血管活性药物对子宫循环影响的研究进展
殷一博 郭文俊
皖南医学院弋矶山医院麻醉科,安徽芜湖 241000
[摘要]子宫循环是母体与胎儿之间营养物质和氧气交换的核心。虽然目前对子宫循环没有一个准确的定义,但影响因素包括血流动力学,液体管理,血管活性药物的使用,产妇的体位和麻醉方式,其中,血管活性药物是重要的影响因素之一。研究表明子宫循环关系到胎儿的远期结局,本文就血管活性药物对子宫循环的影响进行综述,以指导临床,改善产妇、胎儿的远期结局。
[关键词]血管活性药物;子宫循环;脊髓麻醉;剖宫产术
子宫循环是妊娠过程中母体和胎儿交换物质的生理循环,从妊娠到分娩,子宫循环的平稳是关系到母婴结局的重要因素[1]。母体和胎盘之间的血液交换是子宫循环重要组成部分,这一血液的供应主要是依靠子宫动脉,卵巢动脉的供应很少[2]。在功能上,子宫循环又起到一个“平衡器”的作用,从而使得脐静脉血氧指数高度接近子宫静脉[3]。因此在分娩期间要保证子宫循环的稳定,由于不同的血管活性药物通过不同的方式对子宫循环产生影响,进而影响胎儿的结局,故本文就临床讨论的血管活性药物对子宫循环的影响进行综述,为了解妊娠患者的生理特点,合理选择药物,提高麻醉安全,最大程度保护患者和胎儿的安全提供一定的参考。
1 不同因素对子宫循环影响的概述
子宫循环作为胎儿与外界联系的核心通路,妊娠期间,子宫动脉的血流量至少有20 倍的增加,此时的子宫循环是一种动静脉分流,分别是包含营养物质和氧气的子宫动脉和从基底板收集的代谢废物的静脉,从而满足母体和胎儿之间氧气,营养物质和代谢废物的交换需求[4]。产妇自身血流动力学、术中液体管理、血管活性药物的使用和麻醉方式都对子宫循环产生影响,进而影响胎儿远期结局。产妇的血流动力学状态与子宫胎盘的灌注息息相关,剖宫产过程中输入胶体,对增加子宫胎盘的血流,增进物质交换有一定益处[5]。妊娠期间增大的子宫压迫下腔静脉,减少回心血量,因此一些专家和共识推荐产妇分娩过程中应向左侧倾斜,以此增加子宫血流[6]。研究表明,脊髓麻醉和全身麻醉在剖宫产手术中的对比显示,与全身麻醉相比,脊髓麻醉的新生儿脐动脉pH 和碱剩余偏低[7]
2 血管活性药物对子宫循环的影响
目前,脊髓麻醉是一种广泛被接受的技术,但是脊髓麻醉伴发的低血压症状一直是工作中棘手的问题[8]。脊髓麻醉导致节前交感神经阻滞,使得产妇的心输出量和回心血量都显著降低,从而导致低血压,在这种情况下合理的血压治疗成为产科麻醉研究的热门方向之一[9]。由于此时子宫循环血流成倍增加,导致子宫循环自我调节能力有限[10],此时的子宫循环高度依赖外界药物的调控,基于此,本文就不同的药物对子宫循环的影响作出以下阐述。
2.1 麻黄碱
麻黄碱是目前最常用的一种升压药,主要作用与β-肾上腺素受体,但同时也作用α-肾上腺素受体,麻黄碱升高血压的机制是作用于β 受体来提高心率和心肌收缩力,麻黄碱间接作用于肾上腺素受体,这也解释了麻黄碱的起效时间较慢而且作用时间长[11]。最早是由Ralston 等[12]在羊的子宫动脉周围通过特殊压力探针测量子宫动脉变化,在注射麻黄碱之后,全身血压升高,测得子宫动脉周围压力并没有变化,麻黄碱对子宫的循环没有影响。Ducros 等[13]研究发现,静脉注射麻黄碱之后,通过多普勒测量子宫动脉的流速和阻力,给药后子宫动脉血液的流速增加,子宫动脉阻力显著降低,虽然流速的增加是否代表管径的增加目前还存在争议,但是此研究证明了麻黄碱在给药后对子宫循环的血流动力学和分娩不产生影响。另一种评价的方式是通过测量脐动脉pH,脐动脉pH 降低程度与胎儿的死亡率显著相关,而且也会导致如缺血缺氧性脑病、脑室出血和脑瘫等并发症[14]。Wang 等[15]研究发现,在使用麻黄碱之后,发现胎儿脐动脉pH显著降低,同时伴有乳酸和葡萄糖的显著增高。导致这种胎儿酸血症的原因可能是由于麻黄碱的特殊脂性药物分子结构,使得麻黄碱自由地穿过胎盘,进而刺激胎儿的代谢和β-肾上腺素受体,从而增加了胎儿儿茶酚胺的水平和心率,最终导致胎儿酸中毒[16]。随后的研究中,发现这种酸中毒是呼吸性和代谢性混合型酸中毒,但是在后续的跟踪研究中,这些酸中毒最终也没有导致其他并发症,如新生儿死亡或者是脑室出血或者是癫痫等疾病[17]。有学者试图改善麻黄碱对子宫循环的不良作用。Lied 等[18]做了一项关于推注速度的研究,将6 mg 麻黄碱分别快速和慢速输入,最终结果发现缓慢地推注麻黄碱对胎儿的酸碱状态无影响,快速推注组最终有10%的胎儿最后出现了酸中毒,但是两组在维持血液动力学方面的功效相当。后来的研究称使用的剂量也对新生儿状态产生影响,在实验中观察到被输入高剂量麻黄碱孕妇所产下的胎儿酸中毒的概率较高[19]。最新的研究显示通过注射泵以0.5 mg/(kg·min)的速度缓慢泵入麻黄碱时,在1 min 后,随着泵注时间的增加酸中毒的风险也在缓慢增加,这也证明麻黄碱不宜通过注射泵长时间预防性输入[20]
2.2 去氧肾上腺素
去氧肾上腺素是一种作用于α-肾上腺素受体的升压药,在常用的临床剂量下没有β-肾上腺素受体活性,去氧肾上腺素直接作用于肾上腺素受体,起效迅速,但是会导致反射性心率减慢[21-22]。Campbell 等[23]通过超声观察到在注射去氧肾上腺素后,羊的胎盘血管阻力升高,胎盘的血流量在减少。后来的研究者还发现当用去氧肾上腺素维持剖宫产期间血压,通过多普勒测量子宫动脉和胎盘弓状动脉的搏动指数,发现去氧肾上腺素会导致搏动指数的升高,会导致血管阻力的升高[24]。造成人和动物之间巨大生理差异的原因可能是不同的血管重塑机制和受体的分布存在差异[25]。有学者在后续的对照实验中发现,分别用去氧肾上腺素和麻黄碱维持产妇血压,去氧组孕妇的脐动脉氧分压比麻黄碱组低,反映了去氧肾上腺素对子宫胎盘的血管收缩作用[26]。有研究报道,在通过测量胎儿脐动脉血气的方式发现去氧肾上腺素对胎儿酸碱平衡影响较小,去氧肾上腺素通常不会导致胎儿的酸血症,这也是部分研究者和研究共识将去氧肾上腺素列为分娩过程中首选的升压药的原因[27]。特别是对于子痫病人,有研究认为去氧肾上腺素应当是此类病人维持血压的首选升压药[28]
2.3 去甲肾上腺素
去甲肾上腺素也是一种临床常用的儿茶酚胺类药物,它是强效的α-肾上腺素受体激动剂,同时具有适度的β-肾上腺素受体激动剂的活性,它会引起全身的血管收缩,来起到升高血压的作用,与去氧肾上腺素相比,去甲肾上腺素给药后心动过缓发生率低[29]。最早是Ngan 等[30]研究发现,去甲肾上腺素导致胎儿脐动脉氧含量增高,证明去甲肾上腺素与子宫动脉血流增加。但是最近Mohta 等[31]研究发现,使用去甲肾上腺素导致胎儿的脐动脉pH 偏低,该学者认为这是因为去甲肾上腺素具有和麻黄碱类似的脂性结构,这一分子结构使得药物自由地通过胎盘屏障,从而影响胎儿酸碱状态[32]。在最近的研究中发现,推注去甲肾上腺素后,参与实验的33 位产妇,最终有6 位产妇的胎儿出现了酸中毒症状,这一概率不容忽视[33-34]。目前,有国际共识和学者认为,理想的血管活性药物应该包含α-肾上腺素受体和β-肾上腺素受体两种肾上腺素受体激动剂,以此抵消血管负性变时作用,提出去甲肾上腺素是去氧肾上腺素的理想替代品[35]
2.4 美芬特明
美芬特明在结构上与麻黄碱高度相似,是一种同时作用于α-肾上腺素受体和β-肾上腺素受体的激动剂,在结构上与麻黄碱的区别仅在于脂肪链上一个甲基[36]。尽管对于美芬特明对子宫循环和胎盘转移及胎儿代谢的影响的研究很有限,但是在目前的研究看,美芬特明对子宫动脉的血流轻度抑制[37]
3 总结
综上所述,在脊髓麻醉中,对子宫循环的影响是评价一个药物的重要因素之一,但究竟哪一种是最佳的选择,目前还没有统一的定论,严重的子宫血管作用,不仅影响胎儿,也增加了其他并发症的风险。虽然如今越来越多的专家建议对于剖宫产手术的血压控制,去氧肾上腺素是更好的选择。现在的研究方式大多是通过超声或者脐带血等方式,但均不能满足动态检测子宫血流动力学的要求,仍需探索更好的观察子宫血流动力学变化的方法。对于麻醉医生来说,应根据不同的孕妇生理状态来选择最为合适的麻醉药物,充分考虑对胎儿的影响,最大限度降低对子宫循环的影响,以此保证母婴安全。
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Research progress on the effect of vasoactive drugs on uterine circulation
YIN Yi-bo GUO Wen-jun
Department of Anesthesia,Yijishan Hospital of Wannan Medical College,Anhui Province,Wuhu 241000,China
[Abstract]Uterine circulation is the core of nutrient and oxygen exchange between parturient and fetus.Factors affecting uterine circulation include hemodynamics,fluid management,use of vasoactive drugs,maternal posture and mode of anesthesia.However,there is no accurate definition of uterine circulation.Vasoactive drugs are one of the important influencing factors.Studies have shown that uterine circulation is related to the long-term outcome of the fetus.This article reviews the effects of vasoactive drugs on uterine circulation in order to guide the clinic and improve the long-term outcome of parturient and fetus.
[Key word]Vasoactive drugs;Uterine circulation;Spinal anesthesia;Cesarean section
[中图分类号]R714
[文献标识码]A
[文章编号]1674-4721(2021)9(b)-0042-04
(收稿日期:2021-01-21)