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According to the WHO, it is estimated that approximately 300 million people currently suffer from asthma. "In 2000, asthma accounted for 4,487 deaths, approximately 465,000 hospitalizations, an estimated 1.8 million emergency department (ED) visits, and approximately 10.4 million physician office visits among persons of all ages" CDC). Amongst children, asthma is the most common chronic disease. Almost all of the asthma visits were recorded as 'acute asthma'. Asthma occurs in all countries regardless of the level of development. "The cause of asthma is contracting of the bronchial airways. This is a result of inflammation of the bronchi and tightening of the bronchial soft muscle" who). Asthma is a common public health problem, often creating a substantial burden to affected individuals and their families by means of restricting the activities of affected individuals for a lifetime. Asthma is generally under-diagnosed and under-treated and asthma related deaths occur in the majority in low and lower-middle income countries.
Efforts to reduce asthma attacks have had varying degrees of success. One common treatment is administering magnesium sulphate ions to improve airflow.
The usage of magnesium sulphate to treat bronchial asthma (in a clinical setting) dates back to 1936. It was at this time that Rossello and Pal observed that infusion of magnesium sulphate successfully relieved dyspnoea and stridor in patients with an asthmatic condition (Bucca & Rolla, 2003, p.2095). Magnesium interacts with calcium activity by inducing calcium channel blockade. In the airway, calcium is mobilised for smooth-muscles contraction. This comes from either extracellular store via voltage-sensitive calcium channels or from intracellular stores via receptors-operated channels (Bucca & Rolla, 2003, p.2095). Magnesium has been shown to cause bronchial smooth-muscles relaxation by either its action as a "physiologoic calcium antagonist" or by its action on adenyl cyclase activation (Noppen, 2002, p.396).
A literature review of MgSO4 use in patients with exacerbations of severe acute asthma by Row & Camargo, Jr. (2008) shows intravenous MgSO4 is beneficial in acute asthma, while the evidence for inhaled MgSO4 is less convincing. Moreover, the role of replacement therapy with oral magnesium remains to be clarified. The use of intravenous MgSO4 remains uncommon, with emergency physicians appropriately restricting its use to patients with severe exacerbations.
There is conflicting opinion amongst researchers as to the most effective route of administering magnesium sulphate to treat asthma. This is mostly due to varying opinion as to which treatment is best for certain severities of asthma attacks, as opposed to the actual treatment itself. All agree that treatment is important; it is the route that is in debate.
IV vs. NB:
One study evaluated current practices by emergency physicians in the treatment of severe acute asthma in the United Kingdom. Magnesium Sulphate was used to relieve breathlessness and it was mostly given intravenously to patients having acute severe asthma and life-threatening exacerbations (Jones & Goodacre, 2009, p. 784).
In a randomized controlled trial Singh, Gaur & Kumar (2008) show that intravenous administration of MgSO4 as an adjunct to standard therapy in severe acute asthma improves pulmonary function and discharge rates. Silverman et al (2002, p.493) agree with this by specifying the dose, specifically with use of 2g of IV MgSO4 when administered as an adjunct to standard therapy in patients who present to the emergency department with severe asthma. There is some evidence that the doses of MgSO4 in the range of 1.2 to 2 g IV over 20 minutes is beneficial in severe asthma cases, however no benefits were observed in patients with mild to moderate asthma (Sanders, 2009, p.674). Bucca & Rolla ( 2003, p.2095).As the effectiveness of magnesium was limited only to patients with the most severe airway obstruction the overall use of IV MgSO4 did not reduce the rate of admission to hospital.
However, careful monitoring is required for the mode of IV treatment, especially since peripheral vasodilation and systolic hypotension can occur. If this does occur, the patient can present with unpleasant flushing, nausea, and venous phlebitis from the infusion (Hughes et al, 2003, p. 2114)
The benefit of IV magnesium is that the IV method extends to cover other aspects in both healthy and critically ill individuals. In healthy individuals, the level of blood magnesium is remarkably constant and maintained by a poorly understood homeostatic mechanism (Wang, Shaw, & Kao, 2007, p. 579). Up to 65% of patients may have an occurrence of Hypomagnesiema and this is directly related with increased rates of mortality. A severe deficiency of magnesium can lead to a variety of dysrhythmias, muscles weakness and mental status changes, seizures, various endocrine dysfunctions as well as other conditions. In addition, it can also lead to also to bronchospasm and respiratory failure. Magnesium sulphate therefore becomes useful for those critically ill patients (Noppen, 2002, p.396). The blood of patients with chronic, stable asthma sometimes shows the presence of Hypomagnesemia (Wang, Shaw, & Kao, 2007, p. 579). Also, significant abnormalities in divalent magnesium ion concentration level have been found in asthmatic patients with acute asthma exacerbations, which was corrected with IV magnesium (Spektor et al, 2005, p. 659).
With regard to acute asthma exacerbations, this is usually managed by the use of inhaled beta-agonists, systemic corticosteroids, and supplemental oxygen, however not all patients' respond to these treatments (Bucca & Rolla, 2009, p.2095). In the treatment of patients with an acute asthma exacerbation, the use of nebulised magnesium sulphate (particularly when combined with Î²2-agonist 'salbutamol') appears to show improved pulmonary function and has the potential to reduce the number of hospital admissions (Biltz et al, 2005, p. 337).
In a randomised controlled study by Bessmertny et al and his colleague (2000), the bronchodilating effect of nebulised magnesium was similar to that of salbutamol in patients with acute asthma exacerbation. The possible additive bronchodilating effect of magnesium and salbutamol has been investigated: a mild sustained increase in serum magnesium concentration caused a significant leftward shift of the dose-response curve to inhaled salbutamol in asthmatic patients, with no change in the maximum response (Bucca & Rolla, 2003, p.2097). Mangat et al (1999, p.395) and Biltz (2005, p.337) argue that therapy which combines a Î²2-agonist (usually salbutamol) with magnesium sulphate yields results showing improved pulmonary function. However, this therapy did not reduce the number of hospital admissions.
By contrast, the combination of salbutamol and nebulised magnesium sulphate in adults with mild-to-moderate asthma exacerbations provided no additional benefit when compared with salbutamol alone (Bessmertny et al., 2000). Also, the results of one study showed that inhaled magnesium does not act as a bronchodilator in the stable asthma cases (Hughes et al, 2003, p. 2114).
Hughes et al and other colleagues have provided different results in their study regarding cases of patients with severe asthma exacerbations. One study was of a randomised placebo-controlled trial of 52 patients with severe exacerbations of asthma who presented to the emergency departments at two hospitals in New Zealand. This study assessed the effectiveness of isotonic magnesium sulphate as an adjuvant to nebulised salbutamol in severe attacks of asthma. At 90 min the mean FEV1 in the magnesium group was 1.96 L (95% CI 1.68-2.24) and 1.55 L (1.24-1.87) in the saline group. The difference in the mean FEV1 between the magnesium and saline groups was 0.37 L. Use of isotonic magnesium as an adjuvant to nebulised salbutamol results in an enhanced bronchodilator response in treatment of severe asthma (Hughes et al., 2003). In a study by Biltz (2005) there is an agreement with Hughes et al (2003), as the evidence suggests that effectively improving pulmonary function can come from adding ipratropium bromide to Î²2-agonist therapy. Also, with particular regards to patients with severe cases of asthma, such therapy has shown a reduction in the number of hospital admissions in the acute setting.
There is a strong debate about the use of oral magnesium in order to improve asthma conditions. Gontijo-Amaral et al and other colleagues (2007, p.57) found that there was a significant improvement in bronchial responsiveness after 2 months in children and adolescents with moderate persistent asthma when treated on a regular basis with inhaled fluticasone and also oral magnesium supplementation, as assessed by the methacholine test. A clinical improvement was shown by a reduced number of asthma exacerbation episodes as well as reduced usage of inhaled salbutamol. This is linked to a population based study which shows epidemiological evidence which indicates that there is an association between low dietary intake of magnesium and increased incidence of asthmatic symptoms. The study results also show reduced lung function, wheezing, and lower lung volume and flows (Wang, Shaw, & Kao, 2007, p. 579). In contrast, Fogarty et al and his colleague (2003, p. 1533) have proved that there are no clinical benefits to current standard therapy of asthma in primary care patients by the use of regular dietary supplementation with vitamin C or magnesium.
Even though the serious consequences are avoided in most people, the treatment and prevention of asthma exacerbations is an important consideration of their disease. It is possible that because of a considerable impact on lifestyle, there may be increased financial costs to the patient and any associated health-care. This may be directly related to treatment which improves quality of life (Biltz et al 2005, p. 337).
In my clinical settings (acute care) of the hospital I want to manage severe acute asthma patients with and without exacerbations with the best available clinical evidence. Most of the studies, systematic reviews and meta-analysis presented in the above section favors intravenous use of magnesium sulphate as an adjunct therapy for full benefits in severe acute asthma and very little literature is in favor of its use via inhalation or orally. Therefore, it is recommended that MgSO4 be used intravenously. The first step is diagnosis of severe acute and life-threatening asthma.
The severe acute asthma is present when any patient presents with FEV1 30-50% best or predicted; respiratory rate >25/min; heart rate >110/min and inability to complete sentences in one breath. Similarly life-threatening asthma is present when FEV1, 30% best or predicted; SpO2 92%;PaO2, 8 kPa (60 mm Hg), PaCO2 >6 kPa (45 mm Hg); silent chest; cyanosis; feeble respiratory effort; exhaustion; confusion; coma; hypotension and bradycardia (Kennedy, 2006). The critically ill patient can present with clinical features such as noisy, laboured and rapid respiration, tachypnoea, respiratory rate 32/min (normal= 15-20/min) wheeze (more prominent during expiration) and use of accessory muscles of respiration (Kennedy, 2006).
Intravenous magnesium sulphate (2 grams in adults and 25-75 mg/kg up to 2 grams in children) added to conventional therapy reduces hospitalization rates of emergency department patients who present with severe asthma exacerbations (Bethesda, 2007). Two grams of Magnesium Sulphate can be given to patients of 18-60 years of age intravenously, over twenty minutes, in acute severe asthma when FEV1<25% of predicted value (Silverman et al, 2002). When intravenous magnesium sulphate 2g is diluted in 50 ml of saline and given as an infusion over 20-30 min, the result can be to relieve bronchospasm and prevent the need of using intubation and a mechanical ventilator. (Aldington & Beasley, 2007)
Sanders, (2009) describes a case study of a 35 year old female and states that a MgSO4 dose of 5g given intravenously over 5 minutes that reduced severe bronchospasm. However, considering most of the clinical studies recommend the dose of magnesium sulphate is up to 2 g for adults and 25mg-100 mg/kg for children intravenously diluted in saline given in 20-30 minutes; this is the case in my acute care setting.
Since some of the evidence suggests that dietary supplement and oral intake of magnesium has the effect of enhancing the asthmatic condition and prevent bronchospasm, I would educate the patients in the acute care setting about increasing their oral intake of magnesium either naturally by diet or as an oral supplement.