Aerogen Solo, Pro and Ultra can nebulise physician-prescribed medications for inhalation which are approved for use with a general purpose nebuliser.
Aerogen Solo/Pro can be used to nebulise all physician-prescribed drugs approved for use with a general-purpose nebuliser.
Aerogen Ltd cannot provide specific advice on medication dose as it does not have regulatory approvals for drug/device combinations at this time. Information on drug dosing with specific nebulisers must be sourced from the manufacturer’s approved prescribing information for the inhaled formulation.
Should you require information regarding published clinical research for nebulisation of specific medications with Aerogen devices, please contact our Clinical Team directly at firstname.lastname@example.org or within USA/Canada MedicalScience@aerogen.com.
It is recognised that physicians prescribe medications for nebulization that are not approved for use with a general purpose nebulizer based on their perceived clinical need and the Risk:Benefit Ratio for the patient. This is classified as ‘off label’ use of those medications: Aerogen Ltd cannot and does not promote ‘off label’ use of our devices.
Many bench models show increased inhaled dose with dry gas, from pMDI, jet nebuliser, ultrasonic and vibrating mesh nebulisers1. However, Lin et al., (2009) also showed that if you turn off the humidifier for 30 minutes, the inhaled dose was not increased2. Cold dry air can cause bronchospasm, and the majority of drugs given on the ventilator are bronchodilators, so it does not make much sense to turn off the humidifier (creating bronchospasm) to give more bronchodilator3. The biggest risk is forgetting to turn the humidifier back on after the treatment.
Occasionally, there can be a change in the colour of the water in the heated humidifier, for example adrenalin/ epinephrine and Ipratropium bromide/salbutamol can turn the water brown. Any medication which rains out in the chamber will not be aerosolised. Saeed et al., (2017) investigated the chemical stability of specific drugs after incubation at 50oC for 7 days to mimic a humidifier chamber. All drugs retained their integrity with the exception of acetyl cysteine, which had an additional peak in the HPLC chromatogram4.
If the physician is concerned the Aerogen Solo may also be placed at the wye. Please see articles which show deposition rates in these different positions1,5,6.
Saeed et al., (2017) investigated the chemical stability of specific drugs after incubation at 50oC for 7 days to mimic a humidifier chamber. All drugs retained their integrity with the exception of acetyl cysteine, which had an additional peak in the HPLC chromatogram4.
If you observe crystallization in the nebuliser chamber after use of hypertonic saline, you can aerosolise a few drops of normal saline to clear any residual hypertonic saline and prevent further crystal formation.
Rainout is usually condensation of humidified gas and to a lesser extent aerosolised drug that deposits as droplets within the breathing circuit. Drug in the form of rain-out will not be aerosolised and inhaled by the patient.
In order to remove any residues of viscous drugs you can nebulise a few drops of normal saline.
In vitro studies by Ari et al., (2010) assessing aerosol delivery during mechanical ventilation in the presence of bias flow determined that you receive optimal deposition if you place the nebuliser pre humidifier. In the absence of bias flow, optimal deposition was observed when the nebuliser was placed at or close to the wye1, 5. Berlinski & Willis (2013) demonstrated in a paediatric model, that in the presence of bias flow, nebulisers were more effective when placed back at the humidifier as compared to closer to the wye6.
The Aerogen Solo can be used with a HME/HMEf which may contain a filter. Only an HME/HMEf approved for use with a nebuliser should be used. Follow the HME/HMEf manufacturer instructions regarding use with a nebuliser. Ensure the combination of nebuliser, T-piece and HME/HMEf volumes are suitable for the tidal volume being delivered, especially with small tidal volumes, for example, small children.
The main disadvantage of the ultrasonic nebulisers is that heat is generated in the process of producing aerosol, this can break down complex proteins in some of the inhaled medications8. In addition, ultrasonic nebulisers (USN) are not recommended for administration of suspensions such as Pulmicort (Budesonide)8.
They show similar aerosol delivery performance in an adult model when placed in the inspiratory limb at the wye and back at the humidifier when there is no bias used1. In a paediatric model with bias flow, the Aerogen Solo performed better than an ultrasonic when placed on the humidifier, similar deposition was observed at the wye6. Both ultrasonic nebulisers and Aerogen have controllers that drive them – but the ultrasonic nebuliser’s controller is bigger, bulkier and heavier. The Ultrasonic has a higher residual volume left after nebulisation compared to Aerogen which is minimal8. The ultrasonic has a reservoir that is positioned below the ventilator circuit whereby contaminated fluids in the circuit can more readily enter the nebuliser8.
Several in vitro studies have evaluated inhaled dose of albuterol/ salbutamol during HFNC. Reminiac et al., (2017) recently published an article assessing aerosol deposition in a toddler simulated breathing model and an animal model of a new born8. They demonstrated that using the Aerogen Solo inline during HFNC (attached to the humidifier) can provide similar aerosol deposition to using a jet nebuliser independent of the HFNC system. When the jet nebuliser was used with a mask over the HFNC cannula or inline, the results were minimal. Therefore, Aerogen provides a similar dose to the patient with the added benefit of providing HFNC at the same time. In addition, Li et al., (2019) published a study assessing inhaled dose during HFNC in both an infant (5kg) and toddler (15kg) model9. The Aerogen Solo was placed at both the inlet of the humidifier and proximal to the patient. Inhaled dose was higher when the Aerogen Solo was placed on the inlet of the humidifier in most settings and also when the gas flow was below the patient’s inspiratory flow. Inhaled dose decreased as gas flow decreased. The author noted that rain-out in the nasal prongs was increased when the Aerogen Solo was placed closer to the patient and it was difficult to keep the Aerogen Solo upright. It’s important to note that the Aerogen Solo is approved for placement on the dry side of the humidifier10.
The lung dose during HFNC is affected by the flow rate. At lower flow rates, a higher inhaled mass is available. Alcoforado et al., (2016) performed an imaging study which demonstrated that at flow rates of 10-50L/min, between 2-12% lung dose can be achieved where 3.76% of the aerosol dose is available at 30L/min11. Flow rate does affect aerosol deposition and lower flow rates will provide higher lung dose. Reminiac et al. studied the effect of HFNC with the AIRVO in patients with documented airflow obstruction, they suggested that using the Aerogen Solo in line (using the AIRVO adapter) at 30L/min did produce significant bronchodilation similar to using a standard jet nebuliser without HFNC. In addition tolerance and comfort were comparable between the two groups12.
Changes in bias flow can affect aerosol delivery as shown by Ari et al., 20105. Numerous other factors can affect aerosol delivery with mechanically ventilated patients including: inspiratory times, inspiratory pauses, minute ventilation, inspiratory waveform, ventilation mode, duty cycle, respiratory rate and breath triggering13. There seems to be no impact on aerosol delivery with different tidal volumes in paediatric models14.
1. Ari A, Areabi H, Fink JB, Cpft PT, Areabi H, Rrt M et al. Evaluation of aerosol generator devices at 3 locations in humidified and non-humidified circuits during adult mechanical ventilation. Respir Care 2010; 55: 837–844. 2. Lin HL, Fink JB, Zhou Y, Cheng YS. Influence of moisture accumulation in inline spacer on delivery of aerosol using metered-dose inhaler during mechanical ventilation. Respir Care 2009; 54: 1336–1341. 3. Kaminsky DA, Bates JH, Irvin CG. Effects of cool, dry air stimulation on peripheral lung mechanics in asthma. Am J Respir Crit Care Med 2000; 162: 179–186. 4. Saeed H, Abdelrahim MEA, Fink JB. Stability of commonly nebulised drugs in heated and humid condition. Med Sci 2018; 7: 269–76. 5. Ari A, Atalay OT, Harwood R, Sheard MM, Aljamhan EA, Fink JB. Influence of nebuliser type, position, and bias flow on aerosol drug delivery in simulated paediatric and adult lung models during mechanical ventilation. Respir Care 2010; 55: 845–851. 6. Berlinski A, Willis JR. Albuterol delivery by 4 different nebulisers placed in 4 different positions in a paediatric ventilator in vitro model. Respir Care 2013; 58: 1124–1133. 7. Ari A, Fink JB. Aerosol Drug Delivery During Mechanical Ventilation: Devices, Selection, Delivery Technique, and Evaluation of Clinical Response to Therapy. Clin Pulm Med 2015; 22: 79–86. 8. Reminiac F, Vecellio L, Loughlin RM, Le Pennec D, Cabrera M, Vourc’h NH et al. Nasal high flow nebulisation in infants and toddlers: An in vitro and in vivo scintigraphic study. Pediatr Pulmonol 2017; 52: 337–344. 9. Li J, Gong L, Ari A, Fink JB. Decrease the flow setting to improve trans‐nasal pulmonary aerosol delivery via “high‐flow nasal cannula” to infants and toddlers. Pediatr Pulmonol 2019; : ppul.24274. 10. Aerogen Solo System Instruction Manual. Aerogen Ltd. P/N 30-354, Part No. AG-AS3050. 11. Alcoforado L, Ari A, De Melo Barcelar J, Brandao SS, Fink JB, Dornelas De Andrade A. Comparison of Aerosol Deposition with Heated and Unheated High Flow Nasal Cannula (HFNC) in Healthy Adults. Poster Present ATS 2016. 12. Reminiac F, Vecellio L, Bodet-Contentin L, Gissot V, Le Pennec D, Salmon Gandonniere C et al. Nasal high-flow bronchodilator nebulisation: a randomized cross-over study. Ann Intensive Care 2018; 8: 128. 13. Dhand R. Basic techniques for aerosol delivery during mechanical ventilation. Respir Care 2004; 49: 611– 22. 14. Berlinski A, Willis JR. Effect of Tidal Volume and Nebuliser Type and Position on Albuterol Delivery in a Paediatric Model of Mechanical Ventilation. Respir Care 2015; 60: 1424–1430. 15. Dugernier J, Reychler G, Wittebole X, Roeseler J, Depoortere V, Sottiaux T et al. Aerosol delivery with two ventilation modes during mechanical ventilation: a randomized study. Ann Intensive Care 2016; 6: 73. 16. MacIntyre NR, Silver RM, Miller CW, Schuler F, Coleman RE. Aerosol delivery in intubated, mechanically ventilated patients. Crit Care Med 1985; 13: 81–84. 17. Galindo-Filho VC, Ramos ME, Rattes CS, Barbosa AK, Brandao DC, Brandao SCS et al. Radioaerosol Pulmonary Deposition Using Mesh and Jet Nebulisers During Noninvasive Ventilation in Healthy Subjects. Respir Care 2015; 60: 1238–1246. 18. Dugernier J, Hesse M, Vanbever R, Depoortere V, Roeseler J, Michotte JB et al. SPECT-CT Comparison of Lung Deposition using a System combining a Vibrating-mesh Nebuliser with a Valved Holding Chamber and a Conventional Jet Nebuliser: a Randomized Cross-over Study. Pharm Res 2017; 34: 290–300. 19. Abdelrahim ME, Plant P, Chrystyn H. In-vitro characterisation of the nebulised dose during non-invasive ventilation. J Pharm Pharmacol 2010; 62: 966–972. 20. Berlinski A, Velasco J. Albuterol Delivery Efficiency in a Paediatric Model of Noninvasive Ventilation With a Single-Limb Circuit. Respir Care 2019; : respcare.06622. 21. Velasco J, Berlinski A. Albuterol Delivery Efficiency in a Paediatric Model of Noninvasive Ventilation With Double-limb Circuit. Respir Care 2018; 63: 141–146. 22. Berlinski A, Kumaran S. Particle Size Characterization of Nebulised Albuterol Delivered by a Vibrating Mesh Nebuliser Through Paediatric Endotracheal Tubes. POster Present ATS 2016. 23. Dubus JC, Vecellio L, De Monte M, Fink JB, Grimbert D, Montharu J et al. Aerosol deposition in neonatal ventilation. Pediatr Res 2005; 58: 10–14. 24. Ní Mhurchú Sorcha, Brady Paul, McKenna Cathy, Bennett Gavin , Joyce Mary, Sweeney Louise MR. Effect of Nebuliser Position on Aerosol Delivery during Mechanical Ventilation of a Neonate. Irish Thorac Soc poster 2018. 25. Ari A, Fink JB, de Andrade AD, AlHamad B, Sheard M, AlHamad B et al. Performance Comparisons of Jet and Mesh Nebulisers Using Different Interfaces in Simulated Spontaneously Breathing Adults and Children. J Aerosol Med Pulm Drug Deliv 2015; 28: 281–289. 26. Ari A, Pt R, Faarc C, Restrepo RD, Faarc R. AARC Clinical Practice Guideline Aerosol Delivery Device Selection for Spontaneously Breathing Patients: 2012. 2012. doi:10.4187/respcare.01756. 27. Aerogen Pro System Instruction Manual. Aerogen Ltd. Part No. AG-AP1080 P/N 30-040. Aerogen Ltd.