7岁儿童查出蛛网膜囊肿（蛛网膜下腔意外注射氨甲环酸）

7岁儿童查出蛛网膜囊肿（蛛网膜下腔意外注射氨甲环酸）The use of antifibrinolytic agents including tranexamic acid (TXA) aprotinin and aminocaproic acid is popular in cardiac gynecologic and obstetric surgeries to overcome the increased fibrinolytic activity associated with these procedures[1]. Major complications in anesthesia practice have been reported from human errors like lack of vigilance wrong labeling or presentation of the syringes and

编者注：近期因为氨甲环酸脊柱手术局部使用导致严重后果的病例，部分同道不认为是氨甲环酸所致。目前我已获知，中国大陆已有6例氨甲环酸进入脑脊液后导致严重后果的病例，其中4例死亡，2例抢救成功，死亡率应该是67%。但均没有获得完整的病例资料 今天推送一篇2012年发生在埃及的氨甲环酸误注射入蛛网膜下腔导致患者多发肌阵挛的病例，英文文献，我翻译后，采用中英文对照的方式呈现，以便于大家对我的专业学习内容和方式进行监督、批评和指正，同时，也为愿意深入探讨的同道，提供中英文对照的学习和互相探讨相关专业知识的机会。

Accidental intrathecal injection of tranexamic Acid

个案报道：2012埃及蛛网膜下腔意外注射氨甲环酸

原文出处：Khaled Mahmoud Amany Ammar. Accidental intrathecal injection of tranexamic Acid. Case Rep Anesthesiol. 2012;2012:646028. doi: 10.1155/2012/646028. Epub 2012 Mar 26.

作者单位：Faculty of Medicine Minoufiya University Shebin El Kom Minoufiya 32511 Egypt.

Tranexamic acid (TXA) is a popular antifibrinolytic drug that is commonly used in patients with bleeding disorder. Major morbidities and mortalities have been reported following inadvertent intrathecal injection of TXA. In this paper inadvertent intrathecal injection of TXA has resulted from similarities in appearance between TXA and heavy bupivacaine 0.5% ampoules. The patient experienced severe pain in the back and gluteal region upon injection in association with systemic hypertension and tachycardia followed by generalized myoclonic seizures and ventricular fibrillation.

氨甲环酸是一种常用的抗纤维蛋白溶解药物，用于出血性疾病患者。蛛网膜下腔内意外注射氨甲环酸后，已有多起致病和死亡的病例报告。本文中，无意中蛛网膜下腔内注射了氨甲环酸，系由氨甲环酸和0.5%布比卡因安瓿的外观相似所致。意外注射后患者背部和臀部出现剧烈疼痛，伴有高血压和心动过速，随后出现全身性肌阵挛发作和心室颤动。

Introduction前言

The use of antifibrinolytic agents including tranexamic acid (TXA) aprotinin and aminocaproic acid is popular in cardiac gynecologic and obstetric surgeries to overcome the increased fibrinolytic activity associated with these procedures[1]. Major complications in anesthesia practice have been reported from human errors like lack of vigilance wrong labeling or presentation of the syringes and ampoules or underestimation of the double-checking concept [2]. In this case report TXA was injected intrathecally instead of hyperbaric bupivacaine 0.5% because both ampoules were having the same appearance with consequent development of myoclonic seizures and ventricular fibrillation.

抗纤维蛋白溶解剂包括氨甲环酸、抑肽酶和氨基己酸在心脏、妇科和产科手术中广泛使用，以克服与这些手术相关的纤溶活性增加[1]。据报道，麻醉实践中的主要并发症来自人为错误，如缺乏警惕性、注射器和安瓿的标签错误或拿错，或没有严格执行双重检查[2]。本病例报告中，氨甲环酸误注入蛛网膜下腔内，而不是0.5%的布比卡因，因为两种安瓿的外观相同，随后导致肌阵挛发作和心室颤动。

Case Description病例描述

Institutional review board approval and patient consent were obtained prior to reporting the case. A 54-year-old man was scheduled for lower-limb skin grafting. The patient was thoroughly examined and investigated and confirmed to be ASA I physical status. Spinal anesthesia was done with the patient in the sitting position at the L4-L5 interspace using a 22-gauge needle. The anesthesiologist nurse prepared 3mL of 0.5% hyperbaric bupivacaine for the anesthesiology resident. Upon injection of bupivacaine the patient started complaining of severe pain in the back and gluteal region.

本病例报告已获得单位审查委员会的批准和患者同意。患者为一名54岁男子，计划行下肢皮肤移植。对患者进行详细检查，确认其身体状况为ASA I级。患者坐姿，用22号针头，L4-L5间隙穿刺麻醉。麻醉护士为麻醉住院医师准备了3mL 0.5%布比卡因。注射布比卡因后，患者开始抱怨背部和臀部严重疼痛。

The anesthesiologist attributed this pain to intraneural injection. No manifestations of sensory or motor block were noted and the patient continued in severe intractable pain associated with elevation of the arterial blood pressure to 170/95 and pulse rate to 130. The patient received 100μg of fentanyl for analgesia and 2mg of midazolam for sedation and put on oxygen face mask. Ten minutes later the patient developed generalized myoclonic seizures. Consequently the patient received propofol 200mg and succinylcholine 80mg for tracheal intubation and was mechanically ventilated and then transferred to the ICU. The attending anesthesiologist suspected accidental intrathecal injection of a wrong drug and discovered a used TXA ampoule (500mg in 5mL) in the trash can. In the ICU the patient became feverish (40。C) and 2gm IV acetaminophen was given. Three hours later the patient got ventricular fibrillation that responded to electrical shock of 300J. Subsequent treatment included propranolol amiodarone lidocaine and mannitol in addition to continuous mechanical ventilation. Twenty-four hours later the patient was weaned from mechanical ventilation extubated and fully recovered without any neurologic sequelae.

麻醉师认为，患者背部和臀部的剧痛，可能系由麻醉药物注射于神经内所致。感觉或运动阻滞无效，患者感持续严重顽固性疼痛，伴随血压升高至170/95，脉搏升高至130。给予100μg芬太尼镇痛，2mg咪唑安定镇静，并戴氧气面罩。10分钟后，患者出现全身性肌阵挛发作。随即，给予异丙酚200mg和琥珀胆碱80mg，气管插管，机械通气，然后转移到ICU。主治麻醉师怀疑蛛网膜下腔内意外注射了错误的药物，在垃圾桶中发现了一个用过的氨甲环酸安瓿（500mg/5mL）。在ICU，患者发烧(40度)，静脉注射2克对乙酰氨基酚。三小时后，出现心室颤动，300J的电除颤有效。除持续机械通气外，后续治疗包括普萘洛尔、胺碘酮、利多卡因和甘露醇。24小时后，患者脱机，拔管，完全康复，无任何神经后遗症。

Discussion讨论

Tranexamic acid is a competitive inhibitor of plasminogen activation and a noncompetitive inhibitor of plasmin at higher concentrations. Its use in humans is generally well tolerated and its complications are minimal and include mainly gastrointestinal upsets[1].However neurotoxicity and seizures have been reported in animal studies[3–5]. Furthermore Yamaura and coworkers reported elevation of the systemic and intracranial pressure by direct cerebral application of TXA for treatment of ruptured intracranial aneurysm in animal models [4].

氨甲环酸在较高浓度下是一种竞争性纤溶酶原激活抑制剂和非竞争性纤溶酶抑制剂。在人类中的使用通常具有很好的耐受性，并发症小，主要包括胃肠道不适[1]。然而，动物研究中，氨甲环酸具有神经毒性并可导致惊厥发作 [3-5]。此外，Yamura及其同事报告，在动物实验模型中，脑内直接应用氨甲环酸治疗破裂的颅内动脉瘤，可导致血压和颅内压升高[4]。

However we know little about effect of TXA in case it is applied directly to the subarachnoid space in humans. In 1988 Wong and colleagues[6] reported accidental intrathecal injection of 75mg TXA inadult patient undergoing appendectomy operation. The patient developed persistent sensory block of both lower extremities in addition to fever myoclonus and clonic convulsions that progressed to a generalized seizure that responded to intravenous diazepam and the patient was fully recovered without anyneurologic deficits. In 1999 De Leede-van der Maarl and coworkers[7] reported accidental intrathecal injection of 50mg TXA in a 68-year-old man. The patient experienced refractory seizure that was treated by both diazepam and sodium thiopental. Furthermore the patient complained of paresis in all extremities that resolved over time but with persistent bilateral peroneal palsy.

然而，我们对氨甲环酸直接进入人类蛛网膜下腔的后果知之甚少。1988年，Wong及其同事[6]报道接受阑尾切除术的成年患者蛛网膜下腔内意外注射了75mg的氨甲环酸。患者除了发热、肌阵挛和阵挛性抽搐外，还出现持续的双下肢感觉阻滞，并发展为全身性惊厥发作，静脉注射地西泮有效，患者完全康复，无任何神经功能缺损。1999年，De Leede van der Maarl及其同事[7]报告一名68岁男子蛛网膜下腔内意外注射50毫克氨甲环酸。患者出现难治性惊厥发作，用地西泮和硫喷妥钠治疗有效。此外，患者主诉四肢轻瘫，随着时间的推移逐渐缓解，但伴有持续性双侧腓神经麻痹。

In 2003 Yeh and colleagues[8] reported inadvertent intrathecal injection of 500mg of TXA. The patient developed generalized convulsions and hypertensive response followed by refractory ventricular fibrillation that ended the life of the patient. The authors attributed this sequelae to a massive sympathetic discharge induced by TXA which was near to the events encountered in our case. Whereas triggering of seizures was explained by suppression of the inhibitory gamma-aminobutyric acid-(GABA)-A receptors in the cerebral cortex or lowering of cerebral blood flow with consequent cerebral ischemia[9 10]. In 2007 Garcha and colleagues [11]reported mortality after accidental intrathecal injection of TXA. In 2011 Kaabachiet al. [12] reported accidental intrathecal injection of 80mg TXA in a 30-year-old man. The patient experienced severe pain in the back and gluteal region and recurrent attacks of polymyoclonus and seizures in addition to recurrent episodes of ventricular tachycardia that subsided spontaneously. The patient was fully recovered within 4 days without any neurologic sequelae.

2003年，Yeh及其同事[8]报告无意中蛛网膜下腔内注射500mg氨甲环酸，患者出现全身性惊厥和高血压反应，随后出现难治性心室颤动，最后死亡。作者将这一后遗症归因于氨甲环酸引起的大量交感神经放电，这与我们病例中遇到的情况相似。惊厥发作的触发可通过抑制大脑皮层中的抑制性γ-氨基丁酸-(GABA)-A受体或降低脑血流量导致脑缺血来解释[9 10]。2007年，Garcha及其同事[11]报告蛛网膜下腔意外鞘内注射氨甲环酸后死亡的病例。2011年，Kaabachi等人[12]报告一名30岁男子意外鞘内注射80毫克氨甲环酸，患者背部和臀部剧烈疼痛，多发性肌阵挛和惊厥反复发作，此外，室性心动过速反复发作并自行消退。患者在4天内完全康复，无任何神经后遗症。

Conclusion结论

We should emphasize that all the previously mentioned case reports have resulted from confusion between TXA and hyperbaric bupivacaine 0.5% ampoules that were having the same appearance. We recommend that critical drugs like the drugs used for spinal anesthesia have unique appearance and package so possibility of confusion is remote. At the same time both the anesthesiologist and nurse must check the ampoule label precisely and stick to the double-checking concept.

我们应该强调，前面提到的所有病例报告都是由于氨甲环酸和0.5%布比卡因安瓿外观相近，容易导致混淆所致。我们建议关键药物，如用于腰麻的药物应具有独特的外观和包装，这样，混淆的可能性就很小。同时，麻醉师和护士都必须准确检查安瓿标签，并坚持双重核查的理念。