甲针是什么原因引起的(顶针甲啥原因引起的)

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2009年发生在伊朗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，将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。

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原文作者及单位：

Kamal Mohseni, MD; Alireza Jafari, MD; Mohammad Rezvan Nobahar, MD; Ali Arami, MD. the Department of Anesthesia, Milad Hospital, Tehran, Iran.

We present a case of accidental injection of tranexamic acid instead of bupivacaine during spinal anesthesia. One minute after intrathecal injection of 3.5mL of solution, the patient developed myoclonus of his lower extremities. Accidental intrathecal injection of the wrong drug was suspected and a used ampule of tranexamic acid discovered in the trash can. The ampules of tranexamic acid (500mg/5mL) and bupivacaine (5mg/mL, Merck, Darmstadt, Germany) were similar in appearance. General anesthesia was induced. Ten hours later, the patient developed myoclonus of his upper extremities and face. His polymyoclonus was successfully treated with phenytoin, sodium thiopental infusion, sodium valproate and supportive care of the hemodynamic, and respiratory systems. The patient's condition progressively improved to full recovery. (Anesth Analg 2009;108:1984–6)

我们报告一例腰麻时意外将氨甲环酸当作布比卡因注入的病例。鞘内注射3.5毫升氨甲环酸注射液1分钟后，患者出现下肢肌阵挛。怀疑鞘内意外注射了错误的药物，在垃圾桶里找到了一个用过的氨甲环酸安瓿。氨甲环酸（500mg/5ml）和布比卡因（5mg/mL，默克，达姆施塔特，德国）的安瓿外观相似。改为全麻。10小时后，患者的上肢和面部出现肌阵挛。他的多发性肌阵挛通过苯妥英钠、硫喷妥钠输注、丙戊酸钠以及血流动力学和呼吸系统的支持性处理得到成功治疗。病人的病情逐渐好转，直至完全康复。

It is estimated that medication errors occur in 1.5 million people in the United States annually, leading to the death of several thousand, which costs the nation at least US $3.5 billion a year[1]. In other industrialized countries, it has been reported that adverse events from drugs are a leading cause of injury and death within their health care systems[2,3]. In the present case report, injection of the wrong drug for spinal anesthesia by the anesthesiologist resulted in myoclonus.

据估计，美国每年有150万人发生错误用药，导致数千人死亡，每年给国家造成至少35亿美元的损失[1]。在其他工业化国家，据报道，药物不良事件是其医疗系统内伤害和死亡的主要原因[2,3]。在本病例报告中，麻醉医生误用麻醉药物导致肌阵挛。

Case Description病例描述

A 57-yr-old man, presented for orthopedic surgery under spinal anesthesia after left patellar fracture. He had no remarkable medical history except for smoking (20 packs/year) and opioid addiction (opium smoking about 9g/d) for 7–8yr. Physical examination and laboratory investigation revealed no abnormal findings. His arterial blood pressure was 130/80mmHg, preoperatively.

患者为57岁男子，左髌骨骨折，腰麻骨科手术。吸烟（20包/年），阿片类成瘾（每天吸食鸦片约9克）7-8年，无其他异常特殊病史。体检和实验室调查显示未见异常。术前血压130/80mmHg。

Spinal anesthesia was performed with the patient in the sitting position at the L4-5 interspace using a 26-gauge Quincke tip needle. About 30s after injection of 3.5mL of 0.5% bupivacaine, the patient complained of perianal burning. The pain in the fracture site subsided. However, after about 1min, the patient’s arterial blood pressure increased to 165/95 and myoclonic movements developed in the lower extremities. IV sedation with midazolam (2mg) and fentanyl (100g) was administered immediately without effect. Consequently, general anesthesia was induced by the infusion of propofol (120mg) and atracurium (40mg), and the patient’s trachea was intubated. Anesthesia was maintained using propofol infusion (100ug· kg-1·min-1) and 50% O2/N2O.

患者坐姿，用26号Quincke针头穿刺针，L4-5间隙对进行腰麻。注射3.5 mL 0.5%布比卡因约30s后，骨折部位疼痛减轻，但患者感肛周烧灼痛。大约1分钟后，患者血压上升至165/95，下肢出现肌阵挛。立即使用咪唑安定（2mg）和芬太尼（100g）进行静脉镇静，无效。改全麻，输注异丙酚（120mg）和阿曲库铵（40mg），气管插管。持续异丙酚输注（100ug·kg-1·min-1）和50% O2/N2O维持麻醉。

Accidental intrathecal injection of the wrong drug was suspected and a used ampule of tranexamic acid was found in the trash can. The ampules of tranexamic acid (500mg/5mL, Caspian Tamin Pharmaceutical Co, Rasht, Iran) and bupivacaine (5mg/mL, Merck, Darmstadt, Germany) were similar in appearance (Fig. 1).

怀疑鞘内意外注射了错误的药物，垃圾桶里发现了一个用过的氨甲环酸安瓿。氨甲环酸（500mg/5mL，里海塔明制药公司，伊朗拉什特）和布比卡因（5mg/mL，默克，达姆施塔特，德国）的安瓿外观相似（图1）。

图1. Similar appearance of tranexamic acid (Caspian Tamin Pharmaceutical Co, Rasht, Iran) and bupivacaine (Merck, Darmstadt, Germany) ampules led to a spinal anesthesia injection error. 氨甲环酸（伊朗拉什特里海塔明制药公司）和布比卡因（德国达姆施塔特默克公司）安瓿的相似外观导致腰麻药物误用。

Propofol infusion was discontinued 1.5h postoperatively, and the muscle relaxant was reversed with neostigmine (0.06mg/kg) and atropine (0.02mg/kg). However, 1min thereafter, myoclonic movements recurred in a more severe form. Therefore, atracurium (20mg) was administered again, together with IV diazepam (10mg) and dexamethasone (8mg). Propofol infusion (50ug· kg-1·min-1) was also recommenced. After consulting with aneurologist, IV phenytoin (500 mg initial dose, followed by 125mg every 8h) and dexamethasone (8mg every 6h), plus an H2 blocker, were administered.

术后1.5小时停用异丙酚，用新斯的明（0.06mg/kg）和阿托品（0.02 mg/kg）逆转肌松。1分钟后，肌阵挛运动发作更严重，再次给予阿曲库铵（20mg），同时静脉注射地西泮（10mg）和地塞米松（8mg）。继续异丙酚输注（50ug•kg-1•min-1）。咨询神经科医生，静脉注射苯妥英钠（初始剂量500毫克，随后每8小时注射125毫克）和地塞米松（每6小时注射8毫克），加上H2受体阻滞剂。

The patient was transferred to the intensive care unit about 2h after the injection and mechanical ventilation with synchronous intermittent mandatory ventilation mode was established. A Foley urethral catheter, nasogastric tube and central venous and arterial lines were inserted. The first postoperative arterial blood gas analysis revealed metabolic acidosis (pH=7.07, Paco2=36.5, PaO2=134, HCO3=10.4, Base Excess=18.8, Spo2=%96). Therefore, 7.5% sodium bicarbonate (150mL) was infused over a period of 45min. Arterial blood gas analysis 2h later revealed compensated metabolic acidosis. The patient’s arterial blood pressure decreased after the control of acidosis (95/65mmHg) without signs of hypovolemia, and dopamine infusion (5–10 ug•kg-1•min-1) was initiated. Hepatic, renal, and hematological evaluations were done for assessing multiorgan failure. Central venous pressure remained between 8 and10cm H2O. Urinalysis showed ketone body (1+), protein (1+), HB (2+), and erythrocyte (16–18 per high-power field).

麻醉药物误用约2h后，将患者转入重症监护室，机械通气模式为同步间歇指令通气(synchronous intermittent mandatory ventilation)。插入Foley导尿管、鼻胃管、建立中心静脉和动脉通道。术后第1次动脉血气分析显示代谢性酸中毒(pH=7.07, Paco2=36.5, PaO2=134, HCO3=10.4,Base Excess=18.8, Spo2 =%96)。45分钟内注入7.5%碳酸氢钠（150mL）。2小时后的动脉血气分析显示代偿性代谢性酸中毒。控制酸中毒后，患者血压下降（95/65mmHg），却无低血容量表现，使用多巴胺输注（5-10 ug•kg-1•min-1）。进行肝脏、肾脏和血液学评估以评估多器官衰竭。中心静脉压保持在8到10厘米水柱之间。尿液分析显示酮体（1+）、蛋白质（1+）、血红蛋白（2+）和红细胞（每个高倍视野16-18）。

The patient experienced a tonic clonic convulsion in the upper extremities and the face 10h postoperatively, which was treated by an infusion of sodium thiopental (3–5mg•kg-1•min-1). Gastric lavage of sodium valproate tablets (200mg thrice daily) was started (the injection form of sodium valproate was not available) to control polymyoclonus after 24h. The phenytoin was tapered to 50mg twice a day and then discontinued after 24h. Thiopental was also tapered on the second postoperative day.

术后10小时上肢和面部出现高张力强直阵挛性抽搐，输注硫喷妥钠（3–5mg•kg-1•min-1）。24小时后用丙戊酸钠片剂（200mg，每日三次）胃部灌洗（当时没有丙戊酸钠注射液）以控制多发性肌阵挛。苯妥英钠逐渐减量至50毫克，每天两次，24小时后停用。术后第二天，硫喷妥钠也逐渐减量。

On the third postoperative day, the patient’s level of consciousness increased. He moved his head and upper extremities with painful stimulus, but deep tendon reflexes were absent in the lower extremities. His arterial blood pressure increased to 100/60mmHg by the infusion of dopamine on this day. On the fourth postoperative day, he opened his eyes to voice commands, obeyed simple orders, and was tracheally extubated. Deep tendon reflexes were normal and his arterial blood pressure was now 120/80mmHg; therefore, dopamine was discontinued. On the fifth postoperative day, he spoke normally. However, strength of the right leg was weaker than the left (3/5 vs 4/5). Finally, on the sixth postoperative day, all neurologic examinations were normal, including strength of the lower extremities (5/5). He did not remember postoperative events. On the seventh postoperative day, the patient was discharged form the intensive care unit and on the eighth day was subsequently discharged from the hospital without neurologic sequelae.

术后第三天，患者的意识逐渐恢复。疼痛刺激可使其头部及上肢移动，但下肢深肌腱反射未引出。注射多巴胺可使血压上升至100/60mmHg。术后第四天，可睁眼，对语音交流有反应，按照语音提示可做简单动作，脱机。深肌腱反射正常，血压120/80mmHg；停用多巴胺。术后第五天，可正常说话。但右下肢肌力较左下肢弱（3/5比4/5）。术后第六天，所有神经系统检查均正常，包括下肢力量（5/5）。他不记得术后发生的事情。术后第7天，出重症监护病房，术后第8天，出院，无神经后遗症。

Discussion讨论

Some factors that have been identified as contributing to medication errors include labels, appearance and location of ampules and syringes, inattention, poor communication, carelessness, and fatigue on the part of the anesthesiologist[4,5]. In this case report, drug error-induced polymyoclonus occurred from injecting tranexamic acid for spinal anesthesia due to confusing two different ampules with similar appearance. This illustrates the importance of double-checking to reduce such errors[4].

已证实的药物错用常见因素包括：标签、安瓿和注射器的外观和存放位置、注意力不集中、沟通不畅、粗心大意以及麻醉师的疲劳[4,5]。本病例报告中，由于混淆了两个外观相似的不同安瓿，误将氨甲环酸当作布比卡因，用于腰麻，导致多发肌阵挛。说明反复检查核对对于减少此类错误的重要性[4]。

Myoclonus could arise from the cerebral cortex, brainstem, spinal cord, peripheral nerves, plexus, and spinal roots. Some authors have linked it to cerebellar dysfunction[6,7]. There are two clinical types of myoclonus arising from the spinal cord: spinal segmental myoclonus and propriospinal myoclonus. In the second type, the first muscles activated are usually from the thoracic cord with upward and downward spread resulting in generalized myoclonus. Most patients with propriospinal myoclonus have had minor spinal trauma with normal magnetic resonance imaging findings, but the disorder has been reported in severe spinal cord injury, multiple sclerosis, human immunodeficiency virus or lyme infection, syringomyelia, spinal cord tumors and spinal cord infarction[8].

肌阵挛可源于大脑皮层、脑干、脊髓、周围神经、神经丛和脊神经根。一些作者认为其与小脑功能障碍有关[6,7]。脊髓源性肌阵挛有两种临床类型：脊髓节段性肌阵挛和脊髓固有性肌阵挛。在第二种类型中，第一块肌肉阵挛激活通常源于胸髓，可向上和向下扩散，导致全身性肌阵挛。大多数脊髓固有性肌阵挛患者都有轻微的脊髓损伤，磁共振成像结果正常，但这种疾病在严重的脊髓损伤、多发性硬化、人类免疫缺陷病毒或莱姆感染、脊髓空洞症、脊髓肿瘤和脊髓梗死中有报道[8]。

Volumes of local anesthetics injected in the subarachnoid space in the lumbar area can reach the dependent structures in the cranium, such as the cerebellum and lower cranial nerves. Dreskin et al. reported a case of polymyoclonus resulting from accidental subarachnoid injection of a local anesthetic. Because of the dependent anatomical position of the cerebellum and its frequent association with myoclonus, they concluded that a local anesthetic, steroid, or preservative effect on the cerebellum was the most likely cause of the patient’s polymyoclonus[9]. In this setting, polymyoclonus can also represent lidocaine-, steroid-, or preservative-induced seizure-like activity arising from the spinal cord. Spinal myoclonus has been described by Brown et al. in patients after spinal cord trauma and subarachnoid injections of irritating substances during myelography[10,11]. Manconi etal.[12] reported a severe and uncommon case of propriospinal myoclonus that appeared after a vertebral fracture of T11 vertebra and an acute progression into a myoclonic status associated with respiratory failure and loss of consciousness.

腰麻蛛网膜下腔注射的局麻药可上达颅内结构，如小脑和下位颅神经。Dreskin等人报告了一例因蛛网膜下腔意外注射局麻药导致的多肌阵挛。由于小脑的解剖位置及其与肌阵挛的频繁关联，他们认为，局麻药、类固醇激素或对小脑的保护作用是患者多发性肌阵挛的最可能原因[9]。在这种情况下，多肌阵挛也可表现为利多卡因、类固醇激素或保护剂诱发的脊髓惊厥样活动。脊髓造影期间脊髓损伤和蛛网膜下腔注射刺激性物质后，Brown等人观察到患者有脊髓肌阵挛的发生[10,11]。Manconi等人[12]报道了一例严重罕见的脊髓固有性肌阵挛病例，发生在T11椎体骨折后，并快速进展为肌阵挛状态，伴有呼吸衰竭和意识丧失。

Some authors believe that the action of local anesthetic drugs and IV anesthetics, such as etomidate on the spinal cord and/or supraspinal system, may lead to cortical disinhibition and pyramidal tract inhibition[13]. Ford et al.[14] reported a case of spinal myoclonus induced by the tip of an intrathecal catheter in a 35-yr-old patient. The myoclonus resolved promptly once the catheter tip was withdrawn.

一些作者认为，局麻药和静脉麻醉剂（如依托咪酯）对脊髓和/或脊髓上系统的作用可能导致大脑皮层去抑制和锥体束抑制[13]。Ford等人[14]报告了一例35岁患者鞘内导管尖端诱发脊髓肌阵挛的病例。拔出导管尖端后，肌阵挛立即消失。

In the present case, we observed polymyoclonus as propriospinal clonus resulting from spinal cord and possibly brainstem irritation by tranexamic acid, leading to polymyoclonus and seizure. Phenytoin did not terminate such severe contracting movements and myoclonicseizures, but the addition of sodium valproate was effective. Paralysis does not allow for evaluation of continuing myoclonus and seizure activity but may reduce the metabolic requirements. Although clinical features are important, neurophysiologic studies provide the most important clues for the determination of the myoclonus generator. Surface electromyography suggests either a cortical, brainstem or spinal origin[15]. Electroencephalography-electromyography polygraphy is the only test which is able to directly prove the cortical origin of myoclonus[16].

本病例我们观察到多发性肌阵挛是由脊髓引起的脊髓固有性肌阵挛，可能是氨甲环酸刺激脑干，导致多发性肌阵挛和惊厥发作。苯妥英钠不能有效终止这种严重的收缩运动和肌阵挛发作，但使用丙戊酸钠有效。瘫痪状态无法评估持续肌阵挛和惊厥活动，但可降低代谢需求。虽然临床特征很重要，但神经生理学研究为确定肌阵挛的发生提供了最重要的线索，表面肌电图显示源于大脑皮层、脑干或脊髓[15]。脑电图-肌电图-多导图是唯一能够直接证明肌阵挛源于大脑皮层的检查[16]。

参考文献：略