Intracerebral haemorrhage associated with sildenafil citrate
Intracerebral haemorrhage associated with sildenafil citrate
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与枸橼酸西地那非相关的脑出血
DOI：
10.1007/s004150170250
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发表时间：
2001
影响因子：
6
通讯作者：
R. Camarda
中科院分区：
文献类型：
--
作者：
R. Monastero;C. Pipia;L. Camarda;R. Camarda
先生们：西地那非是一种口服有效的、有效的、选择性的 5 型磷酸二酯酶 (PDE-5) 抑制剂，PDE-5 是人体海绵体中环磷酸鸟苷 (cGMP) 的重要调节剂，最近被用于治疗勃起功能障碍。西地那非通过增加海绵体平滑肌细胞中 cGMP 的浓度来发挥作用，导致肌肉松弛、血管舒张和阴茎勃起 [1]。不良反应包括头痛、视力和视网膜障碍、头晕和保留瞳孔的第三神经麻痹[2,5,7]。我们报告了一名患者在服用西地那非后出现脑出血（ICH）。一名 67 岁的牙医被转诊至我们诊所，当时他神志不清，并且出现言语、计算和记忆障碍。从病史来看，入院前 5 天，即服用 1 片 25 mg 西地那非后约 30 分钟，患者主诉头痛、精神错乱和紧张，但性功能没有改善。服用第一片药片一小时后，患者再次服用 25 毫克药片，同样没有性交。据他的妻子说，这些症状随着语言困难而加剧。 5天后患者入住我科。他以前从未使用过西地那非。病史显示无动脉高血压、偏头痛或止血危险因素（例如使用抗凝剂或抗血小板药物、溶栓治疗）、头部外伤史、高胆固醇血症、糖尿病、既往患有心血管疾病或脑血管疾病，如中风或短暂性脑缺血发作。无脑动静脉畸形、脑内动脉瘤、脑内出血家族史。他有 40 年的吸烟史（每天大约 15 支烟），并且否认经常饮酒。他没有服用其他药物。入院时，他的血压为 140/90 mmHg，脉搏为 68 次/分钟。神经系统检查显示右上同向象限，精神检查显示情绪烦躁。检眼镜检查正常。神经心理学测试显示，理解、命名、阅读和写作有中度障碍，但重复、计算能力差、手指失认、颜色失常和情景记忆离散参与相对较少。常规血液检查、血小板计数和凝血因子以及心电图和颅外血管彩色编码双重超声检查均正常。经颅彩色编码双重超声检查显示，左颞叶有一个界限清晰的高回声区域。入院两天后，基础和钆增强 T1/T2 加权脑磁共振成像显示左侧颞叶皮质下大量出血，周围中度水肿（见图 1）。虽然在 67 岁的患者身上发现临床相关血管病变的机会很小，但我们还是希望进行脑血管造影。然而，患者的妻子在得知脑血管造影的潜在风险后，以丈夫年事已高且存在深部脑叶出血为由拒绝同意。患者接受静脉推注 1 g/kg 甘露醇治疗，随后每 4 小时静脉推注 0.5 g/kg，持续 7 天。 5 天后，他因轻度理解、阅读、写作和情景记忆缺陷、中度失算、手指失认和颜色失认症出院。现场缺陷仍然存在。对于没有脑血管意外病史或明显 ICH 危险因素的患者，西地那非摄入与 ICH 引起的神经系统症状发作之间的密切时间关系表明，西地那非与 ICH 存在因果关系。目前吸烟不被认为是脑出血的主要危险因素[4, 6]。由于症状在任何性交尝试之前就开始出现，因此不能将性行为视为给编辑的信
Sirs: Sildenafil is an orally active, potent and selective inhibitor of phosphodiesterase type 5 (PDE–5), an important regulator of cyclic guanosine monophosphate (cGMP) in the human corpus cavernosum which has recently been introduced for the treatment of erectile dysfunction. Sildenafil acts by increasing the concentration of cGMP in the corpus cavernosum smooth muscle cells leading to muscle relaxation, vasodilatation and penile erection [1]. Adverse effects include headache, visual and retinal disturbances, dizziness and a pupil-sparing third nerve palsy [2, 5, 7]. We report a patient who developed intracerebral haemorrhage (ICH) after sildenafil consumption. A 67-year-old dentist was referred to our clinic in a confusional state together with speech, numeracy and memory disturbances. From the history it appeared that 5 days before admission, approximately 30 minutes after the ingestion of one tablet of sildenafil 25 mg, the patient complained of headache, confusion and nervousness without improvement in sexual function. One hour after the ingestion of the first tablet the patient took another 25 mg tablet, again without sexual intercourse. According to his wife, these symptoms increased together with language difficulty. The patient was admitted to our department 5 days later. He had never used sildenafil before. The history revealed no arterial hypertension or migraine or haemostatic risk factors (e. g. use of anticoagulants or antiplatelet drugs, thrombolytic treatment), history of head trauma, hypercholesterolaemia, diabetes mellitus, pre-existing cardiovascular disease or cerebrovascular episodes such as stroke or transient ischaemic attacks. There was no family history of cerebral arteriovenous malformation, intracerebral aneurysms, or intracerebral haemorrhages. He had a 40-year history of tobacco abuse (approximately 15 cigarettes a day) and denied regular alcohol intake. He took no other medications. On admission his blood pressure was 140/90 mmHg and pulse was 68/min. Neurological examination showed a right superior homonymous quadrantopsia and psychiatric examination a dysphoretic mood. Ophthalmoscopic examination was normal. Neuropsychological testing revealed a moderate impairment of comprehension, naming, reading and writing with a relative sparing of repetition, acalculia, finger agnosia, colour anomia, and discrete involvement of episodic memory. Routine blood examination, platelet count and coagulation factors were normal, as well as electrocardiography, and colour-coded duplex sonography of extracranial vessels. Transcranial colour-coded duplex sonography revealed a sharply demarcated hyperechogenic area confined to the left temporal lobe. Two days after admission basal and gadolinium-enhanced T1-/T2-weighted cerebral magnetic resonance imaging revealed a large left temporal subcortical haemorrhage with moderate surrounding oedema (see Fig. 1). Although the chance of finding a clinically relevant vascular lesion in a patient 67 years old is very small, we would have liked to have performed cerebral angiography. However, the patient’s wife, informed of the potential risk of cerebral angiography, refused her consent due to her husband’s advanced age and the presence of a deep lobar ICH. The patient was treated with intravenous bolus of 1 g/kg mannitol, followed by 0.5 g/kg every 4 h for 7 days. He was discharged 5 days later with mild comprehension, reading, writing and episodic memory deficits, moderate acalculia, finger agnosia and colour anomia. The field defect was still present. The close temporal relationship between sildenafil ingestion and onset of the neurological symptoms due to the ICH in a patient without a history of cerebrovascular accident or obvious risk factors for ICH suggest that sildenafil was causally related to the ICH. Smoking is currently not considered a primary risk factor for ICH [4, 6]. Since the symptoms started before any attempt at sexual intercourse, sexual exertion cannot be regarded LETTER TO THE EDITORS