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警惕!头孢曲松钠的8种死法

2016-09-24 徐来 医学界临床药学频道

头孢曲松钠是半合成的第3 代头孢菌素,被列入国家基本药物。头孢曲松通过抑制细菌细胞壁的合成发挥抗菌作用,主要用于敏感的革兰阴性杆菌和部分敏感的革兰阳性球菌所致的严重感染,因其抗菌作用强, 半衰期长,疗效肯定,临床广泛用于治疗呼吸道感染、败血症、腹腔感染、肾盂肾炎、盆腔炎性疾病、骨关节感染、皮肤软组织感染、中枢神经系统感染等。近年来, 随着头孢曲松钠临床应用日益广泛, 其不良反应报告也随之增加,

头孢曲松钠是半合成的第3 代头孢菌素,被列入国家基本药物。头孢曲松通过抑制细菌细胞壁的合成发挥抗菌作用,主要用于敏感的革兰阴性杆菌和部分敏感的革兰阳性球菌所致的严重感染,因其抗菌作用强, 半衰期长,疗效肯定,临床广泛用于治疗呼吸道感染、败血症、腹腔感染、肾盂肾炎、盆腔炎性疾病、骨关节感染、皮肤软组织感染、中枢神经系统感染等。

近年来, 随着头孢曲松钠临床应用日益广泛, 其不良反应报告也随之增加,有报道称头孢曲松钠成为头孢类抗生素中第1位致死药品。下面列举头孢曲松钠的严重不良反应,望各位临床医生知晓。

1、过敏性休克

速发型过敏性休克致死

患者,男,57岁,慢性支气管炎、肺气肿,既往无药物过敏史,给予头孢曲松钠用药后10min,出现过敏性休克,经抢救无效死亡。

迟发型过敏性休克致死

6岁患儿,原药皮试阴性,在头孢曲松钠用药20min时,自诉喉头不舒服,遂停止液体滴入,但其家属要求继续输注,并调慢滴速,1.2h后出现皮疹伴全身发痒,但呼吸平稳、无胸闷气促,以呼吸道感染并药物过敏收住入院。入院 10min后,各项生命体征急剧恶化,最终死亡。

速发型过敏性休克致双眼失明

患者追问病史有青霉素过敏史,用药前未经原药作皮试,使用头孢曲松钠休克后又经转院抢救,最终导致双目失明。

过敏性休克致永久性双目失明鲜见。过敏性休克属 1 型变态反应,变态原使机体致敏后,迅速导致微循环严重瘀血,静脉回流和心输出量急剧减少,动脉血压急骤降低,视路缺血缺氧可导致偏盲及视力下降,严重者引起失明。

血管神经性水肿

患儿,男,8岁,因上呼吸道感染,给予头孢曲松钠1.5g加生理盐水150ml静脉滴注。6min后患儿突然出现眼睑、口唇水肿,随之延至颜面部、四肢及会阴部,同时伴有咽部痒感,即停药。后经治疗水肿缓解。

2、急性溶血

急性溶血致呼吸循环衰竭死亡

患者,男,76岁,因头孢曲松药物过敏收治入院,查体及辅助检查后诊断为:头孢曲松钠致急性血管内溶血。全力抢救,终因病情进一步恶化死亡。死因:呼吸循环衰竭。死亡诊断:头孢曲松钠致急性溶血。

严重溶血反应并发急性肾衰致死

患者第一天使用头孢曲松钠时出现头晕恶心、出冷汗、面色苍白症状,第二天续用引起严重溶血反应,病情进展快,溶血产物引起肾小管细胞坏死和管腔堵塞, 最终合并急性肾功能衰竭, 次日中午死亡。

3、神经系统损害

小儿惊厥

患儿,1岁,因间断发热20余天,先后3次输入不同批号、不同厂家、不同剂量的头孢曲松钠静脉滴注,均出现惊厥症状,对症治疗后缓解。

锥体外系症状

患者,女,23岁,既往无药物过敏史,因右乳腺纤维瘤切除术后,给予头孢曲松钠静脉滴注,出现全身乏力,头及右侧手足不自主摆动,症状持续不能缓解。经查诊断为头孢曲松致椎体外系症状,停药治疗后症状消失。

4、高血压危像

患者,男,67岁,因肺炎静脉注射头孢曲松钠后出现烦躁、四肢厥冷、气促、手足发抖、口唇发绀、咳粉红色泡沫痰及鲜红色血痰。体检BP 195/113mmHg,停药予降压治疗后血压正常,次日静注头孢曲松钠又出现上述症状,经对症治疗后缓解。

5、用药期间饮酒(双硫仑反应)

患者,男性,60岁,因上呼吸道感染给予头孢曲松钠3g加入0.9%氯化钠注射液,静脉滴注,每天一次。第三天上午患者饮酒后,突然出现呼吸困难、乏力、心悸、气短、全身皮肤潮红等双硫仑样反应,立即给予地塞米松10mg静脉注射、10%葡萄糖酸钙20毫升静脉注射、异丙嗪25亳克肌肉注射后,上述症状逐渐减轻。

头孢曲松钠可影响乙醇代谢,使血中乙酰醛浓度上升,出现双硫仑样反应,表现为面部潮红、头痛、眩晕、腹痛、恶心、呕吐、气促、心率加快、血压降低、嗜睡、幻觉等。故用药期间及停药后1周内应避免饮酒,也应避免口服含乙醇类的药物、饮料或静脉输入含乙醇的药物。

6、严重呼吸困难

喉头水肿

患者因肺炎给予头孢曲松钠后出现呼吸困难、胸闷气短等,经检查咽喉部发生水肿,立即停止了输液,并更换输液器,静脉注射地塞米松、异丙嗪、氯丙嗪,并给予吸氧处理,患者各生命体征均恢复正常,终呼吸道症状缓解出院。

7、肝、肾功能损害


肝损害

患者,女,22岁,因急性化脓性胆囊炎就诊,给予头孢曲松钠静脉滴注,第3天出现尿发黄,巩膜轻度感染,查肝功能:丙氨酸转氨酶 451U/L,碱性磷酸酶377U/L,随后2天,黄疸加深。停药后给予保肝、退黄等对症治疗,肝功能逐渐恢复。

肾损害

患者,男,68岁,因胆道感染给予头孢曲松钠静脉滴注,用药后第12d出现腰痛、颜面部、眼睑、双下肢轻度凹陷性水肿。尿少,尿蛋白(++),停药后肾功能恢复。


8、配伍禁忌

由于头孢曲松钠的配伍禁忌药物甚多,故应单独给药。下面列举一些与头孢曲松钠存在配伍禁忌的常用药物:



头孢曲松钠应用前是否需要做皮试?

头孢曲松钠在应用前是否需要做皮试各地并不统一, 说明书和药典中也并无明确规定。临床实际中有不做任何皮试直接使用;也有用青霉素或头孢唑啉代替皮试;亦有原药皮试。但即便是原药皮试,也可能会发生严重过敏性休克致死。

因此,使用头孢曲松钠时最好用原药做皮试,即使皮试阴性者,在使用本品时也应做好用药的全程监护,一旦出现药物不良反应,应立即停药,并作相应处理。

合理用药至关重要

1、用药前应详细询问过敏史。

2、有呼吸系统疾病、特别是过敏体质伴哮喘患者应用头孢曲松钠尤其要慎重。

3、青霉素与头孢菌素类抗生素有不完全的交叉过敏反应,对重复用药、连续使用或曾用过其它β-内酰胺类抗生素者, 也应警惕出现严重过敏反应的情况。

总之,在应用头孢曲松钠过程中,应严格按照药品说明书用药,掌握好其不良反应,把握患者的适应症,询问过敏史,并严格控制剂量,密切观察患者的反应,一旦出现异常及时处理及抢救,以保证患者的用药安全。

附:头孢曲松钠的禁忌症、用法用量及注意事项

禁忌证


1、对本品及其他头孢菌素类抗生素过敏者禁用。

2、新生儿高胆红素血症患者禁用。
3、本品禁止与含钙的药品同时静脉给药,包括继续静脉输注胃肠外营养液等含钙的输液。


用法用量

1、成人,肌内或静脉给药,每24h 1-2g 或每12h 0.5-1g。每日最大剂量4g。治疗单纯性淋病及软下疳均为250mg,单剂肌内注射。


2、儿童,静脉给药。


(1)新生儿(出生体重>2kg者):日龄≤7日者,每日25mg/kg;日龄>7日者,每日50mg/kg。

(2)1个月-12岁儿童,一日50mg/kg,脑膜炎患者可增至一日100mg/kg分2次给予,但一日总量不超过4g。

(3)12岁以上儿童用成人剂量。


注意事项


1、本品不能加入哈特曼氏以及林格氏等含有钙的溶液中使用。本品与含钙剂或含钙产品合并用药有可能导致致死性结局的不良事件。


2、为避免在肺或肾中沉淀头孢曲松-钙盐,造成致命危害,应避免本品静脉给药与含钙的药品(包括胃肠外营养液)静脉给药同时进行。如前后使用,之间应有其他静脉输液间隔,新生儿应有48小时以上的时间间隔。


3、交叉过敏反应,对一种头孢菌素过敏者,对其他头孢菌素也可能过敏。在青霉素过敏患者中少数患者应用头孢菌素可发生交叉过敏,故有青霉素过敏性休克史者避免使用本品。

4、有过敏史,尤其是有药物过敏史者,使用本品发生急性过敏反应的风险增加。

5、有胆汁淤积和胆汁沉积危险因素(疾病严重、全胃肠外营养)者使用本品,继发于胆道阻塞的胰腺炎发生的风险增加。

6、胃肠道疾病史,尤其是结肠炎史者,慎用本品。

7、已有致溶血性贫血的报道,并有病例致死。一旦出现溶血性贫血应立即停药。

8、维生素K合成损害或维生素K储存低的患者使用本品,凝血酶原时间改变的风险增加。

9、营养不良者使用本品,因本身维生素K储存低,凝血酶原时间改变的风险增加。

10、除老年患者虚弱、营养不良或有重度肾功能损害的患者外,老年人应用头孢曲松一般不需调整剂量。

11、慢性肝病患者应用本品时不需调整剂量。有严重肾病的肝功能不全者,药物中毒的风险增加,故有严重肝、肾损害或肝硬化患者应调整剂量。

12、肾功能衰竭患者,药物中毒的风险增加。肾功能不全患者肌酐清除率大于5ml/min,每日应用本品剂量少于2g时,不需做剂量调整。血液透析清除头孢曲松的量不多,透析后无需增补剂量。

13、长期使用本品,可导致二重感染。

14、胆囊中的头孢曲松-钙盐沉淀有可能因超声异常被误诊为胆囊结石。

15、对诊断的干扰,应用本品的患者以硫酸铜法测尿糖时可获得假阳性反应,以葡萄糖酶法则不受影响;血尿素氮和肌酐值可能暂时性升高;血清胆红素、碱性磷酸酶、丙氨酸氨基转移酶和门冬氨酸氨基转移酶皆可升高。


16、妊娠妇女注射给药属美国FDA妊娠风险B级。

参考文献:
1、卞蓉蓉, 孙骏. 6916例头孢曲松钠不良反应报告分析[J]. 医学研究生学报, 2012, 25(6):628-630.
2、孙宝玉. 头孢曲松钠致急性致死性溶血死亡1例分析[J]. 中国医院药学杂志, 2012, 32(7):568-569.
3、高冬虹. 头孢曲松钠致严重不良反应分析[J]. 海峡药学, 2009, 21(6):232-233.
4、贺玉芬, 韩培红. 头孢曲松钠的严重不良反应[J]. 中国冶金工业医学杂志, 2013, 30(2):150-151.
5、临床用药须知

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    2018-10-07 xyfg98

    长知识了,好文章

    0

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    2016-10-11 jyzxjiangqin

    工作中要注意药物的不良反应。

    0

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    2016-09-26 jj000003
  6. [GetPortalCommentsPageByObjectIdResponse(id=348387, encodeId=c89334838e79, content=长知识了,好文章, beContent=null, objectType=article, channel=null, level=null, likeNumber=114, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=fe261399236, createdName=xyfg98, createdTime=Sun Oct 07 17:45:48 CST 2018, time=2018-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1984680, encodeId=f96319846803f, content=<a href='/topic/show?id=000e44349df' target=_blank style='color:#2F92EE;'>#头孢曲松钠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44349, encryptionId=000e44349df, topicName=头孢曲松钠)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1e452500029, createdName=12498568m50暂无昵称, createdTime=Thu Apr 20 02:14:00 CST 2017, time=2017-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=144130, encodeId=d8d4144130c0, content=工作中要注意药物的不良反应。, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160806/IMG57A5698BDB0244113.jpg, createdBy=32a91358059, createdName=jyzxjiangqin, createdTime=Tue Oct 11 12:32:06 CST 2016, time=2016-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1379562, encodeId=8bdd13e95623d, content=<a href='/topic/show?id=d9694434815' target=_blank style='color:#2F92EE;'>#头孢曲松#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44348, encryptionId=d9694434815, topicName=头孢曲松)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=37d0457, createdName=yhj-time, createdTime=Mon Sep 26 13:14:00 CST 2016, time=2016-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1459520, encodeId=25d714595209a, content=<a href='/topic/show?id=82a24434020' target=_blank style='color:#2F92EE;'>#头孢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44340, encryptionId=82a24434020, topicName=头孢)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=acae6165124, createdName=jj000003, createdTime=Mon Sep 26 13:14:00 CST 2016, time=2016-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=134687, encodeId=e3a213468e3c, content=学习了谢谢。, beContent=null, objectType=article, channel=null, level=null, likeNumber=137, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2017/04/21/72142930668371951a41ef4ea4b233e6.jpg, createdBy=dcbc1715228, createdName=刘煜, createdTime=Sun Sep 25 05:34:00 CST 2016, time=2016-09-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=134655, encodeId=890e13465520, content=有用的知识,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=76f6105517, createdName=Jiangyh0406, createdTime=Sun Sep 25 03:48:00 CST 2016, time=2016-09-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=134605, encodeId=2f3413460597, content=继续学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=129, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Sat Sep 24 22:28:00 CST 2016, time=2016-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=134606, encodeId=d022134606f6, content=继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Sat Sep 24 22:28:00 CST 2016, time=2016-09-24, status=1, ipAttribution=)]
    2016-09-25 刘煜

    学习了谢谢。

    0

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    2016-09-25 Jiangyh0406

    有用的知识,谢谢分享

    0

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    2016-09-24 doctorJiangchao

    继续学习

    0

  9. [GetPortalCommentsPageByObjectIdResponse(id=348387, encodeId=c89334838e79, content=长知识了,好文章, beContent=null, objectType=article, channel=null, level=null, likeNumber=114, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=fe261399236, createdName=xyfg98, createdTime=Sun Oct 07 17:45:48 CST 2018, time=2018-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1984680, encodeId=f96319846803f, content=<a href='/topic/show?id=000e44349df' target=_blank style='color:#2F92EE;'>#头孢曲松钠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44349, encryptionId=000e44349df, topicName=头孢曲松钠)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1e452500029, createdName=12498568m50暂无昵称, createdTime=Thu Apr 20 02:14:00 CST 2017, time=2017-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=144130, encodeId=d8d4144130c0, content=工作中要注意药物的不良反应。, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160806/IMG57A5698BDB0244113.jpg, createdBy=32a91358059, createdName=jyzxjiangqin, createdTime=Tue Oct 11 12:32:06 CST 2016, time=2016-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1379562, encodeId=8bdd13e95623d, content=<a href='/topic/show?id=d9694434815' target=_blank style='color:#2F92EE;'>#头孢曲松#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44348, encryptionId=d9694434815, topicName=头孢曲松)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=37d0457, createdName=yhj-time, createdTime=Mon Sep 26 13:14:00 CST 2016, time=2016-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1459520, encodeId=25d714595209a, content=<a href='/topic/show?id=82a24434020' target=_blank style='color:#2F92EE;'>#头孢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44340, encryptionId=82a24434020, topicName=头孢)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=acae6165124, createdName=jj000003, createdTime=Mon Sep 26 13:14:00 CST 2016, time=2016-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=134687, encodeId=e3a213468e3c, content=学习了谢谢。, beContent=null, objectType=article, channel=null, level=null, likeNumber=137, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2017/04/21/72142930668371951a41ef4ea4b233e6.jpg, createdBy=dcbc1715228, createdName=刘煜, createdTime=Sun Sep 25 05:34:00 CST 2016, time=2016-09-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=134655, encodeId=890e13465520, content=有用的知识,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=76f6105517, createdName=Jiangyh0406, createdTime=Sun Sep 25 03:48:00 CST 2016, time=2016-09-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=134605, encodeId=2f3413460597, content=继续学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=129, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Sat Sep 24 22:28:00 CST 2016, time=2016-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=134606, encodeId=d022134606f6, content=继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Sat Sep 24 22:28:00 CST 2016, time=2016-09-24, status=1, ipAttribution=)]
    2016-09-24 doctorJiangchao

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