Takeda K, Nakamoto M, Yasunaga C, Nishihara G, Matsuo K, Urabe M, Kitamura M, Nozoe T
Kidney Center, Saiseikai Yahata Hospital, Kitakyushu, Japan.
Clin Nephrol. 1997 Oct;48(4):266-8.
Acetazolamide (Diamox) is a carbonic anhydrase inhibitor commonly used in patients with glaucoma in order to reduce intraocular pressure. Acetazolamide (AZ) is mostly excreted in the urine, therefore, the blood levels of AZ often tend to increase in patients with chronic renal failure. We experienced a case of chronic renal failure in a patient suffering from acute hemorrhagic gastritis associated with AZ intoxication. A 66-year-old female with chronic renal failure was referred to our hospital because of drowsiness and an acute deterioration of renal function. She had been treated with AZ, 500 mg per every day for eleven days for the treatment of glaucoma. Laboratory studies showed leukocyturia, thrombocytopenia, severe anemia, and tarry stools. The serum concentration of AZ was elevated to a maximum of 76.5 mg/ml. She was thus diagnosed as having AZ intoxication. On further examination, acute extensive hemorrhagic gastritis was also found by gastroscopy. Despite of the administration of intensive therapies, she died of disseminated intravascular coagulation (DIC) and septic shock due to bone marrow depression 6 days after admission. It is generally known that excessive blood levels of AZ inhibit not only the gastric juices but also prostaglandin levels and HCO3- excretion in the gastric mucosal barrier. We thus concluded that an excessive dose of AZ had probably destroyed the gastric mucosal barrier or thrombocytopenia due to bone marrow disorder and thus eventually led to the development of hemorrhagic gastritis. As far as we know, this is the first case report of acute hemorrhagic gastritis associated with AZ intoxication. Even though AZ tends to strongly bind to plasma protein and its clearance is generally poor by hemodialysis (HD), in our patient, HD was observed to be rather effective since the clearance of AZ was 45.8 ml/min on HD and 66 ml/min on direct hemoperfusion (DHP). DHP often reduces the number of platelets, also DHP needs a lot of heparin, therefore, we should have performed HD alone instead of DHP. In patients with an impaired renal function, AZ should therefore be administered very carefully in order to avoid an accumulation of the drug. In addition, HD alone should be used to remove any excessive amounts of AZ from the blood.
乙酰唑胺（醋氮酰胺）是一种碳酸酐酶抑制剂，常用于青光眼患者以降低眼压。乙酰唑胺（AZ）主要经尿液排泄，因此，慢性肾衰竭患者的AZ血药浓度往往会升高。我们遇到一例患有急性出血性胃炎且伴有AZ中毒的慢性肾衰竭患者。一名66岁的慢性肾衰竭女性因嗜睡和肾功能急性恶化被转诊至我院。她因青光眼接受了为期11天的AZ治疗，每天500毫克。实验室检查显示白细胞尿、血小板减少、严重贫血和柏油样便。AZ的血清浓度最高升至76.5毫克/毫升。因此，她被诊断为AZ中毒。进一步检查发现，胃镜检查显示为急性广泛性出血性胃炎。尽管给予了强化治疗，但她在入院6天后因弥散性血管内凝血（DIC）和骨髓抑制导致的感染性休克死亡。众所周知，AZ血药浓度过高不仅会抑制胃液分泌，还会抑制胃黏膜屏障中的前列腺素水平和HCO3-排泄。因此，我们得出结论，过量的AZ可能破坏了胃黏膜屏障，或因骨髓疾病导致血小板减少，最终导致出血性胃炎的发生。据我们所知，这是首例与AZ中毒相关的急性出血性胃炎病例报告。尽管AZ倾向于与血浆蛋白强烈结合，且血液透析（HD）对其清除效果通常较差，但在我们的患者中，HD观察到相当有效，因为HD时AZ的清除率为45.8毫升/分钟，直接血液灌流（DHP）时为66毫升/分钟。DHP常常会减少血小板数量，而且DHP需要大量肝素，因此，我们本应单独进行HD而非DHP。因此，对于肾功能受损的患者，应非常谨慎地使用AZ，以避免药物蓄积。此外，应单独使用HD从血液中清除任何过量的AZ。
