Semester opg. om administrationsformer af Beta2 | ep. 81

Interview med Mads Lyngby – BSc 3. år, 2 semester opgave.

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Link til det omtalte studie fra Nordjylland:

https://ugeskriftet.dk/dmj/prehospital-b2-agonist-administration-spacer-versus-nebuliser

Herunder kan du læse selve opgaves som Mads afleverede på 3 års 2 semester.

Purpose

This literature review aims to investigate which device is better for delivering bronchodilators in adult patients. Considerable preliminary effort has gone into developing a research question and searching databases for relevant literature. This review also seeks to put findings and current practice into a prehospital perspective.

Research question: Are bronchodilators delivered by a metered-dose inhaler (MDI) with a spacer or valved holding chamber superior in treatment compared to nebulization in the adult patient experiencing bronchospasm symptoms?

Introduction

According to a Cochrane review by Cates et al. (2013) focusing only on acute asthma, metered-dose inhalers (MDIs) with a spacer can perform just as good as nebulization in delivering beta₂‐agonists in children. However, the evidence supporting this finding is less convincing for adults. The majority of available literature comparing the two devices is older than 20 years, primarily focuses on children, and is often related to treatment of asthma. This literature review aims to analyze and compare findings from eight selected articles on this topic, comprising three systematic reviews, three randomized controlled trials (RCTs), one cohort study, and one cross-sectorial study.

Article findings and discussion

Unfiltered information

A new cross-sectorial study by Alsuwaigh et al. (2023) aimed to investigate patients’ and health care providers’ attitudes on the use of MDI with spacer versus nebulization for exacerbations in both acute asthma and Chronic Obstructive Pulmonary Disease (COPD) in adults. This study addresses multiple important topics in health care as it seeks to uncover both the patient’s and the health care providers’ attitudes towards the treatment method. Both are key components in evidence-based medicine, as both clinical expertise and patient values serves as guidelines for treatment and decision-making, along with best available evidence (Titler 2008). Secondly, the data were obtained in a post COVID-19 era, which may have changed especially health care providers’ attitudes regarding certain treatments or decisions (Mason et al. 2020). Alsuwaigh et al. (2023) conducted a survey regarding effectiveness, ease of use, preparation and administration, side effects, and infection risk. The survey was completed by 99 patients and 753 health care providers. Both groups believed the nebulizer to be more effective, and patients who found it more comfortable were also more likely to prefer nebulization. Patients’ associating nebulization with a greater risk of infection were less likely to prefer it. Patient comfort and effectiveness influenced health care providers’ preferences. Ease of preparation and administration only influenced the preferences of nurses, which might be due to the fact that these tasks are often their responsibility (Jones et al. 2001). The authors conclude that the majority of both health care providers and patients have misconceptions about the effectiveness of nebulization treatments and that more needs to be done to educate both groups on effectiveness of MDIs with spacers.

A cohort study by Newman et al. (2002) set out to determine the efficiency of beta₂ agonists delivered by MDI with spacer compared to nebulization. The study was an unblinded, nonrandomized trial including 1,420 adult patients with acute exacerbation of asthma. The study design itself poses a risk of bias, and this risk is emphasized by other factors such as smoking not being an exclusion criterion and that patients were not categorized into groups of smokers and non-smokers. Patients receiving treatment in the Emergency Department (ED) with an MDI with spacer were discharged from hospital with asthma education and were provided a peak flow meter, a spacer, and a steroid inhalation for home use. Health care providers were allowed to break this protocol, which meant not all patients in the group received similar treatment. It is unclear whether patients in the nebulization group were provided with similar treatment options. The authors are aware of these risks of bias, which makes it difficult to compare results between the two groups. There was a statistically greater improvement in peak flow rates and oxygenation levels improved slightly in the MDI with spacer group, however, this did not translate into significant differences in readmission rates compared with the nebulization group.  The study concluded that in adult patients with asthma exacerbations presenting in an ED, an MDI with spacer is at least as effective as nebulization.

Filtered information

The three RCTs included share similarities in terms of study design and quality. All three were double blinded, placebo-controlled trials and while two of them were older than 25 years (Colacone et al. 1993; Levitt et al. 1995) the third was less than 15 years old (Dhuper et al. 2011). While albuterol was used as bronchodilator, varying treatment strategies were used in terms of dosages and time intervals. All three studies had rather small sample sizes (between 40 and 85 patients), and except for Levitt et al. (1995), which included patients with COPD exacerbations, only patients with asthma exacerbations were included. It was not possible to extract and differentiate the results from COPD patients and compare them with asthma patients and given the small sample size of only 15 COPD patients, the result would probably not be reliable for drawing any conclusions. Dhuper et al. (2011) mentions that an MDI with spacer may result in a reduction of time and effort invested by the health care provider treating the patient. As for wholesale costs between nebulization and MDI with spacer Levitt et al. (1995) claims that these are incomparable. This might be due to variable factors such as individual patient needs and time consumption, which make it very challenging to calculate exact total expenses. All three studies reached similar conclusions. Both methods are equally effective, provide similar bronchodilation and each method offers advantages.

A systematic review with meta-analysis by Cates et al. (2013) from the Cochrane database included 39 studies with a total of 2,626 patients and close to just one quarter of them being adults. The review included studies by Colacone et al. (1993) and Dhuper et al. (2011) which are included in this literature review as well, while excluding studies from Levitt et al. (1995) and Newman et al. (2002) which has also been included in this literature review. One was excluded for mixing asthma and COPD population and one for being non-randomized. Cates et al. (2013) concludes that there is no evidence supporting that an MDI with spacer is superior to nebulization in the adult patient having an asthma attack, either in hospital admission rates, length of stay in ED, lung function tests, or side effect risks. They do however point out limitations that may have increased the length of stay in ED compared to control groups. The authors review question was answered the best possible way that existing literature allowed to.

Another systematic review by Hendeles et al. (2005) included Colacone et al. (1993) but also Newman et al. (2002) which was excluded from the systematic review by Cates et al. (2013). This article clearly states its purpose as to “…discuss the scientific evidence supporting the use of MDI…” while describing steps taken to accomplish a conversion from nebulization to MDI with spacer at the authors own institution. This agenda suggests that the authors are very likely to be biased towards favoring the MDI with spacer over nebulization. Hendeles et al. (2005) focuses not only on asthma patients, which puts their findings in another perspective than articles focusing explicitly on asthma. Based on three RCTs including COPD patients Hendeles et al. (2005) found both methods to have equivalent efficiency in COPD exacerbations. The authors’ mention that this finding is supported by several additional nonrandomized studies as well. The final conclusion was that an MDI with spacer is as effective as nebulization but offers several advantages.

Finally, a systematic review by Kisch and Paloucek (1992), which analyzed data from 1980 to 1991 and included between 75 and 174 adults. This may be considered outdated, but despite this, the review arrived at conclusions consistent with newer studies finding no significant difference between the two methods in the effectiveness of treating acute asthma. Unlike Levitt et al. (1995), Kisch and Paloucek (1992) points out that wholesale costs are comparable, and that nebulization might be less expensive than an MDI with spacer.

Prehospital implications

It is uncertain whether study findings can be translated into prehospital recommendations. One reason for this is that many of the reviewed articles excluded life-threatening asthma and Emergency Medical Services (EMS) are often the ones to attend to these cases. Another reason is that most of the articles were based on asthma patients only, which makes it unclear whether critically or life-threatening COPD exacerbations benefit more from an MDI with spacer or nebulization (Barjaktarevic and Milstone 2020). As one size does not always fit all, it can be argued that both patient preference and clinical expertise play an even bigger role in prehospital care. This is due to the level of personal crisis patients find themselves in and the limited diagnostic tools available for EMS providers. As for prehospital wholesale costs these are not comparable with ED costs. This is mainly because care provided by EMS, including time spent at patient’s bedside, often occurs during transportation to the hospital, and therefore, there is no time to be saved.

Conclusion

None of the reviewed articles was able to determine if bronchodilators delivered by an MDI with a spacer were superior to nebulization in the adult patient experiencing bronchospasm symptoms. Seven of the studies all reached similar conclusions, emphasizing that neither of the two methods is significantly more effective than the other.

When equal in effectiveness, clinical expertise and patient preference should hold greater significance, as well as the risk of transmission when this holds relevance.

Further research needs to be conducted to determine if an MDI with spacer is superior to nebulization. To help understand and improve treatment methods, future research needs to focus not only on asthma but also other major groups receiving treatment e.g., COPD patients.

Reference

Alsuwaigh, R., Cao, Y., Puan, Y., Yii, A., Mohamed Noor, S.B., Ye, H., Chen, H., Li, X.L., Binte Mohd Noor, N., Liew, J. and Tay, T.R. (2023) ‘Nebulizer versus metered dose inhaler with space chamber (MDI spacer) for acute asthma and chronic obstructive pulmonary disease exacerbation: attitudes of patients and healthcare providers in the COVID-19 era’, The Journal of asthma : official journal of the Association for the Care of Asthma, 60(3), 600-608, available: http://dx.doi.org/10.1080/02770903.2022.2082307.

Barjaktarevic, I.Z. and Milstone, A.P. (2020) ‘Nebulized therapies in COPD: past, present, and the future’, International journal of chronic obstructive pulmonary disease, 1665-1677.

Cates, C.J., Welsh, E.J. and Rowe, B.H. (2013) ‘Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma’, Cochrane Database Syst Rev, 2013(9), Cd000052, available: http://dx.doi.org/10.1002/14651858.CD000052.pub3.

Colacone, A., Afilalo, M., Wolkove, N. and Kreisman, H. (1993) ‘A comparison of albuterol administered by metered dose inhaler (and holding chamber) or wet nebulizer in acute asthma’, Chest, 104(3), 835-841.

Dhuper, S., Chandra, A., Ahmed, A., Bista, S., Moghekar, A., Verma, R., Chong, C., Shim, C., Cohen, H. and Choksi, S. (2011) ‘Efficacy and cost comparisons of bronchodilatator administration between metered dose inhalers with disposable spacers and nebulizers for acute asthma treatment’, The Journal of emergency medicine, 40(3), 247-255.

Hendeles, L., Hatton, R.C., Coons, T.J. and Carlson, L. (2005) ‘Automatic replacement of albuterol nebulizer therapy by metered-dose inhaler and valved holding chamber’, American Journal of Health-System Pharmacy, 62(10), 1053-1061.

Jones, R., Freegard, S., Reeves, M., Hanney, K. and Dobbs, F. (2001) ‘The role of the practice nurse in the management of asthma’, Primary Care Respiratory Journal, 10(4), 109-111.

Kisch, G.L. and Paloucek, F.P. (1992) ‘Metered-dose inhalers and nebulizers in the acute setting’, Annals of Pharmacotherapy, 26(1), 92-95.

Levitt, M.A., Gambrioli, E.F. and Fink, J.B. (1995) ‘Comparative trial of continuous nebulization versus metered-dose inhaler in the treatment of acute bronchospasm’, Annals of emergency medicine, 26(3), 273-277.

Mason, A., Narcum, J. and Mason, K. (2020) ‘Changes in consumer decision-making resulting from the COVID-19 pandemic’, Journal of Customer Behaviour, 19(4), 299-321.

Newman, K.B., Milne, S., Hamilton, C. and Hall, K. (2002) ‘A comparison of albuterol administered by metered-dose inhaler and spacer with albuterol by nebulizer in adults presenting to an urban emergency department with acute asthma’, Chest, 121(4), 1036-1041.

Titler, M.G. (2008) ‘The evidence for evidence-based practice implementation’, Patient safety and quality: An evidence-based handbook for nurses.