1. High Flow Specialty Gas Delivery
A Review of the Mechanisms of Action of High Flow Therapy (HFT) and the delivery of heliox via high flow nasal cannula
Hi, My name is ___________ and I am a Clinical Product Specialist with Vapotherm. This talk is A Review of the Mechanisms of Action of High Flow Therapy and the delivery of heliox via high flow nasal cannula. It is worth 1 CEU credit for Respiratory Therapists.
As my disclosure, I want you to know that I am an employee of Vapotherm.

2. Course Objectives
• Define HFT and how it is accomplished with a nasal cannula
• Explain how the dynamics of flow through the nasopharynx improve
respiratory efficiency and support work of breathing
• Explain the properties of Heliox gas mixture and how heliox can be beneficial in the respiratory system
• Understand how the characteristics of HFT facilitate the breathing of heliox via a nasal cannula
The learning objective for this course are to:
Define HFT and how can it can be accomplished with a nasal cannula
Explain how the dynamics of flow through the nasopharynx improve respiratory efficiency and support work of breathing
Explain the properties of Heliox gas mixture, and how it is beneficial by induction into high flow therapy
Understand the how the characteristics of HFT facilitate the breathing of heliox via a nasal cannula
Understand the patient population that can benefit from heliox HFT
• Understand the patient population that can benefit from heliox HFT

3. Discussion Topics A Review of the HFT and Mechanisms of Action
This [course / seminar] is broken into two sections. In the first section, we’ll briefly introduce the foundational concepts behind high flow therapy, including the critical mechanisms of action for this mode of respiratory support. After we have established these fundamentals, we can go on to the second part where we look at heliox use in respiratory care, and heliox delivery via high flow therapy
Heliox and
Heliox via HFT

4. Definition of High Flow Therapy
High Flow Nasal Cannula
Generic term for flow rates that exceed conventional nasal cannula flow rates
High Flow Therapy
Exceed a patients inspiratory flow demand
Flushes out the anatomical dead space, thus creating an internal reservoir
HFT is between 25 – 35 L/min in adults, or 4-8 L/min in infants
First, we need to establish the difference between high flow therapy and high flow nasal cannula. High flow nasal cannula is a generic term for using flow rates that simply exceed conventional flow rates for a cannula. Conventional flow rates would be at or below 6 L/min for an adult or below 2 L/min for an infant. However, while this definition of high flow nasal cannula encompasses a nearly infinite range of flows, the term High Flow Therapy refers to a specific range of flows that accomplished a specific set of objectives.
To accomplish High Flow Therapy, the cannula flow must be sufficient to:
Exceed a patients inspiratory flow so that they only inspire the gas that is coming from the cannula with negligible entrainment of room air.
In addition, the cannula flow must be sufficient to flush out the anatomical dead space between each breath, creating an internal reservoir in the nasopharyngeal cavity
Thus, the optimal flow is relative to patient size and associated with inspiratory flow demands. But in general, the flow rates to accomplish these goals are between 25 and 35 L/min in adults, and 4-8 L/min in infants.

5. Review of HFT Prior to reaching alveoli, gas must be: Nasopharynx
• Warmed
• Humidified
• Cleaned
Breathing is the process of exchanging atmospheric gas with the alveoli of the lungs so that the blood may pick up oxygen and dispense, or ventilate, carbon dioxide.
However, because the lungs are a visceral organ that surrounds the heart and comes in direct contact with the body’s entire circulating blood volume, gas entering the lungs needs to be warmed, humidified and cleaned prior to reaching the alveoli.
This process of cleaning and conditioning the inspiratory gas is accomplished by pulling air through the nasopharynx where the anatomy and physiological function of specific tissue types can perform these functions.

6. Review of HFT Nasopharyngeal Structure • Non-respiratory anatomical
dead space
• Impacts breathing efficiency
• Provides challenges to
conventional non-invasive
respiratory support
Despite the necessity of this non-respiratory anatomical dead space, nasopharyngeal structure and function impacts the efficiency of breathing and provides challenges to conventional non-invasive respiratory support related to the effect of dead space of alveolar gas equilibrium.

7. Pulmonary Physiology
Fresh atmospheric gas mixes with end-expiratory gas
End-expiratory gas is low in oxygen and high in carbon dioxide
During inspiration, fresh atmospheric gas is drawn into the respiratory system and mixes with remaining end-expiratory gas retained in the dead space. This end-expiratory gas has already been stripped of some oxygen and loaded with some carbon dioxide. Therefore, when the new breath reaches the alveoli where oxygen and carbon dioxide are exchanged with the blood, the new alveolar gas mixture is already different from atmospheric air.
Alveolar gases are different from atmospheric

8. Pulmonary Physiology Nasopharynx Cleaning Warming Humidification
Conducting Airways
Although related to a decrease in respiratory efficiency, anatomical dead space is essential for at lease two functions:
CLICK
1) the nasopharyngeal area is responsible for gas conditioning to insure that the gas reaching the viscera is at body temperature and saturated with water vapor, ….
…. and 2) the large airways conduct the gas to the thorax and distribute it to the lung regions.

9. Pulmonary Pathophysiology
Flushing reduces anatomical dead space
Reduced anatomical dead space compensates for increased physiological dead space
Because High Flow Therapy can eliminate nasopharyngeal dead space, this makes breathing more efficient even under normal conditions in healthy people. In people with lung disease, this reduction in anatomical dead space can compensate for increased physiologic dead space. This, in effect, raises the threshold where a patients would succumb to progressing lung pathology and require invasive ventilatory support.

10. Inspiratory Gas Conditioning
CLICK for animation
Precise gas warming and humidification is critical to support effective use of High Flow Therapy via nasal cannula. This animation shows how HFT purges that end-expiratory gas from the nasopharyngeal dead space during exhalation to facilitate ventilation of CO2, and how each subsequent breath contains more fresh gas from this internal reservoir during inspiration, making oxygenation more efficient.
In high flow therapy, wash out of dead space in the nasopharyngeal cavity is accomplished by a warm, humidified gas stream passing around the nasal chonchae and exiting through both the nose and mouth. This allows the area to become a reservoir for fresh gas. In the application of high flow therapy, Vapotherm recommends that nasal prongs be no larger than ½ the internal diameter of the nares and that the mouth be allowed to open. Under these conditions the nasopharynx can effectively be flushed without the development of concerning nasopharyngeal pressure.

11. Summation of High Flow Therapy
Importance in conditioning of breathing gases to body temperature and saturated with water vapor.
An effective tool to support spontaneous breathing that goes beyond conventional nasal cannula.
Works with your body’s respiratory anatomy and physiology to improve breathing efficiency through basic mechanisms.
A non-invasive means of respiratory support that is simple to apply and improves patient comfort.
In summary, with proper conditioning of breathing gases to body temperature and saturated with water vapor, high flow therapy emerges as an effective tool to support spontaneous breathing that goes beyond conventional nasal cannula.
High flow therapy works with your body’s respiratory anatomy and physiology to improve breathing efficiency through basic mechanisms. Therefore, high flow therapy is a non-invasive means of respiratory support that is simple to apply and improves patient comfort.

12. Summation of High Flow Therapy
Further education and information surrounding the Mechanisms of Action of High Flow Therapy
can be found at:
Vapotherm website (
Highflow website (
We’ve covered the basics of HFT, but there is much more on the topic including the importance of other mechanisms of action as well as specifics pertaining to gas conditioning and circuit design elements. For more information please see the other course in the Vapotherm Education center, at or the review paper by Dysart, Miller and colleagues [show ref in slide].
Key supporting literature includes:
Dysart et al. Respir Med 2009;103:
Frizzola et al, Pediatr Pulmonol 2011;46:67-74

13. High Flow Therapy with Heliox
Keeping the principles of high flow therapy in mind, we will now review how the incorporation of heliox in the therapeutic modality improves respiratory mechanics and how the physical properties of heliox are instrumental.

14. Heliox Review Helium was discovered in the late 19th century.
It is a biologically inert, noble gas that has many useful applications due to its physical properties such as low molecular weight and low density.
When mixed with oxygen for breathing applications to replace nitrogen as the balance or carrier gas, we have what’s know as heliox.
Dr. Barach began studying and advocating the use of Heliox for medical purposes in the 1930’s.
The low density of Helium is the physical property which makes Heliox ideal for certain medical applications.
Helium was discovered in the late 19th century. It is a biologically inert, noble gas that has many useful applications due to its physical properties such as low molecular weight and low density.
When mixed with oxygen for breathing applications to replace nitrogen as the balance or carrier gas, we have what’s know as heliox.
The first clinical use was in the 1920’s, to assist divers in avoiding decompression issues, and is still used in deep diving today because it is less compressible and non-toxic.
Dr. Barach began studying and advocating the use of Heliox for medical purposes in the 1930’s.
The low density of Helium is the physical property which makes Heliox ideal for certain medical applications.

15. Heliox Gas Density
If we take a careful look at the density of breathing gases, you can see here in the graph that air, which is 79% nitrogen and 21% oxygen, has a fairly high density of g/L. Now look at the density of helium, which is only g/L. So what happens if we replace the nitrogen in air with helium. Although oxygen still has a fairly high density of g/L, when 21% oxygen is mixed with 79% helium, as in what we refer to for simplicity as 80/20 heliox, we have a density of for the mixture which is much lower than air. You might think of this mixture as “thin air.”
The real differences are caused by substituting helium (0.179 g/L) for nitrogen. The oxygen contents don’t change in either air mixtures or Heliox mixtures, so the density of oxygen isn’t really that relevant. Also, why there is little value of using Heliox when you add a lot of supplemental oxygen; because the oxygen density becomes the controlling factor – neither the nitrogen nor the helium are at high enough concentrations to significantly affect the total gas density.
Nitrogen
Air
Helium
Oxygen
Heliox*
* 79% helium and 21% oxygen, commonly known as 80 /20 heliox

16. Effects of the Physical Properties of Heliox
Heliox decreases RAW in areas of turbulent flow
Reduced need for driving pressure means less physical effort (WOB)
How do the physical properties of Heliox make it ideal for medical use? It decreases airway resistance making in easier to breath.
Due to the structure of the nasopharyngeal cavity and the larger airway, gas flows can tend to be turbulent. In the absence of physical changes in anatomical structures, heliox decreases airway resistance in these areas of turbulent flow.
With reduced airway resistance, or in other words improved airway conductance, the driving pressure necessary to move gas through the respiratory system is decreased. This reduced need for driving pressure means less physical effort which is a reduction in the work of breathing. The reduction in the work of breathing for patients with acute respiratory exacerbations can mean the difference between being able to breathe themselves or requiring invasive measures.

17. How and where does a lower density gas reduce RAW?
How Heliox works
How and where does a lower density gas reduce RAW?
Relationship between Density and Resistance?
How do we apply Reynolds Number?
In the next few slides we’ll walk through the critical factors in how a lower density gas, such as heliox, decreases total airway resistance, and in what segments of the airways is this effect seen. To do this, we will introduce the relationship between gas density and resistance as well as the concept of Reynolds number which predicts where flow is turbulent versus laminar.

18. How Heliox works: Density and Resistance
Heliox works where flow is turbulent
“Heliox will increase flow rate [through the airways], not because it changes the flow from turbulent to laminar, but rather because in the large airways, the pressure differential needed to drive the flow will be less.”
-From Corcoran and Gamard, 2004
A misconception from some of the earliest literature on heliox use is that the effects of heliox on airway resistance is a result of making tubulent flow laminar. More exhaustive analyses have since lead to a better understanding how heliox works, and therefore under what conditions heliox application can be beneficial.
Corcoran and Gamard explain in a 2004 review paper that density is a factor in airway resistance when flow is turbulent, whereas density is not a factor when flow is laminar. Therefore, heliox works where flow is turbulent. In this regard, Heliox will increase flow rate, not because it changes the flow from turbulent to laminar, but rather because in the large airways, the pressure differential needed to drive the flow will be less.
Based on this reasoning, heliox holds more potential to reduce airway resistance on the large, turbulent areas of the respiratory tract, as opposed to the small airways where the flow is more likely to be laminar and thus unresponsive to changes in gas density.

19. How Heliox works: Reynolds Number and flow characteristics
Re= Reynolds Number
ρ = density
ν = velocity
r= radius
η = viscosity
Laminar Flow occurs at Re < 2000
Turbulent Flow occurs at Re > 2000
We can predict where flow is turbulent versus laminar or transitional by using Reynolds number. Reynolds number is a value calculated from properties of a gas, and the environment through which the gas travels, to predict the tendency for the various flow characteristics.
Laminar flow occurs at low Reynolds numbers, where viscous forces are dominant, and is characterized by smooth, constant fluid motion.
Turbulent flow occurs at high Reynolds numbers and is dominated by inertial forces, which tend to produce flow instabilities.
In this regard, note that with the same gas velocity and size of the conducting pathway, the density value, which is in the numerator of the Reynolds equation, can dramatically alter the flow characteristics. Therefore, using heliox does allow for the tendency of gas flow to be laminar more often, which will have an impact on total airway resistance. However, as we said previously, it is in the regions where flow stays turbulent that heliox has the greatest potential to decrease total airway resistance.

20. How Heliox works
So, as we’ve learned, heliox reduces total respiratory airway resistance by effecting resistance in the segments of the airways that, at least initially, are seeing turbulent flow. Based on the relationship between airway size and Reynolds number, turbulence is more likely in the upper and large airways. As it so happens, these larger upper airways are the segment of the respiratory tract that have the greatest airway resistance even in the healthy lung, and this is due to the overall lesser cross-sectional area as well as the turbulent flow characteristics.

21. How Heliox works Area of greatest effect Area of obstruction
Therefore, the way heliox works is not just to reverse the increase in resistance at a specific site of obstruction or change in airway tone, but rather by decreasing overall respiratory resistance, having its greatest impact on the turbulent upper region. Thus, the increased resistance in certain areas of the respiratory tree during an exacerbation of disease can be offset by a decreased resistance in the same as well as other areas of the system.
The net result is that total resistance is managed such that work of breathing does not become too great for the patients to maintain spontaneous breathing.
Net offset in RAW and WOB

22. Inhalation: Exhalation: How Heliox Works
Better tidal volume + distribution =
Oxygenation
Exhalation:
Better emptying without gas trapping = Ventilation
The effects of heliox can be multifactorial with respect to both inhalation and exhalation. By allowing for easier inhalation with better gas distribution, the patient can get oxygen into the alveoli. With improved exhalation and reduced gas trapping with is associated with a concomitant retention of CO2, heliox can provide for better ventilation. To this later point, remember that exhalation is normally a passive process with a fixed amount in lung recoil, and therefore a lesser resistance to flow translates to better lung emptying.

23. Clinical Applications of Heliox usage
Key Applications
Benefits
Asthma (severe)
Reduced airway resistance (improved laminar flow, lower density) Reduced work of breathing
Acute upper airway obstruction
Improved tidal volumes
Croup
Reduced insp/expiratory ratios
COPD exacerbations
Increased C02 clearance
Vent weaning
Improved homogeneity of gas distribution
Pulmonary Rehabilitation
Improved exercise tolerance
Aerosol drug delivery
Better deposition
Owing to this multifactorial approach, heliox has been used to treat a variety of respiratory disease processes effectively. This chart lists some major obstructive diseases and other situations where heliox can have utility, and the primary objective with each.
In asthma, it might be considered a primary goal to address the overall increase of work of breathing so that the patient does not fatigue and require mechanical ventilation before the medication can release the airway reactivity.
In an upper airway obstruction, improving tidal volumes might be the practical goal.
However, in croup improved gas flow can work towards restoring a normal ratio of inspiratory to expiratory time intervals
With COPD exacerbations, the improved exhalation can be very important for CO2 clearance.
In Vent weaning, heliox can help improve homogeneity of gas distribution by evening out the resistance within mid sized airways.
If we think about other opportunities for heliox use, in pulmonay rehabilitation the improved gas flow can help patients be able to perform more physical work and thus speed up the recovery process, whereas with aerosolized drug delivery studies have shown better drug deposition.

24. Important Heliox References: Core mechanics Evidence
Mechanics and energetics of breathing helium in infants with bronchopulmonary dysplasia
Wolfson et al. J Pediatr 1984, 104(5): 752-7
Mechanics study showing:
Decrease pulmonary resistance and work of breathing
Reduced risk of respiratory muscle fatigue
In these last slides we’ll look at some of the key evidence in the literature supporting the use of heliox.
In a paper by Wolfson and colleagues, they investigated the precise changes in airway mechanics associated with heliox breathing in neonates. They confirmed that in spontaneous breathing infants there was a marked reduction in pulmonary resistance associated with heliox breathing that resulted in a significant reduction in resistive work of breathing with no changes in minute ventilation. and that this reduction was associated with a reduced work of breathing. These authors discus how this reduced efforts and energy expenditure reduces the risk of respiratory muscle fatigue, and subsequently the need for mechanical ventilation.

25. Important Heliox References: Safety
Growth and development in a heliox incubator environment: a long-term safety study
Singhaus et al. Neonatology 2007, 91(1):28-35
rabbits pups raised in heliox environment compared to controls.
No difference in growth parameters or developmental milestones
Although already believed to be biologically inert, the most comprehensive study on safety with helium exposure was done by Singhaus and colleagues. These investigators raised rabbits in a complete heliox environment without exposure to air and found no differences in growth parameters or developmental milestones compared to those raised in a normal air environment.

26. Important Heliox References: Biological Impact
Heliox attenuates lung inflammation and structural alterations in acute lung injury
Nawab et al. Pediatr Pulmonol 2005;40:
Lung morphology showed improved distribution of heliox gas through the lung
Pro-inflammatory mediators and matrix remodeling proteins levels were significantly lower with heliox versus nitrogen-oxygen mix
In an interesting newer line of study, investigators such as Nawab and colleagues are showing reduced pulmonary inflammation when using heliox to ventilation versus air-oxygen mixture. Results from this animal study showed heliox resulted in an improvement in lung morphology as well as a dramatic decrease in pro-inflammatory mediators. Reports on other studies are forthcoming and show similar findings.

27. Important Heliox References: Clinical Outcomes
Blinded, RCTs in Acute Asthma
Heliox versus air-oxygen
Author / Data
# Patients
Key Findings
Rose 2002 36
Less dyspnea
Kress 2002 45
Improved FEV1
Kudukis 2002 18
PP, PEFR and DI improved
Carter 1996 11
FEF25-75 and PEFR%
Henderson 1999
205
PEFR% improved
Moving on to some of the clinical application and outcomes data. There is a fair bit of research in this area, and so here we review only the more important randomized controlled trials. Looking at the impact of heliox use in acute and severe asthma exacerbation, this table lists the five blinded, randomized controlled trials from the set of review papers published in Chest in 2003, authored by Ho and collegues and Rodrigo and colleague.
Note the consistency in improvements for dyspnea and ventilatory parameters with heliox compared to air-oxygen. All five of these studies favored the use of helium in acute asthma.
All in favor of Heliox

28. Important Heliox References: Clinical Outcomes
Prospective Randomized crossover trial with heliox in COPD (n = 19)
Jolliet et al. Crit Care Med Nov;27(11):2422-9
Heliox compared to air-oxygen
↓ Inspiratory / total time ratio (p < 0.05)
↑ PIFR (p < 0.01)
↓ PaCO2 (p < 0.01) and Dyspnea (p < 0.05)
Looking at the other important population of obstructive airway disease, there was one comprehensive published study identified from the 2009 Cochrane review This randomized crossover trial conducted by Jolliet and colleagues compared heliox to air-oxygen mixtures with a non-invasive pressure support in patients presenting with severe COPD exacerbations. Here again, the clinical outcomes data show improved breathing cycles by way of reduced inspiratory time to total breathing cycle time, with an associated increase in peak inspiratory flow rate. This improved breathing pattern resulted in improved ventilation where patients experience reduced PaCO2 and dyspnea while on heliox.

29. Summation – Heliox delivery
Cannula gas flow should exceeds a patient’s spontaneous inspiratory flow rate to inhale the precise gas mixture
The nasopharynx becomes an internal reservoir of heliox.
The effects of helium is not hampered by the entrainment of room air.
The therapeutic affect can be achieved using the minimally invasive interface.
I hope to have demonstrated to you that both HFT and heliox therapy are unique respiratory tool, and that they are well suited to work in conjunction with one another to reduce respiratory work and avoid more invasive modalities. The delivery of heliox by way of high flow nasal cannula presents many advantages over conventional methods:
By providing a nasal cannula gas flow that exceeds a patient’s spontaneous inspiratory flow rate, the patient inhales the precise gas mixture of heliox provided by the cannula without the entrainment of room air.
The nasopharyngeal region of the patient’s upper airway becomes an internal reservoir of heliox, making heliox delivery more precise and efficient.
The effects of helium balance gas on respiratory resistance is not hampered by the dilution of the helium gas by entrainment of room air.
The desired therapeutic affect can be achieved using the minimally invasive cannula patient interface.

30. Questions?