Safety and Efficacy of Heliox Delivery

Andy Brown RRT-NPS Clinical Product Manager

Precision Medical Inc. Northampton, PA

FOCUS FallBally’s Las VegasOct. 1-3, 2013

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

Why the Hindenburg?

A) Sick Joke B) Helium is dangerous C) OOPS

HelioxNot To Be Taken Lightly

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”

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

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

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”

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

Physics of Heliox

• Helium is 2nd lightest element• When mixed with O2, reduces the

density

Gas Density(kg/m3)Viscosity(µP)

Air 1.20 183100% O2 1.33 204Heliox 70/30 0.52 199Heliox 80/20 0.40 198

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)

mr V=

The Logic of Balloon Boy’s Flight

Let’s have a MythBusters vote:A) PlausibleB) BustedC) Confirmed

Laminar vs. Turbulent Flow

Laminar Flow– Flow characterized by

smooth, parallel layers of fluid

Turbulent Flow– Flow characterized by

mixing of adjacent fluid layers

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!!!

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%)

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

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”

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)

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.

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.

Delivery Devices

Masks Simple Aerosol Non-rebreathing

▪ Most Common▪ High Flow Systems▪ Meets Patient’s Inspiratory Demand

Delivery Devices

Nasal Cannula Conventional H3 NC

▪ Gaining popularity▪ Flows that approach the patient’s inspiratory

demand▪ Evidence exists with pediatric patients and

bronchiolitis

Delivery Devices

Hoods and Tents NEVER

Helium’s Density Layering of gasses within the space▪ (Helium balloons float right?)

Meyers adapted from:

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

Delivery Devices

Monitors (Flow and Volume)

Generally differential pressure pneumotachs

Free standing monitors available ▪ NICO

Incorporated into mechanical ventilators for volume monitoring

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

Delivery Devices

Ventilators

Much research completed in the past as to determine ventilator compatibility

Approved devices▪ Avea▪ SERVO-i▪ Hamilton G5▪ GE Aptaer

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

Therapeutic/Diagnostic Benefits

Helium dilution for determining lung volumes

Upper airway obstruction Laryngotracheobronchitis (croup) Post-extubation stridor FBO Anatomical or structural anomalies

Therapeutic/Diagnostic Benefits

Lower airway obstruction Asthma Bronchiolitis COPD

Use in aerosol therapy Heliox powering nebulizer Heliox as a carrier gas

Hazards of Heliox Use

Anoxia

Measurement of Volume

Amount of Medication

Temperature

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

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

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.

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

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

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

IHeAL StudyInhaled Helium for the Treatment of Air Leak Syndromes

Presented at the Pediatric Academic Society Meeting 2006

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

Pre-Therapy

72 hours Post Therapy

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