MDI versus Nebulizer
Running Head: MDI versus Nebulizer
Are metered-dose inhalers as effective as nebulizers?
Advanced Practice in Pediatric Nursing Theory
Rutgers, the State University of New Jersey
Dr. Cynthia Ayres
1
MDI versus Nebulizer
2
Abstract
Beta-agonists administered by means of nebulizers traditionally have been the treatment
of choice in children under 5 years of age presenting with wheezing in emergency
departments for decades. Beta-agonists administered via metered dose inhalers (MDI)
with spacers have been studied in an effort to evaluate effectiveness and reduce
healthcare costs of emergency departments. MDI with spacers have been proven to
provide equivalent relief of symptoms and improve airway function when compared to
nebulizers. A review of the literature revealed multiple studies comparing MDI to
nebulizers in older children and adults, but research is considerably limited in younger
populations. Five research studies have been critiqued comparing the effectiveness of
MDI and nebulizers in children less than 5 years of age. According to the data presented
medications delivered by MDI with spacers are effective at providing resolution of
wheezing with less systemic side effects, and decreasing hospital admission rates when
compared to nebulizers.
MDI versus Nebulizer
3
PICO Question
In young children, are beta-agonists delivered by metered dose inhalers with
spacers versus nebulizers more effective at decreasing hospital admission rates?
P: Children 5 and younger with moderate to severe wheezing
I: Metered dose inhalers with spacers
C: Nebulizers
O: Metered dose inhalers with spacers are more effective at decreasing hospital
admission rates and provide effective resolution of wheezing compared to nebulizers.
Review of the Literature
Study 1
Rubilar, Castro-Rodriguez, and Giardi (2000) conducted a single-blinded,
prospective randomized clinical trial of 123 outpatients aged 1 to 24 months of age. The
purpose of the study was to compare the efficacy of salbutamol delivered through a
metered dose inhaler with a spacer and nebulizer for acute exacerbations of wheezing.
Severity of wheezing was defined with the use of validated clinical scores 1 to 5 (mild); 6
to 7 (moderate); 8 to 10 (severe); 11-12 (very severe).
One investigator blindly enrolled and evaluated all patients without knowledge of
treatment group. Randomization was accomplished by assigning children to one of two
treatment groups by the use of a random table of numbers. The nebulizer group received
salbutamol aerosol 0.5% (0.25 mg/kg) solution in 3.5 mL of normal saline solution
powered by either compressed air if the clinical score was between 6 and 7, or oxygen if
clinical score was between 8 and 10, delivered by a face mask for 7 minutes every 20
minutes during the first hour for a total of three nebulizations per hour. A flow rate of 7
MDI versus Nebulizer
4
L/min was used. Children in the MDI with spacer group received two puffs of
salbutamol (100 micrograms/puff) every ten minutes, five times over one hour for a total
of ten puffs per hour. Both groups received oxygen by nasal cannula if clinical scores
were severe. Treatments in both groups were administered by a registered chest
physiotherapist without informing the investigator of treatment modality used. After one
hour a clinical score of less or equal to five was considered successful. A score of greater
than or equal to five was considered failure after the second hour of treatments.
Results of the study found statistical significant (P=.01) that 90 % or 56/62
patients in the MDI groups had clinical score of less or equal to five versus only 71 % or
43/61 patients in the nebulizer group after the first hour of treatments. After the second
hour of treatment no statistical significance (P = > 0.5) was noted, the MDI group had
100% success rate compared to 94.4% in the nebulizer group. One patient in the
nebulizer group was admitted for treatment failure. Transitory tremors were found in
three children in the nebulizer group versus one in the MDI with spacer group.
The investigators concluded that in children less than two years of age treated
with salbutamol with MDI with spacer had faster response and decreased hospitalization
rates than those treated with nebulizers. In addition, children in the MDI group were
found to have less systemic side effects from salbutamol compared with nebulizer
administration.
Study 2
Ploin et al. (2000) conducted a randomized, double-blinded, parallel group
equivalence trial with the purpose of comparing the effectiveness of albuterol
administered using an asthma spacer device (ASD) with nebulized albuterol in children
MDI versus Nebulizer
5
with acute recurrent wheezing. The sample consisted of 64 children, 12 to 60 months of
age. Recurrent wheezing was defined as a history of at least one prior episode of
wheezing. Random assignment was conducted in blocks of four with the use of computer
software. In addition, the order of the treatment modality used was also randomized,
administration of nebulizer or MDI first. All medications were packaged individually for
each child. The packages included albuterol for inhalation with nebulizer kit, ASD with
spacer, and a placebo. Dosage for nebulized albuterol was 150 micrograms/kg, and ASD
1 puff per 2 kg (maximum 10 puffs). Nebulized albuterol treatments followed with a
placebo via an ASD lasted 10 minutes. A nebulized placebo followed by albuterol ASD
with spacer lasted 1 to 2 minutes. Treatments were given at 20 minute timed intervals for
a total of 60 minutes. Clinical assessment was based on physical assessment and
cardiopulmonary monitoring at T0, T20, T40, and T60. Furthermore, after sixty
minutes, parents were asked to answer two questions and choose the ASD, the nebulizer,
or no preference. The questions asked were: “Which treatment mode looked easier to
administer?” and “Which treatment mode looked more acceptable to your child?”
Results showed the 90% confidence interval of the difference between both
treatment modalities, ASD with spacer and nebulizer, proved to be equivalent [-1; +1].
Clinical improvement was noted after three treatments (time effect: P < .01) despite
treatment modality used. Both the ASD with spacer and nebulizer had 2 treatment
failures requiring hospitalization. Results from the questions asked to parents showed
that 94% found ASD was easier to use and 62% were better accepted by their children
versus nebulizers.
MDI versus Nebulizer
Study 3
In a randomized, double-blinded, placebo controlled trial study conducted by
Mandelberg et al. (2000) of 42 children aged 10 months to 4 years of age, mean age 16
months referred by primary physician or local clinic. The purpose of the study was to
compare efficacy of a metal MDI with spacer and wet aerosol nebulization in young
children with acute wheezing episodes. Patients were selected in permuted blocks of
four according to order of arrival into one of two groups MDI with spacer or nebulizer.
In order to balance the sample according to age, a second randomized selection was
performed with those children less than 24 months and those older than 24 months.
Group I received salbutamol 2.5mg via nebulizer, followed with four puffs of a placebo
MDI administer through a spacer. Group II received a wet aerosol inhalation of saline
followed by four puffs of salbutamol (400 micrograms) through the MDI and spacer.
Timed intervals of 20 minutes were used to collect data inclusive of objective measures.
Clinical scores were defined as (1) objective measures, respiratory rate, pulse rate and
pulse oximetry data and (2) subjective measures wheezing, reduced intensity of breath
sounds and retractions. Assessments were conducted by the principal investigator
blinded to the treatment modality used.
Researchers did not find statistical significance (p=NS [not significant]) between
treatment groups at any point in time. The primary outcomes of the study were
improvement in clinical score and respiratory rate or adverse effects did not differ in
either group. Hospitalization rates were equal as well.
6
MDI versus Nebulizer
7
Study 4
Delgado, Chou, Silver, and Crain (2003), conducted a double-blinded randomized
controlled clinical trial with a placebo in a convenience sample of 85 children aged 2 to
24 months, mean age 11.7 months. The purpose of the study was to evaluate the
effectiveness albuterol administered by a metered dose inhaler with a spacer versus
nebulizer to treat wheezing. Severity of wheezing was defined by clinical measurements
that included saturation rate at room air measured by pulse oximetry, heart rate, and
Pulmonary Index (PI) score. The PI scores were divided into three groups: 0-3 (mild
asthma); 4 to 7 (moderate asthma); 8 to 12 (severe asthma). All children with oxygen
saturation less than 94% received oxygen by mask with nebulized saline at 6L/min.
Study medications albuterol and placebo solutions for nebulization were provided
by the hospital pharmacy in identical dark-brown glass medicine bottles. Albuterol and
placebo for metered-dose inhalers were prepared in similar canisters. The placebo
contained an oleic acid dispersant.
A random number table was used to assign patients to one of two double-blinded
treatment groups. In the nebulizer group, each aerolized treatment consisted of 3 puffs of
a placebo MDI with a spacer, followed immediately by a standard dose of 0.15 mg/kg of
albuterol in 3 mL of saline delivered by oxygen at 6L/min. Patients in the spacer group,
treatment consisted of 3 puffs of albuterol MDI with a spacer, followed by 3 mL of
nebulized saline. Treatments were given at twenty minute intervals.
Administration of
the MDI was performed by the principal investigator one puff of albuterol or placebo was
dispensed into the spacer and held the mask on the child’s face while the child breathed
five to six times through the mask.
MDI versus Nebulizer
8
Results indicated that the patient group treated with MDI with spacer were
statistically significant (P = .003) less likely to be admitted to the hospital for further care
compared to the nebulizer group.
Admission rates in the moderate asthma category
were not as significant (P = .23), as when compared to the severe asthma (P = .04) group,
meaning children in the severe category responded better to MDI with spacer. In
addition, the researchers found that patients in the MDI with spacer group had
significantly lower mean increase in heart rate (P = .02) compared to nebulizers.
These results indicate that the use of MDI with spacers in an emergency
department is as efficient as nebulizers for the treatment of wheezing in younger children.
Moreover, hospitalization was lower in children treated with a MDI with spacer
compared to nebulizer. This study also contributes to a body of literature that betaagonists administered through a MDI produce less systemic side effects.
Study 5
Castro-Rodriguez and Rodrigo (2004) undertook the task of performing a
systematic review with meta-analysis with the purpose of comparing metered dose
inhalers with valve holding chamber (MDI+VHC) versus nebulizers for acute
exacerbation of wheezing or asthma in children under five years of age with a primary
outcome of hospital admissions rates. Researchers reviewed published randomized
prospective control trials from1966 to 2003 with the use of multiple databases to
extrapolate studies. The search was conducted using three search strategies. Medline
and Embase databases were accessed using key terms. Only randomized controlled trials
conducted in an emergency department or equivalent, inclusive of infants or children less
than 5 years of age treated beta-agonists administered with MDI+VHC versus nebulizer
MDI versus Nebulizer
9
were included in the systemic review. Secondly, an advanced search of the Cochrane
Controlled Trials Register was completed using the same search criteria. Lastly,
references from studies, reviews, and texts were searched for citations. Primary and
secondary outcomes were admission to the hospital and final clinical score, duration of
treatment in the ED, respiratory rate, oxygen saturation, heart rate, and side effects.
The studies were reviewed by two independent reviewers for potential relevance
and inclusion based on the described criteria. Quality of the studies was determined by
the Jadad 5 point likert scale, to assess the adequacy of randomization, blinding, and the
handling of withdrawals and dropouts. Studies were assigned scores 1 (low quality) to 5
(highest quality). Eventually only 6 articles were selected for inclusion in the metaanalysis with Jadad scores of 3 to 5.
The results of the systematic review indicated that of the 491 patients aged 1
month to 5 years treated with MDI+VHC showed statistically significant (P = .002)
lower admission rates compared to the nebulizer group. In addition, the analysis also
demonstrated a significant (P = .0003) decrease in the severity of clinical scores in the
MDI +VHC group.
Critique
Study 1
Strengths of this study include randomization of children into treatment group.
Exclusion criteria for study subjects were clearly defined. Interventions and products
were clearly described allowing for replication of the study. In addition, the use of a
validated instrument to collect clinical scores increases the reliability of the results
MDI versus Nebulizer
10
obtained. Interventions were administered by the same respiratory therapists allowing for
consistency.
A limitation of the Rubilar et al (2000) study is its single-blind design. One
investigator blindly enrolled and evaluated patients without knowledge of treatment
modality. Another possible limitation is that investigators did not identify the etiology of
the wheezing either from bronchiolitis or asthma, perhaps decreasing the samples
homogeneity. Additionally, the source of the bronchiolitis may have altered the response
of the treatment. Lastly, the use of a control group with no intervention was considered to
be unethical as treatment with a bronchodilator should be given in all patients presenting
with wheezing. Patients were not followed after discharge from the emergency
department since clinical scores were low and investigators did not expect a relapse.
Relevance of this study to practice is the age of the sample used. Children ages 2
to 24 months were able to tolerated and respond faster to salbutamol administered
through a MDI with spacer versus a nebulizer. This is significant since this population of
children have greater hospitalization rates than other children presenting with wheezing.
Study 2
Strengths of this study include randomization in blocks of four and doubleblinding and the use of a placebo provided control. Inclusion and exclusion criteria of
subjects were also clearly defined. Sample homogeneity was achieved by excluding
subjects with bronchiolitis. Furthermore, the investigators used the Pulmonary Index
scale, an instrument with construct and criterion validity to assess asthma scores.
A limitation to this study was the inconsistency in assessing patients. The
principal investigator assessed 44 patients, the remaining 20 children were assessed by
MDI versus Nebulizer
11
the 8 other trained investigators perhaps increasing interrater reliability. Assessments by
multiple investigators have the potential of producing errors interpreting findings. In
addition, the reliability of the questions asked to parents was not reported.
This study adds relevance to the body of literature that drugs delivered with
spacers are equivalent to nebulizers in tertiary care centers. Moreover, this study reports
the parent’s acceptance of MDI with spacers in their children. Public opinion coupled
with strong clinical evidence promotes change.
Study 3
The Mendelberg et al (2000) study was a randomized, double-blinded, doubledummy placebo controlled study. Children were first randomized in permuted blocks of
four. In addition, the researchers conducted a second round of randomization of patients
to increase homogeneity of treatment groups. A placebo intervention increases control.
Interrater reliability was decreased in the study were by having one investigator assess all
the children blinded to the treatment protocol used.
Limitations of this study include sample size; only 42 patients were evaluated,
thus lacking power to infer results. In addition, researchers did not indicate the number
of patients hospitalized according to the intervention used, but rather pooled them
together.
Relevance to evidenced based practice from this study was that it made no
difference which mode of administration was used since the children in both groups
responded the same. MDI with spacers are as effective as nebulizers in the treatment of
wheezing in this age group.
MDI versus Nebulizer
12
Study 4
Delgado et al. (2003) strengths are its randomized double-blinded placebo design.
Exclusion criteria for the sample included patients with a history of chronic lung disease,
congenital heart disease, intubation for longer than one week during the neonatal period,
symptoms of croup, oxygen saturation less than 90 % or signs of impending respiratory
failure. In addition, the authors clearly delineated the interventions, allowing for
replication for the study. The Pulmonary Index instrument used for clinical
measurements has been found to have construct validity.
Limitations to the study include sample size. According to the researchers a
sample size of 88 subjects in each treatment group was needed to provide a power of at
least 80 % to detect a 15% difference in admission rate. The sample size consisted of 85
in the nebulizer group and 83 in the spacer group. Therefore, this study lacks power and
effect size. Furthermore, subjective observations to the degree of wheezing and
retractions in patients can be considered bias.
Relevance to practice from this study is that MDI with spacers may be utilized
efficaciously in younger patients with moderate to severe asthma exacerbations. In
addition, the observation of albuterol delivered via MDI with spacer promotes less
systemic effects can be safely used in patients with cardiac conditions and co-morbidities
where heart rate elevation can be detrimental.
Study 5
The Castro-Rodriguez and Rodrigo (2004) study meets the rigors of systemic
reviews and meta-analysis as outlined in Polit and Beck (2008). Strengths of the study
include the investigators clearly stating the purpose of the systemic review and meta-
MDI versus Nebulizer
13
analysis and its contribution to the body of literature encompassing the use of MDI with
VHC versus nebulizers. In addition, the authors clearly identified the search criteria for
studies to be included in the review as well as the use of multiple databases to search for
relevant articles. To enhance the integrity of the dataset two independent reviewers
assessed titles, abstracts, and citations for relevance for full review. In addition, the
researchers used Jadad et al (1996) criteria for evaluating randomized controlled trials.
The authors also described the methods used for combining and integrating the data in the
meta-analyses by means of random-effects models using the DerSimonian and Laird
method. Primary and secondary outcomes of the meta-analysis were addressed as well.
The results demonstrated a strong effect in regards to lower hospital admission
rates with beta-agonists given by a MDI with valve holding chambers compared with
nebulizer. Overall clinical scores were lower in the MDI+VHC treatment group.
Lastly, in the discussion, the authors were cognizant of the limitations regarding
the generalization of the meta-analysis to children with wheezing. Limitations to the
meta-analysis are inherent in the studies utilized, such as the heterogeneity of the
population studied. Children with different causes for wheezing were included in the
systemic review and meta-analysis.
A possible limitation of the meta-analysis would include the sample size, only six
studies were included. However, such limitations are innate in the number of RCT
studies completed in this population age. Most studies have been conducted in older
children presenting with wheezing as a result of asthma exacerbations. Consequently,
only those studies that met the inclusion criteria were available for systemic review.
MDI versus Nebulizer
14
Relevance of this study to evidence based practice is that it is the first systemic
review and meta-analysis to address the delivery method for bronchodilators with MDI
with spacers versus nebulizers in children as young as one month of age. A Cochrane
systemic review (2006) included adults and children older than two with acute asthma.
Other causes for wheezing were not included in the review.
Implications for Practice
The RCT and meta-analysis reviewed provide compelling evidence that betaagonists administered by metered dose inhalers provide a safe and efficacious alternative
to nebulizers in younger children presenting with wheezing, and thus have lower hospital
admission. A significant number of children responded well to bronchodilators given by
a MDI preventing hospitalization.
Metered dose inhalers address the clinically relevant
outcome of lower admission rates of children with presenting with wheezing. Wheezing
can be attributed to any respiratory ailment, but it is mostly a result of bronchiolitis from
viral infections or acute exacerbations of asthma. These patients can perhaps be treated
at home or in primary care settings, but research is needed in these settings.
Furthermore, not only does a hospitalization create a stressful situation for child
and parents (Burke et al., 2001), the associated costs are considerable. Cost of betaagonists canisters and spacers are less expensive when compared to nebulizers (Geller,
2005). Costs are also extended to the number of beds occupied in an emergency
department, and the personnel needed to administer the treatments. Administration of
bronchodilators via a MDI with spacer take less time to administer compared to
nebulizers. Rubilar et al. (2000) also found a faster response rate in the MDI group.
MDI versus Nebulizer
15
Faster response rates alleviate congestion, and allows for higher turn over of patients
treated in the emergency department.
Teaching parents to effectively administered bronchodilators via MDI at home
prior to evaluation in the emergency department can significantly decrease signs of
respiratory distress or clinical scores. The ease of use and portability also increases
compliance and can decrease a wheezing episode. Methods that are easier and less
cumbersome usually have greater acceptance by parents as reported in the Ploin et al
(2000) study. However, education is key to proper use; technique must be emphasized
for correct administration of medication.
Beta-agonists administered with MDI and spacers as reported by Delgado et al
(2003), and Ploin et al (2000) have less systemic effects compared to nebulizers. Rubilar
et al (2000) also found more children to have transitory tremors in the nebulizer group
compared to the MDI with spacer group. Tachycardia can be a confounding variable in
the admission of children for further care.
Lastly, more research is needed that may extend to primary care settings. The
randomized controlled studies presented have taken place in emergency departments
across the world. However, there exist some concerns regarding the dosage
bronchodilators via a MDI, exactly how many puffs should be administered?
Consistency is needed in determining the efficacy of MDI with spacers.
According to Scott et al. (2009), despite evidence pertaining to the efficacy of
MDI with spacers, barriers to their use are many. Aside from the usual perceived
increased costs and parental resistance, there exists lack of consensus regarding the
benefits among the staff. They also cite that lack of leadership in the form of a research
MDI versus Nebulizer
16
champion has curtailed progressive change in emergency departments. Creating a culture
of evidence-based practice (EBP) in such institutions can help create change (Melnyk,
2010 [Webinar]). Advanced practice nurses can serve a pivotal role in creating an
environment of EBP, especially with metered dose inhaler with spacer use in emergency
departments. The evidence exists, however implementation is lacking.
MDI versus Nebulizer
17
References
Burke, S. O., Harrison, M. B., Kauffmann, E., & Wong, C. (2001). Effects of stresspoint intervention with families of repeatedly hospitalized children. Journal of
Family Nursing, 7 128-158.
Castro-Rodriguez, J. A., & Rodrigo, G. J. (2004). B-agonists through metered=dose
inhaler with valved holding chamber versus nebulizer for acute exacerbation of
wheezing or asthma in children under 5 years of age: a systematic review with
meta-analysis. The Journal of Pediatrics, 145, 172-177.
Cates, C. J., Crilly, J. A., & Rowe, B. A. (2006). Holding chambers (spacers) versus
nebulisers for beta-agonist treatment of acute asthma. Cochrane Library, 2, 1-99.
Delgado, A., Chou, K. J., Silver, E. J., & Crain, E. F. (2003). Nebulizers vs metred-dose
inhalers with spacers for bronchodilator therapy to treat wheezing in children
aged 2 to 24 months in a pediatric emergency department. Archives of Pediatric
Adolescent Medicine. 157, 76-80.
Geller, D. E. (2005). Comparing clinical features of the nebulizers, metered-dose
inhalers, and dry powder inhaler. Respiratory Care, 50, 1313-1322. Retrieved
March 1, 2010, from http://www.rcjournal.com/contents/10.05/10.05.1313.pdf
Mandelberg, A., Tsehori, S., Houri, S., Gilad, E., Morag, B., & Priel, I. E. (2000). Is
nebulized aerosol treatment necessary in the pediatric emergency department?
Chest, 117, 1309-1313.
Melnyk, B. (2010). Evidence-based practice: Making it Work in Your Organization
[Webinar] March 3, 2010, from http://www.talkpoint.com/viewer/presentation.asp
MDI versus Nebulizer
18
Ploin, D., Capiuis, F. R., Stamm, D., Robert, J., David, L., Chatelain, P. G., et al. (2000).
Pediatrics, 106, 311-317.
Polit, D. F., & Beck, C. T. (2008). Nursing Research Generating and Assessing
Evidence for Nursing Practice. Philadelphia: Lippincott, Williams & Wilkins.
Rubilar, L., Castro-Rodriguez, J. A., & Girardi, G. (2000). Randomized trial of
salbutamol via metered-dose inhaler with spacer versus nebulizer for acute
wheezing in children less than 2 years of age. Pediatric Pulmonology, 29, 264269.
Scott, S. D., Osmond, M. H., Leary, K. A., Graham, I. D., Grimshaw, J., Klassen, T., et
al. (2009). Barriers and supports to implementation to MDI/spacer use in nine
Canadian pediatric emergency departments: a qualitative study. Implementation
Science, 4. Retrieved March 10, 2010, from
http://www.implementationscience.com/content/pdf/1748-5908-4-65.pdf