Détriché Grégoire, Goudot Guillaume, Khider Lina, Galloula Alexandre, Guillet Matthieu, Lillo-Le Louët Agnès, Messas Emmanuel, Mirault Tristan
Vascular Medicine, Hôpital Européen Georges-Pompidou, Assistance Publique Hôpitaux de Paris, APHP centre Université de Paris, Paris, France.
INSERM U970, Paris Cardiovascular Research Center, Paris, France.
Front Pharmacol. 2020 Dec 3;11:560382. doi: 10.3389/fphar.2020.560382. eCollection 2020.
Literature is scarce on acute ischemia after intra-arterial injection of crushed tablets and no effective medical treatment against the progression of lesions is reported. The only factor able to modify the outcome is the delay between injection and management by a specialized vascular team. Moreover the risk of necrosis seems higher after benzodiazepine intra-arterial injection than with other drugs. We tried to find out mechanistic explanations. We report on the case of a 31-year-old drug addict woman who self-injected into her left brachial artery crushed tablets of zolpidem. She developed an acute ischemia of the left hand, with necrosis of the intermediate and distal phalanges of fingers II, III, and IV. Angiogram of the left upper arm confirmed the distal arterial occlusions with no run-off after the palmar arch in the necrotic fingers. Once she was admitted into our vascular unit, intravenous vasodilator therapy by iloprost, heparin and local protective care were rapidly introduced. After delineation between living and necrotic tissues, she required distal amputations of the affected fingers. The clinical severity of arterial injections of benzodiazepine tablets is linked to the association of several pathophysiological mechanisms. Rather than related benzodiazepine pharmacologic effects with tissue ischemia, by the inhibition of phosphodiesterase, a vasodilator intermediate, or through the peripheral benzodiazepine-type receptor, the predominant mechanism is more likely in relation with microcrystalline cellulose, one component of zolpidem tablets, known as potential embolic agents. They are insoluble and resistant to degradation in water. These properties are probably prominent in the case we described here. Through this case report we want to drag attention of physicians in charge of a patient with acute ischemia after crushed tablet accidental intra-arterial injection, not only to look at the drug injected but also the other components of the tablet and especially to microcrystalline cellulose.
关于动脉内注射碾碎药片后急性缺血的文献较少，并且没有报道针对病变进展的有效药物治疗方法。唯一能够改变结果的因素是注射与专业血管团队进行处理之间的时间延迟。此外，苯二氮䓬类药物动脉内注射后的坏死风险似乎高于其他药物。我们试图找出其机制方面的解释。我们报告了一名31岁的吸毒女性的病例，她将碾碎的唑吡坦片自行注射到左肱动脉。她出现了左手急性缺血，伴有示指、中指和环指中节和远节指骨坏死。左上臂血管造影证实了坏死手指掌弓远端的动脉闭塞且无血流。她一被收治入我们的血管科，就迅速开始了伊洛前列素静脉血管扩张剂治疗、肝素治疗及局部保护性护理。在区分存活组织和坏死组织后，她需要对受影响手指进行远端截肢。苯二氮䓬类药片动脉注射的临床严重性与多种病理生理机制的联合作用有关。主要机制不太可能是通过抑制磷酸二酯酶（一种血管扩张剂中间体）、外周苯二氮䓬类受体，从而产生与组织缺血相关的苯二氮䓬类药理作用，而更可能与唑吡坦片的一种成分微晶纤维素有关，微晶纤维素是已知的潜在栓塞剂。它们不溶于水且耐降解。这些特性在我们这里描述的病例中可能很突出。通过本病例报告，我们希望引起负责处理碾碎药片意外动脉内注射后急性缺血患者的医生的注意，不仅要关注注射的药物，还要关注药片的其他成分，尤其是微晶纤维素。
