HFT Nasal Cannula 临床研究

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Humidified High-Flow Nasal Cannula

高流动增湿鼻插管

Respiratory support of the newborn, in particular that of preterm neonates, has long been a mainstay of neonatal care. Balancing the need for appropriate support with the potential for lung damage frequently caused by such support is one of the key factors in selecting the desired mode of support, as well as how and for how long it is applied. The job of clinicians is to select the best treatment for the neonate that can provide effective respiratory support when needed, ideally selecting the most effective, least invasive, and gentlest means of support.

为新生儿，尤其是早产儿准备的呼吸支持设备已成为新生儿护理中一个重要项目。衡量合适的支持设备和由这类设备容易引发的肺损伤是选择适合的支持方式的一个主要因素，同时也要考虑如何使用和使用时长。临床医生的任务就是在新生儿需要的时候为他们挑选最好的治疗方式，有效的提供呼吸支持。理想的支持挑选是最有效、伤害性最小、最温和的方式。

In recent years, the use of humidified high-flow nasal cannula (HHFNC) therapy has become wide-spread. The exact role of HHFNC

has been somewhat loosely defined, but it has become increasingly popular as a support modality in situations when continuous positive airway pressure (CPAP) might traditionally have been used. The trend to provide HHFNC instead of CPAP appears at least in part due to the perceived greater ease of use of the former, as well as reports of improved patient tolerance and possibly greater efficacy with HHFNC. This review aims to explore the evidence base for the use of HHFNC in the neonatal population, in particular its use as a substitute for, or in lieu of, CPAP.

近年来，高流动增湿鼻插管疗法(HHFNC)得到广泛应用。HHFNC疗法的定义并不十分严格，但相比传统的持续正压通气疗法(CPAP)，HHFNC疗法越来越受到大众欢迎。HHFNC 代替CPAP的趋势在某种程度上由于较前者更简易的操作、改善患者抗体和更好疗效的可能性。此文献在于探讨实证HHFNC疗法在新生儿中的应用，尤其是作为一种替代CPAP的疗法。

IS HHFNC THERAPY A FORM OF CPAP? HHFNC是CPAP的一种表现形式吗？

When comparing HHFNC and CPAP, an important question to ask is whether or not HHFNC is in fact a form of CPAP. If so, is it

better than what might be considered conventional CPAP, and how and why might that be the case?

比较HHFNC 和CPAP两种疗法，一个重要的问题是HHFNC本质上是否是CPAP的一种表现形式。如果是的话，将HHFNC就看成传统的CPAP不是更好？为什么呢？ WHAT IS CPAP? 什么是CPAP？

The acronym CPAP reflects a positive pressure applied to the airways of a spontaneously breathing patient throughout the respiratory cycle.It may be generated via continuous flow or variable flow of gas, which is typically heated and humidified, in principle via a closed circuit (ie, one in which pressure is maintained by gas flow through a sealed or “closed” respiratory circuit from the point of gas inflow to the terminal outflow, while some portion of the gas is inhaled and exhaled by the patient). Continuous-flow CPAP is generated using a constant flow of gas throughout the respiratory cycle directed against the resistance of the expiratory limb of the circuit. Commonly used methods of generating continuous-flow CPAP include ventilator-derived (using variable resistance in a valve), bubble or water-sealed devices, and, in some countries,

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the Benveniste gas-jet valve (Dameca, Copenhagen, Denmark). Variable-flow CPAP generates pressure at the airway proximal to the nares, and utilizes a number of principles of physics and physiology to provide a constant airway pressure at flows that vary with inspiration and expiration, thereby decreasing certain components of work of breathing (WOB) when compared with continuous-flow CPAP. Variable-flow CPAP devices include the Infant Flow Nasal CPAP System (VIASYS Healthcare Inc., Coshohocken, Pennsylvania) and the ARABELLA infant nasal CPAP system (Hamilton Medical AG, Bonaduz, Switzerland). At least in design, the aim of each of these devices is to deliver positive air-way pressure that is consistent, predictable, and regulated. The most commonly used interfaces between the CPAP circuit and the neonate are nasal prongs and/or nasal masks.

CPAP 应用于呼吸周期中患者经自然呼吸通道的正压力。它可能经由

持续流或变速流产生加温加湿，原则上，这一过程在一个闭合环道中完成。（例如：由气流造成的持续压力经闭合式呼吸环道从气流流入道最终流出，与此同时，一部分气体将被患者吸入、呼出。）持续流CPAP由一股持续气流贯穿呼吸周期以杜绝周期中呼气相的阻力。常用产生持续气道CPAP的方法包括呼吸机导出（利用在同一阀门上的变阻器）、气泡或水封装置和某些国家使用的Benveniste气体喷流阀（Dameca, 哥本哈根, 丹麦）。变速流CPAP由接近鼻孔处导气管内压

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力和利用物理性和生理机能的一些原理提供的随吸气和呼气而变化的恒定气流。因此，与持续流CPAP相比，变速流CPAP减少了某些呼吸功(WOB)的组成成分。变速流CPAP设备包括Infant Flow Nasal CPAP系统（VIASYS Healthcare Inc.,肯肖霍肯，宾夕法尼亚州）和 ARABELLA infant nasal CPAP系统(Hamilton Medical AG, 博纳图斯, 瑞士)。至少从设计的角度讲，这些设备都是为提供持续的、可预见的、有规律的正压气流。通常用于连接CPAP和新生儿的是鼻插管和/或鼻罩。

The primary goal and effects of CPAP, when effectively applied, is to provide low-pressure distention of the lungs and prevent collapse of the alveoli and terminal airways during expiration.This serves to recruit alveoli and to increase and/or maintain the functional residual capacity (FRC) of the lungs, with secondary benefits including increased lung compliance,

conservation

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surfactant,

decreased

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intrapulmonary shunting, and increased airway diameter. CPAP最主要的目标和效果是当其有效的应用时，它能提供肺部的低压膨胀并且防止呼气时发生肺泡萎陷和终末气道1。它有助于恢复肺泡健康、增加和/或维持肺部功能残气量(FRC)。它还有助于增加肺顺应性、保护表面活性物质、减少肺内分流、增长导气管直径等。

Difficulties with successful application of CPAP are principally related to the relatively bulky interface with the patient leading to problems maintaining proper position and effectiveness (Figure 1). Unless well-designed equipment is appropriately selected, carefully applied, and maintained, leaks around the nares and via the mouth can result in inconsistent air-way pressure generation, increased WOB, and respiratory instability with increased oxygen requirements. Similarly, poor system design, prong selection, or application, along with the inherently bulky nature of most CPAP interfaces, can predispose to nasal irritation and trauma.

成功应用CAPA 的困难主要与患者和CAPA设备之间相对大的接口导致不能维持正确的位置和效果有关（图1.）除非挑选精心设计的设备小心的应用和维持，否则从鼻孔和嘴漏出的气会导致产生不稳定的气压、增加呼吸功、对氧气的需求量增加等导致呼吸不稳定的因素。同样的，不良的系统设计、套管的选择或应用，与大多数CPAP接口一同使用会引起鼻刺激和创伤。 WHAT IS HHFNC? 什么是HHFNC?

Until the recent development of HHFNC devices, the provision of nasal cannula gas at a flow rate of more than 2 L/min in

neonates was not recommended,nor considered practical. In addition, humidification of flow rates of 4 L/min or less was not recommended.Both of these recommendations by the American Association for Respiratory Care (AARC) are based on the limited evidence available, and although neither has changed or been adapted, HHFNC therapy has nonetheless become widely utilized and increasingly popular in the United States. The upper limit for standard or low-flow nasal cannula therapy in infants has been variably defined between 0.5 and 2 L/min.

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Although no single universally accepted definition is available for what constitutes HHFNC therapy in neonates, a widely used and reasonable definition would be optimally warmed and humidified respiratory gases delivered by nasal cannula at flow rates between 2 and 8 L/min.

在最近发展应用HHFNC设备之前，鼻套管中气压流速率在新生儿患者中超过2 L/min是不被建议的，更不会用于实践。此外，湿度流速率小于或等于4 L/min也是不可行的。这些建议是美国呼吸治疗学会通过有限的论证提出的。即使这些建议没有改变也没有完善，HHFNC疗法还是得到了广泛的利用并在美国愈加受到大众青睐。规定的上限或新生儿用低流量鼻套管疗法定义在0.5 L/min和 2L/min之间。虽然针对新生儿的HHFNC 疗法目前没有有效的普遍接受的定义，但广泛使用后得出的合理定义为鼻套管在2 L/min和 8 L/min之间传递最佳增

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温增湿呼吸气。

Despite the aforementioned AARC recommendations, the first Food and Drug Administration (FDA)–approved device approved specifically for the provision of HHFNC in neonates was the Vapotherm 2000i in 2004. In the United States, the formal FDA 510(k) approval specifies the intended use of the Vapotherm device as being “to add moisture to and to warm breathing gases for administration to patients, including neonates/infant, pediatrics and adults.”4

不管上文中提及的有关美国呼吸治疗学会的相关规定，（美）食品及药物管理局于2004年批准Vapotherm 2000i ，即HHFNC在新生儿中运用的条款。在美国，FDA 510(k)正式批准并明确Vapotherm设备定义：“增加患者呼吸气体中的温度和湿度，包括新生儿、儿童及成人。”

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The product uses patented membrane technology to deliver molecular vapor with 95% to 100% relative humidity at body temperature through nasal cannula at flow rates between 5 and 40 L/min. A Vapor Transfer Cartridge allows what the company refers to as “low-flow” use at 1–8 L/min in neonates, although this would be substantially higher than flows traditionally used in this population.

该产品利用膜技术经鼻插管传递同人体温度相对湿度达95%到100%的蒸汽分子，流速率在5 L/min 和40 L/min之间。 蒸汽转换筒可在新生儿中进行“低流速”达1–8 L/min ，尽管在这类患者中这种流速率较传统的流速实质上要高一些。

The expectation is that the heat and humidity should prevent airway water loss, airway cooling, thickened secretions, and nasal irritation, allowing high flow rates without nasal drying or bleeding. The lighter and easier-to-apply interface (when compared with most traditional CPAP interfaces) might lessen nasal septal damage, while allowing practitioners and family members to more easily handle and care for infants (Figures 2–3).5

预期温度和湿度应防止导气管水耗、导气管冷却、分泌物增稠和鼻刺激并在无鼻腔干燥和流鼻血的情况下可承受高流速率。更轻便容易的

接口操作（相对于大多数传统的CPAP接口）有可能减少鼻中隔损伤，同时使操作者和家庭成员能更容易的照料新生儿（图2-3）。5

In the wake of an ongoing Centers for Disease Control and Prevention investigation in 2005 into the role of Vapotherm use as an associated risk factor for recovery of Ralstonia spp. from blood and respiratory tract samples of pediatric patients,

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Vapotherm was recalled from the international market from January 2006 until January 2007. This will be discussed in greater detail later in this review.

紧接着2005年美国疾病控制与预防中心研究表明从儿科患者血液和呼吸道采样中发现使用Vapotherm导致罗尔斯顿菌属感染，6于是2006

年1月至2007年1月国际市场上的Vapotherm仪器全部召回。下文中将就此问题详细讨论。

Following the withdrawal of Vapotherm from the market, there were widespread anecdotal reports of individual neonatal and pediatric centers putting together their own systems for delivery of HHFNC using the basic components of a humidifier, respiratory circuit, adapter, and nasal cannula. The efficacy of such systems and the safety of this practice are highly questionable, especially given the relative lack of evidence of efficacy and safety for even the approved products, as noted later in this review. As such, this practice is not recommended. Subsequently, Fisher & Paykel Healthcare (Auckland, New Zealand) released the RT329 Infant Oxygen Delivery System designed to deliver humidified gas (37°C, 44 mg/L) via nasal cannula at flow rates between 0.3 and 8 L/min.This system is marketed in tandem with the FDA-approved Fisher & Paykel (F&P) MR850 humidifier. Given the apparent growing popularity of HHFNC use, it is likely that additional similar products will be released in the market in the relatively near future. 随着市场上的Vapotherm被召回，一些轶事报道关于一些私人儿科中心将他们自己的设备组合起来，利用加湿器、呼吸管道、适配器和鼻

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套管等基础部件来组装使用HHFNC疗法。这种组装系统的有效性和安全性值得高度怀疑，尤其已被认证的产品都出现无法证明其有效性和安全性，这个问题我们在后面会谈到。同样，这种设备的应用不被推荐。随后，Fisher & Paykel Healthcare（奥克兰，新西兰）发布经鼻套管流速率在0.3 L/min和 8 L/min之间提供增湿气体（37°C, 44 mg/L）的 RT329婴儿供氧系统。7此系统需同通过FDA认证的(F&P) MR850增湿器配套使用。鉴于HHFNC越来越受到大众青睐，很可能在不久的将来一些类似的产品会出现在市场上

Although differences exist in the specifics of the Vapotherm and F&P systems, they, and presumably most of the custom-built center-specific devices previously mentioned, share the following basic design attributes:

虽然Vapotherm和F&P系统在一些细节上有所区别，还有之前提及的个人制定、儿科中心特有的仪器，它们的设计都遵循以下属性特征：

1 A humidifier to effectively warm and humidify respiratory gases.

1.通过加湿器有效的提供增温增湿的呼吸气

2 A respiratory circuit with a means to maintain the temperature—and, by extension, the humidity, thereby preventing excessive precipitation or “rainout”—of the delivered gas until the distal end of the circuit. Vapotherm achieves this by means of a sleeve of recirculated warmed water encasing the delivery tube, and the F&P RT329 by means of a

heated wire coil that extends to the end of the circuit. 2.呼吸环道和一种维持已传送气体温度的工具---相关的还有湿度，以防止沉淀物过量或“雨洗效应”---直到环道末端。Vapotherm通过循环暖水套包住传输管来实现这一功能，F&P RT329通过加热延伸至环道末端的线圈来实现这一功能。

3 A nasal cannula with adapter that connects to the delivery circuit. Of note, the cannula design is such that there is little or no excess tubing between the end of the delivery circuit and the actual nasal prongs, thereby minimizing further any potential for gas cooling and precipitation.

3.鼻套管配合适配器连接到输气环路。值得注意的是，套管的设计长度几乎不会超过传输环道末端到鼻塞之间，因此能最大程度上避免气体冷却和沉淀物的产生。

HHFNC therapy is provided by delivering high-flow gases (in the ranges recommended by the manufacturers, generally between 2 and 8 L/min) via the humidifier and supplied circuit to the nasal cannula that has been secured to the face with the cannula prongs in the nares. Although no uniformly accepted guidelines exist, cannula prongs should be of an external diameter smaller than the internal diameter of the nares in order to prevent an occlusive seal between prongs and nares that might predispose

to excessive airway pressure generation. Gas flow rate is adjusted according to clinical response, generally being increased for increasing respiratory distress or oxygen requirement and decreased for improving respiratory distress or decreasing oxygen requirement.

HHFNC疗法提供高流速气体（厂商推荐通常在2 L/min和 8 L/min之间）经增湿器和可用环道安全的输送到鼻孔里的鼻插管。尽管这些操作指南并没有被一致认同，但是套管塞外径应小于鼻孔内径，这是为了防止堵塞封闭鼻塞和鼻孔而可能产生导气管压力过大。气流速根据临床反应来调节，通常在呼吸窘迫和供氧需要增多时气流速增大，呼吸窘迫改善和供养需求减少时气流速减小。

The exact mechanism of action of HHFNC remains to be elucidated. Aside from the basic concept of being able to provide humidified respiratory gases and an increased fractional inspired oxygen concentration, it has been speculated that HHFNC may work by, among other mechanisms, providing airway pressure, improving mucosal perfusion, or stimulation of respiratory drive.

HHFNC精准的作用机制有待说明。除能够提供基本的增湿呼吸气和增加部分氧气浓度以外，据推测HHFNC在其他机制中可提供气道压力、改善粘膜灌注或刺激吸气机制。

An abstract-only study achieved 95.75% relative humidity with the F&P system versus 98.75% with Vapotherm at flow rates of 1–8 L/min, although the F&P system was not set up according to manufacturer recommendations.Both systems appear to effectively heat and humidify gases.

仅抽象研究结果表明在流速率为1–8 L/min时，F&P系统相对湿度为95.75%，Vapotherm相对湿度为98.75%，尽管F&P系统此时没有按照厂家推荐规范来操作。8这两种系统都能产生有效的增温增湿的气体。 DOES HHFNC DELIVER POSITIVE AIRWAY PRESSURE? HHFNC 能传递正气道压吗？

With regard to the question of whether or not HHFNC is a form of CPAP, we might first ask whether it delivers positive airway pressure, and if so, whether the pressure is, or might expected to be, consistent, predictable, and regulated. It should be noted that although Vapotherm and HHFNC are not synonymous in that there are other devices that may provide HHFNC, to the author’s knowledge all of the limited evidence available to date in the neonatal and pediatric scientific literature is confined to studies and reports of Vapotherm. Unless otherwise noted, all studies quoted are available only in abstract form, underscoring the lack of quality published evidence.

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关于HHFNC是不是CPAP的一种表现形式这个问题，我们首先要了解HHFNC 能否传递正气道压，如果可以，这种气压是否或可能成为一种持续的、可预测的、有规律的气压。值得注意的是，尽管Vapotherm 和 HHFNC并非等意的，可能有其他设备也能提供HHFNC疗法，作者从迄今为止新生儿和小儿科科学文献中得到局限于Vapotherm研究报告的有限论证。除非另行通知，否则所有研究引用都源自抽象形态，下划线表明没有有效的质量报告。

In a bench study using Vapotherm and a simulated lung with a variable leak to mimic in vivo leaks, CPAP of 0.5–4.5 cm H2O was generated at flow rates of up to 8 L/min, and the authors concluded that unless the mouth is closed and the leak around the nares minimized, it is unlikely that the Vapotherm nasal cannula delivers a clinically relevant level of CPAP.A further study measured oropharyngeal pressures in 6 healthy adults using Vapotherm, and showed a small but consistent absolute increase in oropharyngeal pressure during all phases of the respiratory cycle from 1.1 cm H2O at zero flow to 4.5cm H2O at 40 L/min, with the measured increase highly correlated with flow rate.These studies suggest that only modest pressures were generated with Vapotherm and that a relationship between flow and pressure exists as expected. A follow-up study from

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the same group involving 16 neonates of highly variable birth weight and gestation recorded oral cavity pressure on Vapotherm at flow rates between 1 and 5 L/min.With the mouth open, no pressure was generated at any flow rate. With the mouth closed, oral cavity pressure was related to flow rate and weight, with the highest recorded pressure of 4.8 cm H2O at a flow rate of 4 L/min in the 2 smallest neonates. The authors concluded that HHFNC should not be used as a replacement for delivering CPAP. Although this conclusion seems to be based on the lack of significant pressure generated in many cases, it is worth noting that the smallest and least mature neonate(s) in the study was (were) of 900 g and 29.1 weeks’ gestation (it is unclear if these were the same patient). This raises the strong likelihood that smaller neonates and higher flows would result in significantly higher generated pressures.

在利用Vapotherm作用于一个模拟体内不稳地泄漏的肺，CPAP在流速率达8 L/min时产生0.5–4.5 cm氧气，得出的结论是除非嘴闭上并最小化鼻孔周围的气体泄漏，否则Vapotherm鼻套管不大可能达到CPAP临床水平。9利用Vapotherm深入研究6位健康成人的呼吸道压力，结果表明在呼吸周期从流速率为0时的1.1 cm氧气到流速率为40 L/min 时的4.5cm氧气的各个阶段中，呼吸道压力始终保持小量上升。上升量与流速率有很大关系。这些研究表明Vapotherm会产生最合适的气

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压，气压和流速的关系也与实验预料一致。后续试验中， 16名初生重量不一致的新生儿和妊娠记录利用Vapotherm流速率在1 L/min和 5 L/min之间的口腔压。当嘴张开时，在任何流速率下都不会产生气压。当嘴闭上时，口腔压与流速率和体重有关。气压最高记录在2个最小的新生儿在流速率为4 L/min产生4.8 cm氧气。我们得到的结论是HHFNC不应当做一种传递CPAP的替代品。虽然此结论并非建立在有很多产生重要气压意义的案例上，但值得关注的是试验中最小的新生儿体重900克，29.1周妊娠期（不清楚是否指同一患者）。这一结果表明较小的新生儿和较大的流速很可能导致产生更高的压力。

Of further concern is a bench study of nasal cannula, CPAP, and Vapotherm examining the effect of flow on temperature, humidity, pressure, and resistance.Although gas delivered by Vapotherm was more humid than that via nasal cannula and CPAP, Vapotherm produced substantially higher pressure and resistance that may have clinical relevance such as increased WOB. It is unclear from this abstract-only study how and where the pressure and resistance were measured, highlighting the difficulty of appropriately assessing such evidence. 我们进一步关心的实验是鼻套管、CPAP和Vapotherm流速在温度、湿度、压力和抗阻力等方面的效果。虽然经Vapotherm产生的气体比经鼻插管和CPAP产生的气体更加湿润，但Vapotherm能产生可能有临床

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意义的实质上更高的气压和更强的耐受性，比如像增加了的呼吸功。此抽象实验不能清楚的说明测量气压和耐受性的位置、如何测量，从而突出此类似论证的恰当评估的难度。

Given the lack of any specific peer-reviewed publications examining HHFNC and generated pressures, it is useful to review and extrapolate data from 2 such studies using nonhumidified low-flow nasal cannula. The first examined esophageal pressure and thoracoabdominal motion in 13 preterm neonates at gas flow levels of 0.5–2 L/min delivered by nasal cannula, with an outer diameter of either 0.2 or 0.3 cm.The smaller nasal cannula did not deliver pressure or alter thoracoabdominal motion at any flow, whereas the 0.3-cm nasal cannula delivered positive end-distending pressure as a function of increasing levels of gas flow and reduced thoracoabdominal motion asynchrony. The mean pressure generated at 2 L/min was 9.8 cm H2O. The authors concluded that nasal cannula gas flow can deliver positive end-distending pressure and significantly alter breathing strategy, and that this raised important concerns about the indiscriminate therapeutic use, size selection, and safety of nasal cannulae for the routine delivery of oxygen in preterm neonates. The second study examined 40 preterm neonates on CPAP

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for apnea of prematurity using ventilator-generated conventional CPAP or nasal cannula at flow rates of up to 2.5 L/min.The study found that the nasal cannula flow required to generate comparable positive distending pressure varied with patient weight according to the formula:

考虑到缺乏任何同行评审刊审评HHFNC和产生的压力，回顾和推断无湿度低流速鼻套管的两个实验数据是有意义的。第一个被观测的食道内压和胸腹运动是在13个早产新生儿中由外直径为0.2 或 0.3 cm的鼻套管传递0.5–2 L/min气流产生的。13较小的鼻套管在任何流速下都没有产生气压或调节胸腹运动状况，然而，外直径0.3cm的鼻套管根据气流量的增加和胸腹运动异步性减小而传递内腔扩张正压。产生的平均压力为2 L/min流速率下9.8 cm氧气。我们推断出鼻套管气流能传递内腔扩张正压并能极大的改变呼吸模式，这引起了我们对新生儿日常输氧不加区分的治疗使用、尺寸选择和鼻套管安全性能的极大关心。第二个实验针对40名早产儿利用CPAP治疗早产导致的呼吸暂停，传统的CPAP呼吸机或鼻套管流速率达到2.5 L/min。14研究表明按

照以下公式，随着患者体重的不同鼻套管流量需产生相当的扩张正压：

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Flow (L/min) = 0.92 + (0.68 × Weight [in kg]) 流速 (L/min) = 0.92 + (0.68 × 体重 [kg])

The difficulty in determining what, if any, pressure might be produced by HHFNC in different circumstances is underscored

by the variable findings in these studies. Arguably the most relevant would be the latter 2 studies of nonhumidified low-flow nasal cannula, given the study populations and the details available from the full publications. Both these studies show that at relatively modest nonhumidified nasal cannula flow rates of 1.5—2 L/min, pressures of approximately 6—10 cm H2O can be generated in even moderately preterm neonates. In attempting to extrapolate these data to HHFNC, it is interesting to note that a study of healthy adult volunteers on nasal mask CPAP found that in the presence of a significant mouth leak with resultant unidirectional air flow, effective heated humidification substantially decreased resistance across the nasal airway.This would result in more effective transmission of generated CPAP to the distal patient airway. Similarly, it suggests that even higher pressures than those documented in the non-humidified low-flow nasal cannula studies might be delivered to the distal airway with effective heated humidification using the Vapotherm or other HHFNC device.

如果说这些实验中有困难的话，就是HHFNC在不同的环境下产生的压力结果是不一样的。相关可被论证的要算后面的2个考虑到患者类型和所有出版物中可利用信息的无增湿流速鼻套管实验。这些实验都表

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明相对适度的无增湿鼻套管流速为1.5—2 L/min时，适度早产儿中产生的气压约为6—10 cm氧气。为了推断出HHFNC这些数据，值得一提的是一项关于健康的成人志愿者使用鼻罩式CPAP的研究结果表明，在单向气流合成口腔漏气的情况下通过鼻腔导气管很大程度上有效的减少了加温加湿阻力。这会导致CPAP向患者导气管末端产生更有效的传送。同样的，这一研究指出，比文件记录中无增湿低流速鼻套管研究更大的气压可能利用Vapotherm或其他HHFNC设备向导气管末端传递有效的加温加湿气体。

As to the possible physiological and/or clinical effects of any generated airway pressure when using nasal cannula flow, it has been demonstrated that each of variable-flow CPAP, continuous-flow CPAP, and CPAP provided via adapted nasal cannula produce measurable changes in lung volume at set CPAP pressures of 4, 6, and 8 cm H2O in neonates.It should be noted that the adapted nasal cannula in this study was connected to a ventilator set to deliver CPAP with a continuous gas flow of 6 L/min, rather than the typical setup for HHFNC in which flow is adjusted and no airway pressure is set or monitored. In addition, although the adapted nasal cannula was able to recruit lung volume, it did so at the cost of increased respiratory effort and oxygen requirement when compared with

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the variable-flow and continuous-flow CPAP. As such, the potential would seem to exist for clinically relevant physiologic effects secondary to airway pressure generation produced by HHFNC use. Depending on the degree of such effects, they might be helpful, harmful, or of little or no consequence clinically.

至于使用鼻套管流速产生的导气管压力对于生理学和/或临床的效果，我们需论证在新生儿中，经合适的鼻套管分别在变速流CPAP、持续流CPAP和CPAP情况下，设置CPAP压力值为4 cm, 6 cm,和8 cm氧气时肺容量的变化。值得注意的是本实验中的合适的鼻套管是与呼吸机连接，传递6 L/min的连续气流CPAP，而非特别靠调节流量和设置无气道压力的HHFNC。另外，虽然合适的鼻套管能够补充恢复肺活量，但这是以比较变速流和持续流CPAP时增强的呼吸运作和供氧需求为代价的。就其本身而论，与临床相关的生理性效果似乎存在的可能性次于使用HHFNC所产生的气道压。根据这种效果的程度不同，它们可能是有益的、有害的或只有很少（没有）临床研究价值。

Although the latter study sheds some light on the potential effects of nasal cannula flow on lung recruitment, there is no published evidence at this stage to answer the question directly whether or not HHFNC is able to increase and/or maintain FRC, as has been shown to be the primary effect of CPAP.

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Similarly, the secondary physiologic benefits of CPAP have also not been specifically demonstrated in any studies of HHFNC. 即使后一个实验对鼻套管流速恢复肺功能的潜在效果有一定的启示作用，但现阶段还没有官方论证直接回答HHFNC是否能增加和/或维持FRC，就像展示CPAP的初始效应一样。

IS HHFNC THERAPY A FORM OF CPAP?: CONCLUSIONS HHFNC是 CPAP的一种表现形式吗？：结论

It seems clear that humidified high-flow gas via nasal cannula does indeed produce positive airway pressure, and that this pressure is:

显然，增湿高流速气体经鼻套管的确产生气道正压通气，这种气压是： . variable (and may range from trivial to excessive); . 可变的（可能量范围从极少到超多） . relatively unpredictable; . 相对的不可预知 . unregulated; . 不规范的

. related to flow, prong size, and patient size, and likely to effective heated humidification; and

. 与流量、鼻塞尺寸、患者大小且可能与有效的加温加湿有关

. sufficient to produce clinical effects and/or changes in pulmonary function.

. 足以产生临床效果和/或改变肺功能

Based on these characteristics, HHFNC should not be regarded as a form of CPAP. Rather, it is a distinct respiratory support modality that should be assessed on its own merits in the same way that, for example, CPAP, conventional ventilation, and high-frequency oscillatory ventilation are assessed. It should be noted that neither the Vapotherm nor the F&P HHFNC system is approved for or directly marketed by its manufacturer as a device for providing CPAP, although neither company actively discourages what appears to be considerable ambiguity in this area of clinical use. Well-designed randomized controlled trials are urgently needed to clarify the airway pressure effects of HHFNC, as well as to evaluate their potential benefits and/or adverse consequences.

基于这些特征，HHFNC不应看成是CPAP的一种表现形式。相反，它这种独特的呼吸支持疗法应以相同的方式来评估其自身优势。例如，CPAP被评估为一种通用的、高频震荡的通气设备。值得注意的是Vapotherm和F&P HHFNC系统都没有被制造商作为一种提供CPAP的仪器批准或上市，即便这些公司都没有主动阻止这一领域在临床应用上

出现的较大的歧义。急需设计精确的随机对比控制临床试验来阐明HHFNC气道压影响，同时鉴定他们的潜在有利和/或不利的影响。 HHFNC: INDICATIONS FOR USE HHFNC： 使用说明

As previously noted, the indications for use of HHFNC are somewhat nonspecific. No formal recommendations are available for specific clinical indications published by either Vapotherm or Fisher and Paykel. Both manufacturers’ literature limits the description of their products’ use essentially to that of providing warmed and humidified breathing gases. Many centers appear to be using the therapy in circumstances when they might otherwise have used routine low-flow nasal cannulae, and the limited published literature on the subject suggests that many are utilizing HHFNC as a substitute for, or in place of, CPAP. Following is a brief overview of the most relevant available data documenting roles in which HHFNC has been utilized. Again, unless otherwise noted to have been published as a full study in a peer-reviewed journal, quoted studies are available only in abstract form.

如前文所提及的，HHFNC的使用说明并非特别明确。Vapotherm和 Fisher and Paykel都没有针对特定的临床症状出版的正式的推荐规

范。这两个制造商明文规定他们的产品本质上是用于提供增温增湿的呼吸气体。很多中心出现可能本该使用通用低流速鼻套管的情况下却使用这种疗法。就此项目，有限的出版文献表明多数利用HHFNC作为CPAP的代替品。下面是关于利用HHFNC相关的有效数据文献角色的简明概述。当然，除非另有说明来自同行评议期刊的充分研究，否则所有引证仅源于抽象形式。

One center compared the effects of Vapotherm and nasal CPAP in respiratory distress in 28 preterm neonates of approximately 31–32 weeks’ gestation and found that Vapotherm provide as effective respiratory support as CPAP in the initial treatment of respiratory distress.The authors further concluded that efficacy in reducing potential side effects required similar trials involving long-term ventilatory support.

一个中心对28名妊娠期约为31–32周的患有呼吸困难的早产儿进行Vapotherm和鼻腔CPAP治疗的效果对比。得出的结论是Vapotherm同

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CPAP初治呼吸窘迫时提供同样有效的呼吸支持。我们进一步总结，

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有效减小潜在副作用需通过类似的长期呼吸支持实验。

Another center reported on its experience with 109 preterm neonates with a wide range of birth weights (＜500 g to ＞1500 g) in which Vapotherm was used as primary treatment for mild

to moderate respiratory distress syndrome (RDS) in lieu of CPAP or postextubation in place of CPAP.No evidence of barotrauma, CPAP belly, nosocomial infection, nasal trauma, or nasal mucus plugging was reported, and the study concluded that Vapotherm was a safe and effective adjunct to support neonates with respiratory compromise.

另一中心研究报道109名不同体重（＜500 g to ＞1500 g)的早产儿使用Vapotherm代替CPAP或拔管后代替CPAP 作为温和初治缓解呼吸

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窘迫综合症(RDS)的设备。没有报告表明出现气压伤、CPAP胀气、院

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内感染、鼻腔创伤、鼻粘液栓等现象。该实验推论出Vapotherm能为患呼吸窘迫的新生儿提供安全有效的治疗。

In a prospective, observational study of an even more heterogeneous group of 52 preterm and 12 term newborns with respiratory distress (n =27) or following extubation (n =37), Vapotherm was used at decreasing flows as lung disease improved.Only 2 patients required reintubation, and no nasal bleeding, necrotizing enterocolitis, feeding problems, abdominal distention, or failed hearing screens were noted. The study concluded that HHFNC could be used safely in these patients, but that additional studies were needed.

在一个前瞻性观测试验中，更多不同体质的患者包括患有呼吸窘迫(n

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=27)或后期拔管(n =37)的52名早产儿和12名足月新生儿，使用Vapotherm逐渐减低流量使患者的肺功能疾病得到改善。19仅有2名患者需要重新换管插管，但这2名患者都没有出现鼻出血、坏死性肠炎、喂食问题、腹胀、听力失效等问题。由此得出的结论是 HHFNC针对此类患者的使用时安全的， 但也需要其他更多研究。

A study examining the use of Vapotherm for preventing reintubation in 43 neonates with single ventricle following cardiac surgery found that the use of Vapotherm did not decrease the rate of reintubation compared with prior practice, although the abstract did not specify what that prior practice was.一项针对43名经心脏手术留单心室的新生儿为防止重插管而使用Vapotherm的检测试验表明Vapotherm的使用较之前的实验并没有降低重插管率，尽管摘要并没有详细说明之前的实验目的。20

The safety and efficacy of Vapotherm was evaluated following an early extubation protocol designed for neonates of 25–29 weeks’ gestational age, comparing outcomes with historical controls.

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While ventilator days were not statistically

different, more infants in the Vapotherm era were extubated in 14 days or less, and more were extubated from a ventilator rate of 30 breaths per minute or more.

Vapotherm的安全性和有效性的评估是由针对25–29周胎龄的新生儿设计的早期拔管协议比较历史对照结果而得出的。21当使用呼吸机的天数相同，较多新生儿使用Vapotherm14天或不到14天即可拔去套管，更多的因通气率大于等于30次/分钟拔去套管。

Although no details are provided of how patients had previously been managed, the authors concluded that Vapotherm appeared safe and well tolerated, that more patients in the Vapotherm group spent less than 2 weeks on the ventilator and additional benefits may include decreased rate of pneumonia and improved growth.

虽然没有详细资料说明患者在此之前是如何做到的，但我们总结为Vapotherm具有安全性和良好的耐受性。更多使用Vapotherm的患者不到2周时间就不需靠呼吸机来维持，由此产生的附加好处可能包括减少肺炎率和促进成长。

A full peer-reviewed published study examined WOB in 18 stable preterm neonates on CPAP (Inca prongs/Bird ventilator) or Vapotherm for mild RDS, chronic lung disease, or apnea of prematurity.Patients were studied on both devices in random order using CPAP at 6 cm H2O and Vapotherm at flow rates of 3, 4, and 5 L/min. No differences were found in WOB for all settings.

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In addition, changes in end-distending pressure from baseline did not vary significantly over all device settings except Vapotherm at 5 L/min. A nonstatistically significant trend was observed toward increased asynchrony with Vapotherm use. While it is possible that a larger sample size might have found more significant differences, the conclusion was that HHFNC using Vapotherm provides support comparable to 6 cm H2O nasal CPAP for neonates with mild respiratory requirements. The authors did advise caution in clinical use until larger randomized controlled trials at higher flow rates with long-term outcomes are available.

一个完整的同行评议实验针对18名状况稳定早产儿使用CPAP（Inca 鼻塞/Bird 呼吸机)或Vapotherm检测轻微呼吸窘迫综合症、慢性肺疾病或因早产导致的呼吸暂停等呼吸功。22实验中患者将随机使用6 cm 氧气的CPAP和流速率分别为3 L/min, 4 L/min, 和 5 L/min 的Vapotherm。在这些不同的设置中呼吸功并没有产生差异。此外，除了Vapotherm在流速为5 L/min时，其他设置都没有较大的改变基线的膨胀末期压力。没有观测到明确的数字统计趋势表明协调障碍增加。 有可能较大的样本量会产生更显著的差异性。得出的结论是针对有轻微供氧需求的新生儿，与6 cm氧气鼻腔CPAP相比，提供使用Vapotherm用于HHFNC。我们建议除非大量的在高流量率下长期实验得到肯定结果，否则应用于临床应谨慎。

A recent retrospective observational peer-reviewed published study compared frequency of use as well as efficacy and safety of HHFNC following its widespread acceptance into practice in 2 large referral centers with previous outcomes on variable-flow or ventilator-driven CPAP at 3–8 cm H2O. To meet study criteria, neonates had to be placed on one of the support modalities (CPAP or HHFNC) either initially following admission, as an escalation of support from oxyhood or low-flow nasal cannula (≤2 L/min), or immediately following extubation from mechanical ventilation within 96 hours of birth. For neonates with less than 30 weeks’ gestational age, there were no differences in death or bronchopulmonary dysplasia between the groups, but ventilator days per patient were decreased following introduction of HHFNC. In those patients receiving either CPAP or HHFNC as an early mode of respiratory support, more were intubated for failing early CPAP than early HHFNC. A far higher percentage of all neonates was placed on HHFNC in the latter era than those placed on CPAP in the earlier era, and the authors note that some patients may have been placed on HHFNC who otherwise would have done just as well on less respiratory support such as low-flow nasal cannula or room air.

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If true, this might significantly affect outcomes such as intubation and reintubation rates.

近期可追溯的同行评议研究较频繁被使用，同时HHFNC的安全性和有效性随着其在2个大的转诊中心使用3–8 cm氧气变速流或通气设备CPAP的结果被广泛接受并应用于实践。23为达到实验标准，新生儿必须用到一种支持设备(CPAP或 HHFNC)或者初期进气，像是利用加强支持的氧气罩或低流量鼻套管(≤2 L/min),或者出生后96小时使用机械通气然后拔除套管。小于30周胎龄的新生儿组同死亡或支气管肺发育不良没什么区别。但是遵循使用说明的使用呼吸机的患者减少了，见如下HHFNC介绍。这些患者使用CPAP 或者 HHFNC作为早期的呼吸支持工具，与早期HHFNC相比，早期CPAP插管失败率更高。大多数新生儿使用后期HHFNC，少数使用早期CPAP。我们发现一些患者不使用HHFNC的话会减少呼吸支持，比如说低流速鼻套管或室内空气。如此结论成立，这可能是诸如插管法和重插管率之类的重大影响发现。

Another peer-reviewed full study compared 2 methods of delivering high-flow gas therapy by nasal cannula following endotracheal extubation in a prospective, randomized, masked, crossover trial.Thirty moderately preterm neonates averaging 31–32 weeks’ gestation were extubated to Vapotherm for 24 hours, then standard high-flow nasal cannula for 24 hours, or to standard high-flow nasal cannula for 24 hours, then

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Vapotherm for 24 hours. Standard high-flow nasal cannula was not described in detail other than as being provided by a “standard high-flow system,” presumably without effective humidification. Uniform nasal cannulae manufactured by Vapotherm were used for both Vapotherm and standard high-flow nasal cannula support. The nasal gas flow used on Vapotherm was 3.1 ± 0.6 L/min compared with 1.8 ± 0.4 L/min on standard HFNC based on what was considered to be optimal individual support to each patient as judged by the neonatal care team. Vapotherm performed better than standard high-flow nasal cannula in maintaining normal appearing nasal mucosa, a lower respiratory effort, and averting reintubation, with no recognized complications. The better respiratory effort scores were felt to be due at least in part to the higher gas flow used on Vapotherm, with the improved nasal mucosa on Vapotherm the result of the higher humidity and temperature of the gas. As intrathoracic pressures were not measured, it is unclear whether or not the improved respiratory effort scores on higher Vapotherm flow rates were related to any potential generated airway pressure differences between groups.

另一个完整的同行评议可预见、随机、盲、交叉实验研究比较了随气管拔管经鼻套管传递高流速气体的2种方法。24 30个平均妊娠期为

31-32周的中等早产儿在使用Vapotherm24小时后拔管，然后经鼻套管提供24小时的标准高流速气体，或者经经鼻套管提供24小时的标准高流速气体后再使用Vapotherm24小时。标准高流量鼻套管并非像提供“标准高流量体系”那样假定无有效增湿的情况下详细描述细节。Vapotherm公司制造的统一鼻套管既可用于Vapotherm治疗又可用于高流速鼻套管支持。Vapotherm使用的鼻腔气流为3.1 ± 0.6 L/min，相比之下，由新生儿护理团队判断作为个人可选择性呼吸支持的标准HFNC鼻腔气流为1.8 ± 0.4 L/min。在维持正常出现的鼻腔粘液方面、下呼吸道支运作方面、避免重插管方面，Vapotherm比标准的高流速鼻套管效果要好，没有出现其他并发症。更好的呼吸运作记录至少在某种程度上由于使用已改善的鼻粘膜在更高气流的Vapotherm下，产生更加增湿增温的气体。正如胸内压力无法测量一样，我们不清楚在不同分组中更高Vapotherm流速率下，改善的呼吸运作记录是否与其他潜在气压产生有关。

In 40 preterm neonates weighing 1250 g or less who were extubated to what was termed high-flow CPAP (HF-CPAP) of 4.5 cm H2O (calculated using the previously mentioned formula, and using a non-heated bubble humidifier and nasal cannula) or to infant flow CPAP (IF-CPAP) of 6 cm H2O,HF-CPAP failed to maintain extubation status as effectively as IF-CPAP. Patients in the HF-CPAP group also had higher oxygen use and increased

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number of apnea/bradycardia episodes postextubation. Importantly, this study used nonheated, ineffectively humidified gas, and delivered a calculated CPAP in the HF-CPAP group that was lower than that in the IF-CPAP group, as well as being lower than the 5 cm H2O limit that was noted in prior studies to be potentially important in the prevention of reintubation.

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在40名重小于等于1250G的新生儿中，拔管后使用所谓的4.5cm氧气高流速CPAP(HF-CPAP)（由之前提到的公式计算得出，同时使用无加温增湿器和鼻套管），或使用婴儿气流6 cm氧气的 CPAP (IF-CPAP)。

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HF-CPAP同IF-CPAP效果一样，都无法维持拔管后的状态。HF-CPAP

组的患者拔管后出现了更高的氧气需求和数目不断上升的呼吸暂停/心动过缓。重要的是，这次实验使用的是无加温无加湿的气体，并且HF-CPAP组中计算出的CPAP低于IF-CPAP组，同时也低于之前我们提到的预防重插管重要的潜在因素的5cm氧气限制。26 HHFNC: INDICATIONS FOR USE: CONCLUSIONS HHFNC:使用说明：结论

Collectively, these studies suggest a wide potential role for HHFNC in respiratory care of the neonate, and in some cases, the available data are encouraging. However, the highly variable study populations, clinical circumstances, and

abstract-only nature of much of the limited published literature highlight the difficulty in assessing what, if any, role HHFNC should play in respiratory support of the neonate, as well as the efficacy and safety of HHFNC in such role. 所有这些实验都说明HHFNC对新生儿呼吸支持的广泛潜在角色，在某些案例中，一些有效的数据是鼓舞人心的。然而，变化较大的研究对象、临床环境、和许多有限出版的仅抽象特性使得文献强调很难去审评它的本质。如果可以的话，HHFNC的角色应该定义为为新生儿提供有效的、安全的呼吸支持。

IS HHFNC SAFE? 使用HHFNC 安全吗？

Many of the previously quoted studies have commented on the safety of HHFNC (in most cases Vapotherm) in their study populations. Unfortunately, the majority of these studies suffer from one or more of being observational studies, having low study population numbers, heterogeneous study populations, different primary respiratory illnesses, or being available in abstract-only form with limited details. Concerns that have been or might reasonably be expressed include incidence of infection, excessive airway pressure generation, local trauma,

and other as yet unidentified adverse effects.

很多之前引用的研究实验通过其研究对象对HHFNC的安全性做出了评价。不幸的是，这些实验大多数是通过一个或多个观测性研究，研究对象少、研究对象群类似、初期呼吸疾病类似，或从仅抽象形式中获得有限的信息。值得关注的是它可能出现的副作用包括发病感染率、产生过多的气压、局部创伤、和一些尚不明确的不良反应

None of the few publications to date have noted an increased incidence of infection, and a laboratory study testing effectiveness of the Vapotherm cartridge concluded that the cartridge may be expected to act as an effective bacteriological filter.However, the Centers for Disease Control and Prevention launched an investigation in late 2005 regarding Ralstonia spp associated with the use of Vapotherm.

6

27

Ralstonia are gram-negative bacteria found in the environment,

primarily in water, soil, and on plants, and occasionally are isolated from clinical samples. These organisms were formerly included in the genus Pseudomonas or Burkholderia, but DNA characterization has revealed them to be a distinct genus. Signs and symptoms of an infection with Ralstonia are similar to those observed in other bacterial infections. Up to 32 institutions in 16 states reported recovery of Ralstonia from

Vapotherm devices and from approximately 40 pediatric patients. The majority of these cases appeared to represent colonization, although there were 8 reported potential infections and 1 reported death. Cultures of unused Vapotherm cartridges performed by 2 hospitals also yielded Ralstonia. A revised disinfecting protocol recommended by the manufacturer was not found to be consistently effective, and there were isolated reports of contamination of Vapotherm units with other uncommon bacteria

including

Burkholderia cepacia, Klebsiella pneumoniae, and Proteus mirabilis. This led to an FDA

recommendation against use and a voluntary recall of Vapotherm on October 13, 2005, followed by a nationwide recall on January 24, 2006. The product returned to the market with FDA approval on January 4, 2007, with new instructions for use, including the recommendation to utilize only sterile water in the system.

5 、

This experience suggests that, at the very least,

centers using the reintroduced Vapotherm device (or other similar devices) should monitor closely their infection rates and the occurrence of any unusual infections until large randomized controlled trials have addressed this potential problem satisfactorily.

迄今为止，仅出版的少数刊物中没有注明发病感染率的增加。一项实验室研究包括细菌过滤组件的Vapotherm组件有效性测试。27然而，美国疾病控制与预防中心2005年后期启动了一项关于由使用Vapotherm出现的罗尔斯顿菌属的调查研究。罗尔斯顿菌属为环境中发现的革兰氏阴性菌，主要在水里和植物上，偶尔从临床研究样本分离取得。这些生物体之前存在假单胞菌属或伯克氏菌属，但DNA特性使它们成显形菌属。感染罗尔斯顿菌属的症状与其他细菌感染相似。来自16个州的32个研究机构报道了大约40名儿科使用Vapotherm设备后罗尔斯顿菌属感染恢复。大多数这样的案例似乎是在稳定Vapotherm的地位，即便已有8例潜在感染的报告和1例死亡报告。从不使用Vapotherm组件的2个医院也出现了罗尔斯顿菌属感染。制造商推荐的改良的消毒协议并没有起到持续作用，同时个别报道指出Vapotherm污染包括一些罕见细菌，例如洋葱伯克霍尔德菌、肺炎杆菌、变形杆菌属等。2005年10月13日， FDA建议不再使用Vapotherm并自愿召回Vapotherm。随后2006年1月24日在全国范围内开展召2007年1月4日，FDA批准该产品附全新使用说明重新上市。回行动。

使用说明包括建议仅在无菌水中使用该系统。5这次经历至少说明中心在使用重新上市的Vapotherm设备（或其他类似设备）时，在大规模的随机控制实验没有对此潜在问题做出满意的处理方式之前都应密切监控它们的感染率和任何不寻常的感染。

Concerns regarding excessive airway pressure generation with

HHFNC have been addressed earlier in this review. 我们关注的关于HHFNC产生过度呼吸道压力问题，上文中已提及处理方法。

There have been isolated anecdotal reports on Internet news groups of facial chemical burns from improperly cleaned and recycled nasal cannulae, and of a perforated eardrum associated with the use of Vapotherm. It would be inappropriate to assign a cause-effect relationship to such unsubstantiated anecdotal reports that are noted not to suggest that such a relationship necessarily exists, but rather to highlight the need for large randomized controlled trials to adequately address any concerns and to identify any true, currently unidentified, potential adverse effects.

个别来自网站上的面部化学烧伤新闻组的轶事报道称使用的Vapotherm未经正确净化消毒、鼻套管是回收利用的、引起鼓膜破损等。这些无事实根据的轶事报道所列出的必然存在的因果关系是不恰当的，应该强调需要大规模的随机控制实验来充分说明我们所关心的并鉴定出什么是真的、当前所不明确的、潜在的副作用

It is interesting to note the abstract-only study of nursing satisfaction with what were termed 4 nasal distending pressure

devices in the NICU, including Vapotherm (demonstrating again the ambiguous perception of the intended use of Vapotherm).

28

This survey of 17 NICU bedside nurses involved 11 questions regarding nursing satisfaction with Neotech Binasal Airway/ventilator CPAP, Hudson prongs/bubble CPAP, ARABELLA prongs/flow-driver

CPAP,

and

Vapotherm

nasal

cannula/high-flow gas. The Vapotherm device scored consistently highest, with the Neotech Binasal Airway scoring second highest in most categories. No differences were reported between the Hudson prongs and Arabella setup devices, which were the least favored overall. The authors concluded that if safety and efficacy of the 4 devices were equal, then nursing satisfaction could be considered an important factor in choosing a device. It should be noted that a separate study showed that a device very similar in design to the Neotech device had the highest resistance of a wide range of such devices tested, in all likelihood making it the least desirable clinically in terms of effectively transmitting any generated CPAP to the patient airway. This highlights one potential concern with choosing the most convenient or user-friendly device, unless quality efficacy and safety data are also available to support such a choice.

29

有趣的是，护理满意度的仅抽象研究术语中新生儿重症监护室使用的4种鼻腔压力设备就包含Vapotherm（这再次证明了Vapotherm使用目的模糊不清的概念）。2817个新生儿重症监护室床边护士对使用Neotech鼻侧呼吸机CPAP、Hudson鼻塞/气泡CPAP、ARABELLA鼻塞/气流驱动CPAP和Vapotherm鼻套管/高流速气体的护理满意度有11个疑问。Vapotherm得分始终是最高的，其次是Neotech鼻侧呼吸机。没有报告指出最不受欢迎的Hudson 和 Arabella这2个设备的不同之处.我们总结为当这4种设备的安全性和有效性一样的时候，护理值得注意的是一项独立研究显满意度成为选择一种设备的最要因素。

示与Neotech设备设计类似的产品中，Neotech设备与大范围的已测试类似设备相比，其耐受性最高。这很可能使其成为临床上向患者有

29效传输产生任何CPAP最不想用的设备。潜在关注强调选择一种最方

便最容易使用的设备还要考虑到该产品的质量有效性和安全性。

WHY MIGHT HHFNC BE PREFERRED TO (AND POSSIBLY BETTER THAN) CPAP?

为什么HHFNC优于CPAP（可能比CPAP更好）？

Given that CPAP, in design at least, should provide consistent, predictable, and regulated positive air-way pressure, as well as has been extensively researched in the neonatal population, it is important to consider why the use of HHFNC has become so widespread and popular as a respiratory support modality, in

many cases in preference to CPAP, despite not meeting these same criteria. One possibility is that an easy-to-use suboptimal system for delivering positive airway pressure is better and more effective than a hard-to-use but, in theory, more optimally designed system. This presumes both that caregivers are using the HHFNC as a CPAP device and that the HHFNC is achieving its benefits by providing airway pressure. Although some airway pressure generation is highly likely with HHFNC, it is unclear at this stage whether this is therapeutic, trivial, or excessive, or some combination of the 3 at different times. It has been suggested that HHFNC may produce desirable respiratory benefits in some other manner related to flow, improved mucosal perfusion, or respiratory stimulation, although this remains purely speculative at this stage. If true, it is entirely possible that HHFNC may be more effective in certain patients and/or disease processes than conventional CPAP, the current lack of evidence notwithstanding. If, on the other hand, the effect of HHFNC is primarily airway pressure mediated, then the choice of many to use HHFNC over CPAP begs the question of whether what is really needed is a new and better true CPAP device, one that is more user-friendly. The alternatives would be to use HHFNC as a pressure-generating

device (something for which it is neither designed, approved for use, or ideally suited) or to persist with the “no pain, no gain” philosophy of using true CPAP devices, which, when properly used, should provide more optimal positive airway pressure but which are more cumbersome, difficult to use, and labor intensive.

假定至少设计上CPAP应提供连续的、可预见的、可控制的正气压；同时在新生儿群体中进行过大量的研究调查。为什么HHFNC尽管没有达到与CPAP一致的标准却能广泛应用并成为一种受欢迎的呼吸支持方式而且在很多案例中都优于CPAP选择是值得我们思考的。一个可能性就是易于使用的传递正气道压的次优系统比理论上更优设计但操作困难的系统更好更有效。由此推测，照顾者们使用HHFNC作为提供CPAP的一种设备，HHFNC实现其提供气道压的功能。虽然HHFNC产生的一些较高的气道压，但目前尚不清楚这种气压是不是有益于健康，或无关紧要，或压力过度，或在不同的时间段产生以上3种影响。有人建议HHFNC通过流速变化、改进的粘膜灌注或者呼吸道刺激等其他方式可能产生更另人满意的呼吸支持。虽然目前这只是一个纯粹的探索性想法。如果是真的，虽然现在缺少证据，但HHFNC完全有可能比传统的CPAP在某一类患者和疾病治疗中更加有效。另一方面，如果HHFNC的目的主要是传递气道压，那么很多选择HHFNC而非CPAP都选择回避真正需要的是新的更好的CPAP设备还是更容易操作的HHFNC设备。选择HHFNC作为产生气压的设备（有一些既没有设计、批准使用又不是理

想的匹配），或者坚持“一分耕耘，一份收获”的人生哲理而使用准确的CPAP设备，正确的使用CPAP设备能够提供更佳的正气道压，但是它更加繁琐、更难操作、需更多人力。

CONCLUSIONS 总结

With regard to the primary question posed in this review, “Is HHFNC the new and improved CPAP?” it must be concluded that HHFNC and CPAP are not one and the same, that is, that HHFNC is not a form of CPAP. This is primarily because HHFNC is neither designed nor FDA approved to provide true CPAP. The available evidence to date suggests that some positive airway pressure is indeed generated when using HHFNC, but that this pressure is inconsistent, unreliable, and unpredictable. It remains unclear if the purported benefits of HHFNC are due to this pressure effect or to other as yet unproven effects. 至于本文献中提出的主要问题“HHFNC是新型改进的CPAP吗？”我们推断出HHFNC和CPAP并不相同，即HHFNC不是CPAP的一种表现形式。其根本原因是HHFNC既不是为提供准确的CPAP而设计也没有获得FDA认证。迄今为止，有效的论证建议使用HHFNC的确产生了一些正气道压，但是这种压力是不一致的、不可靠的、不可预见的。尚不清楚的是HHFNC声称的效应是否由此压力效应或其他尚未证实的效应造成。

This primary conclusion does not imply that HHFNC is either worse than or better than CPAP as a respiratory support modality, only that they are distinct and different modalities. The secondary question that this then begs is whether HHFNC is a better alternative to CPAP in some or all of the circumstances in which CPAP may typically be used, such as primary treatment in RDS, as a postextubation modality to prevent the need for reintubation, or as a treatment for apnea of prematurity. It seems likely that, for the foreseeable future, HHFNC will be a more user-friendly modality than CPAP and will continue to be widely used. Although high-quality evidence is currently lacking to support or refute the efficacy and/or safety of HHFNC, it is anticipated that such evidence should be forthcoming in the next few years. Until this happens, HHFNC should best be regarded as a potentially valuable respiratory support modality, being easier to use with the possibility of being better tolerated with fewer adverse effects such as local trauma, but also as a potentially dangerous respiratory support modality until concerns regarding infection risk, airway pressure, and other as yet unrecognized possible adverse effects are adequately addressed.

这个基本的结论并没有意指HHFNC是一种比CPAP更差或更好的呼吸支持疗法，仅指出它们各有其独特性并属不同的治疗方式。第二个问题是在某些或所有CPAP可能作为代表性使用的情况下，例如初期治疗呼吸窘迫综合症作为预防重插管的拔管后疗法或者治疗由早产导致的呼吸暂停，HHFNC都是使用CPAP的更好选择。在可预见的未来，HHFNC似乎很可能成为一种比CPAP更易操作的治疗方案并将广泛应用于实践。虽然目前还缺乏有力的论证或HHFNC的有效性和/或安全性遭到批驳，但我们可预见在未来几年内将会得到此类论证。有了相关论证后，HHFNC可被认为是一种有潜在价值的呼吸支持疗法，操作更加容易，可能对少数负面影响，例如局部创伤，有更好的耐受性。同时，在我们关心的关于感染风险、气道压和其他尚未辨识可能存在的负面影响没有得到充分的认识解决之前，HHFNC也是一种潜在危险的呼吸支持疗法。

At this stage, based on the currently available evidence, it seems prudent to make the following recommendations: 现阶段，以现有的有效论证为依据，谨慎的做法是遵循以下推荐规范：

1 HHFNC should not be used routinely in neonatal care until adequate evidence for safety and efficacy becomes available. 1 若无对HHFNC安全性和有效性进行充分的论证则其不应作为新生儿护理中的常规设备。

2 Ideally, use should be limited to participation in well-designed clinical trials to furnish this evidence. 2理想状态是为提供论证而限制其使用范围在设计周到的临床实验上。 3 Any use of HHFNC outside of such trial settings might best be limited to somewhat larger neonates (such as those ＞1000 g in weight) and to more moderate flow rates (eg, ＜2 L/min, in particular for smaller neonates), while close attention is paid to any potential adverse outcome trends such as infection rates.

3. 实验外使用HHFNC最好将使用对象的范围定位为较大的婴儿（例如体重大于1000g）并使用更加温和的气流率（例如：＜2 L/min,尤其针对小一点的新生儿）,同时密切关注是否出现任何副作用，比如感染率等。

It is hoped that ongoing research will define and clarify specific roles for HHFNC therapy, what flow rates may be safest and most effective, and how best to integrate this intriguing modality into the current armamentarium of respiratory support in the NICU.

我们希望正在进行的研究能给HHFNC疗法的特定角色一个清晰的定义。比如，流速率什么时候是最安全有效的，在新生儿重症监护室中，怎样才能最好的使该疗法与现有的医疗设备融为一体。 References

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