Noninvasive Ventilation with Helium-Oxygen in Children☆,☆☆ Federico Martinón-Torres MD, Phd⁎

Journal of Critical Care (2012) 27, 220.e1–220.e9

Noninvasive ventilation with helium-oxygen in children☆,☆☆ Federico Martinón-Torres MD, PhD⁎

Pediatric Emergency, Intermediate and Critical Care Service, Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain Instituto de Investigación Sanitaria de Santiago, Universidad de Santiago de Compostela, Santiago de Compostela, Spain

Keywords: Abstract Most existing literature on noninvasive ventilation (NIV) in combination with helium-oxygen Noninvasive ventilation; (HELIOX) mixtures focuses on its use in adults, basically for treatment of acute exacerbations of Helium-oxygen; chronic obstructive pulmonary disease. This article reviews and summarizes the theoretical basis, Heliox; existing clinical evidence, and practical aspects of the use of NIV with HELIOX in children. There is Bronchiolitis; only a small body of literature on HELIOX in pediatric NIV but with positive results. The reported Continuous positive experience focuses on treatment for patients with severe acute bronchiolitis who cannot be treated with pressure; standard therapies. The inert nature of helium adds no biological risk to NIV performance. Pediatrics Noninvasive ventilation with HELIOX is a promising therapeutic option for children with various respiratory pathologies who do not respond to conventional treatment. Further controlled studies should be warranted. © 2012 Elsevier Inc. All rights reserved.

1. Introduction practical use [1]. Children receiving NIV may simultaneously need supplementary techniques either at the onset of The interest in noninvasive ventilation (NIV) is rapidly treatment or throughout the progression of their pathology growing, but the evidence from the literature is still scarce, [1]. These techniques may be complementary to NIV and and it is coming at a slower pace than the spread of its may even enable synergistic effects [1]. One of these applications is its use in combination with helium. The use of helium-oxygen (HELIOX) mixtures in the ☆ Sources of financial support: Federico Martinón-Torres has written pediatric setting has gained interest in the last few years for this manuscript during research time funded by Consellería de Sanidade the treatment of different respiratory entities, mainly croup, (Xunta de Galicia, RHI07/2-intensificación actividad investigadora) and Instituto Carlos III (Intensificación de la actividad investigadora) of “plan asthma, and bronchiolitis [2,3]. Its use in combination with nacional de I+D+I” and “fondos FEDER.” noninvasive positive pressure has been more selective. Most ☆☆ Potential conflict of interest: FMT has received lecture/consultancy existing articles on NIV in combination with HELIOX focus fee/honorarium from BOC and LindeGAS. on use in adults, basically for treatment of acute exacerba- ⁎ Pediatric Emergency, Intermediate and Critical Care Service, Hospital tions of chronic obstructive airways disease [4-10]. This Clinico Universitario de Santiago, A choupana s.n. 15706 Santiago de Compostela (Spain) Tlf: +34 981950615; Fax: +34 981950596; Fax: +34 article reviews and summarizes the theoretical basis, existing 981950596. clinical evidence, and practical aspects of the use of NIV E-mail address: [email protected]. with HELIOX in children.

2. Fundamentals of HELIOX Table 1 Main clinical uses of HELIOX in children Obstruction mainly of the upper airway Helium, a noble gas, is inert, colorless, and odorless and Infectious etiology (eg, laryngitis, epiglottitis, tracheitis) has very low density [3]. If the nitrogen in inspired air Inflammatory etiology Postextubation subglottic edema (composed of 78% N2 and 22% O2) is replaced with helium— Postradiotherapy edema that is 7 times less dense—a mixture (78% He and 22% O2) is obtained that is 3 times less dense than normal air [3]. The Angioedema Edema through inhaled injury therapeutic use of HELIOX mainly lies in this significant Recurrent or spasmodic croup difference in density; when a patient breathes HELIOX instead Mechanical etiology of air-oxygen, airway resistance to gas flow is reduced leading Foreign body to a reduction in respiratory work. Furthermore, HELIOX also Vocal chord paralysis improves gas exchange, above all, in alveolar ventilation; in Subglottic stenosis small airways where elimination of CO2 is facilitated by Laryngotracheomalacia diffusion, this diffuses 4 to 5 times faster in HELIOX than in Neoplastic etiology air-oxygen mixture [3]. Laryngeal or tracheal growths Helium was first introduced into the medical arena in the Extrinsic compression of the larynx, trachea, or bronchi 1930s by Barach [11], who showed that when it was combined Obstruction mainly of the lower airways with oxygen, the resulting mixture (which he dubbed Acute asthmatic crisis Bronchiolitis “HELIOX”) improved airflow in patients with obstructive Bronchial hyperreactivity laryngeal, tracheal, or lower airway lesions. Since then, studies Neonatal respiratory distress syndrome on the pediatric use of HELIOX have demonstrated its use and Bronchopulmonary dysplasia efficacy for treatment of various conditions, including upper Driving gas for drug nebulization airway obstruction caused by diverse pathologies as well as Fiberoptic bronchoscopy and/or instrumental manipulation asthma and acute bronchiolitis [2,3]. of the airway Other indications Hyperammonaemia Pneumothorax 3. Clinical applications of HELIOX

Helium-oxygen lacks any intrinsic therapeutic effect 3.1. Helium-oxygen therapy in the spontaneously because of the inert nature of helium [3]. However, it can breathing infant act as a “therapeutic bridge” maintaining the patient in improved conditions, delaying onset of muscle fatigue and For patients with spontaneous breathing, the preferred respiratory failure, and obviating the use of more aggressive method is via nonrebreathing mask with reservoir and treatments until either other therapies can be administered unidirectional low pressure valves at flows of 10 to 15 L/min or the patient's condition spontaneously resolves itself [3]. [3,12,13]. If required, supplementary oxygen can be delivered Furthermore, this absence of any potential biological through nasal cannulae but at the lowest flow possible (always interaction provides an excellent safety profile for its b2 L/min) because a higher flow could reduce the helium clinical use, being a therapy without inherent risks; using concentration excessively [3,12,13]. Warming and humidifi- HELIOX does not mean taking any biological risk for our cation of HELIOX, which are especially important for very patient [3]. small children, can readily be achieved by modifying standard Helium-oxygen is most effective at the highest possible equipment used for air-oxygen mixtures. Oxygen hoods or concentrations of helium (typically, 60%-80%); neverthe- tents are not ideally suited to HELIOX therapy because less, there may be beneficial effects at much lower mixture with room air is greater, with the helium (less dense) concentrations, although with proportionately lower effec- going to the top and the air (more dense) going to the bottom, tiveness [3]. Given its physical properties, the main clinical close to the patient's airway [14]. Simple face masks or nasal uses of HELIOX predominantly relate to obstructive cannulae may be amenable to HELIOX therapy; however, they respiratory problems, those that pathophysiologically have too tend to cause dilution of the HELIOX flow with external both raised airway resistance and increased respiratory work, air, thereby markedly reducing the chances of a successful and also where alveolar ventilation is compromised to a treatment [14]. greater or lesser extent. Table 1 summarizes the main pediatric clinical indications for the use of HELIOX. According to most existing studies of HELIOX use in 3.2. Helium-oxygen as nebulization source children, usual practice is in those breathing spontaneously or, if in intubated patients, by adaptation of conventional A further application for which significant evidence exists mechanical ventilation systems [3]. in both children and adults is to use HELIOX to nebulize NIV with HELIOX in children 220.e3 medicines [2,3,15-17]. For this use, gas flow is usually provides greater minute volumes—and therefore, better increased by 20% to 25%, ensuring that minimum flow is not alveolar ventilation—than air-oxygen mixtures [32]. Increas- below 10 to 12 L/min. Note that the nebulization time of any ing the expiratory flow reduces air trapping and generation of particular volume of solution is much longer than with air or auto–positive end-expiratory pressure, thereby improving oxygen at a similar flow. To obtain the maximum benefits, a lung compliance, restoring the mechanical advantage to nebulization system with reservoir (such as the nonrebreathing inspiration, and decreasing work of breathing. This, in turn, reservoir face mask with a “Y” piece) should be used, ensuring expands the tidal volume generated per centimeter H2O of that patient's minute volume demands are covered with pressure used. Moreover, NIV with HELIOX improves the HELIOX. Alternatively, an ultrasonic nebulizer can be used, patient's elimination of CO2 and reduces their sensations of intercalated in the HELIOX flow to the patient [3,18]. dyspnea [32]. Helium-oxygen has complementary effects when used 3.3. Helium-oxygen therapy in the intubated child with NIV; indeed, the combination of HELIOX and NIV can even be considered synergistic. As positive pressure, NIV When used invasively, the method depends upon the type can help reduce the load on respiratory muscles, prevent or of respirator. Helium-oxygen is usually introduced via the correct atelectasis, prevent airway collapse, and promote and pressurized air input of the respirator; however, given its facilitate distribution of HELIOX throughout obstructed physical properties, it can interfere with a wide range of key airways. Helium-oxygen can further reduce work of breathing and improve CO elimination. It can also provide functions (volume settings, levels of FIO2, trigger sensitivities, 2 flow rates, etc) [3,19-23]. Therefore, it is necessary to check higher expiratory flow than air-oxygen mixtures at the same before use that the ventilator is compatible with HELIOX and pressure, which, in turn, can help improve passive expiratory to consider specific correction factors. In general, the safest lung mechanics, reducing the risk of barotrauma by gas form of patient ventilation with HELIOX is to use a pressure- trapping and thereby limiting any deleterious side effects controlled ventilatory mode using pressure goals as a guide from CPAP in obstructed airways [32]. (see references [19-23] for details) and ensuring expiratory Application of continuous positive pressure can lower the times long enough for adequate lung emptying. Presently, patient's FIO2 requirements, enabling them to be treated with there are ventilators available specifically designed—and ahigherconcentrationofheliumand,consequently, Food and Drug Administration cleared—to be used with increasing the likelihood of treatment success. The reduction HELIOX mixtures, although they are not widely distributed in the oxygen requirements further protects the lung. yet. Helium-oxygen has also been used with other invasive Hypoxia secondary to development of atelectasis has ventilatory modes such as high-frequency jet, high-frequency been described in patients treated with HELIOX [33]. percussive ventilation, and high-frequency oscillatory venti- Neonates and small infants are at especially high risk for lation [3,24,25]. this complication. However, this potentially serious side effect—although anecdotally reported and debatably related to HELIOX—can easily be prevented through concomitant use of CPAP. 4. Rationale for using HELIOX in NIV and Given that HELIOX can reduce the pressure gradient clinical experience required to maintain a given flow, less pressure can be used to obtain the target tidal and minute volumes, which, in turn, Based on the studies published in the late 1990s by the diminishes peak pressures and minimizes the risk of Swiss group Jolliet et al [10], interest rose in the combination barotrauma or volutrauma. By substituting air-oxygen for of NIV and HELIOX in the treatment of acute exacerbations HELIOX, NIV may be performed in a more lung protective in patients with chronic pulmonary disease, even showing its fashion: for a given target pH/CO2 level, lower pressure efficiency [5-10]. The use of NIV with HELIOX in place of swings and even lower volumes will be required [32]. air-oxygen occurred for the first time (successfully) in Lastly, HELIOX delivered by NIV can delay or even children in the mid 1970s in weaning off small children from obviate endotracheal intubation of the patient and subsequent mechanical ventilation after cardiac surgery [26]. However, invasive mechanical ventilation, each of which carries its this practice was not repeated (as few used NIV in children at respective complications. Although endotracheal intubation that time), and there are no earlier publications on NIV with is the preferred method for airway isolation, it can produce HELIOX in children before those of our own group on use in local inflammation, ischemia of the mucosa, subglottal young infants with refractory acute bronchiolitis [27-30]. edema, and/or stenosis [34,35]. Likewise, invasive positive More recently, the use of helmet-delivered HELIOX pressure ventilation can cause lung damage by altering lung continuous positive airway pressure (CPAP) has also been mechanics, specifically, barotrauma, volutrauma, atelectrauma, reported in small infants with bronchiolitis as an alternative and biotrauma [34,35]. mode of NIV with HELIOX [31]. Based on the experience of the author's unit, HELIOX in Both experimental models and clinical data on adults combination with nasal CPAP (nCPAP) is a safe and demonstrate that, at a given target pressure, HELIOX effective treatment in unresponsive severe acute bronchiolitis 220.e4 F. Martinón-Torres as measured clinically or by tcPCO2 and by satO2 values [27- 1. Children already receiving HELIOX therapy who are not 30]. Furthermore, nCPAP with HELIOX in place of an air- achieving adequate levels of oxygenation. The positive oxygen mixture is clearly more efficacious, as shown by pressure will enhance alveolar recruitment/oxygenation, approximately twice the level of improvement in clinical allowing us to reduce FIO2 (and thus to increase FiHe); and scores and tcPCO2 levels after 30 minutes of therapy [28]. 2. Children already on NIV with inadequate ventilation Between 1999 and 2010, only 1 (0.28%) of 352 patients according to pH/pCO2 levels, dyspnea, or clinical admitted to our unit with moderate to severe acute score. The effect of HELIOX on alveolar ventilation bronchiolitis and managed according to our protocol— not only through higher expiratory flows but also over centered in the use of HELIOX alone or in combination with CO2 may resolve the situation without further increase NIV—has needed intubation and mechanical ventilation in the NIV parameters. (95% confidence interval, 0.01%-1.12%). Although this is a single-center experience and that there may be influencing One further indication, at least from the theoretical factors other than HELIOX and nCPAP treatment in perspective, would be in those children receiving NIV intubation practices (etiology, admission-discharge criteria, whose underlying pathology or illness requires protective RSV season, etc), such low incidence is in stark contrast to ventilatory strategy (ie, the lowest possible pressure-volume the levels noted in a literature review suggesting that 25% to swing [amplitude/inspiratory airway pressure - expiratory 60% of infants with bronchiolitis admitted to a pediatric airway pressure] for achieving a target pH/CO2 level). From intensive care unit may need intubation and ventilatory the practical point of view, infants with severe unresponsive support [28,36-38]. Importantly, in our experience, there bronchiolitis and children with status asthmaticus are the were no adverse effects related to HELIOX, and the most frequent clinical indications of NIV with HELIOX. technique used was tolerated well in all of the patients.

6. Practical guide for using HELIOX with NIV 5. Indications of NIV with HELIOX in pediatric patients 6.1. Equipment designed for HELIOX delivery

No well-established indications of NIV with HELIOX in Currently, there are 6 commercially available ventilators children exist. The author of this review has compiled a list designed for HELIOX delivery: Aptaer HELIOX Delivery of potential indications of HELIOX used with NIV for System (GE Healthcare, Buckinghamshire, United King- pediatric patients based on the physical properties of dom), Inspiration (E-Vent Medical Ltd, Galway, Ireland), HELIOX, published data from experimental reports and Avea (Viasys Healthcare, Loma Linda, CA), Helontix Vent clinical studies on adult patients, as well as—and mainly— (Linde Gas Therapeutics, Höllriegelskreuth, Germany), G5 his personal accumulated and reported experience. These (Hamilton, Reno, NV), and Servo-I (Maquet, Rastatt, comprise (Table 2): Germany). The main characteristics of these machines are summarized in Table 3. Their distribution and use remain limited; indeed, none of these devices have appeared in any Table 2 Indications of NIV with HELIOX instead of air-oxygen of the few works on pediatric patients published to date. The Children already receiving HELIOX therapy a with Aptaer features inspiratory and expiratory triggers, enabling inadequate oxygenation use of pressure support with HELIOX. The Inspiration is a Not meeting their oxygenation goals-requirements conventional ventilator that includes an option for NIV Whose FIO2 requirement is either N0.40 or increasing delivery of HELIOX. The Avea offers all the standard modes Children already receiving NIV with inadequate ventilation used for invasive ventilation plus the option for invasive or Ventilation level achieved is inadequate according to pH/pCO2 NIV with HELIOX. The Helontix Vent was specifically Require high or increasing pressure levels (PIP/IPAP) developed for HELIOX therapy. It allows use of pressure Show insufficient improvement (or worsening) in dyspnea support and only comes in a single model for adults and older Show insufficient improvement (or worsening) in clinical children. To properly work with HELIOX, both the respiratory score Inspiration and G5 devices require a specific module/ Children receiving NIV whose underlying pathology or illness requires protective ventilatory strategy (ie, the lowest possible software that needs to be purchased separately. pressure/volume swing (amplitude/IPAP-EPAP) for achieving a target pH/CO2 level) 6.2. Equipment adapted for HELIOX delivery a Helium-oxygen therapy defined as HELIOX mixture (60%-80% helium proportion) administered to a spontaneously breathing child Helium-oxygen can be safely delivered by modifying through nonrebreathing reservoir facemask with adequate HELIOX standard NIV ventilators according to literature guidelines. flow (usually about 10 L/min). PIP, peak inspiratory pressure; IPAP, However, as with use of any equipment beyond its inspiratory airway pressure; EPAP, expiratory airway pressure. manufacturer's indications, extreme caution must be applied NIV with HELIOX in children 220.e5

Table 3 Noninvasive ventilation with HELIOX Model Aptaer Avea Event Helontix Vent G5 Servo-i Distributor Datex Ohmeda Vyasis Healthcare Event Inspiration Ltd Linde Gas Therapeutics Hamilton Maquet

Adjustable FIO2 No Yes Yes Yes Yes Yes Adjustable PEEP No Yes Yes Yes Yes Yes Pressure support Yes Yes Yes Yes Yes Yes Pediatric model No Yes Yes No Yes Yes Standard ventilation modes No Yes a Yes No Yes a Yes a HELIOX consumption Low Medium Medium Low Medium Medium Difficulty for portable use Medium High High Low High Low Price Low High High Low High High Main features of the commercially available ventilators designed for noninvasive delivery of HELIOX with positive pressure. PEEP indicates positive end- expiratory pressure. a Helium-oxygen ventilation modes can only be performed if the ventilator includes the HELIOX module (software and/or specific pneumotacograph); not included in the standard configuration. when using this approach [3,32,39]. Hospital staff must have (Figs. 2 and 3). The helium or HELIOX source is connected to technical expertise in both the ventilator and in HELIOX the ventilator's air inlet (probably the best option) or oxygen therapy to minimize any potential risks in this method. In inlet. In the former case, the FIO2 is regulated using the these cases, we should consider the following: ventilator's FIO2 control, whereas in the latter case, the FIO2 control is set to 1.0 to ensure that only HELIOX is being 1. When HELIOX is used with NIV, the average flow and delivered. If supplementary oxygen is required, it can be added volume readings are not reliable unless an external through a T piece attached to the respiratory circuit. pneumotacograph (which is not influenced by gas density) Alternatively, an oxygen blender can be attached to the is used. Hence, ventilation should be programmed and ventilator's air inlet or oxygen inlet so that helium and oxygen controlled as a function of the programmed pressures can be added simultaneously before entering the ventilator. (which are not affected by HELIOX) and the resulting For cases in which the gas flow is directly regulated (eg, in blood gas values (arterial O2 saturation and CO2 levels); the Infant Flow System), the following factors are used to 2. Noninvasive ventilation with HELIOX instead of air- convert flow meter readings from air-oxygen values to oxygen mixtures generates greater inspiratory and HELIOX values: for 80% He and 20% O2, multiply by 2.1; expiratory flows at the same pressure and provides far for 70% He and 30% O2, multiply by 1.7; and for 60% He and superior CO2 diffusion. In terms of protecting the 40% O2, multiply by 1.4. These conversions enable determi- patient's lungs, this implies that the pressure gradient nation of the real amount of HELIOX required to maintain the required to reach a given target CO2 level will be lower target pressure. If HELIOX is introduced through the air inlet, with HELIOX than with an air-oxygen mixture. then the automatic limits of the alarm should be adjusted by 3. If pure helium is used—which is generally not recom- first temporarily setting the FIO2 control to the same percentage mended and is prohibited by legislation on therapeutic as the oxygen in the HELIOX used and then resetting it to 0.21. gases in most European countries—then the patient must The aim of this technique is to avoid false alarms caused by be continuously monitored by oximetry to prevent discrepancy between the concentration set on the oxygen hypoxic conditions. Nonetheless, the safest and most blender and the concentration detected by the oximeter (whose practical clinical option is to use HELIOX mixtures at minimum value is the percentage of oxygen in the HELIOX predetermined concentrations (typically, 80:20 or 70:30) introduced at the air inlet). and then add any required supplemental oxygen according Noninvasive ventilations delivery of HELIOX using the to the patient's needs. BiPAP Vision ventilator has been validated in an experimental model [39]. However, if this device is used, the initial There are 2 ways of adapting standard NIV equipment for leakage test of the expiratory valve should not be performed; delivery of HELIOX: predilution connection and postdilu- paradoxically, this will provide better functioning of the tion connection (Figs. 1-3). ventilator, including greater accuracy of the trigger. Using this method with the FIO2 set at 1.0 enables safe and accurate 6.2.1. Predilution connection administration of helium at concentrations higher than 60%. In this approach, HELIOX is directly connected to the The NIV ventilators best suited to modification for ventilator through a pressurized-gas inlet or a blender. It can be HELIOX delivery (ie, those for which HELIOX causes the used with the BiPAP Vision (Respironics/Philipps, Amster- least interference in functioning, including in measurements) dam, The Netherlands), and the Infant Flow, Infant Flow comprise, in decreasing order of preference: Servo 300 Advance and SiPAP (EME/Viasys, Loma Linda, CA) systems (Rastatt, Germany), Galileo (Reno, NV), Galileo Gold 220.e6 F. Martinón-Torres

Fig. 1 Modes of adaptation of standard NIV equipment for delivery of HELIOX. Both predilution connection and postdilution connection modes are detailed in the text.

(Reno, NV), and Veolar FT (Reno, NV). For volume- setup, the concentration of helium that the patient receives is controlled ventilation, there are specific correction factors for primarily dictated by the flow of helium used. Thus, it tidal volume and FIO2 to be used with the most popular NIV requires external oximetry to guarantee adequate FIO2 ventilators (see references for more detailed data). delivery. Furthermore, because the parameter values regis- tered by the ventilator are not reliable, external pneumotaco- 6.2.2. Postdilution connection graphy is also needed. This setup is 1 option in some In this method, the HELIOX is introduced directly into ventilators (eg, BiPAP Vision), whereas it is the only option the respiratory circuit tubing after the ventilator and ideally in others, which generates pressure by drawing in ambient air as close to the patient (interface) end as possible. In this (eg, BiPAP S/T-D30 [Respironics/Phillips, Amsterdam, The

Fig. 2 BiPAP Vision noninvasive ventilator adapted for HELIOX delivery; the HELIOX is introduced through the device's pressurized- oxygen inlet. NIV with HELIOX in children 220.e7

Fig. 3 InfantFlow Advance (EME) noninvasive ventilator adapted for HELIOX delivery; the HELIOX is introduced through the device's pressurized-air inlet.

Netherlands], Knightstar 335 [Mallinckrodt/Puritan-Bennet, • hypoxemia Mansfield, MA], Quantum PSV [Respironics/Phillips, ◦ The primary side effect is insufficient oxygenation Amsterdam, The Netherlands], and Sullivan VPAP II ST because this treatment implies use of the lowest FIO2 [ResMed, San Diego, CA]). Analogously to the case in possible to maximize the positive effects of helium. standard NIV of trying to increase the FIO2 by introducing Hence, strongly hypoxemic patients who are character- oxygen in the circuit or interface, this approach is limited by ized by high oxygen requirements cannot be treated with the fact that the operator cannot determine exactly how much HELIOX (at least not at any well-proven therapeutically helium is being introduced into the circuit (and therefore, significant concentration of helium). Hypoxemia can delivered to the patient), which carries a risk of affecting also be caused by inadvertent use of a hypoxic mixture ventilator function. Nonetheless, it has been validated (FIO2 b21%) in cases in which the helium and oxygen experimentally (39). Using any of the aforementioned are mixed manually. This can be avoided by using tanks ventilators with HELIOX (80% He and 20% O2) flows of of premixed HELIOX at known concentrations or by 18 L/min ensures delivery to the patient of helium at using continuous oximetric monitoring (with an alarm) concentrations higher than 60%. Furthermore, at this flow of the mixture delivered to the patient. rate, HELIOX only causes minimal interference (BiPAP S/ • hypothermia TD30 and the Quantum) with ventilator function or does ◦ One of the most therapeutically important physical not interfere at all (Knightstar, Sullivan, and BiPAP Vision) properties of HELIOX is its high thermal conductivity nor does it alter the programmed inspiratory or expiratory (6-7 times that of air); hence, prolonged HELIOX pressure in any of these models. Logically, with this treatment at temperatures under 36°C carries a risk of HELIOX delivery approach, the final concentration of hypothermia. Neonates and small infants are at the helium delivered to the patient is influenced by the tidal highest risk for this side effect, which can be prevented volume obtained: higher inspiratory pressure and greater by ensuring proper warming and humidification of the tidal volume at a constant HELIOX flow correlate with a HELIOX and by carefully monitoring the patient's body lower concentration of helium administered to the patient. temperature. In our experience, this side effect has been only a theoretical concern.

7. Side effects and drawbacks 7.2. Drawbacks

7.1. Side effects • Cost ◦ There have not been any studies on the cost effective- Although HELIOX is inert (nontoxic), when used with ness of NIV HELIOX treatment in children. Compared NIV, it may lead to certain side effects, namely, with other clinically used gases, HELIOX is quite 220.e8 F. Martinón-Torres

expensive: at least 2 to 3 times as much as air and 8 to References 10 times as much as oxygen. Using non–NIV-specific devices for delivery of HELIOX can lead to increased [1] Medina A, Pons M, Martinon-Torres F. Non-invasive ventilation in costs because of internal gas consumption, leakage pediatrics (2nd edition). Madrid: Ergon; 2009. compensation and/or excessive internal leaks. However, [2] Gupta VK, Cheifetz IM. Heliox administration in the pediatric NIV-specific ventilators also have their respective intensive care unit: an evidence-based review. Pediatr Crit Care Med drawbacks that vary according to model (Table 3). 2005;6(2):204-11. • Technical difficulties [3] Martinón Torres F, Martinón Sánchez JM. Heliox therapy. In: Casado Flores J, editor. Mechanical ventilation in newborns, infants ◦ The physical properties of HELIOX—above all, its low and children. (2nd edition). Madrid: Editorial Ergón; 2011. density—can interfere with fundamental ventilator p. 265-74.4. operation, especially recording of FIO2 volumes as [4] Maggiore SM, Richard JC, Abroug F, Diehl JL, Antonelli M, Sauder well as trigger functioning, flow measurements, and the P, et al. A multicenter, randomized trial of noninvasive ventilation with automatic leakage compensation featured on some helium-oxygen mixture in exacerbations of chronic obstructive lung disease. Crit Care Med 2010;38(1):145-51. models. These technical difficulties vary with the [5] Colebourn CL, Barber V, Young JD. Use of helium-oxygen mixture in ventilator used and are primarily dictated by the type adult patients presenting with exacerbations of asthma and chronic of valves and pneumotacograph used. In any case, obstructive pulmonary disease: a systematic review. Anaesthesia 2007;62: pressure transducers are generally not affected by 34-42. HELIOX; hence, treatment should be adjusted accord- [6] Hess DR. Heliox and noninvasive positive-pressure ventilation: a role for heliox in exacerbations of chronic obstructive pulmonary disease? ing to the programmed pressures. Respir Care 2006;51:640-50. [7] Hess D, Chatmongkolchart S. Techniques to avoid intubation: noninvasive positive pressure ventilation and heliox therapy. Int Anesthesiol Clin 2000;38:161-87. 8. Conclusions and future perspectives [8] Hilbert G. Noninvasive ventilation with helium-oxygen rather than air- oxygen in acute exacerbations of chronic obstructive disease? Crit Care Med 2003;31:990-1. In conclusion, HELIOX is complementary to NIV, and [9] Jolliet P, Tassaux D, Thouret JM, Chevrolet JC. Beneficial effects of together, they may even have synergistic effects. There is helium: oxygen versus air: oxygen noninvasive pressure support in only a small body of literature on HELIOX in pediatric NIV patients with decompensated chronic obstructive pulmonary disease. —focusing on treatment for patients with severe acute Crit Care Med 1999;27:2422-9. [10] Jolliet P, Tassaux D, Roeseler J, Burdet L, Broccard A, D'Hoore W. bronchiolitis who cannot be treated with standard therapies Helium-oxygen versus air-oxygen noninvasive pressure support in —but the results are positive. Helium-oxygen and NIV may decompensated chronic obstructive disease: a prospective, multicenter provide time for other therapeutic agents to work or for the study. Crit Care Med 2003;31:878-84. disease to resolve naturally and might help to avoid more [11] Barach AL. Use of helium as a new therapeutic gas. Proc Soc Exp Biol aggressive intervention such as endotracheal intubation and Med 1934;32:462-4. [12] Martinon-Torres F, Rodriguez Nunez A, Martinon Sanchez JM. Heliox invasive mechanical ventilation. The ideal ventilators for therapy in infants with acute bronchiolitis. Pediatrics 2002;109:68-73. HELIOX delivery are devices that are specifically designed [13] Martinon-Torres F, Rodriguez-Nunez A, Martinon-Sanchez JM. for this task. Alternatively, other ventilators can be modified Heliox questions. Pediatrics 2003;111:441-3. to administer HELIOX in NIV, although these must be used [14] Stillwell PC, Quick JD, Munro PR, Mallory Jr GB. Effectiveness of with extra precautions. Theoretically, NIV with HELIOX open-circuit and oxyhood delivery of helium-oxygen. Chest 1989;95(6):1222-4. represents a new strategy for lung treatment and protection, [15] Kim IK, Saville AL, Sikes KL, Corcoran TE. Heliox-driven albuterol and the inert nature of helium adds no biological risk to nebulization for asthma exacerbations: an overview. Respir Care NIV performance. 2006;51(6):613-8. Using HELIOX with NIV is a promising therapeutic [16] Anderson M, Svartengren M, Bylin G, Philipson K, Camner P. option for children with various respiratory pathologies Deposition in asthmatics of particles inhaled in air or in helium- oxygen. Am Rev Respir Dis 1993;147(3):524-8. who do not respond to conventional treatment. According [17] Svartengren M, Anderson M, Philipson K, Camner P. Human lung to the author's experience, HELIOX in combination with deposition of particles suspended in air or in helium/oxygen mixture. CPAP is a safe and effective tool to be considered for Exp Lung Res 1989;15(4):575-85. the management of infants with severe acute bronchiolitis. [18] O'Callaghan C, White J, Jackson J, Crosby D, Dougill B, Bland H. However, this technique must be further evaluated in this The effects of Heliox on the output and particle-size distribution of salbutamol using jet and vibrating mesh nebulizers. J Aerosol Med and other settings and in both experimental and clinical Winter 2007;20(4):434-44. studies. Noninvasive ventilation with HELIOX indications [19] Migliori C, Gancia P, Garzoli E, Spinoni V, Chirico G. The effects of and treatment guidelines (ideal initial and maintenance helium/oxygen mixture (heliox) before and after extubation in long- settings, duration of treatment) must be more clearly term mechanically ventilated very low birth weight infants. Pediatrics established. Furthermore, NIV with HELIOX theoretically 2009;123(6):1524-8. [20] Kneyber MC, van Heerde M, Markhorst DG, Plötz FB. Mechanical embodies a new strategy for lung treatment and ventilation with heliox decreases respiratory system resistance and protection, and studies exploring this possibility should facilitates CO2 removal in obstructive airway disease. Intensive Care be warranted. Med 2006;32(10):1676-7. NIV with HELIOX in children 220.e9

[21] Brown MK, Willms DC. A laboratory evaluation of 2 mechanical Usefulness of heliox in the management of a serious airway ventilators in the presence of helium-oxygen mixtures. Respir Care obstruction caused by a subglottic hemangioma. An Pediatr 2005;50(3):354-60. (Barc) 2007;67:61-4. [22] Berkenbosch JW, Grueber RE, Dabbagh O, McKibben AW. Effect of [31] Mayordomo-Colunga J, Medina A, Rey C, Concha A, Los Arcos M, helium-oxygen (heliox) gas mixtures on the function of four pediatric Menéndez S. Helmet-delivered continuous positive airway pressure ventilators. Crit Care Med 2003;31(7):2052-8. with heliox in respiratory syncytial virus bronchiolitis. Acta Paediatr [23] Tassaux D, Jolliet P, Thouret JM, Roeseler J, Dorne R, Chevrolet JC. 2010;99(2):308-11. Calibration of seven ICU ventilators for mechanical ventilation with [32] Martinon-Torres F. Non-invasive ventilation with heliox. In: Medina helium-oxygen mixtures. Am J Respir Crit Care Med 1999;160(1):22-32. A, Pons M, Martinon-Torres F, editors. Non-invasive ventilation in [24] Gupta VK, Grayck EN, Cheifetz IM. Heliox administration during Pediatrics. 2nd ed. Madrid: Ergon; 2009. p. 99-106. high-frequency jet ventilation augments carbon dioxide clearance. [33] Butt WW, Koren G, England S, Shear NH, Whyte H, Bryan CA, et al. Respir Care 2004;49(9):1038-44. Hypoxia associated with helium-oxygen therapy in neonates. J Pediatr [25] Cros AM, Guenard H, Boudey C. High-frequency jet ventilation with 1985;106:474-6. helium and oxygen (heliox) versus nitrogen and oxygen (nitrox). [34] Tobias JD: Airway management for pediatric emergencies. Pediatr Anesthesiology 1988;69(3):417-9. Ann 25(6):317-20, 323-8, 1996 [26] Tatsuno K, Imai Y, Konno S. Therapeutic use of helium-oxygen [35] Kacmarek RM. Ventilator-associated lung injury. Int Anesthesiol Clin mixture in continuous positive airway pressure for early weaning from 1999;37(3):47-64. mechanical ventilation after cardiovascular surgery in infants. J Thorac [36] Leclerc F, Scalfaro P, Noizet O. Mechanical ventilatory support in Cardiovasc Surg 1976;72(1):119-22. infants with respiratory syncytial virus infection. Pediatr Crit Care Med [27] Martinon-Torres F, Rodriguez-Nunez A, Martinon-Sanchez JM. Nasal 2001;2(3):197-204. continuous positive airway pressure with heliox in infants with acute [37] Eriksson M, Bennet R, Rotzen-Ostlund M, von Sydow M, Wirgart BZ. bronchiolitis. Respir Med 2006;100:1458-62. Population-based rates of severe respiratory syncytial virus infection in [28] Martinon-Torres F, Rodriguez-Nunez A, Martinon-Sanchez JM. Nasal children with and without risk factors, and outcome in a tertiary care continuous positive airway pressure with heliox versus air-oxygen: a setting. Acta Paediatr 2002;91(5):593-8. crossover study. Pediatrics 2008;121:1190-5. [38] Prais D, Schonfeld T, Amir J, Israeli RSV Monitoring Group. [29] Martinon-Torres F, Crespo Suarez PA, Silvia Barbara C, Castello Admission to the intensive care unit for respiratory syncytial virus Munoz A, Rodriguez Nunez A. Martinon Sanchez JM: Noninvasive bronchiolitis: a national survey before palivizumab use. Pediatrics ventilation with heliox in an infant with acute respiratory distress 2003;112(3 pt 1):548-52. syndrome. An Pediatr (Barc) 2005;62:64-7. [39] Chatmongkolchart S, Kacmarek RM, Hess DR. Heliox delivery with [30] Castello Muñoz A, Carreira Sande N, Bouzón Alejandro M, noninvasive positive pressure ventilation: a laboratory study. Respir Pérez Valle S, Rodriguez A, Martinon Sánchez JM, et al. Care 2001;46:248-54.