蛛网膜下腔出血可以用氨甲环酸吗（2011突尼斯个案报道）

蛛网膜下腔出血可以用氨甲环酸吗（2011突尼斯个案报道）Key words: Intrathecal seizures tranexamic acid ventricular tachycardiaSome factors have been identified as contributing to medical errors such as labels appearance and location of ampules. In this CASE REPORT inadvertent intrathecal injection of 80mg tranexamic acid was followed by severe pain in the back and the gluteal region myoclonus on lower extremities and agitation. General Anesthes

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2011年发生在突尼斯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。

个案报道：意外蛛网膜下腔注射氨甲环酸

原文出处：Olfa Kaabachi Mongi Eddhif KarimRais Mohamed Ali Zaabar. Inadvertent intrathecal injection of tranexamic acid. Saudi J Anaesth. 2011 Jan;5(1):90-2. doi: 10.4103/1658-354X.76504.

原文作者及单位：

Olfa Kaabachi Mongi Eddhif Karim Rais Mohamed Ali Zaabar

Department of Anaesthesiology and Intensive Care Kassab Orthopaedic Institute of Tunis Tunisia

ABSTRACT

Some factors have been identified as contributing to medical errors such as labels appearance and location of ampules. In this CASE REPORT inadvertent intrathecal injection of 80mg tranexamic acid was followed by severe pain in the back and the gluteal region myoclonus on lower extremities and agitation. General Anesthesia was induced to complete surgery. At the end of anesthesia patient developed polymyoclonus and seizures needing supportive care of the hemodynamic and respiratory systems. He developed ventricular tachycardia treated with Cordarone infusion. The patient’s condition progressively improved to full recovery 2 days after. Confusion between hyperbaric bupivacaine and tranexamic acid was due to similarities in appearance between both ampules.

Key words: Intrathecal seizures tranexamic acid ventricular tachycardia

摘要

已知易导致医疗错误的原因包括：安瓿的标签、外观和存放位置。在本病例报告中，意外蛛网膜下腔注射80mg氨甲环酸后出现背部和臀部剧烈疼痛、下肢肌阵挛和躁动。改为全身麻醉完成手术。麻醉结束时，患者出现多发性肌阵挛和惊厥发作，给予血流动力学和呼吸系统支持。接着出现室性心动过速，用盐酸胺碘酮处理。术后2天，患者病情逐渐好转，直至完全康复。布比卡因和氨甲环酸之间的误用是由于两个安瓿的外观相似。

关键词：鞘内注射(蛛网膜下腔注射)、癫痫发作、氨甲环酸、室性心动过速

INTRODUCTION

In industrialized countries it has been reported that adverse events from drugs are a leading cause of injury and death. Some factors have been identified as contributing to medical errors such as labels appearance and location of ampules and syringes the lack of double-checking inattention poor communication and fatigue on the part of the anesthesiologist[1 2]. Tranexamic acid (TXA) is being widely used during surgery to reduce bleeding and has been associated with previous accidental intratechal injection with fatal issue in some cases[3-7]. In this case report the injection of TXA instead of hyperbaric bupivacaine for Spinal anesthesia was due to confusion between two different ampules with similar appearance and was responsible of polymyoclonus seizure and ventricular arrhythmia.

前言

据报道，在工业化国家，药物不良事件是造成伤害和死亡的主要原因。已知导致医疗错误的原因包括标签、安瓿和注射器的外观和存放位置、缺乏双重检查、注意力不集中、沟通不良以及麻醉师疲劳[1 2]。氨甲环酸（TXA）广泛用于减少术中出血，但有文献报道意外蛛网膜下腔内注射会有致命危险[3-7]。本病例报告中，因两药安瓿外观相似，误将TXA代替布比卡因用于腰麻，导致多发性肌阵挛、惊厥发作和室性心律失常。

CASE REPORT

A 30-year-old man ASA I physical status was scheduled for arthroscopic knee anterior ligament reconstruction. Spinal anesthesia was performed with the patient in the sitting position at the L4-L5 interspace using a 26-gauge Quincke tip needle. About 60s after injection of 8mg (1.6ml) of 0.5% hyperbaric bupivacaine the patient complained of severe pain in the back and the gluteal region and developed myoclonic movements in the lower extremities. The patient’s arterial blood pressure increased to 160/100mmHg and the heart rate to 120 beats/min. IV sedation with midazolam (3mg) and fentanyl (100μg) was administered immediately without effect.

病例报告

患者为一名30岁男性，身体状况评级为ASA I级，计划进行关节镜下膝前韧带重建手术。采用26号Quincke针头，患者坐姿L4-L5间隙穿刺腰麻。注射8mg（1.6ml）0.5%布比卡因约60s后，患者主诉背部和臀部疼痛严重，下肢出现肌阵挛，血压160/100 mmHg，心率120次/min。立即使用咪达唑仑（3mg）和芬太尼（100μg）进行静脉镇静，无效果。

Consequently general anesthesia was induced by the infusion of propofol (200mg) and celocurine (100mg) and the patient’s trachea was intubated. Anesthesia was maintained using propofol infusion(10 mg/kg/h) and Fentanyl (2μg/kg/45min) and surgery was continued. At the end of surgery and 5mins after the propofol infusion was discontinued recurrent polymyoclonus and seizures developed. Clonazepam (1mg) and phenobarbital (800mg) were administered and continuous sedation using midazolam and fentanyl was started. Accidental intrathecal injection of the wrong drug was suspected and a used ampule of TXA was found in the trash can [Figures 1 and 2].

随即，输注异丙酚（200mg）和白藜芦碱（100mg），改全身麻醉，气管插管。异丙酚输注（10mg/kg/h）和芬太尼（2μg/kg/45min）维持麻醉，继续手术。停用异丙酚5分钟后手术结束时，多肌阵挛和惊厥发作复现。给予氯硝西泮（1mg）和苯巴比妥（800mg），并开始使用咪唑安定和芬太尼进行持续镇静。怀疑蛛网膜下腔意外注射了错误的药物，在垃圾桶中发现了一个用过的TXA安瓿[图1和图2]。

Figure 1: TXA and old bupivacaine ampules

图1：氨甲环酸和旧布比卡因安瓿

Figure 2: TXA and new bupivacaine ampules

图2. 氨甲环酸和新布比卡因安瓿

The patient was transferred to the intensive care unit about 2h after the injection and mechanical ventilation with volume controlled ventilation mode was continued. Central venous and arterial lines were inserted to the patient. The first postoperative arterial blood gas analysis revealed metabolic acidosis (pH=7.3 PaO2=183 PaCO2=35 HCO3–=17.7). The blood analysis did not reveal any renal hepatic or hematological failure.

药物误用约2小时后将患者转移到重症监护室，并继续采用容量控制通气模式进行机械通气。建立中心静脉和动脉导管通道。术后第一次动脉血气分析显示代谢性酸中毒(pH=7.3 PaO2=183 PaCO2=35 HCO3–=17.7)。血液分析未发现任何肾、肝或血液学衰竭。

The patient experienced tonico-clonic convulsions in the upper extremities and the face 3h postoperatively which were treated by an infusion of sodium thiopental (3–5mg/kg/h). Gastric administration of Phenobarbital 200mg daily was initiated. Cranial computed tomography was without abnormalities. A prophylactic infusion of cordarone at the rate of 10 mg/kg/24h was administered for 24h in order to prevent ventricular arrhythmia. The patient developed several episodes of ventricular tachycardia that regressed spontaneously.

术后3小时患者出现上肢和面部强直阵挛性抽搐，输注硫喷妥钠（3–5mg/kg/h），每日鼻饲200mg苯巴比妥治疗。头颅CT扫描无异常。为预防室性心律失常，以10mg/kg/24h的速度预防性输注盐酸胺碘酮，持续24小时。患者出现几次室性心动过速，并自发消退。

On the second postoperative day the sedation was arrested. The patient’s level of consciousness increased. He moved his head and upper extremities with painful stimulus deep tendon reflexes were absent in the lower extremities. On the third postoperative day he opened his eyes to voice commands obeyed to simple orders and breathe spontaneously. Tracheal was extubated. Finally on the fourth postoperative day all neurologic examinations were normal. The patient was discharged from the intensive care unit and on the sixth day was subsequently discharged from the hospital without neurological sequelae. Six months later neurological evaluation was still normal.

术后第二天，停止镇静。患者意识逐渐恢复。对疼痛刺激有反应，疼痛刺激时可移动头部和上肢，但下肢深部肌腱反射仍未引出。术后第三天，可唤醒睁眼，对语音交流有反应，按照语音提示可做简单动作，可自主呼吸 然后脱机。最后，术后第四天，所有神经系统检查均正常，出重症监护室，术后第六天出院，无神经后遗症。术后六个月后，神经评估仍然正常。

DISCUSSION讨论

Little is known about the effect of direct intrathecal administration of TXA. Wong et al.[3] reported the first case of inadvertent intrathecal injection of 75mg TXA in an ASA I physical status 18-year-old man scheduled for appendectomy. Four hours after the spinal injection he experienced persistent motor and sensory block of lower extremities and urinary incontinence. He developed clonic convulsions that progressed to a generalized seizure and hyperthermia of 40.5°C 5.5h after the injection. His seizure and fever gradually subsided over the next 5h after treatment with intravenous diazepam and diclofenac and the patient recovered completely without any sequelae.

关于直接蛛网膜下腔内注射氨甲环酸的后果知之甚少。1988年，Wong等人[3]报道了第一例蛛网膜下腔内意外注射氨甲环酸的病例。该病例为一18岁男性，身体状况为ASA I级，准备行阑尾切除术，腰麻时意外蛛网膜下腔内注射75mg氨甲环酸。腰麻注射后4小时，患者出现下肢持续躁动、感觉障碍以及尿失禁，阵挛性抽搐。注射后5.5小时发展为全身性惊厥发作和40.5°C的高温。静脉注射地西泮和双氯芬酸后的5小时内，惊厥发作和发烧逐渐消退，患者完全康复，没有任何后遗症。(注：中文版《麻醉学杂志》，但我在中国大陆和台湾范围内没有找到该杂志和此篇文章的全文)。

De Leede-Van der Maarl et al.[4] reported a case of a 68-year old man who accidentally received an intrathecal injection of 50mg TXA. Immediately after the administration of the drug he developed status epilepticus. The outcome was complicated with hypotonic paresis of all four extremities which resolved but resulted in residual bilateral peronealpalsy. In the case reported by Yeh et al.[5] generalized convulsions and refractory ventricular fibrillation after intrathecal administration of 500mg of TXA was associated with fatal outcome. In two others case reports intrathecal injection of a dose of 150mg of TXA lead to a poor issue in one case because of a refractory ventricular fibrillation.[6 7] Our patient received an intrathecal injection of 90mg TXA with a full recovery 4 days after.

De Leede Van der Maarl等人[4]报告了一例68岁男子意外蛛网膜下腔内注射50 mg氨甲环酸的病例。给药后，他立即出现癫痫持续状态。结果比较麻烦，所有四肢出现低张力性瘫痪，后期部分缓解，残余双侧腓神经麻痹。Yeh等报告的病例中[5]，蛛网膜下腔内注射500mg 氨甲环酸后导致全身性惊厥和难治性心室颤动，最后导致死亡。在另外两个病例报告中，蛛网膜下腔内注射150mg氨甲环酸导致一例因难治性心室颤动而死亡[6 7]。我们的病例蛛网膜下腔内注射了90mg氨甲环酸，4天后完全恢复。

The exact mechanism by which TXA induces convulsions or ventricular arrhythmia is unknown. High doses of TXA would cause massive sympathetic discharge as evidenced by the initial hypertensive response and the subsequent ventricular arrhythmia reported in our case report and also in some patient.[4 5 7] TXA-induced seizures either from direct cerebral ischemia secondary to decreases in regional or global cerebral blood flow [8] or blockage of inhibitory cortical-aminobutyric acid (GABA)-A receptors.[9] There is evidence for a dose-related neurotoxicity in animal model with greater severity and duration of seizure with increasing TXA dosage.[10] Use of high-dose TXA in patients undergoing cardiac surgery increased at the incidence of convulsive seizures from 1.3 to 3.8%.[11]。

氨甲环酸诱发惊厥或室性心律失常的确切机制尚不清楚。高剂量氨甲环酸会引起大量交感神经放电，我们病例报告中初始血压升高和随后的室性心律失常证明如此，在一些其他患者中也是如此[4 5 7]。氨甲环酸诱发的惊厥发作可能是由于局部或整体脑血流量减少引起的直接脑缺血[8]或阻断抑制性皮质氨基丁酸(GABA)-A受体[9]。有证据表明，氨甲环酸在动物模型中存在剂量相关的神经毒性，随着氨甲环酸剂量的增加，惊厥发作的严重程度和持续时间会增加[10]。心脏手术患者使用大剂量氨甲环酸时惊厥发作发生率从1.3%增加到3.8%[11]。

Finally all these case reports were due to confusion between hyperbaric bupivacaine and TXA. The ampules of TXA (100mg/mL) and bupivacaine (5mg/mL) were similar in appearance [Figure 1]. But all these publications have leaded the manufacturer to change ampule of hyperbaricbupivacaine [Figure 2] so such serious complication could not happen again.

最后，所有这些病例报告都是由于布比卡因和氨甲环酸之间的混淆所致。氨甲环酸（100mg/mL）和布比卡因（5 mg/mL）的安瓿外观相似[图1]。所有这些负面个案病例文献报道会使药物生产商更换布比卡因的安瓿[图2]，因此这种严重并发症应该不会再次发生。

参考文献：略