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DISCLOSURES Bayer Pharmaceuticals ARC Medical NEBULIZATION THERAPY IN INFANTS, CRITICALLY ILL AND IN THE ICU ARZU ARI PhD Associate Professor SELECTING THE RIGHT NEBULIZER SELECTING THE RIGHT NEBULIZER Principles of Aerosol Generation

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1 ARZU ARI PhD Associate Professor

NEBULIZATION THERAPY IN INFANTS, CRITICALLY ILL AND IN THE ICU

DISCLOSURES

Bayer Pharmaceuticals ARC Medical

SELECTING THE RIGHT NEBULIZER

Mazela & Polin. Eur J Pediatr 2011; 170: 433-444.

Jet Nebulizer Mesh Nebulizer Ultrasonic Nebulizer Pressurized gas forms a jet passing over a capillary tube that draws liquid formulation into the jet stream. Aerosol is produced by micropumping action of the mesh containing 1,000 funnel-shaped holes. Piezoelectric crystal converts an electrical signal into high-frequency vibrations, which create a standing wave in the medication to produce aerosol.

Principles of Aerosol Generation of Jet, Mesh and Ultrasonic Nebulizers Characteristics of Jet, Mesh and Ultrasonic Nebulizers

SELECTING THE RIGHT NEBULIZER

Mazela & Polin. Eur J Pediatr 2011; 170: 433-444.

Jet Nebulizer Mesh Nebulizer Ultrasonic Nebulizer Gas Flow Active Passive Passive Residual Volume Large Small Small Aerosol Temperature Low Ambient Ambient Efficacy (expressed as inhaled dose % of nominal dose) Lower Higher Mid

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2 Front-loaded versus Bottom-loaded Nebulizer

SELECTING THE RIGHT NEBULIZER

Smaldone et al. J Aerosol Med 2007; 20: Suppl 1: S66-S77.

Front-loaded versus Bottom-loaded Nebulizers

SELECTING THE RIGHT NEBULIZER

Smaldone et al. J Aerosol Med 2007; 20: Suppl 1; S66-S77.

Types of Interfaces used with Nebulizers:

Face Mask Hood Soother Mask High Flow Nasal Cannula

SELECTING THE RIGHT INTERFACE

Ari A. World Journal of Clinical Pediatrics 2016; 5(3): 281-287

The performance of face mask was affected by various factors:

Seal between face and mask Contour Flexibility Weight Dead volume

Janssens HM & Tiddens HA. J Aerosol Med 2007; 20(1):59-63. Smaldone et al. J Aerosol Med 2005; 18:354-363. Esposito-Festen et al. J Aerosol Med 2004; 17:1-6. Amirav I & Newhouse MT. Pediatrics Pulmonology 2008; 43:268-274.

FACE MASK

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The lack of face-mask seal leads to reduced aerosol

delivery.

Even small leaks around the face mask decrease

drug inhaled by infants more than 50%

FACE MASK

Janssens & Tiddens. J Aerosol Med 2007, 20: Suppl1: S59-S65

Contour

Refers to the shape of the leading edge of the mask that is in

direct contact with the child’s face.

Use of a mask with anatomical contours minimizes the risk of poor

placement as they are easy to apply.

Flexibility

Flexible masks are better tolerated by infants. Stiff masks will resist compression by the infant’s face so that the

reduction in the dead space will be potentially much less than with flexible masks.

Amirav I & Mandelberg A. Pediatr Pulmonol 2010; 45(3):221-223. Erzinger & Schueepp. J Aerosol Med 2007; 20(1): S78-83. Geller DE. J Aerosol Med 2007; 20(1): 100-108. Sangwan S Pediatr Pulmonol 2004; 37(5): 447-452.

FACE MASK

Weight

The lighter the mask, the easier it is for infants and/or

caregivers to handle and hold.

Dead Volume

Face masks with larger dead volume reduce aerosol delivery

to infants.

FACE MASK

Amirav et al. J Aerosol Med 2008;21(2):207-214. Amirav et al. J Pediatr 2005; 147(5):627-631.

HOOD

The hood is preferred by parents as it is better tolerated by

infants.

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Amirav et al. Pediatrics 2002

AEROSOL DEPOSITION WITH THE HOOD & FACE MASK IN INFANTS

Hood Face Mask 2.6% 2.4%

The hood is as efficient as the face mask in aerosol delivery It has minimal deposition at the infant’

’ ’ ’s eyes.

Amirav et al. J Aerosol Med 2008;21(2):207-214. Amirav et al. J Pediatr 2005; 147(5):627-631. Kugelman et al. J Perinatol 2006; 26:31-36.

HOOD

The likelihood of agitating infants and making them cry

with the use of hood for inhalation therapy is less than face masks.

Similar lung deposition was found with face-up and face-

down positions.

Face-side position had less facial-ocular deposition than

face-up position.

A new and innovative development of children oriented

drug delivery interface.

SOOTHER MASK

Reproduced with permission from InspirX.

It was designed to achieve therapeutic lung deposition

in infants by

Keeping babies calm with a pacifier during aerosol therapy Eliminating their discomfort, fear and cry with face mask Improving compliance to aerosol treatments in infants Lung deposition with the Soother Mask was similar to that

with the conventional face mask.

SOOTHER MASK

Amirav et al. BMJ Open 2014; 4: e004124. Amirav et al. J Aerosol Med 2014; 27: 272-278. Amirav et al. Arch Dis Child 2012: 97: 497-501.

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Objective: To compare heliox with oxygen in aerosol drug delivery

using a pediatric high flow nasal cannula (HFNC).

Methods:

In-vitro lung model Gases: 100% Oxygen and 80/20% Heliox Flow rates: 3 L/min and 6 L/min Albuterol sulfate through a pediatric HFNC.

Ari A, Harwood R, Sheard M, Dailey P, Fink J. Pediatric Pulmonology 2011; 46(8): 795-801

HIGH FLOW NASAL CANNULA

Ari A, Harwood R, Sheard M, Dailey P, Fink J. Pediatric Pulmonology 2011; 46(8): 795-801

HIGH FLOW NASAL CANNULA

2 4 6 8 10 12 14

Heliox Oxygen

% Inhaled Dose

3 L/min 6L/min

Heliox increased aerosol delivery more than oxygen. Reducing flow rate that is used with heliox and oxygen

increases aerosol drug delivery in children.

Objective: To compare aerosol

delivery via HFNC, bubble CPAP and SiPAP in a model of spontaneously breathing preterm.

Methods:

In-vitro model of a preterm infant Vt: 9 mL, RR: 50 bpm, Ti: 0.5 sec. Albuterol sulfate (2.5 mg/0.5 mL) The mesh nebulizer was placed

near the patient or prior to the humidifier.

Sunbul F, Fink JB, Ari A. Pediatric Pulmonology 2015; 50(11): 1099-1106.

HFNC, BUBBLE CPAP, SiPAP HFNC, BUBBLE CPAP, SiPAP

HFNC Bubble CPAP SiPAP P value

Proximal to the patient (µg)

22±6.5 17±4.0 14±4.9 0.101

Distal to the patient (µg)

32±4.5 30±6.1 19±2.7 0.002

P value

0.43 0.03 0.13

Inhaled Mass (µg) of Albuterol Deposited Distal to the Trachea

Sunbul F, Fink JB, Ari A. Pediatric Pulmonology 2015; 50(11): 1099-1106.

Aerosols can effectively be delivered with HFNC, bCPAP & SiPAP. Delivery efficiency of HFNC is better than bCPAP and SiPAP. Placement of the nebulizer prior to the humidifier increased deposition

with all devices.

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Murakami et al. Ann Allergy 1990; 64:383-387.

CRYING QUITE BREATHING

CRYING KILLS LUNG DEPOSITION

Erzinger et al. J Aerosol Med 2007 Suppl S78 – S84. NON-TIGHTLY FITTED FACE MASK Nebulizer TIGHTLY FITTED FACE MASK Screaming during Inhalation Nebulizer TIGHTLY FITTED FACE MASK Quite Breathing Nebulizer

0.3% 1.4% 8.2%

SCREAMING KILLS LUNG DEPOSITION

A technique that is used by placing a nebulizer within a

distance from the child and directs aerosol plume towards the patient’s face

Commonly used for crying babies & uncooperative children Aerosol deposition decreases as the distance from the device

to the child’ ’ ’ ’s face is increased.

It is less efficient compared with face mask. Using blow-by should be discouraged.

Rubin BK. Respir Care 2007; 52(8): 981. Lin et al. Respir Care 2007; 52(8): 1021-1026. Restrepo et al. Respir Care 2006; 51(1): 56-61.

BLOW-BY

Esposito et al. Chest 2006: 130: 487-492. Janssens et al. J Aerosol Med 2003; 16: 395-400. Everard ML. Arch Dis Child 2000; 37: 451-459. Iles et al Arch Dis Child 1999; 81:163-165. Ari A. A Guide to Aerosol Delivery Devices for Respiratory Therapists. 2009: AARC.

HOW TO DELIVER AEROSOLS TO DISTRESSED AND CRYING BABIES

Don’t agitate the infant Positive reinforcement to hold the mask firmly against

the child’s face

Play activities Parental education & support

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Janssen JM et al. J Aerosol Med 2003, 16: 4: 395-400

Typical breathing pattern of a 10-month-old child while

IS ADMINISTRATION DURING SLEEP AN ALTERNATIVE?

Awake Asleep

Janssen JM et al. J Aerosol Med 2003, 16: 4: 395-400

Comparison of lung dose for pMDI/spacer with awake

and asleep breathing patterns of 18 children.

IS ADMINISTRATION DURING SLEEP AN ALTERNATIVE?

The type of nebulizer affects the lung dose

Mesh nebulizers are superior to jet nebulizers

Increasing flow rate decreases aerosol delivery

Aerosol deposition with jet nebulizers was 4.8%, 3.7% and 2.7% at

5, 6.5 and 8 L/min.

Breath-synchronized nebulization may improve drug delivery

compared with continuous nebulization.

Nebulizer should start generating aerosol early in the inspiration

Nebulizers should be placed on the inspiratory arm of the circuit

Dubus et al. Pediatr Res 2005; 58(1): 10-14. Turpeinen & Nikander Respir Care 2001; 46(1):43-48. Nikander et al. Pediatr Pulmonol 2000; 29:120-126.

AEROSOL DRUG DELIVERY DURING MECHANICAL VENTILATION

Aerosol delivery during HFOV is effective in neonates. Efficiency of mesh nebulizers is greater than jet nebulizers during HFOV Drug delivery in proximal position was nearly threefold greater during

HFOV than during conventional ventilation.

AEROSOL DELIVERY DURING HFOV

DiBlasi et al. Pulm Circ 2016; 6(1): 63-69. Fang et al. J Aerosol Med 2016; 29(5):447-453. Siobal & Hess. Respir Care 2010; 55:144-157.

Author Drug Pattern Placement Device Drug Dose% DiBlasi Iloprost Neonate Prox/Distal VMN P:30% D:1% Fang Salbutamol Neonate Proximal VMN/JN VMN: 8-17% JN: 0-3% Siobal Albuterol Neonate Proximal VMN 18%

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8 SUMMARY

Selecting the right nebulizer Jet, Mesh or Ultrasonic Nebulizer Selecting the right interface Face Mask, Hood, Soother Mask, High Flow Nasal Cannula What to do in crying and distressed babies Calm the baby down Positive Reinforcement, Play Activities, Parental Education and Support Deliver aerosols during sleep, if possible How to deliver aerosolized medications during mechanical vent Type and placement of nebulizer, Breath-synchronized nebulization How to deliver aerosols during high frequency oscillatory ventilation Nebulizer type and placement in the ventilator circuit at the airway.