You must unlearn what you have learned—Master Yoda

Learning is a vital skill and ought to be a lifelong pursuit for everyone. While we all sort of inadvertently learn all the time, I am referring to something different. I suggest to you that you need to practice active learning. I would define this as consciously seeking new knowledge about a subject that you might think you already know almost everything about. I suggest to you that much more often than not, you will be surprised to learn that what you thought was so, just is not so.

The health care field is fertile ground for unlearning and relearning. This field grows and changes in spastic spurts and sprints that sometimes make my head spin. You have to run to keep up. Of course, the blessing of learning new stuff can have an attendant curse—the need to unlearn old stuff. Do not get me wrong. Unlearning is not a bad thing, although it can be hard to do. The famous physicist Max Planck once said, “A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die, and a new generation grows up that is familiar with it.”

Some of the more interesting examples of unlearning that the respiratory therapy profession has had to master include intermittent positive pressure breathing, negative end expiratory pressure, ribavirin for bronchiolitis, bland aerosols, chest physiotherapy, and—my sentimental favorite—blow-bottles. There are many more. Some of this unlearning is still going on.

Pediatric aerosol administration is one of the clinical areas that has had its share of unlearning opportunities. Myth can be an ugly word, and implies that the holders of the myth are willing to believe almost anything. I prefer to use the word legend, as it has a better feel to it. Legend in this context can be thought of as an unproved or false collective belief. Much of what we have done to and for patients in the last 50 years has been introduced largely untested. Some of these interventions, once adequately tested, turned out to be of no benefit (and some were even harmful). Interventions that are untested are not necessarily of no benefit, however; it just means we do not know for sure.

Before we get too far into some of the science about pediatric aerosol administration, I want to say that selecting delivery devices and methods is a blend of art and science. Your judgment about the patient you are treating has to be combined with what has been tested and proven about these treatment techniques. An excellent review of some of the advantages and limitations of various aerosol delivery devices in infants and children is a paper by Rubin and Kelly.

For the purposes of our discussion, nebulizers refer to pneumatically powered, disposable, small volume jet nebulizers. When thinking about nebulization in children, remember three important characteristics of aerosol behavior that affect drug delivery: impaction, coalescence, and sedimentation. Impaction is when aerosol particles touch any surface material, the result being that they cling or “rain out.” This effect is increased when gas flow rates are higher, which causes the velocity of the aerosol particles to be higher and increases their inertia. This increased inertia of the suspended aerosol particles tends to cause them to strike more surfaces as they traverse the twists and turns of the upper airway, thus decreasing deposition in the medium and smaller airways. Coalescence happens when two aerosol particles touch one another and combine to form a single larger particle. This also increases as gas velocity rises since higher flow rates tend to cause more turbulent flow and thus more collisions of aerosol particles. Larger particles are much less likely to make it to the medium and small airways. Sedimentation occurs when aerosol particles settle out of the suspension onto the surface of the air spaces of the lung because of gravity. Sedimentation is good, when it happens in the medium to small airways. This essential effect can be enhanced through breath holding and slow inspiration.

Following are some legends related to pediatric aerosol administration that warrant examination:

Nebulization is an efficient way to give inhaled drugs to spontaneously breathing infants and small children. Since RTs spend so much time giving nebulized medications, you might naturally assume that this method of administration has been thoroughly tested and shown to be effective. But remember that assumptions do not improve with age nor are they strengthened by being widely believed. It has been well established that only approximately 2% to 8% of drugs administered via nebulizer to spontaneously breathing wheezy infants and children get past the upper airway. Lung deposition is even worse when giving an aerosol to intubated pediatric patients, being in the range of 0.5% to 3%. This then calls into question the entire practice of weight-based dosing, but more on that later.

Nebulizers are more efficient than metered dose inhalers (MDIs) in small children and infants. One of the legends about this suggests that this population cannot cooperate sufficiently to use an MDI, and, thus, nebulizers are more efficient. Allow me to summarize the data about this. Not. It has now been repeatedly established in many studies that drug delivery with MDIs is at the least equivalent to drug delivery with nebulizers. But this is true only if valved holding chambers (VHCs) or, in some cases, spacers are used. More on valved holding chambers later. Further, there are a number of studies in which the MDI-VHC is more effective in drug delivery than a nebulizer in infants and children.

Nebulizers are efficient ways of giving inhaled medications to intubated infants and children. Numerous studies show that nebulization into the ventilator circuit of infants results in about 0.5% to 3%% of a nebulized dose delivered past the end of the endotracheal tube. This compares with 1.5% to 14.5% when a metered dose inhaler with spacer is used.

Nebulizers are cheaper. This is one of the most enduring legends, particularly related to inpatient nebulizer treatments for pediatrics. To adequately examine this presumption, you have to consider all the costs related to aerosol administration. These include medication, supplies, and labor (labor being the costliest component by far). At Children’s Hospital and Regional Medical Center, Seattle, we developed protocols and systems to promote the use of MDI-VHC instead of nebulizers for the administration of bronchodilators to our inpatient population. We went from having about 9% of our albuterol administration to asthmatics delivered via MDI-VHC, to nearly 90%; and, in doing this, we demonstrated a 21% reduction in albuterol administration costs when all the factors listed above are taken in account. Others have argued that valved holding chambers or spacers are too expensive to be used outside the hospital by low income patients and families. It turns out the low cost alternatives include simply using an empty plastic soda bottle as a spacer with an MDI, which appears to be as effective as a nebulizer.

Crying during treatment is a good thing. I used to think that crying during treatment was OK. My logic went like this: If a baby or toddler was crying, then the child was taking deep breaths, and deep breaths are good for drug deposition. But this view has largely fallen from grace. The breaths an infant takes during crying are spastic, erratic things, with high inspiratory flow rates and most likely lots of turbulent flow. As I noted earlier, turbulent flow causes increased coalescence and impaction and lessens sedimentation, none of which helps lung deposition.

Children and their families prefer nebulizers. It has been shown that children and families who have previously used nebulizers for home medication delivery overwhelmingly preferred MDI-VHC over nebulizers, once they had been converted. The beauty of the valved holding chamber is that it requires very little patient timing and coordination between MDI actuation and inspiratory effort. It has also been studied and shown that even young children can demonstrate effective MDI-VHC technique if they are properly trained.

An MDI with spacer in a ventilator can cause CO2 buildup. Ralph Lugo, Jim Keenan, and I studied this issue in a series of laboratory studies in Utah and demonstrated that this effect was very minor and clinically unimportant when the spacers were left in the circuit for the length of time typically associated with giving an MDI, using a neonatal ventilator-lung model.

Dosing regimens should be weight based. This has perplexed me for some time. Inhaled albuterol is essentially a topical application of a drug. Thus, basing the dose on weight seems illogical to me. It would be like dosing hydrocortisone cream for your skin according to your body weight. This is particularly vexing in neonates, as it results in very small doses of drug. Combine this with the very small amounts of the aerosolized solution that reaches the lung, and it is most probable that these patients are getting little, if any, drug. This could account for my clinical observations that the vast majority of the nebulized bronchodilators given to these intubated patients had no apparent clinical effect. We were probably seriously underdosing them.

MDI Dosing

There is not a lot of solid clinical science to guide you in figuring out how to convert doses of albuterol via nebulizer to albuterol via MDI-VHC. Typical practice has albuterol via MDI-VHC being given in the two- to four-puff range per dose, with a reluctance to go much higher. I believe this may account for some anecdotal observations that the MDI-VHC did not seem as effective as nebulizers: The patients were being underdosed. We set our conversion rates higher. We consider 2.5 mg of albuterol via nebulizer to be equivalent to four puffs via MDI-VHC, and 5 mg via nebulizer equivalent to eight puffs via MDI-VHC. This has been very effective for us.

Bye-Bye Blow-by

I wish I could say I thought up this catchy phrase but actually it was Bruce Rubin. He points out that even under ideal circumstances in vitro, there is a 40% to 85% decrease in aerosol delivery when the mask is held 2 cm away from the child’s face. The same is true for FiO2 delivery, which we tested for a variety of devices using a simulated breathing infant with a face. The concentration of oxygen given infants using “blow-by” is much less than when they are just put on a simple mask or a nasal cannula.

Washing Spacers and Valved Holding Chambers

Most of the spacers and holding chambers on the market tend to build up an electrostatic charge on their inner surfaces. This charge attracts suspended particles from the plume of the MDI and reduces drug delivery. This reduction can be substantial. One way to lessen this effect is to wash the inside of the chambers with soap and water. While this is effective, it is not nearly as effective as using a spacer or valved holding chamber that is made of charge-dissipative materials. These improve drug delivery even more than does washing of spacers.


The science and practice of pediatric aerosol administration is evolving. As with all applied science, our clinical practice is an iterative process where we learn incrementally over time. By its very nature, this presumes that some of what we thought we knew turns out to be untrue. Some use this to criticize the scientific method and processes, but I suggest to you that this is what is so very good about the evolving science of what we do. It gives us a chance to practice unlearning and relearning that continues in an endless cycle.

John Salyer, RRT-NPS, MBA, FAARC, is director, respiratory care, Children’s Hospital and Regional Medical Center, Seattle. For further information, contact [email protected].


  1. Arnon S, Grigg J, Nikander K, Silverman M. Delivery of micronized budesonide suspension by metered dose inhaler and jet nebulizer into a neonatal ventilator circuit. Pediatr Pulmonol. 1992;13:172–5.
  2. Benson JM, Gal P, Kandrotas RJ, Watling SM, Hansen CJ. The impact of changing ventilator parameters on availability of nebulized drugs in an in vitro neonatal lung system. DICP. 1991;25:272–5.
  3. Cameron D, Clay M, Silverman M. Evaluation of nebulizers for use in neonatal ventilator circuits. Crit Care Med. 1990;18:866–70.
  4. Coleman DM, Kelly HW, McWilliams BC. Determinants of aerosolized albuterol delivery to mechanically ventilated infants. Chest. 1996;109:1607–13.
  5. Cotterell EM, Gazarian M, Henry RL, O’Meara MW, Wales SR. Child and parent satisfaction with the use of spacer devices in acute asthma. J Paediatr Child Health. 2002;38:604-7
  6. Delgado A, Chou KJ, Silver EJ, Crain EF. Nebulizers vs metered-dose inhalers with spacers for bronchodilator therapy to treat wheezing in children aged 2 to 24 months in a pediatric emergency department. Arch Pediatr Adolesc Med. 2003;157:76-80.
  7. Erzinger S, Schueepp KG, Brooks-Wildhaber J, Devadason SG, Wildhaber JH Facemasks and aerosol delivery in vivo. J Aerosol Med. 2007;20:S78-84.
  8. Esposito-Festen J, Ijsselstijn H, Hop W, van Vliet F, de Jongsten J, Tiddens H. Aerosol therapy by pressured metered-dose inhaler-spacer in sleeping young children: to do or not to do? Chest. 2006;130:487-92.
  9. Everard ML, Stammers J, Hardy JG, Milner AD. New aerosol delivery system for neonatal ventilator circuits. Arch Dis Child. 1992;67(7 Spec No):826–30.
  10. Flavin M, MacDonald M, Dolovich M, Coates G, O’Brodovich H. Aerosol delivery to the rabbit lung with an infant ventilator. Pediatr Pulmonol. 1986;2:35–9.
  11. Fok TF, Monkman S, Dolovich M, et al. Efficiency of aerosol medication delivery from a metered dose inhaler versus jet nebulizer in infants with bronchopulmonary dysplasia. Pediatr Pulmonol. 1996;21:301–9.
  12. Fok TF, Lam K, Ng PC, et al. Randomised crossover trial of salbutamol aerosol delivered by metered dose inhaler, jet nebuliser, and ultrasonic nebuliser in chronic lung disease. Arch Dis Child Fetal Neonatal Ed. 1998;79:F100–4.
  13. Janssens HM, Tiddens HA. Facemasks and aerosol delivery by metered dose inhaler-valved holding chamber in young children: a tight seal makes the difference. J Aerosol Med. 2007;20:S59-65.
  14. Keenan J, Lugo RA, Salyer JW, Ward RM. Performance comparison of four spacers in a neonatal mechanical ventilator-lung model [abstract]. Respir Care. 1998;43:84.
  15. Kerem E, Levison H, Schuh S, et al. Efficacy of albuterol administered by nebulizer versus spacer device in children with acute asthma. J Pediatr. 1993;123: 313-317.
  16. Lee H, Arnon S, Silverman M. Bronchodilator aerosol administered by metered dose inhaler and spacer in subacute neonatal respiratory distress syndrome. Arch Dis Child Fetal Neonatal Ed. 1994;70:F218–22.
  17. Leversha AM, Campanella SG, Aickin RP, Asher IA. Cost and effectiveness of spacer versus nebulizer in young children with moderate to severe acute asthma. J Pediatr. 2000;136:497-502.
  18. Lin YZ, Hsieh KH. Metered dose inhaler and nebuliser in acute asthma. Arch Dis Child. 1995;72:214-8.
  19. Liu EA, Heldt GP. A trial of the safety of inhaled beclomethasone in ventilator-treated neonates. J Pediatr. 1996;129:154–6.
  20. Lugo RA, Ballard J. Albuterol delivery from a metered-dose inhaler with spacer is reduced following short-duration manual ventilation in a neonatal ventilator-lung model. Respir Care. 2004;49:1029 –34.
  21. Lugo RA, Kenney JK, Keenan J, Salyer JW, Ballard J, Ward RM. Albuterol delivery in a neonatal ventilated lung model: nebulization versus chlorofluorocarbon- and hydrofluoroalkane-pressurized metered dose inhalers. Pediatr Pulmonol. 2001;31:247–54.
  22. Lugo RA, Keenan J, Salyer JW. Accumulation of CO2 in reservoir devices during simulated neonatal mechanical ventilation. Pediatr Pulmonol. 2000;30:470–5.
  23. Marshall LM, Francis PW, Khafagi FA. Aerosol deposition in cystic fibrosis using an aerosol conservation device and a conventional jet nebulizer. J Paediatr Child Health. 1994;30:65-7.
  24. Nikander K, Berg E, Smaldone GC. Jet nebulizers versus pressurized metered dose inhalers with valved holding chambers: effects of the facemask on aerosol delivery. J Aerosol Med. 2007;20:S46-58.
  25. Osmond M, Diner B. Nebulizers versus inhalers with spacers for acute asthma in pediatrics. Ann Emerg Med. 2004;43:413-5.
  26. Ploin D, Chapuis FR, Stamm D, et al. High-dose albuterol by meter-dose inhaler plus a spacer device versus nebulization in preschool children with recurrent wheezing: a double-blind, randomized equivalence trial. Pediatrics. 2000;106:311-7.
  27. Rau JL Jr, Harwood RJ. Comparison of nebulizer delivery methods through a neonatal endotracheal tube: a bench study. Respir Care. 1992;37:1233–40.
  28. Restrepo RD, Dickson SK, Rau JL, Gardenhire DS. An investigation of nebulized bronchodilator delivery using a pediatric lung model of spontaneous breathing. Respir Care. 2006;51:56–61.
  29. Rubin BK. Bye-bye, blow-by. Respir Care. 2007;52:981.
  30. Salyer JW, Diblasi R, Crotwell D, et al. The Conversion to Meter Dose Inhaler with Valved Holding Chamber to Administer Inhaled Albuterol: a Pediatric Hospital Experience. Respir Care 2008:53 (in press).
  31. Scolnik D, Coates AL, Stephens D, Da Silva Z, Lavine E, Schuh S. Controlled delivery of high vs low humidity versus mist therapy for croup in emergency departments: a randomized controlled trial. JAMA. 2006;295:1274-80.
  32. Zar HJ, Streun S, Levin M, Weinberg EG, Swingler GH. Randomised controlled trial of the efficacy of a metered dose inhaler with bottle spacer for bronchodilator treatment in acute lower airway obstruction. Arch Dis Child. 2007;92:142-6.
  33. The impact of drug delivery devices in asthma management (in J Respir Dis 2002: April Supplement; S36-S43)38.