1. High Flow Therapy (HFT) in the Pediatric Population
Brief introduction---”Hello Everyone, I’m **, a Clinical Specialist for Vapotherm”---and the focus off today’s talk is on high flow therapy and our technology in the pediatric population.

2. Agenda HFT Clinical Review Precision Flow Overview
Precision Flow Demonstration
Q & A
The goal of the presentation is to review:
- Outline the Mechanisms of Action of how High Flow Therapy works----what it’s actually doing physiologically to the airway.
- Discuss Patient Application----what types of patients will benefit from this therapy.
- Precision Flow Overview---a look at our core technology
- Questions and Answers

3. High Flow Therapy: Definitions
Flow rate that exceeds patient flow demands at various minute volumes
A method to achieve actual FiO2 of 1
Eliminate entrainment of ambient air
- Accomplished in the nasopharynx only with proper gas conditioning
Conventional cannula therapy limited by nasal damage
HFT becomes more than oxygen therapy
Combination of technologies to achieve optimal temperature, humidity and flow rate at the point of delivery
Let’s start out with “What is High Flow Therapy”. Quite simply put, and by definition of the AARC, high flow therapy is defined as flow rates that meet or exceed the patients inspiratory demand at various minute volumes.
In practice, HFT via nasal cannula is the application of conditioned breathing gas delivery to effect washout of the nasopharyngeal dead-space and support breathing effort.
Optimal outcomes with high flow therapy can only be accomplished with ideal conditioning of breathing gases, which is gas delivered at body temperature, and saturated with water vapor. With proper conditioning, higher gas flows can be used while avoiding mucosal damage, and provide optimal outcomes in the manner of improved respiratory efficiency with respect to both oxygenation and carbon dioxide ventilation.
It is only recently with a combination of new technologies in delivering heated/humidified breathing gases to patients that High Flow Therapy via nasal cannula has accomplished this. So, where do we start?

4. Flow First™ 5-20Lpm HFT Clinical Review
To start, high flow should be the first intervention a respiratory clinician makes when the situation calls for respiratory support for a spontaneously breathing patient. This means flow first in rescue situations in the ER or ICU, Flow first in maintenance situations, and flow first in weaning.
Clinically, it also means that high flow therapy allows the clinician to utilize flow, ahead of Fi02 to manage patients. The Flow First method contributes to a lot of variables that will become clear as we progress through this presentation.
As disease states progress…more invasive therapies are initiated. By implementing those more invasive modalities, patient interfaces include masks, a definite “fear factor” for children already in distress. In the following presentation, we will show you how to treat the symptoms of progressive disease processes with a simple nasal cannula, meeting or exceeding the patients inspiratory demand, increasing compliance of therapy while most importantly, in the Pediatric population, making them more comfortable and feeling at ease.

5. Continuum of Care: Old Model
Rescue
Weaning
Acuity
Mechanical
Ventilation
Bi-Level
Bi-Level
CPAP
CPAP
Through the progression of respiratory insufficiency, multiple therapies are initiated in an effort the alleviate symptoms and subsequently attempt to avoid more invasive therapies, such as mechanical ventilation. Arguably, there is a gap between the ability of simple oxygen to correct the problem and the initiation of pressure support therapies that take at least some control over respiratory volumes during breathing. These early pressure therapies induce anxiety and are very unpleasant for a patient, which can worsen their status by causing harder breathing in an already delicate balance of distress vs. fatigue. And, it’s not until bi-level therapy is initiated that an effect on CO2 can be anticipated.
Note that the curve for extuabtion/weaning is not a mirror image of the rescue curve. Once a clinician has full control over a patient’s respiration, the decision to extubate becomes challenging. You have to consider questions such as, “Have the patient's lungs improved to a point where they can oxygenate without requiring extreme physical work effort?,” and “Does the patient have the muscular integrity to support their own ventilatory needs?” In this regard, and considering the hazards of re-intubation, the clinician typically does not take high risks on extubating prematurely. A patient is typically extubated when their respiratory parameters indicate that they are well enough to need only minimal support, so the relative acuity scale shifts downward; however, it is still likely that simple oxygen therapy will, at least initially, not be enough.
General 02
Therapy
General 02
Therapy
Choice of Therapy 5 5

6. Continuum of Care: New Model
Rescue
Weaning
Acuity
Mechanical
Ventilation
Bi-Level
Bi-Level
CPAP
CPAP
High Flow
Therapy
High Flow therapy fills that gap, where a patient has not truly reached insufficiency and can be supported by a little more help than just some oxygen. This is valuable in both rescue and weaning paradigms.
However, this is not to say that CPAP and Bi-PAP don’t have a roll. In a rescue scenario, when a patient’s disease exacerbation progresses to the point where they are experiencing de-recruitment of lung tissue and/or no longer have the physical stamina to draw in adequate breath volumes, then pressure support is needed. In weaning, it is always desirable to have minimally invasive pressure support available if it can mean avoiding re-intubation. Plus, in scenarios such as following thoracic surgery, the pressure support is critical for acting against pulmonary edema. Therefore, CPAP and Bi-PAP will certainly always play critical rolls in the clinician’s armamentarium.
General 02
Therapy
General 02
Therapy
Choice of Therapy 6 6

7. at the point of delivery.
Control the Factors that Matter…
Combination of proprietary technology to achieve optimal:
Flow
Fi02
Temperature
Humidity
at the point of delivery.
So, what is required of a device to meet patient’s needs to deliver a safe and effective modality that makes an oxygen delivery system a more aggressive mode of therapy and enables to you to achieve better outcomes on higher acuity patients? Most importantly, how do we increase the success rate of optimal patient outcomes by decreasing the need for more invasive therapies?
INDIVIDUAL control of four primary factors which allows for oxygen therapy to be delivered at higher flow rates, thus allowing a simple therapy to function as a more aggressive modality: Flow, FiO2, Temperature and Humidity. As a clinician is able to individually AND most importantly, independently control those four factors, simple oxygen therapy evolves into a high flow, more effective yet least invasive therapeutic modality. As this simple therapy evolves, optimal patient outcomes become apparent.

8. High Flow Therapy: Mechanisms of Action
Flush Dead Space
CO2 Elimination
Oxygen Efficiency
Supports Inspiration
Cannula Flow > inspiratory
Work of Breathing
Why is it important to condition the gas to body temperature, pressure saturated? To accomplish the true mechanism of action of High Flow Therapy. Although some may believe that high flow therapy is unregulated CPAP due to the fact that some pressure inevitably develops, we believe it is not the most critical mechanism of action:
Remember earlier we defined what high flow therapy was; not a few extra liters, but rather a flow rate that exceeds patient demand. This creates a number of very important physiologic scenarios which elevates a nasal cannula to a more aggressive form of therapeutic modalities:
Flush dead space and therefore remove CO2 as well as making oxygen delivery more efficiency by way of an internal reservoir
Support inspiration by providing flow. This eliminates the inertia of gas movement through the resistance offered by the nasopharynx and allow for greater inspiratory flow for the same work effort
The gas conditioning that allows for HFT, also has it own impact on the mechanics of the lungs and airways, which include improving lung compliance and reducing airway resistance. Secretion mobilization is another important outcome of warm, saturated breathing gas delivery.
Humidify / Warm Airways
Mobilization of Secretions
Nasal comfort 8 8 8

9. Humidify / Warm Airways
Inspiratory Gas Conditioning
Nasopharynx is highly efficient at conditioning inspiratory gas
Anatomical Structure
Mucosal Architecture
However, before we start flushing the nasopharynx and support the WOB demands of our patients, we must first overcome meeting its efficiency at warming and humidifying inspiratory gas. Delivering high flows without matching BTPS could cause damage and expedite a disease state.
This efficiency is a result of both the large surface area created by the anatomical structure of the nasal cavity and the conchae, which brings the gas in close proximity to the walls of the cavity.
And of course, the architecture of the mucosal tissue…

10. Humidify / Warm Airways
As seen in the electron micrograph on the left, the nasopharynx is lined with tightly assembled, stratified squamous epithelial cells with microvilli. In addition to the squamous cells, ciliated cells help propel mucus and foreign debris to the back of the pharynx for expulsion.
As you can see in the high magnification panel on the right, the microvilli dramatically increase epithelial cell surface area to make the nasopharynx extremely efficient at warming and humidifying inspiratory gas. These microvilli may also serve functions in sweeping the air of foreign debris.
Given this architecture, the biggest limitation to conventional nasal cannula therapy is destruction of the nasal mucosa through cooling and dehydration with improperly conditioned breathing gas.
This is particularly important when delivering high levels of oxygen. Oxygen has a much greater thermal conductance than the nitrogen in room air, causing faster and more severe damage to the nasal tissues. This later point is even more significant with alternative therapeutic breathing gases such as heliox, where the thermal conductance is greater still.
Therefore, in the “first step” to ensure optimal patient outcomes utilizing high flow therapy, proper conditioning of the inspired gas to body temperature, pressure saturated is a vital component towards minimizing moving towards more invasive modalities.

11. Conditioning Prevents Injury
Humidify / Warm Airways
Conditioning Prevents Injury
Inadequate warming and humidification can cause:
Thickened Secretions
Decreased mucocilliary action
Thermal challenge
Bloody secretions
Lung atelectasis
No matter what the device, oxygen concentration or liter flow, humidification is critical for safe and effective delivery of respiratory gas. The lack of humidity can cause:
Thickened secretions – resulting in plugged airways
Decrease in mucocilliary action – hampering clearance of debris
Thermal challenge to the upper airway to adequately heat and humidify the gas – leading to excess energy expenditure and dehydration.
Bloody secretions – as a result of cellular damage
Also, later stages of progression may include atelectasis in the lung.
All of these symptoms contribute towards the patient possibly requiring more invasive therapies, such as CPAP/BiPaP or ultimately, intubation!

12. Inspiratory Gas Conditioning
Why BTPS?
Importantly, it is critical that HFT via nasal cannula be done with optimal warming and humidification. The level of flow that brings therapeutic benefit beyond simple oxygen supplementation, can support nasal mucosal function if the humidification is correct, but overwhelm nasal mucosa if humidification is inadequate.
This graph from Williams and colleagues shows how important proper humidification is to proper mucosal function. Significant deviations from BTPS on the x axis, which is 44 mg/l of water vapor, results in thick secretions and decreases in mucus transport velocity shown in the y axis. When the nasal mucosa is overwhelmed, the results can be cell damage contributing to lung injury seen as atelectasis.
Williams et al, 1996, Crit Care Med 24(11):

13. Flush Dead Space & Support Inspiration
Now that we have adequately conditioned the gas – we can look at the other mechanisms. Most importantly is the elimination of anatomical dead space by flushing out end-expiratory gas during expiration so each subsequent breath contains more fresh gas and less end-expiratory gas.

14. Pulmonary Physiology Oxygenation Ventilation PiO2 ~150 mmHg
Ambient Air
PiCO2 ~0 mmHg
Even under normal conditions in a healthy respiratory system, when fresh ambient air is mixed with end-expiratory air remaining in the anatomical dead space regions of the respiratory tract, alveolar gases are significantly different from ambient.
Alveolar oxygen tension is about 2/3 of ambient, and different from blood values by only a small margin due to a normal degree of anatomical shunt.
While there is virtually no carbon dioxide in ambient air, alveolar air has a carbon dioxide tension around 40 mmHg, equal to that of the blood.
PAO2 ~100 mmHg
Alveolar
PACO2 ~40 mmHg
PaO2 ~95 mmHg
Blood
PaCO2 ~40 mmHg

15. Pulmonary Physiology and Dead Space
Although related to a decrease in respiratory efficiency, anatomical dead space is essential for at lease two functions: 1) the nasopharyngeal area is responsible for gas conditioning to insure that the gas reaching the viscera is at body temperature and saturated, ….

16. Pulmonary Physiology and Dead Space
…. and 2) the large airways conduct the gas to the thorax and distribute it to the lung regions.

17. Pulmonary Pathophysiology
Now when we think about pulmonary pathophysiology, physiologic dead space in the lungs should normally be very small. However, with progressing lung disease, physiologic dead space increases as a result of increasing ventilation-perfusion mismatch secondary to dysfunctional alveolar units or gas trapping in obstructive diseases. Therefore, respiratory efficiency is reduced in cases of disease and patients need to work harder to keep alveolar gas concentrations adequate.

18. Pulmonary Pathophysiology
Eliminating nasopharyngeal dead space by flushing with fresh gas makes breathing more efficient even under normal conditions in healthy people.
In this regard, flushing nasopharyngeal dead space can counterbalance physiologic dead space, effectively raising the threshold were patients may succumb to disease and require more invasive ventilatory support.
Importantly, HFT does not treat disease, but rather improves respiratory efficiency related to dead space, allowing for a more functional reserve.

19. Flush Dead Space & Support Inspiration
Here is a look in a clinical model where a nasal cannula (on the left), at high flows, flushes out the dead space as opposed to a mask (on the right) which acts as an external reservoir and the patient’s inspiratory demand determines if the delivered gas arrives into the airway.
High nasal flow, unimpeded at mouth, fills the upper airways – storing O2 during exhalation and flushing CO2
High mask flow, impeded by pressure at the mouth - stores less O2 in the upper airways during exhalation and adds prosthetic dead space
Tiep, et al: Resp Care, 2002: High Flow Nasal vs High Flow Mask oxygen delivery: Tracheal Gas Concentrations Through an airway model

20. Mechanism of Action for HFT
Dead space washout
Supports CO2 ventilation
Enhances oxygenation
Matched inspiratory flow
Attenuates nasopharyngeal resistance
Adequate gas conditioning
Improves conductance and compliance
Reduces energy cost of gas conditioning
So lets review the mechanisms by which HFT works.
When appropriately conditioned, the use of high flows of respiratory gases does not overwhelm the mucosa and facilitates addition mechanism beyond basic oxygen therapy.
Research is now demonstrating that among these mechanisms are:
Dead space washout, which supports CO2 ventilation as well as oxygenation
Matched or exceeded inspiratory flow which attenuates nasopharyngeal resistance and facilitates inspiration effort
Adequate gas conditioning which improves pulmonary mechanical parameters and reduces the energy cost of gas conditioning

21. Mechanisms by Application
HFT DOES NOT TREAT A DISEASE, THE MECHANISMS TREAT SYMPTOMS
Oxygen
Flush
Humidity
Mild Pressure
RSV CF
RDS
Asthma
Its importantly to understand that HFT, like other forms of respiratory support, does not treat a disease, but it impacts symptoms. Much in the same way your cold medicine suppresses sneezing while the cold virus runs its course. Within various disease states, the combination of mechanisms that are most impactful vary based on the symptoms that are characteristic of that disease. Here is an example of how various mechanisms come into play during some of the major adult respiratory disease states.
Here are merely a few pediatric disease states and how the mechanisms of action treat the symptoms.
Can you think of other respiratory insufficiencies where the symptoms can be treated by HFT?

22. Is Cannula Size Important?
Platform A
Platform B
Premature
1.5
2.4
Neonatal
Infant
1.9
2.7
Intermediate Infant
Pediatric
3.7
Another crucial component to effectively delivering HFT via nasal cannula is the patient interface itself.
From the HFT device, through the circuit and finally the nasal cannula to the patient, how the conditioned gas is delivered to the patient will determine the effectiveness of the therapy, and ultimately, either the success or failure of it. The circuit carrying the flow to the patient must be designed to withstand excessive pressures within, to maintain such a high flow rate to the patient.
As the flow is delivered to the patient via the interface (in this case, the cannula), it is imperative, to meet the proposed mechanisms of action mentioned previously, the diameter of the nasal prongs should never occlude greater than 50% of the internal diameter of the nares. The common approach to reducing circuit pressures is to increase the internal diameter of the nasal prongs on a cannula. The actual nasal prongs are the specific location where the bottle neck occurs and there is the most resistance to flow. Think of increasing the prong size as opening the flood gate on the river dam; by widening the orifice the resistance to flow goes down and the water lever and associated pressure behind the dam will fall. Therefore, in HFT more flow can get through the cannula while producing less back pressure.
While this is an effective strategy in terms of reducing circuit pressures to protect the circuit, the problem with increasing the internal diameter of the nasal prongs is that it also increases outside diameter. The pictures shown here shows the outside diameters of HFT cannula nasal prongs from the product platforms of two different device manufacturers. The cannula in platform B has a prong size appreciably greater than the cannula from platform A.
So why is this an issue? Increasing the outside diameter of the nasal prongs gives a tighter cannula fit in the nose. This is important for two reasons. First, research shows that a smaller prong allows for better flush of the nasopharynx. Secondly, larger prongs impact airway pressure, because room for air to exhaust out of the nose around the prong is limited, and therefore these larger prongs are harder to breathe against.

23. Calculating Minimal Flow
Calculation for flow and effective FIO2 puts us at starting values 25 L/min for the typical adult, based on text-book values for respiratory parameters. This graph shows an extrapolation of the adult equation from Mosby’s Respiratory Care Equipment, 7th Edition, demonstrating HFT as flow rate that provides an effective FIO2 of 1 when administering 100% oxygen. In this regard, the AARC defines HFT as flows that exceed a patient’s inspiratory demand at various minute volumes.
But kids come in all shapes and sizes, so we have to consider a couple of factors when it comes Pediatric patients.
Extrapolated from equations in Mosby’s Respiratory Care Equipment, 7th Ed.

24. PEDS: VT are less, but rates are much greater
Calculating Flows
PEDS: VT are less, but rates are much greater
Breaths per Minute
Infant (0 – 1 yr)
Toddler (1 - 3 yrs)
Preschooler (3 - 6 yrs)
School Age (6 – 12 yrs)
Adolescent (12 – 18 yrs)
In the Pediatric population we are all mindful that the smaller the patient, the lower the tidal volumes. However, kids have a much faster respiratory rate, especially when they are in distress, which in turn means that their inspiratory time is much less. Therefore, even though tidal volumes are significantly less than for adults, inspiratory flow rates may not be so much less. In keeping with the AARC definition that flow rates in high flow therapy must meet or exceed a patient’s inspiratory demand, nasal cannula flow rates must meet or exceed this inspiratory flow. Vapotherms pediatric cannulae are designated for use with up to 20L/min of flow. Note that older and larger kids may be suited by the adult cannulae which offer a greater flow range, as long as the prongs do not occlude more than 50% of the nares.
Tidal Volume 6-8 ml/kg

25. Flow Requirements: Pediatrics
Younger than 6 yrs, more like an infant
Older that 6 yrs, more like an adult
Numa and Newth, 1996

26. Indications for Use: Indications: Contraindications:
Spontaneously breathing patients who are requiring supplemental oxygen therapy
Any patient who is on an oxygen mask that is: 1. Not compliant, 2. not improving, 3. Or has an increase in work of breathing
Post- extubation support or weaning from NPPV
Patients requiring supplemental heat & humidity for artificial airways
So we read the literal indications for use from the 510 k (FDA), which means Vapotherm is indicated for what is really a broad range of applications. So what does that mean in terms of patient selection
First, indications include
-Spontaneously breathing patients who are requiring supplemental oxygen therapy
-Any patient who is on an oxygen mask that is: 1. Not compliant, 2. Not improving, 3. Or has an increase in work of breathing
-Post extubation support or weaning from NPPV
-Patients requiring supplemental heat & humidity for artificial airways
On the flip side, there are actually not many contraindications.
-Patients not spontaneously breathing
-Patients that have a deviated septum
-Patients with severe facial trauma or disfigurement
These indications are general, without being case specific to alleviate any potential off-labeling (such as we cure RSV). Also it keeps the possibilities wide open.
Contraindications:
Patients not spontaneously breathing
Patients that have a deviated septum
Patients with severe facial trauma or disfigurement

27. Clinical References
Spentzas et al. - J Intensive Care Med 2009;24:323-8
- Children w/ Respiratory Distress treated with High Flow Nasal Cannula, Published Paper showing the pronounced physiologic improvements in 46 pediatric patients at Le Bonheur Children’s Hospital, Memphis, Tn. University of Tennessee Critical Care Division.
Byerly et al. - Burns 2006;32:121-5
- Demonstrates what effect the humidification can have on airway function, although they also reinforce the physiologic impact that flush and pressure have on respiratory function with RDS.
Hasani et al. - Chron Respir Dis 2008: 5, 81-6
- Although derived from adult patients, it shows mucocilliary clearance functions are dramatically improved with heated, humidified high flow cannula treatment. Patients with RSV and CF should be considered when looking at these results.
To Date there are many research papers and peer reviewed research available in nearly every major journal from neonatal to adult. If you visit our website at you will also find clinical based evidence supporting the mechanisms of action that we have reviewed today.

28. Precision Flow® Overview
Flow, FiO2, Temperature All In One
One Control, Easy To Use
Smart Technology
Robust Design w/ Limited Maintenance
Audio/Visual Alarm Functionality
Quick Start Up
No Disinfecting
Precision Flow® Integrates Humidification and Gas Blending in One Device

29. Main Unit - Front Panel Flow Display Oxygen Display
Temperature Display
Run, Standby Button
Alarm Mute and Display Dim
Setting Control Knob

30. Safety Features Battery Low, Charging Blocked Tube Alarm
Disposable Water Path Fault or Absent
Cartridge Fault
Water Out Alarm
High and Low Cartridge Indicators
Gas Supply Fault
System Fault Alarm

31. Disposable Patient Circuit (DPC)
The Precision Flow™ Disposable Patient Circuit (DPC) Consists of
Three Components:
1. Disposable Water Path (DWP)
2. Vapor Transfer Cartridge (VTC)
3. Patient Delivery Tube
30 Day on Single Patient
Available Low or High Flow Kits
Filter Membrane
Water
Spike
Cartridge
Sensors
Impeller
Heater Plate
Delivery Tube

32. Precision Flow® Overview
Vapor Transfer Cartridge:
Key to efficient, high performance humidification and gas conditioning
Also serves as filter--pore size much smaller than 0.05 microns
Patient Delivery Tube:
Patented triple lumen design
Design prevents rain-out
Keeps gas conditioned out to patient
Safer than traditional heater wire design

33. Indications for Use: 5-20Lpm
Spontaneously breathing patients who are requiring supplemental oxygen therapy
Any patient who is on an oxygen mask that is: 1. Not compliant, 2. not improving, 3. Or has an increase in work of breathing
Post extubation support or weaning from NPPV
Patients requiring supplemental heat & humidity for artificial airways
So we read the literal indications for use from the 510 k, which means Vapotherm is indicated for what is really a broad range of applications. So what does that mean in terms of patient selection
First, indications include
-Spontaneously breathing patients who are requiring supplemental oxygen therapy
-Any patient who is on an oxygen mask that is: 1. Not compliant, 2. Not improving, 3. Or has an increase in work of breathing
-Post extubation support or weaning from NPPV
-Patients requiring supplemental heat & humidity for artificial airways
On the flip side, there are actually not many contraindications.
-Patients not spontaneously breathing
-Patients that have a deviated septum
-Patients with severe facial trauma or disfigurement
These indications are general, without being case specific to alleviate any potential off-labeling (such as we cure RSV). Also it keeps the possibilities wide open. When we talk about evaluation best practices a little later, we will emphasize looking for these factors rather than getting bogged down waiting for that 'perfect' pneumonia patient or CHF patient.
Contraindications:
Patients not spontaneously breathing
Patients that have a deviated septum
Patients with severe facial trauma or disfigurement

34. Q & A