CN113975377B - 一种心脏停搏液 - Google Patents
一种心脏停搏液 Download PDFInfo
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- 239000008280 blood Substances 0.000 claims abstract description 65
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- 239000007788 liquid Substances 0.000 claims abstract description 19
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims abstract description 16
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims abstract description 16
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 16
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Abstract
本发明公开了一种心脏停搏液，属于医疗安全技术领域。所述心脏停搏液的核心组分是晶体停搏液，每1000mL晶体停搏液包括：甘露醇6‑18g，硫酸镁3‑9g，碳酸氢钠2.5‑7.5g，氯化钾3.2‑9.6g，利多卡因0.24‑0.72g，氯化钠0.585‑1.755g，醋酸钠1.845‑5.535g，葡萄糖酸钠3.863‑11.595g，葡萄糖1.25‑3.75，胰岛素1‑18单位。本发明的心脏停搏液便于保存运输，无低钠血症、高钾血症、急性血液稀释、心肌细胞水肿等副作用，可有效使心脏停跳，长效保护心肌。
Description
技术领域
本发明属于医疗安全技术领域。
背景技术
心脏停搏液(简称“停搏液”)是一种在心脏直视手术中经冠状动脉口或冠状静脉窦口灌注心脏、起化学诱导作用、使心脏迅速停跳的液体。主要分为晶体停搏液和含血停搏液。
晶体停搏液是指一种分子量小、无变态反应发生的，由钾离子、镁离子、利多卡因等多种组分组成的具有心肌保护功能的等渗液体。按照液体类型，又可分为细胞内液型(Custodial-HTK液)和细胞外液型(St.Thomas液)。St.Thomas液因心肌保护效果不好而逐渐退出历史舞台。HTK成为目前最常使用的晶体心脏停搏液。HTK为细胞内液型液体，其特征为低钠、高钾，含有丰富的代谢底物和巨大的缓冲能力，但必须低温保存。并且想达到比较好的灌注效果，必须保证足够的灌注时间和灌注容量。根据患者的体重，心脏需要的灌注量约为30ml/kg，这也是与其他停搏液相比HTK液用量大的原因。然而，如此大量的液体进入血液，则可能急性血液稀释，且容易导致低钠血症、高钾血症。低钠血症的问题容易克服，只需提高钠离子浓度；但高钾血症的问题不容易靠降低钾离子浓度来克服，因为高浓度钾离子是令心脏停跳的关键，降低钾离子浓度很可能导致无法有效停跳，保证心脏停跳效果同时降低高钾血症很难做到。
含血停搏液是指晶体停搏液与血液按照一定比例混合后，灌注进入心脏。前期的报道多为血液∶晶体停搏液＝4∶1的含血停搏液，但配方不一，虽然心肌保护效果肯定，但其单次灌注效果不确切，一般要求20～30min复灌，影响手术连续性。目前报道的Del-Nido液为血液∶晶体停搏液＝1∶4的含血停搏液，单次灌注效果肯定，但短时间内大量晶体停搏液进入血液循环，仍然会导致急性血液稀释。
因此，目前停跳液的设计仍不完善，并且缺乏足够的证据支持，尤其对于存在冠状动脉狭窄的缺血性心肌病的高危患者，单次灌注更无证据证明其安全性。
发明内容
本发明要解决的问题是：提供一种不依赖低温保存，大量进入血液后不会导致低钠血症、急性血液稀释，单次灌注可维持长时间心肌保护的停搏液。
本发明的技术方案如下：
一种用于配制心脏停搏液的晶体停搏液，每1000mL包括：
甘露醇6-18g，硫酸镁3-9g，碳酸氢钠2.5-7.5g，氯化钾3.2-9.6g，利多卡因0.24-0.72g，氯化钠0.585-1.755g，醋酸钠1.845-5.535g，葡萄糖酸钠3.863-11.595g，葡萄糖1.25-3.75，胰岛素1-18单位。
如前述的晶体停搏液，每1000mL包括：
甘露醇12g，硫酸镁6g，碳酸氢钠5g，氯化钾6.4g，利多卡因0.48g，氯化钠1.17g，醋酸钠3.69g，葡萄糖酸钠7.73g，葡萄糖2g，胰岛素12单位。
一种含血停搏液，所述心脏停搏液由权利要求1或2任一所述晶体停搏液与电解质注射液、血液按照(1～4)∶(0～3)∶(1～4)的体积比构成。
如前述的含血停搏液，所述晶体停搏液与电解质注射液、血液的比例为：1∶0∶4。
如前述的含血停搏液，所述晶体停搏液与电解质注射液、血液的比例为：1∶3∶1。
如前述的含血停搏液，所述血液为氧合血。
如前述的含血停搏液，所述血液为自体氧合血。
如前述的含血停搏液，所述电解质注射液为市售勃脉力A。
通过对成分的优化，本发明的停搏液具有如下有益效果：
1)本发明的晶体停搏液理化性质稳定，不需要低温保存，储运方便；
2)含血停搏液的离子浓度合理，不会引起低钠血症、高钾血症、急性血液稀释，并可有效使心脏停跳。
3)晶体停搏液和含血停搏液的甘露醇含量高，可有效降低心肌细胞水肿。
4)物质用量配比合理，12年临床经验表明，含血停搏液单次灌注可持续40min以上保护心肌，不对手术的连续性造成干扰，满足疑难复杂手术的需求。
显然，根据本发明的上述内容，按照本领域的普通技术知识和惯用手段，在不脱离本发明上述基本技术思想前提下，还可以做出其它多种形式的修改、替换或变更。
以下通过实施例形式的具体实施方式，对本发明的上述内容再作进一步的详细说明。但不应将此理解为本发明上述主题的范围仅限于以下的实例。凡基于本发明上述内容所实现的技术均属于本发明的范围。
具体实施方式
实施例1一种含血停搏液
含血停搏液由晶体停搏液和自体氧合血按1∶4的体积比混合而成。
每1000ml晶体停搏液由如下组分构成：
甘露醇12g，硫酸镁6g，碳酸氢钠5g，氯化钾6.4g，利多卡因0.48g，氯化钠1.17g，醋酸钠3.69g，葡萄糖酸钠7.73g，葡萄糖2g，胰岛素12单位，余量为水。
含血停搏液的各种离子(物质)的最终工作浓度：
钾离子(K+)：20.36mmol/L，
镁离子：12mmol/L，
钠离子：144mmol/L，
氯离子：106.56mmol/L，
HCO3 -：31.1mmol/L，
醋酸根：9mmol/L，
葡萄糖酸根：7.1mmol/L，
利多卡因：0.42mmol/L，
硫酸根：11.6mmol/L，
甘露醇：13.18mmol/L，
葡萄糖：7.7mmol/L。
临床工作中，使用实施例1的含血停搏液，至少可以提供40分钟的安全停跳时间。
实施例2一种含血停搏液
含血停搏液由晶体停搏液、勃脉力A(一种市售复方电解质注射液产品)和自体氧合血按1∶3∶1的体积比混合而成。
每1000ml晶体停搏液由如下组分构成：
甘露醇12g，硫酸镁6g，碳酸氢钠5g，氯化钾6.4g，利多卡因0.48g，氯化钠1.17g，醋酸钠3.69g，葡萄糖酸钠7.73g，葡萄糖2g，胰岛素12单位，余量为水。
含血停搏液的各种离子(物质)的最终工作浓度：
钾离子(K+)：20.7mmol/L，
镁离子：12.42mmol/L，
钠离子：154.8mmol/L，
氯离子：102.36mmol/L，
HCO3 -：16.7mmol/L，
醋酸根：36mmol/L，
葡萄糖酸根：20.9mmol/L，
利多卡因：0.42mmol/L，
硫酸根：36mmol/L，
甘露醇：13.18mmol/L，
葡萄糖：4.7mmol/l。
实施例3一种含血停搏液
含血停搏液由晶体停搏液和自体氧合血按1∶4的体积比混合而成。
每1000ml晶体停搏液由如下组分构成：
甘露醇6g，硫酸镁3g，碳酸氢钠5g，氯化钾3.2g，利多卡因0.42g，氯化钠0.585g，醋酸钠1.845g，葡萄糖酸钠3.863g，葡萄糖1.25g，胰岛素1单位，余量为水。
含血停搏液的各种离子(物质)的最终工作浓度：
钾离子(K+)：11.78mmo1/L，
镁离子：5.8mmol/L，
钠离子：128mmol/L，
氯离子：90.58mmol/L，
HCO3 -：25.15mmol/L
醋酸根：4.5mmol/L
葡萄糖酸根：3.55mmol/L
利多卡因：0.21mmol/L
硫酸根：6.6mmol/L
甘露醇：6.59mmol/L
葡萄糖：6.31mmol/L
实施例4一种含血停搏液
含血停搏液由晶体停搏液和自体氧合血按1∶4的体积比混合而成。
每1000ml晶体停搏液由如下组分构成：
甘露醇18g，硫酸镁9g，碳酸氢钠7.5g，氯化钾9.6g，利多卡因0.72g，氯化钠1.755g，醋酸钠5.535g，葡萄糖酸钠11.595g，葡萄糖3.75g，胰岛素18单位，余量为水。
含血停搏液的各种离子(物质)的最终工作浓度：
钾离子(K+)：28.95mmol/L，
镁离子：15.75mmol/L，
钠离子：160mmol/L，
氯离子：111.75mmol/L，
HCO3-：37.06mmol/L
醋酸根：13.5mmol/L
葡萄糖酸根：10.64mmol/L
利多卡因：0.61mmol/L
硫酸根：16.55mmol/L
甘露醇：19.76mmol/L
葡萄糖：10.94mmol/L
以下以实验例进一步说明本发明的有益效果。
实验例1在二尖瓣置换、三尖瓣成型术中的应用
受试对象：患者60kg，男性，行二尖瓣置换、三尖瓣成型术。
方法和结果：术前血钾3.49mmol/L，注冷含血停搏液1200mL【血液∶晶体液(实施例1)＝4∶1】。灌注流量为240mL/min，灌注30秒后心脏停跳。5分钟后灌注完成。此时人工心肺完全代替患者心肺工作。灌注5分钟后复查血气，血钾为4.39mmol/L。心脏灌注停跳后39分钟，再次复查血气，血钾为4.13mmol/L。心脏灌注停跳后42分钟(心肌缺血42分钟)后，心脏恢复血液供应。恢复血供2分钟后，心脏自动复跳。复跳10分钟后，心电图、心脏功能恢复正常，顺利停止体外循环，人工心肺工作停止，患者心肺独立工作。
结论：本发明的含血停搏液灌注后，血钾水平变动不大，未引起高钾血症(通常钾离子浓度超过5.5mmol/L)，且同时能维持40分钟以上的心脏停跳，解决了停跳和防高钾血症两者不能兼得的问题。
实验例2在多疾病中的应用
受试对象：年满18周岁的成人心脏手术患者22例，年龄31～75岁，其中男性12例，女性10例。行主动脉瓣置换+二尖瓣置换者4例，冠心病1例，二尖瓣置换+三尖瓣成型4例，主动脉瓣置换7例，二尖瓣置换1例，三尖瓣置换1例，房间隔缺损修补1例，心脏肿瘤摘除1例，肺动脉狭窄矫治1例，部分型心内膜垫缺损修补1例；
方法：观察性研究本停搏液(实施例1的含血停搏液)对于心肌的保护效果。于麻醉至体外循环前、体外循环开始后、停体外循环前分别抽取患者1mL血液进行血气分析，检测患者内环境、血钾、血糖及其他情况。并于升主动脉开放后观察心脏自动复跳、心律失常的发生及体外循环停止时血管活性药使用的情况。
结果：本停搏液灌注心脏30秒，心脏停跳。平均平均每台手术的心脏阻断时间为103分钟，灌注本停搏液3次。开放升主动脉后，所有患者均自动复跳，其中1例患者于开放后3分钟室颤，150J体表除颤后恢复窦性心律。所有患者均在第二天拔管，并于5-7天后顺利出院。体外循环前、体外循环后以及停体外循环前的血钾、血糖趋势如下表所示。
结论：本发明的停搏液对心脏阻断效果稳定，且其对血糖和血钾的影响较小，适用于多种心血管手术的心脏停搏与保护。
综上，本发明的含血停搏液不会引起高钾血症，单次灌注可持续40min以上保护心肌，效果稳定，适用手术类型广泛。另外，本发明的含血停搏液还不会引起低钠血症、急性血液稀释、心肌细胞水肿等其他副作用。本发明的晶体停搏液还具有理化性质稳定，不需低温保存，储运方便的优点。
Claims (7)
1.一种含血停搏液，其特征在于：所述含血停搏液由晶体停搏液与电解质注射液、血液按照(1～4)：(0～3)：(1～4)的体积比构成；
其中，每1000mL晶体停搏液由如下组分构成：甘露醇12g，硫酸镁6g，碳酸氢钠5g，氯化钾6.4g，利多卡因0.48g，氯化钠1.17g，醋酸钠3.69g，葡萄糖酸钠7.73g，葡萄糖2g，胰岛素12单位，余量为水。
2.如权利要求1所述的含血停搏液，其特征在于：所述晶体停搏液与电解质注射液、血液的比例为：1：0：4。
3.如权利要求1所述的含血停搏液，其特征在于：所述晶体停搏液与电解质注射液、血液的比例为：1：3：1。
4.如权利要求1～3任一所述的含血停搏液，其特征在于：所述血液为氧合血。
5.如权利要求4所述的含血停搏液，其特征在于：所述血液为自体氧合血。
6.如权利要求1～3任一所述的含血停搏液，其特征在于：所述电解质注射液为市售勃脉力A。
7.权利要求1～6任一项所述含血停搏液的制备方法，其特征在于：它是将晶体停搏液与电解质注射液、血液按照所述比例混匀，即得。
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