mg/kg every 6 hours in all the trials. The results of all the trials recorded oxygen index and death. Oxygen index was seen to improve 6-8 hours after sildenafil administration whereas little to no improvement was seen after placebo administration. Combing participants from 3 of the trials, 3 of 51 infants taking sildenafil died before hospital discharge. In contrast, 16 of 37 infants receiving placebo died. In conclusion, term infants exposed to sildenafil had a relatively low mortality risk. However, although sildenafil improved oxygen index in the trials, there are still no guidelines available for dosing sildenafil in term and premature infants.

 

Clin Ther. 2015;37(11):2598-2607.

Link to Article

 

This article made me think back to pediatric calculations with Dr. Howrie in PDA. Although this review article finds evidence to suggest that sildenafil is effective and potentially safe in infants, its use should still be utilized carefully. Dosing must dramatically be reduced for infants who have yet to develop complete organ function, especially for premature infants. While reading this article, a question about dosage form in infants came to my mind. Do you think IV is the best dosage form compared to oral or inhaled therapies to use to treat infants nfants because of their inadequate organ function?