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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

  1. 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 of Jet, Mesh and Ultrasonic Nebulizers Characteristics of Jet, Mesh and Ultrasonic Nebulizers Jet Nebulizer Mesh Nebulizer Ultrasonic Nebulizer Gas Flow Active Passive Passive Residual Large Small Small Volume Jet Nebulizer Mesh Nebulizer Ultrasonic Nebulizer Aerosol Low Ambient Ambient Temperature Pressurized gas forms Aerosol is produced by Piezoelectric crystal Efficacy a jet passing over a micropumping action of converts an electrical (expressed as capillary tube that the mesh containing signal into high-frequency inhaled dose draws liquid 1,000 funnel-shaped vibrations, which create a Lower Higher Mid % of nominal formulation into the holes. standing wave in the dose) jet stream. medication to produce aerosol. Mazela & Polin. Eur J Pediatr 2011; 170: 433-444. Mazela & Polin. Eur J Pediatr 2011; 170: 433-444. 1

  2. SELECTING THE RIGHT NEBULIZER SELECTING THE RIGHT NEBULIZER Front-loaded versus Bottom-loaded Nebulizers Front-loaded versus Bottom-loaded Nebulizer Smaldone et al. J Aerosol Med 2007; 20: Suppl 1: S66-S77. Smaldone et al. J Aerosol Med 2007; 20: Suppl 1; S66-S77. SELECTING THE RIGHT INTERFACE FACE MASK The performance of face mask was affected Types of Interfaces used with Nebulizers: by various factors: � Face Mask � Seal between face and mask � Hood � Contour � Soother Mask � Flexibility � High Flow Nasal Cannula � 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. Ari A. World Journal of Clinical Pediatrics 2016; 5(3): 281-287 Esposito-Festen et al. J Aerosol Med 2004; 17:1-6. Amirav I & Newhouse MT. Pediatrics Pulmonology 2008; 43:268-274. 2

  3. FACE MASK FACE MASK direct contact with the child ’ s face. � The lack of face-mask seal leads to reduced aerosol � Contour � Refers to the shape of the leading edge of the mask that is in delivery. � Even small leaks around the face mask decrease � Use of a mask with anatomical contours minimizes the risk of poor drug inhaled by infants more than 50% 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. Janssens & Tiddens. J Aerosol Med 2007, 20: Suppl1: S59-S65 FACE MASK HOOD � The hood is preferred by parents as it is better tolerated by infants. � 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. Amirav I & Mandelberg A. Pediatr Pulmonol 2010; 45(3):221-223. Erzinger & Schueepp. J Aerosol Med 2007; 20(1): S78-83. Amirav et al. J Aerosol Med 2008;21(2):207-214. Geller DE. J Aerosol Med 2007; 20(1): 100-108. Amirav et al. J Pediatr 2005; 147(5):627-631. Sangwan S Pediatr Pulmonol 2004; 37(5): 447-452. 3

  4. AEROSOL DEPOSITION WITH THE HOOD & HOOD FACE MASK IN INFANTS � The hood is as efficient as the face mask in aerosol delivery � It has minimal deposition at the infant ’ ’ s eyes. ’ ’ � The likelihood of agitating infants and making them cry with the use of hood for inhalation therapy is less than face masks. Face Mask Hood � Similar lung deposition was found with face-up and face- down positions. � Face-side position had less facial-ocular deposition than face-up position. Amirav et al. J Aerosol Med 2008;21(2):207-214. 2.6% 2.4% Amirav et al. J Pediatr 2005; 147(5):627-631. Kugelman et al. J Perinatol 2006; 26:31-36. Amirav et al. Pediatrics 2002 SOOTHER MASK SOOTHER MASK � A new and innovative development of children oriented � It was designed to achieve therapeutic lung deposition drug delivery interface. 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. Amirav et al. BMJ Open 2014; 4: e004124. Amirav et al. J Aerosol Med 2014; 27: 272-278. Reproduced with permission from InspirX. Amirav et al. Arch Dis Child 2012: 97: 497-501. 4

  5. HIGH FLOW NASAL CANNULA HIGH FLOW NASAL CANNULA 14 � Objective: % Inhaled Dose 12 � To compare heliox with oxygen in aerosol drug delivery 10 using a pediatric high flow nasal cannula (HFNC). 8 3 L/min 6 6L/min � Methods: 4 � In-vitro lung model 2 0 � Gases: 100% Oxygen and 80/20% Heliox Heliox Oxygen � Flow rates: 3 L/min and 6 L/min � Heliox increased aerosol delivery more than oxygen. � Albuterol sulfate through a pediatric HFNC. � Reducing flow rate that is used with heliox and oxygen increases aerosol drug delivery in children. Ari A, Harwood R, Sheard M, Dailey P, Fink J. Pediatric Pulmonology 2011; 46(8): 795-801 Ari A, Harwood R, Sheard M, Dailey P, Fink J. Pediatric Pulmonology 2011; 46(8): 795-801 HFNC, BUBBLE CPAP, SiPAP HFNC, BUBBLE CPAP, SiPAP Inhaled Mass (µg) of Albuterol Deposited Distal to the Trachea � Objective: To compare aerosol delivery via HFNC, bubble CPAP and HFNC Bubble CPAP SiPAP P value SiPAP in a model of spontaneously 22 ± 6.5 17 ± 4.0 14 ± 4.9 breathing preterm . 0.101 Proximal to the patient (µg) 32 ± 4.5 30 ± 6.1 19 ± 2.7 � Methods: 0.002 Distal to the patient (µg) � In-vitro model of a preterm infant 0.43 0.03 0.13 P value � Vt: 9 mL, RR: 50 bpm, Ti: 0.5 sec. � Aerosols can effectively be delivered with HFNC, bCPAP & SiPAP. � Albuterol sulfate (2.5 mg/0.5 mL) � Delivery efficiency of HFNC is better than bCPAP and SiPAP. � The mesh nebulizer was placed � Placement of the nebulizer prior to the humidifier increased deposition near the patient or prior to the with all devices. humidifier. Sunbul F, Fink JB, Ari A. Pediatric Pulmonology 2015; 50(11): 1099-1106. Sunbul F, Fink JB, Ari A. Pediatric Pulmonology 2015; 50(11): 1099-1106. 5

  6. CRYING KILLS LUNG DEPOSITION SCREAMING KILLS LUNG DEPOSITION CRYING QUITE BREATHING NON-TIGHTLY FITTED FACE MASK TIGHTLY FITTED FACE MASK TIGHTLY FITTED FACE MASK Screaming during Inhalation Quite Breathing Nebulizer Nebulizer Nebulizer 0.3% 1.4% 8.2% Erzinger et al. J Aerosol Med 2007 Suppl S78 – S84. Murakami et al. Ann Allergy 1990; 64:383-387. HOW TO DELIVER AEROSOLS TO DISTRESSED BLOW-BY AND CRYING BABIES � Don’t agitate the infant � A technique that is used by placing a nebulizer within a distance from the child and directs aerosol plume towards the patient’s face � Positive reinforcement to hold the mask firmly against the child’s face � Commonly used for crying babies & uncooperative children to the child ’ ’ ’ s face is increased. ’ � Play activities � Aerosol deposition decreases as the distance from the device � Parental education & support � It is less efficient compared with face mask. � Using blow-by should be discouraged. 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. Rubin BK. Respir Care 2007; 52(8): 981. Iles et al Arch Dis Child 1999; 81:163-165. Lin et al. Respir Care 2007; 52(8): 1021-1026. Ari A. A Guide to Aerosol Delivery Devices for Respiratory Therapists . 2009: AARC. Restrepo et al. Respir Care 2006; 51(1): 56-61. 6

  7. IS ADMINISTRATION DURING SLEEP AN IS ADMINISTRATION DURING SLEEP AN ALTERNATIVE? ALTERNATIVE? � Comparison of lung dose for pMDI/spacer with awake Typical breathing pattern of a 10-month-old child while and asleep breathing patterns of 18 children. Awake Asleep Janssen JM et al. J Aerosol Med 2003, 16: 4: 395-400 Janssen JM et al. J Aerosol Med 2003, 16: 4: 395-400 AEROSOL DRUG DELIVERY DURING AEROSOL DELIVERY DURING HFOV MECHANICAL VENTILATION � The type of nebulizer affects the lung dose � Aerosol delivery during HFOV is effective in neonates. � Mesh nebulizers are superior to jet nebulizers � Efficiency of mesh nebulizers is greater than jet nebulizers during HFOV � Increasing flow rate decreases aerosol delivery � Aerosol deposition with jet nebulizers was 4.8%, 3.7% and 2.7% at � Drug delivery in proximal position was nearly threefold greater during 5, 6.5 and 8 L/min. HFOV than during conventional ventilation. � Breath-synchronized nebulization may improve drug delivery Author Drug Pattern Placement Device Drug Dose% compared with continuous nebulization. DiBlasi Iloprost Neonate Prox/Distal VMN P:30% D:1% � Nebulizer should start generating aerosol early in the inspiration VMN: 8-17% Fang Salbutamol Neonate Proximal VMN/JN JN: 0-3% � Nebulizers should be placed on the inspiratory arm of the circuit Siobal Albuterol Neonate Proximal VMN 18% Dubus et al. Pediatr Res 2005; 58(1): 10-14. DiBlasi et al. Pulm Circ 2016; 6(1): 63-69. Turpeinen & Nikander Respir Care 2001; 46(1):43-48. Fang et al. J Aerosol Med 2016; 29(5):447-453. Nikander et al. Pediatr Pulmonol 2000; 29:120-126. Siobal & Hess. Respir Care 2010; 55:144-157. 7

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