Acute asthma
Asthma has been described as a chronic inflammatory disorder of the airways with an increase of bronchial responsiveness to a variety of stimuli. It is often reversible, either spontaneously or with treatment (Bateman et al., 2008[12]).
Standard treatments for asthma crisis include bronchodilators (short-acting), agonists of β2-receptors, inhaled ipratropium bromide, corticosteroids, anticholinergic drugs and general managements (Bateman et al., 2008[12]). Researchers have suggested MgSO4 as a treatment option for patients who are resistant to standard therapy (Bateman et al., 2008[12]; Gontijo-Amaral et al., 2007[47]; Jones and Goodacre, 2009[74]; Kew et al., 2014[77]). Life-threatening conditions like severe asthma attacks require intensive medical care. The beneficial effects of MgSO4 have been shown in children and adult patients with severe asthma in the ICU (Boonyavorakul et al., 2000[16]; Daengsuwan and Watanatham, 2016[31]; Griffiths and Kew, 2016[52]; Kew et al., 2014[77]; Kokturk et al., 2005[83]; Rowe, 2013[128]; Rowe and Camargo, 2008[129]; Rower et al., 2017[130]; Singh et al., 2008[143]).
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Mechanisms of Mg action for the management of severe asthma include: (1) reduction of intracellular calcium level (blockade of calcium entry, calcium release and activation of Na+-Ca2+ pumps), (2) muscle relaxation (inhibition of myosin and calcium interaction), (3) reduction of inflammatory mediators (inhibition of degranulation of mast cells and T-cells stabilization), (4) depression of the irritability of muscle fibers, and (5) inhibition of prostacyclin and nitric oxide synthesis. These mechanisms lead to a reduction in the severity of asthma (Gontijo-Amaral et al., 2007[47]; Rowe, 2013[128]).
MgSO4 is used via intravenous and inhalation routes for the management of acute asthma (Shan et al., 2013[139]). Use of MgSO4 through intravenous route in adult and children patients improves respiratory function (Boonyavorakul et al., 2000[16]; Daengsuwan and Watanatham, 2016[31]; Griffiths and Kew, 2016[52]; Kew et al., 2014[77]; Kokturk et al., 2005[83]; Rowe, 2013[128]; Rowe and Camargo, 2008[129]; Rower et al., 2017[130]; Singh et al., 2008[143]). In some countries, the intravenous form of MgSO4 is broadly used as an adjunctive therapy for severe acute asthma, especially in patients not responding to initial treatments (British Thoracic Society Scottish Intercollegiate Guidelines, 2008[20]; Jones and Goodacre, 2009[74]). Unlike adults, in children MgSO4 has a significant effect on hospital admission (Ciarallo et al., 2000[28], 1996[29]; Gurkan et al., 1999[55]; Porter et al., 2001[120]; Scarfone et al., 2000[133]). The impact of MgSO4 on forced expiratory volume in 1 second (FEV1) and peak expiratory flow rate (PEFR) were assessed in different clinical trials (Bessmertny et al., 2002[13]; Bloch et al., 1995[15]; Boonyavorakul et al., 2000[16]; Devi et al., 1997[32]; Gallegos-Solorzano et al., 2010[43]; Green and Rothrock, 1992[51]; Hughes et al., 2003[65]; Mahajan et al., 2004[97]; Silverman et al., 2002[141]; Tiffany et al., 1993[152]). In children, brief infusion and maximum weight-based dosage of MgSO4 have been suggested for the management of severely ill asthmatic patients in the ICU (Egelund et al., 2013[36]; Liu et al., 2016[94]). Up to 2.5 gram of Mg loading dose with β-agonist and corticosteroid (methylprednisolone, hydrocortisone, and dexamethasone) were reported to be efficacious in the management of asthma (British Thoracic Society Scottish Intercollegiate Guidelines, 2008[20]). Ipratropium, aminophylline, theophylline and ephedrine are additional drugs in the management of acute asthma (Bloch et al., 1995[15]; Devi et al., 1997[32]; Green and Rothrock, 1992[51]; Singh et al., 2008[143]; Tiffany et al., 1993[152]). However, in contrast to intravenous MgSO4, the effect of the inhaled form remains controversial. Up to 500 mg MgSO4 for each dose of nebulization has been used in several clinical trials (Aggarwal et al., 2006[3]; Ahmed et al., 2013[4]; Bessmertny et al., 2002[13]; Chande and Skoner, 1992[24]; Gallegos-Solorzano et al., 2010[43]; Gandia et al., 2012[44]; Hill et al., 1997[62]; Hughes et al., 2003[65]; Kokturk et al., 2005[83]; Mangat et al., 1998[98]; Nannini and Hofer, 1997[116]; Nannini et al., 2000[117]; Rolla et al., 1987[126]; Zandsteeg et al., 2009[173]). Respiratory functions and hospital admission were assesed in all studies and, similar to intravenous MgSO4 therapy, β-agonists and corticosteroids were used in all patients (Aggarwal et al., 2006[3]; Ahmed et al., 2013[4]; Chande and Skoner, 1992[24]; Gandia et al., 2012[44]; Hill et al., 1997[62]; Mangat et al., 1998[98]; Nannini and Hofer, 1997[116]; Nannini et al., 2000[117]; Rolla et al., 1987[126]; Zandsteeg et al., 2009[173]). In one study, nebulized MgSO4 was compared to nebulized salbutamol (Mangat et al., 1998[98]). The authors showed that there is no significant difference between the bronchodilatory effect of nebulized MgSO4 and salbutamol in the management of acute asthma (Gonzalez et al., 2013[48]). In 2016, Ling and colleagues reported that nebulized MgSO4 is not useful to improve pulmonary function or reduce the number of patients admitted to the hospital in adults with acute asthma (Ling et al., 2016[92]). In children, treatment with nebulized magnesium sulfate showed no significant effect on respiratory function or hospital admission and further treatment (Su et al., 2016[149]). Adverse events have been occasionally reported in the clinical trials, but the most common adverse reactions with MgSO4 are cardiac arrhythmia, confusion, drowsiness, flushing, hypotension, loss of deep tendon reflexes, muscle weakness, nausea, respiratory depression, thirst, and vomiting. Rarely, administration of MgSO4 can lead to cardiac arrest and coma (Martindale and Westcott, 2008[100]).
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