Reassessing the Role of Heated Humidification During Nebulization: Implications for Clinical Practice

Over 2 decades ago, a series of in vitro and in vivo studies compared aerosol delivery using dry gas versus heated humidified gas during invasive mechanical ventilation.^1-5 These studies found that aerosol delivery efficiency was greater with dry gas than with heated humidified gas,^1-5 likely due to the increased diameter of aerosol particles caused by absorbing water vapor from the heated humidification. As a result, some clinicians and researchers have recommended turning off humidifiers during nebulization, particularly to optimize the delivery of aerosolized antibiotics for mechanically ventilated patients.⁶ In clinical practice, 8–37% clinicians have reported turning off humidifiers during aerosol delivery for mechanically ventilated patients.^7-9 However, concerns have been raised regarding the potential harms of turning off humidification.

In this issue, Lellouche et al¹⁰ critically evaluated the hygrometry of dry gas, heated humidified gas, and the dynamic process of turning off humidifiers. They observed a rapid decrease in humidity to below 30 mg H₂O/L after turning off humidifiers,¹⁰ while 30 mg H₂O/L is the recommended minimum humidity level for mechanically ventilated patients to avoid airway injury.^11,12 Their findings underscore the potential risks associated with recommendations to turn off humidifiers in order to enhance aerosol delivery.

Notably, there is a disconnect between these recommendations and the actual findings of more recent studies. It is important to recognize that earlier studies compared dry gas with heated humidified gas^1-5 rather than the gas conditions that occur after humidifiers are turned off. Until recently, researchers investigated the effects of interrupting humidification on aerosol delivery efficiency.^13,14 Lin et al¹³ reported that the efficiency of aerosol delivery via pressurized metered-dose inhaler during mechanical ventilation was not improved when humidifiers were turned off compared to aerosol delivery during heated humidification. Similarly, Jacquier et al¹⁴ found no improvement in aerosol delivery efficiency after humidifiers were turned off, even after 1 h—a finding corroborated by 3 different laboratories using various small-volume nebulizers, ventilators, humidifiers, and ventilation settings. These findings suggest that the practice of turning off humidifiers to promote aerosol delivery lacks sufficient evidence to support its efficacy.

Additionally, recommendations suggest that humidifiers should be turned back on after nebulization is complete.⁶ However, in clinical practice, there is a real risk that clinicians might forget to do so. Prolonged inhalation of dry gas can lead to severe complications, such as mucous plugs and airway injury.¹⁵ Therefore, after thoroughly reviewing the evidence, a group of international experts reached the consensus that humidifiers should not be turned off for aerosol therapy during mechanical ventilation.¹⁶

Some may argue that nebulization alone, even with dry gas, could provide sufficient humidity. To improve aerosol delivery, especially for aerosolized antibiotics, it has been suggested to change ventilator circuits to new sets of dry circuits.⁶ However, this practice carries significant risks, including alveolar de-recruitment, environmental contamination during circuit disconnection, and an increased risk of pneumonia. The potential benefits of improved aerosol delivery must be weighed against these risks, highlighting the need for further evaluation. Furthermore, Jacquier et al observed that gas humidity quickly decreased from 35–40 mg H₂O/L to below 30 mg H₂O/L within 5–7 min after turning off humidifiers, regardless of the nebulizer type and placement. With dry gas, nebulization alone could not provide humidity levels exceeding 20 mg H₂O/L.¹⁴ Given that 30 mg H₂O/L is the recommended minimum humidity level for mechanically ventilated patients to avoid airway injury,^11,12 it is evident that nebulization alone is insufficient to meet these needs.

Another important clinical implication of the findings by Lellouche et al is the emphasis on the importance of heat in the humidification process. Some may suspect that passover humidifiers without heat could still provide adequate humidity. However, Lellouche et al found that while the water inside a passover humidifier could add some humidity compared to dry gas, the humidity level remained below 10 mg H₂O/L.¹⁰ This finding highlights the fact that the ability of gas to hold water is temperature dependent. It also serves as a reminder that in clinical scenarios where humidifiers are discontinued, such as during patient transport, the use of a heat-and-moisture exchanger is essential.¹²

This study not only provides crucial evidence on the hygrometry of humidification but also underscores the importance of critically evaluating existing recommendations and generating new evidence where needed. As respiratory therapists and clinicians, it is imperative that we practice evidence-based medicine, but it is equally important that we critically assess the evidence we rely on.¹⁷