Kitchen Sink versus Out the Door Asthma Management
Larry B. Mellick
Department of Emergency Medicine, Georgia Regents University Hospital, 1120, 15th Street, Room AF-2053 Augusta, GA 30912, USA
*Corresponding Author: Larry B. Mellick, Department of Emergency Medicine, Georgia Regents University Hospital1120 15th Street, Room AF-2053 Augusta, GA 30912, USA, Tel: + 706 533-2931; Email: lmellick@gru.edu
Received Date: 14 December, 2016; Accepted Date: 14 December, 2016; Published Date: 20 December, 2016
Citation: Mellick LB (2016) “Kitchen Sink” versus “Out the Door” Asthma Management. Emerg Med Inves: 125. DOI: 10.29011/2475-5605.000025
1.Inhaled Corticosteroids
One of the first best supported asthma management options that of inhaled corticosteroids. The literature supporting this intervention is consistently positive and appears to support the use of inhaled steroids in addition to other systemic corticosteroids. In our shop we typically give one dose of oral dexamethasone (0.6 mg/kg) up to a maximum of 16 mg for asthma exacerbations that have been ongoing for one to two days and resistant to home management. My choice for an inhaled or nebulized corticosteroid is 0.5 mg of budesonide, but other options are also effective.
A published review article and a Cochrane review of the benefits of inhaled corticosteroids provide excellent supporting evidence for routinely adding this intervention to patients with recalcitrant bronchospasm [1,2]. The Cochrane review states the following: “This review found that inhaled corticosteroids used alone or in combination with systemic corticosteroids helped to relieve asthma.”[1] The review article by Volovitz summarizes its findings as follows, “The current evidence base revealed encouraging results regarding the efficacy of the ICS budesonide in patients with wheeze and acute worsening of asthma”.
2.Intramuscular or Nebulized Epinephrine
Epinephrine has always worked for bronchospasm. Older clinicians remember well using subcutaneous epinephrine every twenty minutes as the standard management for asthma exacerbations. And, despite the tears caused by the painful injections, it worked.
In truth, the literature is packed with papers that describe both injected and nebulized epinephrine as being non-inferior to older agents such as terbutaline oralbuterol. In other words, it works equally well to the bronchodilator medications that we currently use. It is just easier and less objectionable to nebulize medications rather than inject needles into adults and children. And, there is always some consideration for the known but minor side effects of epinephrine, a non-selective β2 agonist. Therefore, most clinicians reserve epinephrine, if they use it at all, for the patient presenting with severe and status asthma.
However, nebulized epinephrine probably works just as well as intramuscular epinephrine and possibly delivers a greater quantity epinephrine with minimal side effects. Both regular epinephrine (5 mg maximum) and racemic epinephrine (11.25 mg maximum) can be nebulized in the treatment of asthma and croup. However, it seems to be much easier to use the current commercially supplied preparations of racemic epinephrine for nebulization. Again, there is good evidence for the effectiveness of nebulized racemic epinephrine in the treatment of asthma [3-7]. While it is probably no better than currently used bronchodilators, it is clearly a different option to consider when nebulized albuterol has not successfully resolved the bronchospasm.
3.Antihistamines
Asthma causes or triggers can be divided into allergic and non-allergic etiologies. It is reported that allergies trigger asthma attacks in 60 to 90% of children and 50% of adults [8]. Sensitization to mite and cockroach antigens commonly found in the environment has been shown to increase asthma morbidity [9]. While complicated the bottom line is that IgE binds to high-affinity receptors on the surface of mast cells and basophiles leading to mast cell and basophil degranulation. Mast cell mediators, histamine, pro-inflammatory cytokines and proteases, are released leading to an early allergic response. Histamine is a known inflammatory mediator in the patho physiology of asthma. Therefore, it would seem to make intuitive sense that antihistamines could play a role in the treatment of asthma. Evidence for benefit from first generation antihistamines in asthma is relatively limited. This may be due the fact that for many years the teaching was to avoid antihistamines because of possible drying and studies have shown mixed results, but no detrimental effects are noted and definite positive effects of antihistamines can be documented especially with the second generation antihistamines [11-14]. Consequently, despite the weaker but positive evidence and because histamine is a known factor in the patho physiology of asthma, the addition of intravenous or oral antihistamines during and acute asthma event, seems both safe, reasonable and disease mechanism based. And, it is possible that the benefit of antihistamines may be interdependent or synergistic with other anti-inflammatory interventions.
4.Ibuprofen and NSAIDS
Another and more controversial option is the use of ibuprofen in asthma. Ibuprofen is a non-selective inhibitor of the enzyme cyclooxygenase (COX) which is required for the synthesis of prostaglandins via the arachidonic acid pathway. This pathway is active in the pathogenesis of asthma [15]. (Figure 1) [16]
Ibuprofen as a therapeutic intervention for asthma is often immediately rejected because of concerns about exacerbating asthma in the context of aspirin sensitivity. However, literature analysis seems to indicate that the use of ibuprofen in the pediatric population does not exacerbate asthma morbidity [17,18]. In fact, one author states the following: “Given the infrequent occurrence of aspirin/NSAID sensitivity in children with asthma, it seems reasonable to allow the use of ibuprofen in this population unless there is a personal or family history of aspirin-induced asthma. In addition, the inflammatory pathogenesis of asthma, anti-inflammatory effect of ibuprofen, and evidence suggesting ibuprofen may reduce morbidity in children with asthma raises the intriguing possibility that ibuprofen might actually have therapeutic benefit for at least some children with asthma.”[17] Lesko et al. stated that rather than supporting the hypothesis that ibuprofen increases asthma morbidity among children who are not known to be sensitive to aspirin or other nonsteroidal anti-inflammatory drugs, their study suggested that compared with acetaminophen, ibuprofen may reduce such risks [19]. Another study showed that single dose ibuprofen inhibits early and late asthmatic responses to allergen broncho provocation and recommended that ibuprofen be withheld for at least 24 h prior to investigations utilizing allergen broncho provocation [20]
In summary, while the evidence is limited, ibuprofen may actually decrease morbidity in asthma and based on its mechanism of action ibuprofen should theoretically decrease the inflammatory factors causing bronchospasm in asthma through its actions on the arachidonic acid pathway.
5.Nebulized MgSO4
Other options potentially exist and one of these includes nebulized magnesium sulfate. What is fascinating about nebulized MgSO4 is that the multiple systematic reviews and meta-analyses have come to exactly opposite conclusions. The evidence for this intervention was reviewed in a 2012 Cochrane review and the final implications for practice statements were as follows: [21]
1. Treatment with nebulised MgSO4 could be considered in addition to inhaled β2-agonists and ipratropium bromide in combination as per most national guidelines in asthma exacerbations, particularly in those patients with more severe exacerbations. However this point, regarding severity, requires further investigation in clinical trials. More data are required especially in pediatric studies.
2. There is no evidence that nebulised MgSO4 can be used as a substitute for inhaled β2-agonists.
3. Nebulised MgSO4 appears to be effective and safe to administer to patients experiencing asthma exacerbations.
However, a 2013 systematic review and meta-analysis by Shan et al. reported that the use of nebulized magnesium sulfate appears to produce benefits just for adults and not children [22]. And then, a 2016 systematic review and meta-analysis by Su et al. came to the conclusion that while intravenous magnesium sulfate was an effective treatment in children, nebulized magnesium sulfate treatment showed no significant effect on respiratory function or hospital admission and further treatment [23]. And another 2016 meta-analysis of adult patients treated with nebulized magnesium sulfate stated that evidence to date suggests thatnebulizedMgSO4has no role in the management of adult patients with acute or stable asthma [24].
The bottom line is that while there are studies that conclude nebulized MgSO4 alone or combined with salbutamol has a clinically significant bronchodilator effect in acute asthma and leads to clinical improvement, increase in PEFR, reduction in heart rate and reduction in respiratory rate, [25,26] other studies come to the exact opposite conclusion [27]. No studies, however, found that nebulized magnesium sulfate was harmful. Finally, the actual dosage of MgSO4 nebulized may vary between the studies and could be a contributing factor to this variability in findings and conclusions.
6.Conclusion
For the clinician who finds himself or herself regularly frustrated with asthma patients improving but lingering at clinical asthma scores incompatible with discharging home, consider trying some of the other treatment modalities that have either been overlooked or put on the shelf because of our newer therapeutic tools for treating asthma. It is possible that more patients will have their bronchospasm successfully treated and be eligible for discharge after responding to these other “out-the-door” asthma management options.
Figure 1: Ibuprofen pathways.
- Edmonds ML, Milan SJ, Camargo Jr CA, Pollack CV, Rowe BH (2012) Early use of inhaled corticosteroids in the emergency department treatment of acute asthma. Cochrane Database of Systematic Reviews 12: CD002308.
- Volovitz B (2007) Inhaled budesonide in the management of acute worsenings and exacerbations of asthma: a review of the evidence. Respir Med 101: 685-695.
- Wiebe K and Rowe BH (2007) Nebulized racemic epinephrine used in the treatment of severe asthmatic exacerbation: a case report and literature review. CJEM 9: 304-308.
- Plint AC, Osmond MH, Klassen TP (2000) The efficacy of nebulized racemic epinephrine in children with acute asthma: a randomized, double-blind trial. Acad Emerg Med 7: 1097-1103.
- Rodrigo GJ and Nannini LJ (2006) Comparison between nebulized adrenaline and beta2 agonists for the treatment of acute asthma. A meta-analysis of randomized trials. Am J Emerg Med 24: 217-222.
- Adoun M, Frat JP, Doré P, Rouffineau J, Godet C, et al. (2004) Comparison of nebulized epinephrine and terbutaline in patients with acute severe asthma: a controlled trial. J Crit Care 19: 99-102.
- Kjellman B, Tollig H, Wettrell G (1980) Inhalation of racemic epinephrine in children with asthma. Dose-response relation and comparison with salbutamol. Allergy 35: 605-610.
- William F Kelly (2016) Allergic and Environmental Asthma Overview of Asthma. J Drug and Diseases 2016.
- Calderón MA, Linneberg A, Kleine-Tebbe J, De Blay F, Hernandez Fernandez de Rojas D, et al. (2015) Respiratory allergy caused by house dust mites: What do we really know?. J Allergy ClinImmunol 136: 38-48.
- Gelfand EW (2002) Role of histamine in the pathophysiology of asthma: immunomodulatory and anti-inflammatory activities of H1-receptor antagonists. Am J Med 116: Suppl 9A: 2S-7S.
- Wilson AM (2002) Are antihistamines useful in managing asthma?. CurrOpin Allergy ClinImmunol 2: 53-59.
- Wilson AM (2006) The role of antihistamines in asthma management. Treat Respir Med 5: 149-158.
- Zitt MJ (2003) The role of non sedating antihistamines in asthma therapy. Allergy Asthma Proc 24: 239-252.
- Nelson HS (2003) Prospects for antihistamines in the treatment of asthma. J Allergy Clin Immunol 112: S96-100.
- Wenzel SE (1997) Arachidonic acid metabolites: mediators of inflammation in asthma. Pharmacotherapy 17: 3S-12S.
- Mazaleuskaya Liudmila L, Theken Katherine N, Gong Li, Thorn Caroline F, FitzGerald Garret A, et al. (2014) PharmGKB summary: ibuprofen pathways. Pharmacogenetics and genomics 25: 96-106.
- Kauffman RE and Lieh-Lai M (2004) Ibuprofen and increased morbidity in children with asthma: fact or fiction? Paediatr Drugs 6: 267-272.
- Kanabar D, Dale S, Rawat M (2007) A review of ibuprofen and acetaminophen use in febrile children and the occurrence of asthma-related symptoms. Clin Ther 29: 2716-2723.
- Lesko SM, Louik C, Vezina RM, Mitchell AA (2002) Asthma morbidity after the short-term use of ibuprofen in children. Pediatrics 109: E20.
- Nomani S, Cockcroft DW, Davis BE (2016) Allergen inhalation challenge, refractoriness and the effects of ibuprofen.Allergy Asthma ClinImmunol 12: 24.
- Powell C, Dwan K, Milan SJ, Beasley R, Hughes R, et al. (2012) Inhaled magnesium sulfate in the treatment of acute asthma. Cochrane Database of Systematic Reviews.
- Shan Z, Rong Y, Yang W, Wang D, Yao P, et al. (2013) Intravenous and nebulized magnesium sulfate for treating acute asthma in adults and children: a systematic review and meta-analysis. Respir Med 107: 321-330.
- Su Z, Li R, Gai Z (2016) Intravenous and Nebulized Magnesium Sulfate for Treating Acute Asthma in Children: A Systematic Review and Meta-Analysis. Pediatr Emerg Care.
- Ling ZG, Wu YB, Kong JL, Tang ZM, Liu W, et al. (2016) Lack of efficacy of nebulized magnesium sulfate in treating adult asthma: A meta-analysis of randomized controlled trials. Pulm Pharmacol Ther 41: 40-47.
- Sarhan HA, El-Garhy OH1, Ali MA, Youssef NA (2016) The efficacy of nebulized magnesium sulfate alone and in combination with salbutamol in acute asthma. Drug Des Devel Ther 10: 1927-1933.
- Hossein S, Pegah A, Davood F, Said A, Babak M, et al. (2016) The effect of nebulized magnesium sulfate in the treatment of moderate to severe asthma attacks: a randomized clinical trial. Am J Emerg Med 34: 883-886.
- Alansari K, Ahmed W, Davidson BL, Alamri M, Zakaria I, et al. (2015) Nebulized magnesium for moderate and severe pediatric asthma: A randomized trial. Pediatr Pulmonol 50: 1191-1199.
© by the Authors & Gavin Publishers. This is an Open Access Journal Article Published Under Attribution-Share Alike CC BY-SA: Creative Commons Attribution-Share Alike 4.0 International License. Read More About Open Access Policy.