Coleman M D, Coleman N A
Department of Pharmaceutical Sciences, Aston University, Birmingham, England.
Drug Saf. 1996 Jun;14(6):394-405. doi: 10.2165/00002018-199614060-00005.
In normal erythrocytes, small quantities of methaemoglobin are formed constantly and are continuously reduced, almost entirely by the reduced nicotine adenine dinucleotide (NADH) diaphorase system, rather than the reduced nicotine adenine dinucleotide phosphate (NADPH) diaphorase system. Methaemoglobinaemias are usually the result of xenobiotics, either those that may directly oxidise haemoglobin or those that require metabolic activation to an oxidising species. The most clinically relevant direct methaemoglobin formers include local anaesthetics (such as benzocaine and, to a much lesser extent, prilocaine) as well as amyl nitrite and isobutyl nitrite, which have become drugs of abuse. Indirect, or metabolically activated, methaemoglobin formation by dapsone and primaquine may cause adverse reactions. The clinical consequences of methaemoglobinaemia are related to the blood level of methaemoglobin; dyspnoea, nausea and tachycardia occur at methaemoglobin levels of > or = 30%, while lethargy, stupor and deteriorating consciousness occur as methaemoglobin levels approach 55%. Higher levels may cause cardiac arrhythmias, circulatory failure and neurological depression, while levels of 70% are usually fatal. Cyanosis accompanied by a lack of responsiveness to 100% oxygen indicates a diagnosis of methaemoglobinaemia, which should be confirmed using a CO-oximeter. Pulse oximeters do not detect methaemoglobin and may give a misleading impression of patient oxygenation. Methaemoglobinaemia is treated with intravenous methylene blue (methyl-thioninium chloride; ;1 to 2 mg/kg of a 1% solution). If the patient does not respond, perhaps because of glucose-6-phosphate dehydrogenase (G6PD) deficiency or continued presence of toxin, admission to an intensive care unit and exchange transfusion may be required. Dapsone-mediated chronic methaemoglobin formation can be reduced by coadministration of cimetidine to aid patient tolerance. Increasing knowledge and awareness of drug-mediated acute methaemoglobinaemia among physicians should lead to prompt diagnosis and treatment of this potentially life-threatening condition.
在正常红细胞中，会不断形成少量高铁血红蛋白，并持续被还原，几乎完全是通过还原型烟酰胺腺嘌呤二核苷酸（NADH）黄递酶系统，而非还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）黄递酶系统。高铁血红蛋白血症通常是外源性物质所致，这些外源性物质要么可直接氧化血红蛋白，要么需要代谢活化成为氧化物质。临床上最相关的直接高铁血红蛋白形成剂包括局部麻醉药（如苯佐卡因以及程度轻得多的丙胺卡因）以及已成为滥用药物的亚硝酸异戊酯和亚硝酸异丁酯。氨苯砜和伯氨喹间接或经代谢活化形成高铁血红蛋白可能会引起不良反应。高铁血红蛋白血症的临床后果与血液中的高铁血红蛋白水平有关；当高铁血红蛋白水平≥30%时，会出现呼吸困难、恶心和心动过速，而当高铁血红蛋白水平接近55%时，会出现嗜睡、昏迷和意识恶化。更高的水平可能会导致心律失常、循环衰竭和神经抑制，而70%的水平通常是致命的。伴有对100%氧气无反应的发绀提示高铁血红蛋白血症的诊断，应使用一氧化碳血氧计予以确诊。脉搏血氧仪检测不出高铁血红蛋白，可能会对患者的氧合情况给出误导性的印象。高铁血红蛋白血症用静脉注射亚甲蓝（亚甲硫堇氯；1%溶液1至2mg/kg）治疗。如果患者无反应，可能是由于葡萄糖-6-磷酸脱氢酶（G6PD）缺乏或毒素持续存在，可能需要入住重症监护病房并进行换血治疗。联合使用西咪替丁可减少氨苯砜介导的慢性高铁血红蛋白形成，以帮助患者耐受。医生对药物介导的急性高铁血红蛋白血症的认识和了解不断增加，应能促使对这种潜在危及生命的病症进行及时诊断和治疗。
