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有机磷中毒治疗的现代策略。

Modern strategies in therapy of organophosphate poisoning.

作者信息

Thiermann H, Szinicz L, Eyer F, Worek F, Eyer P, Felgenhauer N, Zilker T

机构信息

Institut für Pharmakologie und Toxikologie, Sanitätsakademie der Bundeswehr, Garching/Hochbrück, Germany.

出版信息

Toxicol Lett. 1999 Jun 30;107(1-3):233-9. doi: 10.1016/s0378-4274(99)00052-1.

Abstract

Considering the various microscopic reactions as well as toxicokinetic and pharmacokinetic principles in therapy of organophosphate poisoning, the administration of obidoxime by an initial bolus dose followed by continuous infusion appears rational. Using this protocol, six patients each with parathion or oxydemeton methyl poisoning were treated. In parathion poisoning, reactivation was possible up to 7 days. At paraoxon concentrations > 0.1 microM obidoxime only partially reactivated acetylcholinesterase (AChE) of erythrocytes in vivo although reactivation could be assessed in vitro, which roughly fitted theoretical calculations. AChE-inhibitory material was detected up to 5 days. Cholinergic signs soon subsided when AChE was above 20% of normal, and atropine plasma levels could be kept below 7 ng/ml. In one patient brain damage persisted. Oxydemeton methyl poisoning responded to obidoxime therapy only when the oxime was instituted shortly after poisoning. Out of six patients one died. No intermediate syndrome and no signs of permanent hepatic dysfunction were found in the 12 patients.

摘要

考虑到有机磷中毒治疗中的各种微观反应以及毒代动力学和药代动力学原理,先给予奥比多克斯首剂推注剂量,随后持续输注的给药方式似乎是合理的。按照该方案,对6例分别患有对硫磷或氧化乐果中毒的患者进行了治疗。在对硫磷中毒中,长达7天内都有可能实现酶再活化。当对氧磷浓度>0.1微摩尔时,尽管在体外可以评估再活化情况,但奥比多克斯在体内仅能部分再活化红细胞乙酰胆碱酯酶(AChE),这大致符合理论计算。在长达5天的时间内都检测到了AChE抑制物质。当AChE高于正常水平的20%时,胆碱能体征很快消退,并且阿托品血浆水平可以维持在7纳克/毫升以下。有1例患者持续存在脑损伤。氧化乐果中毒只有在中毒后不久就使用肟类药物时才对奥比多克斯治疗有反应。6例患者中有1例死亡。12例患者中未发现中间综合征和永久性肝功能障碍的迹象。

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