当前位置: X-MOL 学术Adv. Sci. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Comment on “A Pumpless Microfluidic Neonatal Lung Assist Device for Support of Preterm Neonates in Respiratory Distress”
Advanced Science ( IF 15.1 ) Pub Date : 2021-05-03 , DOI: 10.1002/advs.202004382
Li Wang 1, 2 , Fang Li 3 , Zhichun Feng 4 , Yuan Shi 3
Affiliation  

Very recently, Dabaghi et al. operated a microfluidic, artificial placenta-type neonatal lung assist device (LAD) on a newborn piglet with respiratory distress.[1] Results from the piglet experiments revealed the effectiveness of this LAD in gas exchange without complications. The authors indicated that the LAD has a potential application as a biomimetic artificial placenta to support the respiratory needs of preterm neonates. We consider their study findings to be an incredibly important contribution to reduce the mortality of premature infants, especially those born earlier than 28 weeks of gestational age.

As we know, mechanical ventilation is often used for respiratory support of neonates with respiratory failure. However, it is invasive and associated with severe complications such as pulmonary injury, chronic lung disease, and related diseases of prematurity such as retinopathy of prematurity, intraventricular hemorrhage, or necrotizing enterocolitis, which would lead to several long-term side effects.[2, 3] In late-preterm and term infants, extracorporeal membrane oxygenation (ECMO) could be an alternative choice of treatment, but ECMO requires central vascular access by surgery, as well as their high priming volume and external pump for perfusion are not suitable for neonatal infants.[4] Through the experiment by Dabaghi et al.,[1] we learned that LAD has the characteristics of high-performance, and pumpless. In addition, an important element of LAD is that the newborn will continue to breathe while the LAD provides additional gas exchange and allows the lungs to heal. In this way, some complications and limitations due to performing mechanical ventilation or ECMO could be prevented. Therefore, we believe that the LAD has very important clinical application value and prospect in newborn infants with respiratory failure.

After reading the article carefully, we have some questions to discuss with authors and other neonatologist.

First, one of the characteristics of the microfluidic device reported by the authors is pumpless extracorporeal support, which uses the pressure generated solely by the piglet's heart to promote blood circulation. We noticed that, at this developmental stage of experiment, authors still used the vascular access via carotid artery and jugular vein that is near the heart and is helpful to promote the blood circulation by the pressure difference produced by the heart. However, the concept of the artificial placenta is designed to be connected to the umbilical vessels. We would, therefore, like to enquire how could this kind of pumpless device ensure the proper flow rate to fully oxygenate the blood if the umbilical cord is connected according to the author's idea in the further step, whether the research team has conducted relevant experimental evaluation?

Second, although the hydraulic resistance of the oxygenator can be customized according to the baby's weight to generate sufficient blood perfusion and oxygen uptake, with the increase of neonatal weight and the remission of lung disease, the heart's pumping capacity will change, which will inevitably affect the blood flow rate and oxygen supply of LAD circulation. How to adjust it in real time? Increase or decrease the number of microfluidic blood oxygenators (MBOs)? Is it difficult to adjust accurately?

Third, Dabaghi et al. chose to use the vascular access via carotid artery and jugular vein as they found the umbilical vessels in newborn piglets were fragile and will shrink within a few hours after birth, so the catheters used were small and could not reach the intended flow rate of 30 mL kg–1 min–1 when LAD was connected to the umbilical vessels in the piglet model.[5] Moreover, according to the previous experience of umbilical catheterization in newborn infants, the time for umbilical cord to retain function and reduce the risk of infection after birth is limited. In the limited time, it could not ensure that the lung development of premature infants is mature enough to leave the artificial placenta for oxygen supply. How to solve these problems?

In addition, it is well known that fetal circulation should be transferred to postnatal circulation after birth. The LAD device is expected to connect to umbilical cord for oxygen supply. Have authors assessed whether the retention of fetal circulation will affect the decrease of pulmonary circulation pressure and the expansion of alveoli?

Finally, authors described in the original article that the LAD was exposed to pure oxygen and air and the blood flow through the LAD loop, but it was not described in detail whether the device of artificial placenta/MBOs is in a relatively closed space or some necessary measures have been taken to prevent infection. Could the author specify?

In conclusion, respiratory support technology plays an important role in reducing the mortality of newborns, especially premature infants. From mechanical ventilation, ECMO, to artificial placenta, it has witnessed the continuous improvement of neonatal respiratory support technology. We appreciate the authors’ excellent research work, from in vitro experiments, to in vivo experiments on newborn lambs, and to in vivo experiments on newborn piglets (of similar size to neonates). However, there are still many details to be discussed and improved in the application of LAD to newborns with respiratory failure. We hope that more neonatologists could pay attention to this great technology and participate in its development, and we expect LAD could be used clinically as soon to help those preterm infants with respiratory failure.



中文翻译:

评“一种支持呼吸窘迫早产儿的无泵微流控新生儿肺辅助装置”

最近,Dabaghi 等人。对一头呼吸窘迫的新生仔猪操作了微流体、人工胎盘型新生儿肺辅助装置 (LAD)。[ 1 ]仔猪实验的结果揭示了这种 LAD 在气体交换中的有效性,而不会出现并发症。作者指出,LAD 具有作为仿生人工胎盘的潜在应用,以支持早产新生儿的呼吸需求。我们认为他们的研究结果对降低早产儿死亡率做出了极其重要的贡献,尤其是那些早于 28 周出生的早产儿。

众所周知,机械通气常用于呼吸衰竭新生儿的呼吸支持。然而,它是侵入性的,并与严重的并发症有关,如肺损伤、慢性肺病和早产儿相关疾病,如早产儿视网膜病变、脑室内出血或坏死性小肠结肠炎,这将导致一些长期的副作用。[ 2, 3 ]在晚期早产儿和足月儿中,体外膜肺氧合 (ECMO) 可能是治疗的替代选择,但 ECMO 需要通过手术进入中央血管,并且其高启动容量和用于灌注的外部泵不是适合新生儿。[ 4 ]通过Dabaghi等人的实验,[ 1 ]我们了解到LAD具有高性能、无泵的特点。此外,LAD 的一个重要因素是新生儿将继续呼吸,而 LAD 提供额外的气体交换并允许肺部愈合。通过这种方式,可以防止由于执行机械通气或 ECMO 引起的一些并发症和限制。因此,我们认为LAD在新生儿呼吸衰竭中具有非常重要的临床应用价值和前景。

仔细阅读文章后,我们有一些问题要与作者和其他新生儿科医生讨论。

首先,作者报道的微流体装置的一个特点是无泵体外支持,它使用仅由仔猪心脏产生的压力来促进血液循环。我们注意到,在这个实验的发展阶段,作者仍然使用靠近心脏的颈动脉和颈静脉的血管通路,通过心脏产生的压力差有助于促进血液循环。然而,人造胎盘的概念被设计为连接到脐带血管。因此,我们想询问,如果按照作者的想法在下一步中连接脐带,这种无泵装置如何确保适当的流速使血液充分充氧,

第二,虽然可以根据宝宝的体重定制氧合器的水力阻力以产生足够的血液灌注和摄氧量,但是随着新生儿体重的增加和肺部疾病的缓解,心脏的泵血能力会发生变化,这必然会影响LAD 循环的血流量和氧气供应。如何实时调整?增加或减少微流体血液氧合器 (MBO) 的数量?很难准确调整吗?

第三,Dabaghi 等人。选择通过颈动脉和颈静脉的血管通路,因为他们发现新生仔猪的脐带血管脆弱,出生后几小时内会收缩,因此使用的导管很小,无法达到30 mL的预期流速kg –1  min –1当 LAD 连接到仔猪模型中的脐带血管时。[ 5 ]而且,根据以往新生儿脐带导尿的经验,脐带在出生后保留功能和降低感染风险的时间是有限的。在有限的时间内,无法保证早产儿肺部发育成熟,离开人工胎盘供氧。如何解决这些问题?

此外,众所周知,出生后应将胎儿循环转移到产后循环。预计 LAD 设备将连接到脐带以供氧。作者有没有评估过胎儿循环滞留是否会影响肺循环压力的降低和肺泡的扩张?

最后,作者在原文章中描述了 LAD 暴露在纯氧和空气中,血液流经 LAD 环路,但没有详细描述人工胎盘/MBOs 的装置是在相对封闭的空间还是一些已采取必要措施防止感染。作者能具体点吗?

总之,呼吸支持技术在降低新生儿尤其是早产儿死亡率方面发挥着重要作用。从机械通气、ECMO,到人工胎盘,见证了新生儿呼吸支持技术的不断进步。我们感谢作者出色的研究工作,从体外实验到新生羔羊的体内实验,再到新生仔猪(与新生儿大小相似)的体内实验。但是,LAD在新生儿呼吸衰竭中的应用还有很多细节需要讨论和改进。我们希望更多的新生儿专家能够关注这项伟大的技术并参与到它的发展中来,我们期待 LAD 能够尽快应用于临床,以帮助那些呼吸衰竭的早产儿。

更新日期:2021-06-24
down
wechat
bug