metered-dose inhaler

An 8-year-old is brought in by her parents with shortness of breath and wheezing. She’s been receiving her “rescue inhaler” at home and continues to have symptoms. You examine her and find that she has normal oxygen saturation, mild tachypnea and retractions, and diffuse wheezes. You think that she’s experiencing an acute asthma exacerbation. Given the current pandemic, and a recent report that administering nebulizer treatments to COVID-19 positive patients was correlated with transmission of COVID-19 to healthcare workers [1], what is the best way to treat the patient?

Metered dose inhalers (MDIs) and nebulizers are the two main methods of delivering medications to patients’ lungs for a variety of disease processes including asthma, croup, cystic fibrosis, and COPD. Compared to MDIs, nebulizers are preferred by emergency department providers, with one survey indicating that the majority of ED providers choose them for all cases of pediatric asthma exacerbation, often due to their perceived ease of use and to satisfy patients [2]. However, in light of a renewed focus on respiratory pathogen transmission due to the COVID-19 pandemic, emergency physicians have to weigh the pros and cons of aerosolizing procedures like nebulized albuterol. Is the risk worth the mist or is a puff just enough?

Metered-dose inhalers

MDIs have been around since the 1950s. These handheld devices consist of 3 major components:

  1. A pressurized canister with suspended or dissolved medication mixed with a propellant to force the medication out of the canister
  2. A “meter” valve to ensure delivery of a consistent dosage
  3. An “actuator” to aerosolize the medication formula [3]
metered-dose inhaler

Figure 1: Metered-dose inhaler

Most MDIs also have a mechanism to inform the user of how many doses remain. MDIs can sometimes be referred to as an “HFA Inhaler.” This is because modern inhalers use a hydrofluoroalkane (HFA) propellant rather than a chlorofluorocarbon (CFC) propellant, which was banned by the FDA in 2008 due to their detrimental environmental effects [4, 5].

Depending on the medication, using an MDI correctly requires multiple steps:

  1. Shaking the canister if it is a suspended medication
  2. Slow inhalation prior to initiating the dose
  3. Slow inhalation for 3-4 seconds after initiating the dose
  4. Breath holding for up to 10 seconds after delivery of the medication.

Poor inhalation technique can result in ineffective drug delivery but can be improved by using spacers.

metered-dose inhaler

Figure 2: Spacer attached to albuterol metered-dose inhaler

Spacers can reduce the need for a coordinated inhalation and have been shown to increase the inhalable portion of the dose and, with beta agonist MDIs, to improve bronchodilation [6,7,8].

A note on powdered inhalers:

Powdered inhalers are another method of delivering medications to the lungs which are similar to MDIs, although differ from typical MDIs. The medication is dry and powderized, and these inhalers typically rely on users’ inhalation force to deliver the medication [9]. Powdered inhalers are not commonly used in the pediatric emergency department.

Nebulizers

Nebulizers are devices that continuously aerosolize medication solutions to create a stream of droplets to deliver to the lungs. The typical main components of a nebulizer are:

  1. A vial of medication solution
  2. The nebulizing component
  3. An oxygen or air intake tract
  4. A mouthpiece or mask for delivery of aerosolized particles to the patient.

Figure 3: Nebulizing setup with oxygen intake, medication chamber, nebulizing component, facemask, medication vial

The nebulizing component will typically utilize one of three main aerosolizing mechanisms – jet, ultrasonic, or mesh nebulizers. Jet nebulizers are the most common type. Mesh nebulizers may deliver drugs with less drug waste, however their effectiveness can be impacted by device position: a significant drawback for use in pediatric patients [10,11].

What are the advantages and disadvantages of MDIs and nebulizers?

Many factors weigh into the decision to use an MDI or a nebulizer, including whether a patient can cooperate with treatment and the need for simultaneous oxygen administration. In many cases, however, they are interchangeable. During the COVID-19 pandemic, special consideration must be given to the increased risk of aerosolization of pathogens with nebulizer use as compared to MDI use [12].

Given this drawback, it’s important to know if nebulizers offer increased efficacy compared to MDIs.

  • A 2013 Cochrane review demonstrated that an MDI with a spacer delivered beta agonist therapy equal to or better than a nebulizer for pediatric patients aged 2 or older and adults with asthma in the emergency department [13].
    • Compared to nebulized albuterol, albuterol administered via MDI resulted in similar admission rates, forced expiratory volumes, and peak flow measurements.
    • Using MDIs was associated with shorter ED stays, lower pulse rate, and fewer cases of tremors in pediatric patients compared to nebulized albuterol.
  • In children aged 2-14 years, administration of albuterol and ipratropium via MDI resulted in lower rates of hospital admission and improved clinical assessments of asthma severity as compared to nebulizer treatment [14].
  • In children between 2-24 months, MDI use resulted in fewer side effects and reduction in admission rate [15].

Additional MDI benefits

  • MDIs offer the potential for significant cost savings [16].
  • Use of an MDI with a spacer in the emergency department provides an opportunity to teach proper use, which could potentially reduce return visits.
MDINebulizer
Advantage
  • Less potential for aerosolizing pathogens
  • Short dose delivery time
  • Does not require power source
  • Equal or greater efficacy compared to nebulizer for acute asthma exacerbations in pediatric patients
  • Reduced ED length of stay
  • Potential for cost savings
  • Opportunity to teach patients proper use technique
  • Does not require coordinated inhalation from patient
  • Variety of attachments including masks for less cooperative patients
  • Can administer oxygen and nebulized medication simultaneously for hypoxic patients
  • Some medications (e.g. racemic epinephrine, hypertonic saline) will only be on formulary as a nebulizer solution
Disadvantage
  • Requires coordinated inhalation from user, although this is improved by spacer use
  • Improper use can result in questionable drug delivery, which may obscure evaluation of patient response
  • Potentially increased risk of aerosolization of pathogens
  • Longer dose delivery time
  • Some units require an outside power source
  • Some units (e.g. jet nebulizers) require compressed oxygen or air

Table 1: Overview of MDI and nebulizer advantages and disadvantages

Converting from nebulizer dosages to MDIs

Given the likelihood of increased MDI usage in the emergency department for acute asthma exacerbation, it’s important to know the dose conversion from nebulized albuterol to MDI. The Children’s Hospital of Philadelphia’s Asthma Pathway provides a useful weight-based conversion chart for albuterol MDI and nebulizer [17].

 

Weight (Kg)Unit Dose (0.5%)MDI PuffsContinuous nebulization
5-102.5 mg (0.5 mL)47.5 mg/hr
> 10-203.75 mg (0.75 mL)611.25 mg/hr
> 205 mg (1.0 mL)815 mg/hr

Table 2: Albuterol Weight-based Dosing. Courtesy of CHOP.

Summary:

  • Nebulizers may increase the risk of transmission of COVID-19 and other respiratory pathogens to healthcare workers.
  • Metered-dose inhalers require coordination to use, however this, and drug delivery, are improved with spacers.
  • Compared to nebulizers, evidence suggests metered-dose inhalers are as effective as nebulizers in acute asthma exacerbation in pediatric patients.
  • Metered-dose inhalers appear to confer fewer side effects and reduce emergency department length of stay compared to nebulizers.
  • Metered-dose inhaler use can reduce costs of asthma treatment in the emergency department.

Trying to classify your patient’s asthma severity? ALiEM has a Paucis Verbis card for asthma classification. Working a shift in the pediatric emergency department? Review some facts with ALiEM’s PEM pearl archives.

References:

  1. Heinzerling A, Stuckey MJ, Scheuer T, et al. Transmission of COVID-19 to Health Care Personnel During Exposures to a Hospitalized Patient – Solano County, California, February 2020. MMWR Morb Mortal Wkly Rep. 2020;69(15):472‐ PMID: 32298249
  2. Tien I, Dorfman D, Kastner B, Bauchner H. Metered-dose inhaler: the emergency department orphan. Arch Pediatr Adolesc Med. 2001;155(12):1335‐ PMID: 11732952
  3. Stein SW, Sheth P, Hodson PD, Myrdal PB. Advances in metered dose inhaler technology: hardware development. AAPS PharmSciTech. 2014;15(2):326‐ PMID: 24357110
  4. Lavorini F, Buttini F, Usmani OS. 100 Years of Drug Delivery to the Lungs. Handb Exp Pharmacol. 2019;260:143‐ PMID: 31792683
  5. Center for Drug Evaluation and Research. Transition from CFC Propelled Albuterol Inhalers to HFA Propelled Albuterol Inhalers: Questions and Answers. U.S. Food and Drug Administration. https://www.fda.gov/drugs/questions-answers/transition-cfc-propelled-albuterol-inhalers-hfa-propelled-albuterol-inhalers-questions-and-answers. Published 2008. Accessed May 28, 2020.
  6. Fontana GA, Lavorini F, Chiostri M, Castellani W, Boddi V, Pistolesi M. Large and small airway responses to procaterol hydrochloride administered through different extension devices in asthmatic patients. J Aerosol Med. 1999;12(3):177‐ PMID: 10623334
  7. Johnson JL, Guthrie D, Hyde J, Hanson T, Karlage K, Myrdal PB. The effect of a holding chamber on albuterol metered-dose inhaler product differences. Ann Allergy Asthma Immunol. 2016;117(3):246‐ PMID: 27613457
  8. Vincken W, Levy ML, Scullion J, Usmani OS, Dekhuijzen PNR, Corrigan CJ. Spacer devices for inhaled therapy: why use them, and how?. ERJ Open Res. 2018;4(2):00065-2018. PMID: 29928649
  9. Martin AR, Finlay WH. Nebulizers for drug delivery to the lungs. Expert Opin Drug Deliv. 2015;12(6):889‐ PMID: 25534396
  10. Hardaker LE, Hatley RH. In vitro characterization of the I-neb Adaptive Aerosol Delivery (AAD) system. J Aerosol Med Pulm Drug Deliv. 2010;23 Suppl 1:S11‐ PMID: 20373905
  11. Skaria S, Smaldone GC. Omron NE U22: Comparison between vibrating mesh and jet nebulizer. J Aerosol Med Pulm Drug Deliv. 2010;23(3):173‐ PMID: 20500093
  12. Amirav I, Newhouse MT. Transmission of coronavirus by nebulizer: a serious, underappreciated risk. CMAJ. 2020;192(13):E346. PMID: 32392488
  13. Cates CJ, Welsh EJ, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2013;2013(9):CD000052. PMID: 24037768
  14. Iramain R, Castro-Rodriguez JA, Jara A, et al. Salbutamol and ipratropium by inhaler is superior to nebulizer in children with severe acute asthma exacerbation: Randomized clinical trial. Pediatr Pulmonol. 2019;54(4):372‐ PMID: 30672140
  15. 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(1):76‐ PMID: 12517199
  16. Dhuper S, Chandra A, Ahmed A, et al. Efficacy and cost comparisons of bronchodilatator administration between metered dose inhalers with disposable spacers and nebulizers for acute asthma treatment. J Emerg Med. 2011;40(3):247‐PMID: 19081697
  17. Zorc, J. et al. Asthma Clinical Pathway – Emergency. Asthma Clinical Pathway – Emergency. http://www.chop.edu/clinical-pathway/asthma-emergent-care-clinical-pathway. Published August 12, 2014. Accessed May 28, 2020.
Kevin Rolnick, MD

Kevin Rolnick, MD

Resident
UCSF-ZSFGH Emergency Medicine Residency
Department of Emergency Medicine
University of California, San Francisco
Kevin Rolnick, MD

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