Renal Unit, Royal Preston Hospital, Preston, UK
Sir,
Sildenafil therapy, as the first effective oral treatment, has revolutionized erectile dysfunction treatment. It is a selective inhibitor of cyclic guanozine monophosphate (cGMP)specific phosphodiesterase type 5 (PDE5) [1]. It exerts its inhibitory action on the corpus cavernosum via increasing cGMP. This enhances the relaxant effect of endogenous nitric oxide (NO) on the smooth muscles facilitating flow of blood in the penis [2]. Maximum plasma concentration is achieved within 30120 min and the terminal phase half-life is 35 h [3].
A number of short-term studies, in clinical practice, proved safety, efficacy and tolerability of this medication by patients suffering erectile dysfunction due to various aetiological factors. Recognized side-effects include headache, nausea, gastro-oesophageal reflux, flushing, nasal congestion, colour vision disturbance, pupil sparing and third nerve palsy [4]. Most of these adverse effects were explained by the drug's mode of action. Significant hypotension has been reported in patients with ischaemic heart disease and its use is contra-indicated in patients receiving concurrent nitrate therapy.
Current guidelines allow the use of sildenafil in patients with chronic renal failure and erectile dysfunction, however, this agent has not been fully evaluated in this group of individuals, particularly those receiving renal replacement therapy (RRT) [5]. We report the case of a patient with erectile dysfunction on maintenance haemodialysis, with no known cardiac history, who developed symptomatic hypotension delaying haemodialysis (HD) following initiation of sildenafil therapy.
Case.
A 49-year-old male patient with an underlying diagnosis of polycystic kidney disease had been on maintenance HD for 5 years with no known cardiovascular disease. The only drugs he was receiving were erythropoietin 2000 units thrice weekly (haemoglobin 11.7 g/dl), omeprazole, phosex, ascorbic acid, ferrous sulphate, quinine sulphate, senna and lactulose. His erectile dysfunction was of 6 years duration and started 1 year before commencing RRT.
A test dose of 50 mg was taken at 21 : 30 h on a non-dialysis day at home. No therapeutic effect was achieved. One hour after ingestion he felt unwell with headache, nausea, epigastric pain and flushing, followed by light-headedness and dizziness. The next day he reported for his dialysis still experiencing dizziness and light-headedness, 12 h after the initial dose. He was hypotensive with a blood pressure of 80/50 mmHg. Mean pre-dialysis BP over the preceding 10 days was 120/75 mmHg. His pre-dialysis weight was 82.5 kg, 0.5 kg above target. Dialysis was not performed. His blood pressure rose spontaneously to 180/65 mmHg 17 h after the administration of sildenafil. There was no evidence of an acute cardiac event with normal ECG and enzymes. A subsequent echocardiography confirmed normal left ventricular function (ejection fraction 6070%) with no evidence of any chamber enlargement or segmental contractility abnormality. There was no evidence of valvular dysfunction; however, the mitral valve annulus was calcified. Mild left ventricular hypertrophy was present. Dialysis was performed uneventfully 6 h after admission; post-dialysis BP was 111/60 mmHg. No long-term sequalae have been identified and the patient has remained on HD without further incident.
Discussion.
No previous cases have been reported of significant hypotension secondary to sildenafil in HD patients. These patients are at high risk of occult cardiovascular disease. The use and safety of sildenafil has not been evaluated in patients on maintenance HD programmes. Our patient developed a significant adverse reaction following sildenafil therapy with no therapeutic benefit.
Hypotension occurred shortly after the administration of this agent for which no other cause was identified. The exclusion of hypovolaemia as a cause of hypotension in dialysis patients is difficult. In this case a number of factors argue against hypovolaemia. The patient was well and haemodynamically stable before the initiation of sildenafil. The onset of his symptomatology started 1 h after ingesting the tablet, within the predicted time of efficacy of sildenafil. Given that there is a shared pathway for mechanism of action and adverse effects it is highly probable that the administration of sildenafil was temporally implicated. He had also been stable on HD prior to exposure to this agent and has had no further episodes of hypotension since. In the absence of any other aetiological factors we have identified sildenafil as the most likely cause of his transient hypotension.
In patients on maintenance peritoneal dialysis this treatment was well tolerated [7]. An important question remains the timing of administration of sildenafil in relation to HD as sildenafil may potentiate hypotension during dialysis. After dialysis the patient may remain relatively hypovolaemic for some time and thus be vulnerable to the potential systemic effects of sildenafil. We recommend that sildenafil should be used on non-dialysis days. However, further work is required to evaluate the timing of sildenafil therapy in HD patients.
References