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High Velocity Nasal Insufflation An Important Therapeutic Approach for Use in the Emergency Department Presented by Vapotherm Accredited for 1 CEU by the American Association for Respiratory Care Provider approved by the California Board of Registered Nursing, Provider Number CEP16476, for 1 contact hours Disclosure Bernadette Zelaya, RRT Area Clinical Manager Employee of Vapotherm, Inc. Learning Objectives Current therapeutic modalities used in the management of undifferentiated respiratory distress Likely mechanisms of action for high velocity nasal insufflation The differences between high velocity & high flow Evidence supporting the utility of high velocity nasal insufflation as an alternative to NIPPV How to implement HVNI in your emergency department 1

I Can t Breathe Ø Patient in tri-pod position Ø Increased work of breathing Ø Bilateral wheezing Ø Wet Cough Ø Known Frequent Flyer What do the blood gases show? HR RR ph PaCO2 PaO2 HCO3 SaO2 124 36 7.28 74 78 34 93 What respiratory modality will you use? NIPPV?? Application of NIPPV NIPPV is the current first line ventilatory therapy for most undifferentiated respiratory distress presenting in the ED Pressure-based therapy to help manage ventilation Compared to intubation, NIPPV: Improved mortality Greater patient comfort Reduced cost of care 2

Not Every Patient Wants to Wear the Mask Patient dissatisfaction Feelings of claustrophobia, anxiety Nasal congestion Skin Breakdown Clinician frustration Time spent fitting the mask Struggling with the patient for compliance What do you do? Elevate the acuity of care: Sedation Intubation More expensive care area 33% of NIPPV Failure Attributed to Mask Intolerance Is there another effective option? Carron M et al, Complications of non-invasive ventilation techniques: a comprehensive qualitative review of randomized trials, British Journal of Anaesthesia, 110 (6): 896 914 (2013). 3

A Viable Alternative to NIPPV Tool to manage the signs and symptoms associated with respiratory distress, including hypercapnia, hypoxia and dyspnea. Small bore nasal cannula provides a more comfortable experience for the provider and the patient High Velocity Nasal Insufflation (Hi-VNI) is demonstrated to be a good tool for treating respiratory distress. The mechanisms of action for Hi-VNI Heated Humidification of inhaled gas Warm, humidified gas may mobilize secretions to open congested airways and promote airway health. Increases Mucous Clearance Increases Airway Conductance Inspiratory Flow Decrease inspiratory resistance (work of breathing) and allow patients to breathe in more supplemental oxygen and humidified gas. Decreases Work of Breathing Increases Supplemental Oxygen High Velocity Flows Flush Upper Airway Deadspace Washout of Upper Airways Reduces Dead Space Reduces Rebreathing of Gas High in CO2 Positive Airway Pressure The high flow rate create mild distending pressure as the patient exhales against the incoming flow. Increases Mean Airway Pressure Increases Gas Exchange Optimally heated & humidified gas via a small-bore nasal cannula flushes dead space of expiratory gas, creating a reservoir that facilitates oxygenation & alveolar ventilation 4

Respiratory Physiology and Ventilation Ventilation Efficiency Alveolar Ventilation At least 30% of inspired tidal volume is anatomical dead space At start of inspiration anatomical dead space is filled with expiratory gas, which is oxygen depleted and high in CO 2 Dead-space volume and gas composition impact ventilatory efficiency Minute Ventilation = Tidal Volume x Respiratory Rate Alveolar Ventilation = (Tidal Volume Dead Space) x Resp. Rate = 0 Alveolar ventilation improves with a reduction in dead space volume independent of tidal volume and respiratory rate HVNI purges the anatomical dead space of pooled exhaled CO 2 so that the subsequent breath contains more fresh gas and less endexpiratory gas How is VELOCITY achieved? & How does this compare to HIGH FLOW? 5

Velocity and Flow Velocity, at a constant volume of flow, varies inversely with the cross sectional area of a tube Hi-VNI Technology delivers gas in a similar way using a smaller cannula and circuit design. Prong Size Dictates Flow Velocity Gas velocity impacts efficiency of expiratory gas flush from the dead space. Volume of Flow = 5 L/min 5 L/min 5 L/min Vent Humidifier Adapted for HFNC Hi-VNI Technology Velocity = 16.4 cm/sec A = 5.08 cm 2 Velocity = Distance/Time From Kacmarek, Robert M., James K. Stoller, Albert J. Heuer, and Donald F. Egan. Egan's Fundamentals of Respiratory Care. St. Louis, MO: Elsevier/Mosby, 2013. Print. Velocity = 32.8 cm/sec A = 2.54 cm 2 Small-Prong Cannula- Flush: 2.2 Seconds Travel Time (sec) 0 3 Note: CFD model assumes an open mouth. Large-Bore Cannula- Flush: 3.6 Seconds 6

Prong Size and Flow Comparison Time to Flush is a Function of Respiratory Rate Prong Size Also Dictates Efficiency of Expiratory Gas Egress Expiratory Phase (seconds) 3 2.5 2 1.5 1 0.5 0 Adult Respiratory Distress 12 16 20 24 28 32 36 40 44 48 52 56 60 The small-bore cannula allows greater opening for expiratory gas egress Large-bore Low Velocity Inner Diameter: 5.4mm Nares Simulated Cannula Small-bore High Velocity Inner Diameter: 2.7mm Small-Prong Cannula Large-Bore Cannula Respiratory Rate 7

Velocity (m sec-1) Hi-VNI Technology can deliver gas >3x the velocity of humidifiers adapted for HFNC. 60 50 40 30 20 10 Humidified Breathing Gas Supports Mucosal Function What is Optimal Humidification? The balance between avoiding condensation at low flow rates & providing sufficient humidity at higher flow rates * How it s delivered to the patient is as important as how it is created Optimally Humidified, Energetically Stable Vapor How is the vapor created? 0 10 20 30 40 50 60 Volumetric Flow (L min-1) Hi-VNI Technology Humidifier Adaptedfor H FN C Is More Always Better?? Adapted from: Williams, Robin; Rankin, Nigel; Smith, Tony; Galler, David; Seakins, Paul, Relationship between humidity and temperature of inspired gases and the function of airway mucosa, Critical Care Medicine. 24(11):1920-1929, November 1996. 8

Delivered All the Way to the Patient Warm water Mitigating Rainout Although this study represents the outcomes for one patient at Athens Regional Medical Center, individual results may vary. Breathing gas Warm water Vapotherm believes this is a powerful example of the effect HVNI can have in the Emergency Department Breathing gas Flow Patient Case Study - Disclaimer Return Cross-section of tubing Heated Wire- radiating Water Jacket- insulating 9

Patient Case Study Initial ABGs Patient History and Presentation Patient Response HR RR ph PaCO2 PaO2 HCO3 SaO2 124 36 7.28 74 78 34 93 A 60 year-old patient with history of COPD, having been intubated in the past month for a COPD exacerbation, arrived in the Emergency Department at Athens Regional Medical Center. Initial assessment noted tachypnea with nasal flaring and purse lipped breathing, as well as bilateral wheezing and wet cough. ABG Drawn and Hi-VNI Initiated at 25 L/min 60% FiO2 RR quickly dropped ph Increased PaCO2 Decreased Acute Respir. Acidosis w chronic respir. failure NIV was ordered but not initiated; HVNI was started at 25 L/min with an FiO2 of 60%. An ABG was drawn upon immediate application of HVNI and 44 minutes after initiation. Hi-VNI avoided an ICU admission and more invasive respiratory modalities 10

Randomized Controlled Multi-Center Trial High-Velocity Nasal Insufflation in the Treatment of Respiratory Failure: A Randomized Clinical Trial Doshi, P., et al., Annals of Emerg Med. 2017 e-pub ahead of print First RCT of HVNI to include Undifferentiated Respiratory Failure, including Hypercapnia Doshi et al, HVNI in the Treatment of Respiratory Failure, Ann of Emerg Med, The following materials describe certain outcomes in relation to the use of Vapotherm s Hi-VNI Technology, but individual results may vary. Practitioners should refer to the full indications for use and operating instructions of any products referenced herein before prescribing them. Hypothesis / Methods HVNI is non-inferior to NIPPV in the treatment of undifferentiated respiratory failure Prospective multi-centre RCT of two methods of ventilatory support using a non-inferior design Sites : 3 community, 2 academic Emergency Departments Doshi et al, HVNI in the Treatment of Respiratory Failure, Ann of Emerg Med, Patients Inclusion: >18 years, in Acute Respiratory Failure Adults presenting to ED requiring escalation to NIPPV in judgement of clinical team Exclusion: Suspected drug overdose Cardiovascular instability (hypotension req Tx) End stage cancer, life expectancy < 6mo Significant respiratory depression / GCS score <9 Cardiac or respiratory arrest / emergent intubation Known/suspected CVA or STEMI Patients with increased risk of aspiration (NIPPV contraindication) Doshi et al, HVNI in the Treatment of Respiratory Failure, Ann of Emerg Med, 11

Endpoints Primary Endpoint Treatment Failure Failure requiring Intubate / Mechanical Ventilation Failure of primary assignment including crossover to other arm Secondary Endpoint Ability of HVNI v NIPPV to affect indices of breathing, including PCO2, RR, HR, SpO2 Patient perception of dyspnea and discomfort Treating physicians perception of efficacy at end of treatment period Disposition of patient and length of stay Doshi et al, HVNI in the Treatment of Respiratory Failure, Ann of Emerg Med, Primary Outcomes HVNI is non-inferior to NIPPV for the treatment of adult ED patients in type I and II respiratory failure due to various causes Initial Randomization HVNI NiPPV % Intubated in 72 Hours 0 5 10 15 20 25 Used from Doshi et al, HVNI in the Treatment of Respiratory Failure, Ann of Emerg Med, Primary Outcomes HVNI All-cause Arm Failure (incl. Intubation) is non-inferior to NIPPV for patients presenting in the ED with undifferentiated respiratory distress HVNI NIPPV All Cause Arm Failure 0% 5% 10 % 15 % 20 % 25 % 30 % 35 % 40 % Intubation Rate Used from Doshi et al, HVNI in the Treatment of Respiratory Failure, Ann of Emerg Med, 12

Secondary Outcomes Markers of Ventilatory Effect no significant difference between HVNI & NIPPV, with comparable change over time (HR, RR SpO 2, PCO 2, BORG) Patient Characteristics Discharge Diagnosis 33% COPD/Hypercapnia, 20% CHF, 15-20% Pneumonia, 28% hypoxic / mixed respiratory failure Patient Discharge Diagnosis (n=204) Acut e Hype rca pnic Failure AECOPD Physician Perception Physician Perception of Patient Comfort, Patient Response, Simplicity favours HVNI Physician Perception of Need for Monitoring & Technical complexity not different Mix ed Hyp erc apn ic/hypo xem ic Fa ilur e Asthma Acut e Decomp He art Failure Pneumonia/Sepsis Doshi et al, HVNI in the Treatment of Respiratory Failure, Ann of Emerg Med, Acut e Hypoxemic Fa ilure Doshi et al, HVNI in the Treatment of Respiratory Failure, Ann of Emerg Med, Doshi et al, HVNI in the Treatment of Respiratory Failure, Ann of Emerg Med, 13

Why is this Important? Implementing an HVNI Emergency Department Protocol 14

Requirements for Effective Therapy Who are the right Patients? Assess Patient Condition Nares are not obstructed Adequate flow and velocity to flush dead space Patient is spontaneously breathing Facilitates CO2 ventilation by reduction of dead space Signs and Symptoms General Dyspnea Hypercapnia Hypoxemia Increased cardiac workload Increased Work of Breathing Conditions Acute COPD Exacerbation Mild/Moderate Congestive Heart Failure Asthma Pneumonia Bronchitis Bronchiolitis (RSV) Influenza Assess these parameters to determine therapy initiation: PaO2 < 80 mmhg SaO 2 < 90% PaCO2 > 45 mmhg Tachycardia Tachypnea Is the patient Hypoxemic? Is the patient Hypercapnic? 15

Starting Settings Titrate to Effect Start Flow High and Go Low HVNI is a De-Escalation Therapy Hypoxemia Flow: 35 L/min FiO2: 100% Temp: 37C Hypercapnia Flow: 35 L/min FiO2: 50% Temp: 37C These guidelines are based on assessment of peer-reviewed published literature, physician interviews, and physiological modeling. Providers should refer to the full indications for use, operating instructions, and/or prescribing information of any products referenced before exercising their independent Choose the Appropriate Interface Cannula should be sized not to occlude greater than 50% of the nares Allow the system to reach at least 33 before connecting delivery tube to the cannula Summary HVNI flushes expiratory gas from the dead space to facilitate oxygenation and improve ventilation efficiency HVNI is optimally humidified to mobilize secretions and make the therapy more comfortable for patients HVNI may be used in the Emergency Department to manage patients with the signs and symptoms of respiratory distress in adult patients 16

Questions? Thank You! 17