Pediatrics in mechanical ventilation

Transcription

1 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

2 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 E.Di Paolo - Lyon

3 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

4 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

5 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 Ehrmann S et al. Intensive Care Med 2013

6 Introduction: Factors influencing aerosol delivery in mechanical ventilation E.Di Paolo - Lyon Dhand R. Respir Care 2008

7 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 Sidler-Moix AL et al. Respir Care 2015

8 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 ± ± ± 0.08 Ultrasonic NEB (Multisonic ) 5.8 ± ± ± 0.11 Vibrating mesh NEB (Aeroneb Pro ) 9.9 ± ± ± 0.03 Vibrating mesh NEB (Aeroneb Solo ) 10.2 ± ± ± 0.01 Nebulizers Filters retention (%) Nebulizer retention (%) Connectors retention (%) Jet NEB (Sidestream ) 28.4 ± ± ± 1.7 Ultrasonic NEB (Multisonic ) 48.4 ± ± ± 2.3 Vibrating mesh NEB (Aeroneb Pro ) 75.1 ± ± ± 4.6 Vibrating mesh NEB (Aeroneb Solo ) 76.6 ± ± ± 4.6 E.Di Paolo - Lyon Sidler-Moix AL et al. Respir Care 2015

9 In vitro simplified model - Results Osmolality and salbutamol concentration during nebulization VMN VMN E.Di Paolo - Lyon Sidler-Moix AL et al. Respir Care 2015

10 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

11 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 FIO 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

12 In vitro 10-kg child model 1- Methods 120 cm E.Di Paolo - Lyon Di Paolo ER et al. Pediatr Crit Care Med 2005

13 In vitro 10-kg child model 1- Results Microneb Sidestream I / I Cont. I / E E.Di Paolo - Lyon Di Paolo ER et al. Pediatr Crit Care Med 2005

14 In vitro 10-kg child model 1- Results I / E : spacer effect E.Di Paolo - Lyon Di Paolo ER et al. Pediatr Crit Care Med 2005

15 In vitro 10-kg child model 1- Results E.Di Paolo - Lyon Di Paolo ER et al. Pediatr Crit Care Med 2005

16 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

17 In vitro 10-kg child model 2- Results Sidler-Moix AL et al. Pediatr Crit Care Med 2013 E.Di Paolo - Lyon

18 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

19 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 Sidler-Moix AL. PhD Thesis 2012

20 In vivo model - Results Position 2 : spacer effect E.Di Paolo - Lyon Sidler-Moix AL. PhD Thesis 2012

21 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 Ari A et al. Respir Care 2010

22 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 ± ± ± ± 0.1 JN Salter ± ± ± ± 0.4 USN Maquet 12.8 ± ± ± ± 0.7 VMN Aeroneb Solo 28.5 ± ± ± ± 2.5 E.Di Paolo - Lyon Berlinski A, Willis JR. Respir Care 2013

23 Literature: animal study JN vs VMN Neonatal ventilation in 4 macaques Inhaled dose % JN MistyNeb VMN Aeroneb Cont. VMN Aeroneb Insp. 0.5 ( ) 12.6 ( ) 14.0 ( ) E.Di Paolo - Lyon Dubus JC et al. Pediatr Res 2005

24 Literature: clinical study MDI vs JN Infants with bronchopulmonary dysplasia Radiolabelled salbutamol Nonventilated Ventilated E.Di Paolo - Lyon Fok TF et al. Pediatr Pulmonol 1996

25 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 Dolovich MB et al. Chest 2005

26 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 E.Di Paolo - Lyon

27 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 E.Di Paolo - Lyon

28 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