Aortic dissection after sildenafil-induced erection.

To the Editor: We report on a patient who experienced vomiting, diarrhea and abdominal pain shortly after ingestion of sildenafil and was found to have aortic dissection upon admission to the hospital. To our knowledge, this has not been previously reported. Vomiting and diarrhea are not known manifestations of aortic dissection.

A 61-year-old patient with a history of arterial hypertension, venous insufficiency and atrial fibrillation was admitted because of abdominal pain, diaphoresis, vomiting and diarrhea 30 minutes after ingestion of 50 mg of sildenafil. He did not have sexual intercourse after taking the sildenafil, but presented to the hospital. He had been using sildenafil for erectile dysfunction for 2 years without any side effects. His regular medications were digitoxin, isosorbid-5-mononitrate, allopurinol, ranitidine, flavonoid, diosmin and phenprocoumon. Six hours before onset he had taken 0.07 mg of digitoxin, 50 mg of isosorbid-5-mononitrate, 100 mg of allopurinol, 50 mg of flavonoid and 450 mg of diosmin. At admission, his blood pressure was 150/50 mm Hg. Red and white blood cell count, serum electrolytes, creatinine, C-reactive protein, creatine phosphokinase and troponin-T were normal, lactate-dehydrogenase was 335 U/L (normal: <248) and INR was 2.4. Electrocardiogram showed atrial fibrillation and signs of left ventricular hypertrophy. Abdominal ultrasound and plain abdominal x-ray were normal. Two hours after onset, the patient complained of chest pain. Echocardiography and computed tomography established the diagnosis of ascending aorta dissection. Surgically, aortic dissection type A with an intimal tear above the aortic valve was found and an aortic Vascutek 32 mm prosthesis was implanted. Unfortunately, the patient died on the 4th postoperative day due to recurrent dissection and mesenteric ischemia.

A causal relationship between sildenafil intake and aortic dissection remains speculative but there are indications:

1. The strong temporal relationship between sildenafil intake and dissection. Dissection occurred at a time when sildenafil reaches its peak plasma concentration.

2. Aortic dissection type B has been reported after cocaine sniffing and ingestion of 50 mg of sildenafil. (1)

3. In humans, sildenafil leads to a decrease in aortic stiffness, (2) and in vitro sildenafil has a relaxant effect on rat aortae. (3) Possibly this effect differs between the layers of the aortic wall, thus inducing tension and favoring intimal tears.

4. Sildenafil has an antiproliferative effect on cultured human pulmonary artery smooth muscle cells. (4) Possibly, similar effects in the aorta make the wall thinner and more vulnerable to mechanical stress.

5. Concomitant medication may have favored the dissection.

It can be speculated that some of the sudden deaths which have been observed in association with sildenafil intake might also have been due to aortic dissection, since the pathomechanism of these sudden deaths is not completely understood, and autopsy has not been performed in all patients. (5)

Diarrhea and abdominal pain have never been reported as side effects of sildenafil. Since the patient had tolerated sildenafil for 2 years, it is unlikely that these symptoms are a side effect of this drug. This patient's vomiting and diarrhea were probably due to affection of the abdominal aorta and mesenteric arteries, or due to vagal mechanisms. The delayed occurrence of thoracic pain may have been due to the fact that the dissection was initially more pronounced inside the abdominal aorta and later affected the thoracic aorta more extensively.

Aortic dissection should be a differential diagnosis of vomiting and diarrhea, especially if associated with migrating pain.

Anna Nachtnebel, MD

Claudia Stollberger, MD

2nd Medical Department

Krankenanstalt Rudolfstiftung

Marek Ehrlich, MD

Department of Cardiothoracic Surgery

Allgemeines Krankenhaus

Josef Finsterer, MD

Krankenanstalt Rudolfstiftung

Wien, Osterreich

References

1. Famularo G, Polchi S, Di Bona G, et al. Acute aortic dissection after cocaine and sildenafil abuse. J Emerg Med 2001;21:78-79.

2. Vlachopoulos C, Hirata K, O'Rourke MF. Effect of sildenafil on arterial stiffness and wave reflection. Vasc Med 2003;8:243-248.

3. Mochida H, Inoue H, Takagi M, et al. Sildenafil and T-1032, phosphodiesterase type 5 inhibitors, showed a different vasorelaxant property in the isolated rat aorta. Eur J Pharmacol 2002;440:45-52.

4. Tantini B, Manes A, Fiumana E, et al. Antiproliferative effect of sildenafil on human pulmonary artery smooth muscle cells. Basic Res Cardiol 2005;100:131-138.

5. Herrmann HC, Chang G, Klugherz BD, et al. Hemodynamic effects of sildenafil in men with severe coronary artery disease. New Engl J Med 2000;342:1622-1626.

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