Evidence-Based Practice for the Respiratory Therapist

The underlying clinical question for the proposed study is that for children aged between 5 and 15 years, in severe acute asthma refractory to nebulization by SABA/LAMA combination, how effective is using IV methylprednisolone alone versus IV methylprednisolone and heliox at reducing respiratory difficulties over a period of one hour of admission? Severe acute asthma is a clinical condition that can easily be managed using various therapies.

Nonetheless, poor management of severe acute asthma in children can also cause death upon cardiorespiratory collapse. When managing severe acute asthma in children, the therapies often target to increase air passage through oxygen supplementation and bronchodilators dilation. As per Batabyal & O’Connell (2018), the different therapies for severe acute asthma in children of aged 5-15 years should enable the patient to achieve a stable breathing condition.

There are only limited treatment therapies for acute severe asthma refractory to SAA/LAMA combination because the other ones are either prohibitively expensive or unsafe. But because the patients must be treated, physicians are often left with the choice of either IV steroids with or without heliox. This explains why many pieces of research have focused on IV methylprednisolone and heliox as the two most feasible options for treating acute severe asthma in children of age between 5-15 years old.

Using corticosteroids as a treatment option for severe acute asthma in children has however been well-established. Several clinical trials have investigated the benefits of corticosteroids and have provided indications of early improvement in peak expiration flow rates, reduced hospital admission, reduced morbidity, and decreased use of beta agonists (Fishe et al. 2019a). Some practitioners strongly believe that when presented with acute asthma exacerbations, intravenous corticosteroids should be a number one option for achieving the desired pharmacologic effect. However, other piece literature has revealed that this should not be the case (Ferrante & La Grutta 2018, Kenyon et al. 2020).

Specifically, according to Doymaz et al. (2020), corticosteroids should not be a top of the list option for acuter severe asthma exacerbation because their early onset of pharmacologic effects have not been confirmed. Specifically, corticosteroids have been suspected to alter leukocyte function, decrease vascular permeability and inhibition of arachadon acid pathway (Fishe et al. 2019b). Henderson et al. (2018) observed that corticosteroids cause a leukocyte response peak effect within 4-6 hours after administration, which is a delayed pharmacologic response.

Published guidelines and expert opinion on the treatment of acute asthma exacerbations recommend the use of oral corticosteroids within the first 48 hours of treatment (Tesse et al. 2018). However, according to Indinnimeo et al. (2018), some practitioners are hesitant on using oral therapy. Ideally, this hesitation is attributable to a perceived delay in the action onset, a longer duration of hospitalization associated with the use of oral corticosteroids, and potentially decreased potency of the therapy (Leung, 2021).

Some other trials (Ferrante & La Grutta 2018, Kenyon et al. 2020) have demonstrated a few therapeutic equivalencies of intravenous and oral corticosteroids, demonstrating similar improvements in peak expiratory flow rates, and forced expiratory volumes within one second (FEV₁) between intravenous and oral groups. However, only a few of the studies have assessed the clinical outcomes of these therapies such as length of hospital stay.

There is an established threshold in the management of acute severe asthma in children of age 5-15 years, that any therapy must be able to achieve. First, early treatment of asthma exacerbations is the best treatment strategy, and there are various important elements of early treatment that any therapeutic intervention must observe. For example, the therapy must be able to relieve hypoxemia when the patient is experiencing mild to severe exacerbations (Leung, 2021).

Similarly, according to Seliem & Sultan (2018), SABA must be able to reverse airflow obstruction, especially during severe exacerbations where additional inhaled ipratropium bromide is used. The corticosteroids must be able to reduce airway inflammation, especially in patients who fail to respond to SABA (Ferrante & La Grutta 2018, Kenyon et al. 2020). more importantly, the therapy must be able to prevent the relapse of exacerbation through follow-up care.

Since the 1940s, corticosteroids have been the widely used treatment of acute severe asthma. However, the long-term systemic use of corticosteroids such as IV methylprednisolone have been associated with adverse events such as adrenal suppression, and even cardiovascular disease (Ferrante & La Grutta 2018). As a result, clinicians have often questioned the mechanism of action of as well as their side effects to refute or support the use of IV methylprednisolone or heliox.

Typically, corticosteroids are synthetic analogue of the natural steroid hormones produced in the body within the adrenal cortex. Their synthetic compounds are like those of natural hormones and may have mineralocorticoid or glucocorticoid properties (Seliem & Sultan, 2018). According to Batabyal & O’Connell (2018), Mineralocorticoids affect ion transportation in the renal tubule’s epithelial cells and are majorly involve water balance and electrolyte regulation. On the other hand, glucocorticoids are primarily involved in protein and fat metabolism, with anti-proliferative, immunosuppressive, and anti-inflammatory properties.

Most of the immunosuppressive and anti-inflammatory actions of glucocorticoids are either directly or indirectly attributable to the interaction with the cytosolic glucocorticoid receptors, which changes the gene transcription to either repress or indue gene transcription in both structural cells and inflammatory leukocytes (Seliem & Sultan, 2018). Therefore, glucocorticoid have a clinical effect on asthma primarily by upregulating the transcription of anti-inflammatory genes to cause a downstream reduction in the number of pro-inflammatory chemokine and cytokine proteins, cell adhesion molecules and other important enzymes that initiate or maintain the host’s inflammatory response.

There are several side effects of systemic corticosteroids in children and adolescents that must be examined to evaluate whether IV methylprednisolone and/or heliox is effective in respiratory difficulties in children of age 5-15 years. For instance, the paediatric population receiving IV glucocorticoids such as IV methylprednisolone have been associated with growth suppression, which manifests in delay in growth among children with asthma as well as those with other diseases such as nephrotic syndrome (Leung, 2021). Evidence by Lew et al. (2021) also suggest that the final height of children with a history of glucocorticoid may have compromised final height.

An underlying hypothesis is that both IV methylprednisolone alone and IV methylprednisolone and heliox can reduce respiratory difficulties over a period of one hour of admission. However, considering the evidence on the side effects associated with systemic corticosteroids, practitioners must have evidence-based recommendations on how they can safely use the therapies to treat paediatric asthma.

But before any long-term use of systemic corticosteroids, the physician must have a thorough physical and patient history evaluation to examine the pre-existing conditions or risk factors that may be exacerbated by corticosteroids therapies including osteoporosis, affective disorders, dyslipidemia, and diabetes (Seliem & Sultan, 2018). According to Batabyal & O’Connell (2018), the use of corticosteroids must be preceded with thorough baseline measures such as height, body weight as well as blood pressure, alongside other important information such as blood glucose levels, pubertal status and nutritional status, lipid profile and complete blood count.

It is also important to assess the children’s exposure or symptoms of serious infections before the use of corticosteroids because they are usually contraindicated in patients with untreated systemic infections. According to Serebrisky & Wiznia (2019), patients without a history of chicken pox should avoid close contact to those with shingles or chicken pox, with a caution to seek immediate medical attention in case they do. Physicians should also be keen on concomitant use of other medications before initiating any corticosteroids therapy because existing research has shown drug interactions between corticosteroids and various drug classes.

Conclusion

IV methylprednisolone alone and IV methylprednisolone and heliox seem to be effective at reducing respiratory difficulties during acute asthma exacerbation in children of age 5-15 and may therefore be a good adjunctive therapy in for paediatric asthma management. However, while either IV methylprednisolone alone or IV methylprednisolone and heliox may be a viable constructive treatment option for emergency asthma treatment in children of age 5 – 15, physicians must be cautious of the various side effects associated with these therapies.

For example, IV glucocorticoids have been associated with a delay in growth among children with asthma as well as those with other diseases such as nephrotic syndrome. Also, systemic corticosteroids have been associated with perceived delay in the action onset, a longer duration of hospitalization associated with the use of oral corticosteroids, and potentially decreased potency of the therapy. The proposed investigation will delve into the benefits and side effects of IV methylprednisolone alone or IV methylprednisolone and heliox for managing acute severe asthma in children of age 5 – 15, before coming up with a comprehensive and evidence-based conclusion on which one among the two treatment regimens is more effective.

References

Batabyal, R. A., & O’Connell, K. (2018). Improving Management of Severe Asthma: BiPAP and beyond. Clinical Pediatric Emergency Medicine, 19(1), 69-75. https://doi.org/10.1016/j.cpem.2018.02.007
Doymaz, S., Ahmed, Y. E., Francois, D., Pinto, R., Gist, R., Steinberg, M., & Giambruno, C. (2020). Methylprednisolone, dexamethasone or hydrocortisone for acute severe pediatric asthma: does it matter?. Journal of Asthma, 1-10. https://doi.org/10.1080/02770903.2020.1870130
Fishe, J. N., Gautam, S., Hendry, P., Blake, K. V., & Hendeles, L. (2019a). Emergency medical services administration of systemic corticosteroids for pediatric asthma: A state-wide study of emergency department outcomes. Academic Emergency Medicine, 26(5), 549-551. https://doi.org/10.1111/acem.13660
Fishe, J. N., Palmer, E., Finlay, E., Smotherman, C., Gautam, S., Hendry, P., & Hendeles, L. (2019b). A statewide study of the epidemiology of emergency medical services’ management of pediatric asthma. Pediatric emergency care. doi: 10.1097/PEC.0000000000001743
Ferrante, G., & La Grutta, S. (2018). The burden of paediatric asthma. Frontiers in Pediatrics, 6, https://doi.org/10.3389/fped.2018.00186
Henderson, M. B., Schunk, J. E., Henderson, J. L., Larsen, G. Y., Wilkes, J., & Bratton, S. L. (2018). An assessment of asthma therapy in the pediatric ICU. Hospital Pediatrics, 8(6), 361-367. DOI: https://doi.org/10.1542/hpeds.2017-0003