Sildenafil citrate ingestion and prolonged priapism and tachycardia in a pediatric patient

Abstract

Introduction. Little is known about the toxicity of sildenafil overdose in the pediatric population. We present a case of prolonged priapism and tachycardia due to unintentional sildenafil overdose in a child. Case report. A 19-month-old male ingested up to six 50 mg Viagra tablets 45 minutes prior to presentation at the emergency department. Initial vital signs included temperature 98.2°F, blood pressure 90/58 mmHg, heart rate 140, respirations 20, and oxygen saturation of 100% on room air. The child weighed 10.4 kg. Physical exam revealed a happy, smiling, laughing toddler who was cooperative with all aspects of his exam. He had mild facial flushing and an erect penis which was normal in color and had a capillary refill of two seconds. Precordial palpation did not show evidence of increase dynamic force, his heart sounds were regular, and no ectopy was noted. His peripheral pulses were strong and regular in all four extremities. No gastrointestinal decontamination was performed. The patient was started on maintenance IV fluids and admitted to the pediatric floor for observation. The patient had a non-painful tumescent penis and mild tachycardia for about 24 hours post-ingestion. The child never had pain from the constant erection. Sildenafil concentration drawn approximately seven hours after ingestion was 3900 ng/ml (reporting limit 24 ng/ml) and N-desmethylsildenafil level was 1700 ng/ml (reporting limit 24 ng/ml). Conclusion. This case of pediatric sildenafil ingestion (up to 30mg/kg) initially resulted in facial flushing and priapism. The child had asymptomatic tachycardia and prolonged priapism that persisted until hospital discharge approximately 24 hours after ingestion. The erection was non-painful and required no urologic intervention, most likely representing a high flow state. In this ingestion, only supportive care was required.

Keywords: :

• Sildenafil
• Priapism
• Overdose
• Toxicity

Introduction

In 1998, sildenafil citrate was approved by the United States Food and Drug Administration as the first oral medication indicated for the treatment of erectile dysfunction. Little is known about the toxicity of sildenafil in the pediatric population. We present a case of prolonged priapism and tachycardia due to unintentional sildenafil overdose in a child.

Case report

A 19-month-old male ingested up to six 50 mg sildenafil tablets 45 minutes prior to presentation to the emergency department. He was found by his mother playing with a bottle which had contained eight tablets. She could only find two remaining tablets in the bottle. The patient had no past medical or surgical history and no known drug allergies. In the emergency department, initial vital signs were temperature 98.2°F, blood pressure 90/58 mmHg, heart rate 140, respirations 20, and oxygen saturation of 100% on room air. The child weighed 10.4 kg. Physical exam revealed a happy, smiling, laughing toddler who was cooperative with all aspects of his exam. He had mild facial flushing and an erect penis which was normal in color and had a capillary refill of two seconds. Precordial palpation did not show evidence of increase dynamic force, his heart sounds were regular, and no ectopy was noted. His peripheral pulses were strong and regular in all four extremities. No gastrointestinal decontamination was performed. The patient was started on maintenance IV fluids and admitted to the pediatric floor for observation. The patient had a non-painful tumescent penis and mild tachycardia for approximately 24 hours post-ingestion. The child never appeared to have pain from the erection. The patient was discharged the following afternoon after complete resolution of symptoms. Serum sildenafil concentration obtained approximately 7 hours after ingestion was 3900 ng/ml (reporting limit 24 ng/ml) and N-desmethylsildenafil level was 1700 ng/ml (reporting limit 24 ng/ml).

Discussion

Sildenafil citrate was originally investigated as an antihypertensive agent and is currently used for the treatment of erectile dysfunction and pulmonary hypertension. The primary mechanism of action of sildenafil is inhibition of phosphodiesterase type 5 (PDE₅) which results in increased nitric oxide-stimulated release of cyclic guanosine monophosphate (cGMP) and subsequent smooth muscle relaxation, vasodilation, and engorgement of penile tissues (1). Modest decreases in blood pressure are noted with therapeutic doses (1). Sildenafil is metabolized by cytochrome 3A4 which could potentially result in multiple drug interactions and could have varying responses between ethnic groups. A well known drug interaction is with nitrates which can potentiate hypotension and has lead to fatalities (2).

Priapism is defined as a prolonged erection, not associated with sexual stimulation. Low-flow priapism is generally a painful erection due to obstruction of venous outflow and subsequent ischemia. Corporal damage can begin within 12 hours of onset resulting in fibrosis and permanent erectile dysfunction (3). High-flow priapism is due to increased arterial inflow with preserved venous outflow (4). High-flow priapism is generally not painful and less likely to result in erectile dysfunction. Initially all types of priapism start in a high flow state (3). This patient had a prolonged painless erection. Given the lack of symptoms and the pharmaceutical effect of the drug, it is postulated that the priapism was a high-flow state.

Priapism with therapeutic use of sildenafil has been documented (5). In patients with sickle cell disease, sildenafil has been reported to cause a low-flow priapism yet has also successfully treated priapism due to vasoocclusive crisis (6,7). Decreased expression of PDE₅ in sickle cell patients may be a contributor of stuttering priapism (characterized by repeated erections that are usually reversible but painful) (4) and could theoretically be potentiated by sildenafil. Conversely, a case series of sickle cell patients with recalcitrant priapism were successfully treated with sildenafil (7). The mechanism was postulated to be due to vasodilatation of the corpus cavernosum.

Experience with sildenafil overdose is limited, especially in the pediatric population. In a previously reported case, a 2-year-old ingested approximately 5 mg/kg of sildenafil. Facial flushing and transient penile engorgement were documented however, there were no effects on heart rate or blood pressure (8). A large overdose of 2000 mg in a 42-year-old female patient was well tolerated with the only abnormalities being flushing, headache and mild tachycardia (9). One review of national poison center data on sildenafil exposures recorded 129 sildenafil-only cases. Of these, five resulted in serious outcomes or death (10). Common adverse effects included flushing (14%), dizziness (8%), headache (8%), tachycardia (8%), chest pain (6%), drowsiness (6%), hypotension (4%), nausea (4%), and syncope (4%) (10).

Little is known about the relationship between sildenafil concentrations and clinical toxicity. Peak sildenafil concentrations from oral “therapeutic” doses of 50mg, 100 mg, and 0.68 mg/kg were 260, 450, and 212 ng/ml, respectively (11). Pharmacogenetic differences may exist between ethnic populations. Substantially higher peak sildenafil concentrations of 1044 ng/ml were found after an oral dose of 100mg in Mexican volunteers (12). One paper documenting a fatality from sildenafil overdose reported a concentration of 6270 ng/ml (13). In our case report, the sildenafil and N-desmethylsildenafil concentrations were 3900 and 1700 ng/ml, respectively, representing the highest non-fatal levels reported in the medical literature.

Conclusion

This case of pediatric sildenafil ingestion (up to 30mg/kg) initially resulted in facial flushing and priapism. The child had asymptomatic tachycardia and prolonged erection that persisted for approximately 24 hours. The erection was non-painful and required no urologic intervention, most likely representing a high flow priapism. No hypotension was observed and only supportive care was required.

Acknowledgment

The opinion and assertions contained herein are the views of the author and are not to be construed as official or as reflecting the views of the United States Department of Defense.

Notes

* An abstract of this article was presented at the North American Congress of Clinical Toxicology annual meeting, Orlando, Florida, USA, September 2005.