Safety and Efficacy of Heliox Delivery

1. FOCUS Fall Bally’s Las Vegas Oct. 1-3, 2013 Andy Brown RRT-NPS Clinical Product Manager Precision Medical Inc. Northampton, PA Safety and Efficacy of Heliox Delivery

2. Disclosure • Yes, I do like the Pittsburgh Steelers! • Sorry (I am from PA and lived in Pittsburgh) • I work for Precision Medical Inc. • We do manufacture and sell products for use with Heliox • I have been a Clinical Specialist with Bunnell • Not really a heliox ventilator • I have done research and published on the topic of Heliox

3. Why the Hindenburg? • A) Sick Joke • B) Helium is dangerous • C) OOPS

4. HelioxNot To Be Taken Lightly

5. History of Helium • Janssen is credited with its discovery in 1868 • Dr. Alvan Barach is considered to be the grandfather of heliox therapy • Dr. Barach established the use of a low-density gas therapy in 1934 • He continued to present its use in asthma until 1976 • “Remember to cure the patient as well as the disease”

6. History of Helium • Helium/Oxygen mixtures have been used in diving applications since 1938 • Its first true test came in 1939 in the salvage of the submarine “Squalus” at a depth of 240 ft. It has been used since then for dives up to 2000 ft. • Dr. Barach used a simple mouthpiece as well as tight fitting masks to administer heliox

7. Chemical Characteristics of Helium • Chemical symbol – He • Helium is the second lightest element in the atmosphere with a molecular weight of 4.003 and an atomic number of 2 • It is considered a rare gas with natural concentrations of 5 ppm • Helium is chemically inert, nontoxic, tasteless, and nonflammable

8. Chemical Characteristics of Helium • Helium has the lowest melting point of any element • Helium remains liquid down to absolute zero but can be solidified by increasing the pressure • Apart from hydrogen, helium is the most abundant element • The fusion of hydrogen into helium is the source of a hydrogen bomb’s energy • Helium exits the tissues faster than other gasses decreasing the tendency to develop “the bends”

9. Physics of Heliox • Density • Viscosity • Laminar flow • Airway resistance • Raw = ΔP/flow • Diffusibility • 80/20 = 1.81 • 70/30 = 1.59 • Varies inversely with the square root of density

10. Physics of Heliox • Helium is 2nd lightest element • When mixed with O2, reduces the density • GasDensity(kg/m3)Viscosity(µP) • Air 1.20 183 • 100% O2 1.33 204 • Heliox 70/30 0.52 199 • Heliox 80/20 0.40 198

11. m r = V Physics of Heliox • Density(symbol: ρ – Greek: rho) is a measure of mass per unit of volume. • The higher an object's density, the higher its mass per volume. The average density of an object equals its total mass divided by its total volume. A more dense object such as lead will have less volume than an equal mass of some less dense substance such as water. The SI unit of density is the kilograms/cubic meter (kg/m3) • where • ρ is the object's density (measured in kilograms per cubic meters) • m is the object's total mass (measured in kilograms) • V is the object's total volume (measured in cubic meters)

12. The Logic of Balloon Boy’s Flight Let’s have a MythBusters vote: A) Plausible Busted Confirmed

13. Laminar vs. Turbulent Flow • Laminar Flow • Flow characterized by smooth, parallel layers of fluid • Turbulent Flow • Flow characterized by mixing of adjacent fluid layers

14. Helium/Oxygen Mixtures • “Heliair” (80% helium and balance air) • Rarely used in medical applications • 80/20 Heliox (80% helium and 20% oxygen) • 70/30 Heliox (70% helium and 30% oxygen) • 60/40 Heliox (60% helium and 40% oxygen) • THE CHOICE IS UP TO YOU!!!

15. Helium/Oxygen Mixtures cont. • 100%oxygen has a density of 1.429 • 40% oxygen has a density of 1.32 • 80/20 heliox mixture has a density of 0.43 (@1/3 100% and 40% oxygen) • 70/30 heliox mixture has a density of 0.55 (@1/2 of 100% and 40%)

16. Helium/Oxygen Mixtures cont. • 80/20 heliox has a flowmeter conversion of 1.805 • 10LPM of 80/20 flow on an oxygen flowmeter equals a flow of 18LPM of 80/20 • 70/30 heliox has a flowmeter conversion of 1.586 • 10LPM of 70/30 flow on an oxygen flowmeter equals a flow of 16LPM of 70/30

17. Helium/Oxygen Mixtures • Tank duration factors must also be taken into account when heliox is being used • 80/20 heliox in a H cylinder has a factor equal to 2.50 • 70/30 heliox in a H cylinder has a factor of approximately of 2.70-2.80 • D(iameter)ISS/P(in)ISS/CGA considerations • Available in “Egan’s Fundamentals of Respiratory Care”

19. Word of Caution (NOW FOR THE SAFETY PART) • While heliox has considerable potential to benefit patients in various settings, the success of heliox therapy depends on the methods and devices used. Innovation has been key to introducing heliox into clinical practice, but the practice of modifying commercially available devices to function outside of their intended design constraints creates considerable risk and liability for the patient, clinician, and institution. • Only by understanding how helium affects devices and by becoming familiar with how a device or system performs with heliox can researchers and clinicians safely administer heliox. One of the best ways to minimize risk is to use devices that are designed for heliox and cleared by the Food and Drug Administration (FDA) for use with heliox, as they become available on the market. • 100% Helium should never be used. James Fink MSc RRT FAARC: June 2006 Respiratory Care • There are no known contraindications for the use of Heliox • Lung compliance issues (IHeAL Study)

20. IMPORTANCE of 510K • Establishments involved in the production and distribution of medical devices intended for marketing or leasing (commercial distribution) in the United States (U.S.) are required to register with the FDA. This process is known as establishment registration. Registration provides FDA with the location of medical device manufacturing facilities and importers. A registration fee is under consideration by Congress. • A 510k is a premarket submission made to FDA to demonstrate that the device to be marketed is at least as safe and effective, that is, substantially equivalent, to a legally marketed device • A 510k requires demonstration of substantial equivalence to another legally U.S. marketed device. Substantial equivalence means that the new device is at least as safe and effective as the predicate. • The holder of a 510k must have design control documentation available for FDA review during a site inspection. In addition, any changes to the device specifications or manufacturing processes must be made in accordance with the Quality System regulation (21 CFR 820) and may be subject to a new 510k.

21. ON LABEL VS. OFF LABEL • Put simply, FDA prohibits companies from marketing medical devices for uses that the federal agency has not approved. Off-label promotion comes in two forms—marketing a device that has not received FDA approval and promoting an approved device for an unapproved use. • Off-label promotion must not be confused with off-label use. The FDCA expressly states that FDA is not permitted “to limit or interfere with the authority of a healthcare practitioner to prescribe or administer any legally marketed device to a patient for any condition or disease within the legitimate health care practitioner-patient relationship.” That means physicians are free to use approved devices for unapproved uses—and, indeed, they frequently do.

22. Delivery Devices • Masks • Simple • Aerosol • Non-rebreathing • Most Common • High Flow Systems • Meets Patient’s Inspiratory Demand

23. Delivery Devices • Nasal Cannula • Conventional • H3 NC • Gaining popularity • Flows that approach the patient’s inspiratory demand • Evidence exists with pediatric patients and bronchiolitis

24. Delivery Devices • Hoods and Tents • NEVER • Helium’s Density • Layering of gasses within the space • (Helium balloons float right?) Meyers adapted from:

25. Delivery Devices • Blenders • First free standing heliox blender introduced in November 2009 • Blending of gasses in mechanical ventilation has been available for a few years • Avea (CareFusion) • SERVO-I (Maquet) • G5 (Hamilton) • eVent Medical

26. Delivery Devices • Monitors (Flow and Volume) • Generally differential pressure pneumotachs • Free standing monitors available • NICO • Incorporated into mechanical ventilators for volume monitoring

27. Delivery Devices • Nebulizers • Controversy exists in the literature as to use heliox as a carrying gas or to power the nebulizer with the gas • HOPE neb • Aeroneb PRO • Asthma Rescue Kit

28. Delivery Devices • Ventilators • Much research completed in the past as to determine ventilator compatibility • Approved devices • Avea • SERVO-i • Hamilton G5 • GE Aptaer

29. Delivery Devices • Heliox can generally be utilized with any oxygen administration device • Infants – nasal cannulas effective as well as masks or ventilatory adjuncts (CPAP or conventional mechanical ventilation) • Oxyhoods • Children and adults – high flow systems are necessary

30. Therapeutic/Diagnostic Benefits • Helium dilution for determining lung volumes • Upper airway obstruction • Laryngotracheobronchitis (croup) • Post-extubation stridor • FBO • Anatomical or structural anomalies

31. Therapeutic/Diagnostic Benefits • Lower airway obstruction • Asthma • Bronchiolitis • COPD • Use in aerosol therapy • Heliox powering nebulizer • Heliox as a carrier gas

33. Hazards of Heliox Use • Anoxia • Measurement of Volume • Amount of Medication • Temperature

34. Current Literature • Heliox Inhalation Therapy for Bronchiolitis in Infants • Cochrane Database Syst Rev. 2010 Apr 14;4:CD006915 • Randomized controlled trials (RCTs) and quasi-RCTs of heliox in infants with acute bronchiolitis (84 infants under the age of 2 with respiratory distress with bronchiolitis caused by RSV requiring PICU admission) • AUTHORS' CONCLUSIONS: Current evidence suggests that the addition of heliox therapy may significantly reduce a clinical score evaluating respiratory distress in the first hour after starting treatment in infants with acute RSV bronchiolitis. Nevertheless, there was no reduction in the rate of intubation, in the need for mechanical ventilation, or in the length of PICU stay. Further studies with homogeneous logistics in their heliox application are needed. Such studies would provide necessary information as to the appropriate place for heliox in the therapeutic schedule for severe bronchiolitis

35. Current Literature • Vocal Cord Dysfunction • Am Fam Physician. 2010 Jan 15;81(2):156-9 • Treatment of acute episodes includes reassurance, breathing instruction, and use of a helium and oxygen mixture (heliox). Long-term management strategies include treatment for symptom triggers and speech therapy

36. Current Literature • Heliox for Croup in Children • Cochrane Database Syst Rev. 2010 Feb 17;2:CD006822 • SELECTION CRITERIA: Randomized controlled trials (RCTs) and quasi-RCTs comparing the effect of helium-oxygen mixtures with placebo or any active treatment in children with croup. • MAIN RESULTS: Two eligible RCTs were included (22 intervention, 22 controls). Neither trial compared heliox inhalation with placebo. One study compared heliox with 30% humidified oxygen whilst the other compared it to 100% oxygen with additional racaemic epinephrine nebulization. There was no significant difference in change of croup score between intervention and control groups. • AUTHORS' CONCLUSIONS: At present there is a lack of evidence to establish the effect of heliox inhalation in the treatment of croup in children. A methodologically well-designed and adequately powered RCT is needed to assess whether there is a role for heliox therapy in the management of children with croup.

37. Current Literature • Growth and Development in a Heliox Incubator Environment: A Long-Term Safety Study • Neonatology. 2007;91(1):28-35. Epub 2006 Nov 10 • DESIGN/METHODS: Four-day-old rabbit pups (n = 27) were randomized into control (21% O(2); 79% N(2)) or heliox (21% O(2); 79% He) groups, then raised for 14 days at 26.7 degrees C and 50% relative humidity. Pups were euthanized on day 14, blood drawn and primary organs, diaphragm and gastrocnemius weighed and snap-frozen. Results: All pups thrived in both environments, achieving expected developmental milestones. There were no physiologically significant group differences in weight, growth factors, tissue weight, blood chemistry or muscle enzyme activity • CONCLUSIONS: No observed long-term differences in growth or development. Results demonstrated that long-term heliox exposure is safe in this rabbit model. These data suggest that heliox administration may provide time for pulmonary improvement in the BPD population, warranting appropriate clinical trials

38. Current Literature • A search of PubMed on Heliox therapy yields 352 results • Positive results for: • COPD • Asthma management • Upper airway obstructions • Nebulizing bronchodilators • Pulmonary rehabilitation • Negative results for: • COPD • Asthma management • Croup • Nebulizing bronchodilators • Lack of large enough patient enrollment • Poorly controlled studies

39. Current Literature • Heliox for the treatment of bronchiolitis seems to have some of the strongest evidence • Use of heliox as an adjunct or bridge to definitive therapy is successful • Trauma • VCD • Acute episodes of Respiratory Distress • It is another form of therapy in a Respiratory Therapist’s armamentarium • Common sense seems to lead to success • If a patient is not responding to therapy do not delay increasing the intensity of the therapy • Heliox therapy has fickle results in the literature • Properly designed studies and study populations • What are the measureable goals of the therapy? • Mortality • Intubation free days • Stay in the ICU • Decrease in WOB score

40. Inhaled Helium for the Treatment of Air Leak Syndromes IHeAL Study Presented at the Pediatric Academic Society Meeting 2006

41. IHeAL • Retrospective Case Matched • Randomized to Nitrogen (4) or Helium (5) • Inclusion • Evidence of PIE on CXR • Mechanically Ventilated • Unilateral or Bilateral • SpO2 • OI • Conclusion: Heliox therapy reduced PIE on CXR by @40 hours

45. Pre-Therapy

46. 72 hours Post Therapy

47. Heliox Therapy Conclusion • Literature is present on its use • Mainly small studies and anecdotal reports on its use in small airway obstruction and nebulizer use • Commonly used in treatment of large airway obstruction • Common sense and knowledge of potential benefits and side effects is encouraged on its utilization