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1 Neonatal Intensive Care Unit, Great Ormond Street Hospital, London WC1N 3JH, UK
2 Department of Visual Neuroscience, Imperial College London, Room 9L02, Charing Cross Campus, St Dunstan’s Road, London W6 8RP, UK
Correspondence to:
A R Fielder
Department of Visual Neuroscience, Imperial College London, Room 9L02, Charing Cross Campus, St Dunstan’s Road, London W6 8RP, UK; a.fielder@imperial.ac.uk
Accepted for publication 13 July 2004
Keywords: retinopathy of prematurity; sildenafil
Marsh and colleagues1 raise the spectre of a possible association between the use of sildenafil and the development of retinopathy of prematurity (ROP) in a baby of 26 weeks gestation with pulmonary hypertension. We are concerned that this report offers no real evidence for its claims and that a potentially lifesaving agent is being unfairly maligned.
The report describes the use of intravenous sildenafil of unspecified dose for 16 days in a 525 g preterm infant with a very difficult intensive care course. The management included a litany of recognised causes of ROP, including extreme prematurity, >6 weeks of mechanical ventilation with 80–100% oxygen, and bacterial and fungal infections.
Despite this, Marsh et al chose to incriminate sildenafil as the causal agent. The suggestion is even more perplexing as the baby had already received inhaled nitric oxide at high levels (40 ppm for 2–3 weeks) before the sildenafil; both are vasodilators and have the same mechanism of action.
The authors make the further statement that they observed a recent increase in treatable ROP in their unit, coinciding with the use of sildenafil. Where is their evidence?
As far as we are aware there is no evidence in the literature that sildenafil has any significant effect on either retinal or choroidal blood vessels. Pache et al reported2 that in adults, sildenafil induced a 5.8% dilatation of retinal vessels but this was not confirmed by Grunwald et al on either retinal or choroidal circulations.3,4 To date there are no data on the effect of sildenafil on the developing ocular circulations.
We entirely agree that vigilant monitoring and responsible reporting of side effects are mandatory for any new drug application. To our knowledge the only available intravenous sildenafil is being released on a named patient basis in a prospective study in neonates. How did the authors obtain and administer the drug in neonates? Sildenafil and inhaled nitric oxide are experimental therapies within the preterm population and as clinicians we have a responsibility to ensure that they are used as part of prospective randomised controlled trials with the appropriate short and long term follow up. Although being well intentioned, such unconvincing reports may impede the use of agents that might have an important future role in the management of primary pulmonary hypertension of the newborn.
References
Marsh CS, Marden B, Newsom R. Severe retinopathy of prematurity (ROP) in a premature baby treated with sildenafil acetate (Viagra) for pulmonary hypertension. Br J Ophthalmol 2004;84:306–7.
Pache M, Meyer P, Prünte C, et al. Sildenafil induces retinal vasodilatation in healthy subjects. Br J Ophthalmol 2002;86:156–8.
Grunwald JE, Siu KK, Jacob SS, et al. Effect of sildenafil (Viagra) on the ocular circulation. Am J Ophthalmol 2001;131:751–5.
Grunwald JE, Metelisina T, Grunwald L. Effect of sildenafil (Viagra) on retinal blood vessel diameter. Am J Ophthalmol 2002;133:809–12.