Pediatrics Optimization Intitulé du cours of aerosol therapy in mechanical ventilation Thèmes donnés Ermindo Di Paolo, PhD Departments of Pharmacy and Pediatrics Lausanne University Hospital Switzerland Ermindo.Di-Paolo@chuv.ch 27.03.2015
Optimization of aerosol therapy in invasive mechanical ventilation Introduction In vitro simplified model In vitro 10-kg child models 1 & 2 In vivo study Comparison with literature Conclusion www.inhalatorium.com E.Di Paolo - Lyon - 27.03.2015 2
Introduction: Types of aerosols Metered-dose inhaler MDI Jet nebulizer JN Ultrasonic nebulizer USN Vibrating-mesh nebulizer VMN Prescribed dose => Aerosolized dose => Inhaled dose => Pulmonary dose E.Di Paolo - Lyon - 27.03.2015 3
Introduction: Pediatric specificities Jet nebulizer output Small tidal volume More rapid respiratory rate Narrow airway diameter Fewer alveoli Fink JB. Respir Care 2004; O Leary F et al. ADC 2015 E.Di Paolo - Lyon - 27.03.2015 4
Introduction: International survey (n = 854, 611 departments in 70 countries) Ipratropium br. (n = 738) Salbutamol (n = 685) Epinephrine (n = 601) Budesonide (n = 505) Colistin (n = 500) Terbutaline (n = 456) Tobramycin (n = 263) Amikacin (n = 233) MDI exclusively 2% Nebulizers exclusively 43% Both 54% Jet nebulizers 55% Ultrasonic nebulizers 45% Vibrating mesh nebulizers 14% E.Di Paolo - Lyon - 27.03.2015 5 Ehrmann S et al. Intensive Care Med 2013
Introduction: Factors influencing aerosol delivery in mechanical ventilation E.Di Paolo - Lyon - 27.03.2015 6 Dhand R. Respir Care 2008
In vitro simplified model - Methods Salbutamol sulf. 0.05% 4 ml A. Sidestream B. Multisonic C. Aeroneb Pro B. Aeroneb Solol E.Di Paolo - Lyon - 27.03.2015 7 Sidler-Moix AL et al. Respir Care 2015
In vitro simplified model - Results Nebulizers Duration of nebulization (min) Aerosol output (g of solution/min) Albuterol emitted dose (mg) Jet NEB (Sidestream ) 15.0 ± 0.0 2 0.15 ± 0.01 0.87 ± 0.08 Ultrasonic NEB (Multisonic ) 5.8 ± 0.6 0.52 ± 0.05 1.41 ± 0.11 Vibrating mesh NEB (Aeroneb Pro ) 9.9 ± 1.8 0.40 ± 0.08 1.99 ± 0.03 Vibrating mesh NEB (Aeroneb Solo ) 10.2 ± 1.0 0.39 ± 0.04 2.01 ± 0.01 Nebulizers Filters retention (%) Nebulizer retention (%) Connectors retention (%) Jet NEB (Sidestream ) 28.4 ± 4.9 59.2 ± 4.1 6.9 ± 1.7 Ultrasonic NEB (Multisonic ) 48.4 ± 6.0 32.7 ± 5.2 13.4 ± 2.3 Vibrating mesh NEB (Aeroneb Pro ) 75.1 ± 10.3 3.7 ± 1.2 14.2 ± 4.6 Vibrating mesh NEB (Aeroneb Solo ) 76.6 ± 5.0 2.2 ± 0.5 12.0 ± 4.6 E.Di Paolo - Lyon - 27.03.2015 8 Sidler-Moix AL et al. Respir Care 2015
In vitro simplified model - Results Osmolality and salbutamol concentration during nebulization VMN VMN E.Di Paolo - Lyon - 27.03.2015 9 Sidler-Moix AL et al. Respir Care 2015
In vitro simplified model - Results Temperature of reservoir (A) and nebulized (B) solutions during nebulization USN VMN USN JN JN VMN Sidler-Moix AL et al. Respir Care 2015 E.Di Paolo - Lyon - 27.03.2015 10
In vitro 10-kg child model 1- Methods Model: 12-cm flexible tubing with 4-mm ETT Pressure-limited mode Rate 25/min Peak inspiratory pressure 25 mbar Positive end-expiratory pressure 5 mbar Inspiratory time 0.8 secs Expiratory time 1.6 secs FIO2 0.21 Humidification chamber : off Galileo Hamilton Jet nebulizers (n = 5) during 30 min with Salbutamol sulf. 0.25% 4 ml Microneb (Europe Medical) Sidestream durable (Medic-Aid) Acorn II (Marquest) Cirrus (Intersurgical) Upmist (Hospitak) Micro Mist (Hudson) Di Paolo ER et al. Pediatr Crit Care Med 2005 E.Di Paolo - Lyon - 27.03.2015 11
In vitro 10-kg child model 1- Methods 120 cm E.Di Paolo - Lyon - 27.03.2015 12 Di Paolo ER et al. Pediatr Crit Care Med 2005
In vitro 10-kg child model 1- Results Microneb Sidestream I / I Cont. I / E E.Di Paolo - Lyon - 27.03.2015 13 Di Paolo ER et al. Pediatr Crit Care Med 2005
In vitro 10-kg child model 1- Results I / E : spacer effect E.Di Paolo - Lyon - 27.03.2015 14 Di Paolo ER et al. Pediatr Crit Care Med 2005
In vitro 10-kg child model 1- Results E.Di Paolo - Lyon - 27.03.2015 15 Di Paolo ER et al. Pediatr Crit Care Med 2005
In vitro 10-kg child model 2- Methods 160 cm A. Jet nebulizer Sidestream Disposable B. Ultrasonic neb. Multisonic InfraControl C. Vibrating-mesh neb. Aeroneb Pro with Salbutamol sulf. 0.05% 4 ml Sidler-Moix AL et al. Pediatr Crit Care Med 2013 E.Di Paolo - Lyon - 27.03.2015 16
In vitro 10-kg child model 2- Results Sidler-Moix AL et al. Pediatr Crit Care Med 2013 E.Di Paolo - Lyon - 27.03.2015 17
In vitro 10-kg child model 2- Results Laser diffraction: Malvern Mastersizer S Sidler-Moix AL et al. Pediatr Crit Care Med 2013 E.Di Paolo - Lyon - 27.03.2015 18
In vivo model - Methods 16 healthy volunteers, 8 females and 8 males Salbutamol sulf. 5 mg/4 ml Charcoal in stomach JN Sidestream disp.: Intermittent mode during the inspiratory phase at position 1 Intermittent mode during the expiratory phase at position 2 VMN Aeroneb Pro: Continuous mode at position 1 Continuous mode at position 2 E.Di Paolo - Lyon - 27.03.2015 19 Sidler-Moix AL. PhD Thesis 2012
In vivo model - Results Position 2 : spacer effect E.Di Paolo - Lyon - 27.03.2015 20 Sidler-Moix AL. PhD Thesis 2012
Literature: in vitro JN vs VMN Inhaled dose % Galileo Hamilton, VT 500 or 100 ml Continuous bias flow 2 L/min vs 5 L/min JN Misty Finity 2.5 L/min VMN Aeroneb Solo Salbutamol sulf. 2.5 mg/3 ml E.Di Paolo - Lyon - 27.03.2015 21 Ari A et al. Respir Care 2010
Literature: in vitro JN vs USN vs VMN Servo-i Maquet, VT 200 ml JN during 5 min, USN and VMN during 15 min Salbutamol sulf. 2.5 mg/3 ml Inhaled dose % At ventilator At humidifier 30 cm before Y At Y-piece JN Updraft II 5.4 ± 0.6 4.7 ± 0.8 4.3 ± 0.8 2.0 ± 0.1 JN Salter 8900 3.1 ± 0.9 4.6 ± 0.9 2.9 ± 0.7 2.8 ± 0.4 USN Maquet 12.8 ±1.5 17.1 ± 1.5 10.5 ± 2.0 8.7 ± 0.7 VMN Aeroneb Solo 28.5 ± 8.6 33.3 ± 3.6 10.3 ± 3.3 8.7 ± 2.5 E.Di Paolo - Lyon - 27.03.2015 22 Berlinski A, Willis JR. Respir Care 2013
Literature: animal study JN vs VMN Neonatal ventilation in 4 macaques Inhaled dose % JN MistyNeb VMN Aeroneb Cont. VMN Aeroneb Insp. 0.5 (0.4-1.3) 12.6 (9.6-20.6) 14.0 (12.2-23.7) E.Di Paolo - Lyon - 27.03.2015 23 Dubus JC et al. Pediatr Res 2005
Literature: clinical study MDI vs JN Infants with bronchopulmonary dysplasia Radiolabelled salbutamol Nonventilated Ventilated E.Di Paolo - Lyon - 27.03.2015 24 Fok TF et al. Pediatr Pulmonol 1996
Literature: recommendations Both nebulizers and MDIs can be used to deliver β2-agonists to mechanically ventilated patients (qual. evid.: fair). High doses of β2-agonists are associated with a higher incidence of tachycardia and premature heart beats in mechanically ventilated patients (NEB = MDI) (qual. evid.: fair). Careful attention to details of the technique employed is critical, since multiple technical factors may have clinically important effects on the aerosol delivery (qual. evid.: low). Vibrating-mesh nebulizers? E.Di Paolo - Lyon - 27.03.2015 25 Dolovich MB et al. Chest 2005
Literature: recommendations MDI Minimize the inspiratory flow rate during administration. I/E ratio > 0.3. Ensure that the ventilator breath is synchronized with the patient s inspiration. Shake the MDI vigorously. Place the canister in the actuator of the spacer situated in the inspiratory line. Actuate the MDI to synchronize with precise onset of inspiration by the ventilator. Allow passive exhalation. Repeat actuations after 20 to 30 sec until total dose is delivered. Fink JB, Ari A in Walsh BK. Neonatal and pediatric respiratory care. 2015 E.Di Paolo - Lyon - 27.03.2015 26
Literature: recommendations JN Place drug solution in the JN (2-5 ml). Place the JN in the inspiratory line, about 30 cm from the patient s Y-piece. Ensure sufficient airflow (6-8 L/min) to operate the JN. Ensure adequate tidal volume. Duty cycle > 0.3 if possible. Adjust the minute volume, sensitivity trigger, and alarms to compensate for additional airflow through the JN if nec. Remove the heat moisture exchanger from between the JN and the patient. Observe the JN and disconnect it when no more aerosol is being produced. Rinse with sterile water and air dry between uses. Reconnect the ventilator circuit and return to original settings. Vibrating-mesh nebulizers? Fink JB, Ari A in Walsh BK. Neonatal and pediatric respiratory care. 2015 E.Di Paolo - Lyon - 27.03.2015 27
Conclusion MDI, JN, USN, VMN can be used in ventilated infants and children. The inner resistance of a JN is an important factor affecting aerosol delivery. VMN and USN are more expensive, but deliver more aerosol to the lungs than JN, without adding gas flow into the ventilator circuit. The inspiratory line of the circuit can play the role of a spacer. Clinical studies (efficacy, drug doses) are lacking and new guidelines with VMN would be useful. E.Di Paolo - Lyon - 27.03.2015 28