Acute Exacerbation of COPD and Nebulized Magnesium Sulphate
Condition: Chronic Obstructive Pulmonary Disease Exacerbation; Magnesium Sulfate
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Disease Progression
Study type: Interventional

Summary: 
      This study is designed to determine the effect of Nebulized Magnesium Sulphate as an add-on
      therapy with conventional treatment on In-hospital outcome in patients having acute
      exacerbation of COPD.
    

Detailed description: 
      Chronic obstructive pulmonary disease (COPD) is called as the second highly common
      respiratory disorder after pulmonary Tuberculosis in Pakistan. It is characterized by chronic
      and progressive breathlessness, cough, sputum production and airflow obstruction, which
      progressively lead to restricted activity and impaired life quality (1). According to the
      World Health Organization, COPD would be the third leading cause of mortality by 2020. It
      imposes a significant economic burden on account of its morbidity (2). This chronic
      debilitating disorder is accompanied by various comorbid factors that contribute to a spiral
      of decline, leading to an increase in mortality (3). Episodes of acute deterioration
      associated with COPD is called exacerbations. These exacerbations are among one of the most
      common causes of hospital admissions in the country. Acute exacerbation is triggered by
      bacterial and viral infections and can also be precipitated by environmental factors,
      including air pollution, second-hand smoke, and periodically variations, i.e., low
      temperature (winter season) (1). Acute exacerbation lead to deterioration in the patients'
      quality of life, adverse effects on symptoms and lung functions that may last for many weeks,
      reduction in lung functions, frequent hospital visits, increase in health expenditure, and
      significant mortality as lung function cannot recover entirely afterwards (1,2). Acute
      exacerbations of COPD are treated by oxygen, inhaled bronchodilators, i.e., beta-2 agonists
      and anticholinergics, antibiotics, and steroids (2,3).

      Exacerbations, during the illness, drastically affect the quality of life of the patient, put
      a burden on healthcare expenses, and are associated with an increase in mortality.
      Exacerbations also result in the worsening of airway obstruction and an increase in the
      inflammatory response (5). While smoking is said to be the most significant risk factor in
      the etiology of COPD, infections mainly account for recurrent episodes of exacerbation
      occurring during this illness. With advancing industrialization, environmental factors in the
      form of increasing air pollution contribute to COPD exacerbation pathogenesis (1,2).
      Effective management of acute exacerbations of COPD will slow disease progression, improve
      the patient's health status, and lessen the burden on healthcare services (5). It increases
      interest in optimizing COPD treatment and devising new modalities to prevent episodes of
      exacerbations. Pulmonary rehabilitation, oxygen inhalation, inhaled and systemic
      corticosteroids, bronchodilators (β2-agonists and anticholinergic agents), and, if required,
      mechanical ventilation constitute the standard treatment regimen in COPD. There is a
      compelling interest in devising increased new strategies to effectively manage and decrease
      the severity and frequency of exacerbations (4).

      Magnesium is a Calcium-mediated bronchodilator that acts with different mechanisms such as
      calcium antagonism via Calcium-Channels and counteraction of Calcium-medicated smooth muscle
      contraction, inhibiting the release of Histamine and Acetylcholine from mast cells and
      cholinergic nerve endings, respectively (2). It is proven that Magnesium helps in providing
      enhanced bronchodilator effect in acute exacerbations of asthma. However, fewer data and
      conflicting results are seen regarding its use in acute aggravation of COPD. So far, only six
      studies have investigated the bronchodilator efficacy of magnesium sulphate in COPD.
      Intravenous administration of Magnesium during exacerbations of chronic obstructive pulmonary
      disease (COPD) resulted in the improvement of peak flow.

      Randomized, single-blinded, placebo-controlled trials showed that intravenous magnesium
      sulphate (MgSO4), when given as an adjunct to standard therapy in severe acute asthma, causes
      pulmonary function improvement and decreases in-hospital admissions (4). Nebulized MgSO4,
      either separately or in combination with salbutamol, has a visible bronchodilator impact in
      severe asthma and shows proven betterment (5).

      Acute intravenous magnesium in stable COPD patients resulted in a decline of lung
      hyperinflation as well as improved respiratory muscle strength (5). There are very few
      placebo-based clinical trials evaluating the efficacy of magnesium sulphate administered via
      intravenous, nebulized, or both routes in COPD exacerbations. One such trial showed that
      Intravenous administration of magnesium sulphate has no bronchodilating effect in patients
      with COPD exacerbations. However, it enhances the bronchodilating effect of other inhaled
      short-acting bronchodilators (6). Nebulized magnesium sulphate, when added to standard
      bronchodilator treatment, provides additional relief of dyspnea in patients of acute
      exacerbations (2). However, these studies showed inconclusive results, and the clinical
      potential of Magnesium deserves to be further investigated.

      Nebulized magnesium sulphate may show promising bronchodilator effect as an add-on therapy to
      the conventional treatment for COPD exacerbations due to its intracellular effects. In case
      of a positive outcome, this practice can be incorporated in the management of COPD in its
      acute exacerbations because of its low cost, being readily available in our hospital
      settings, convenient mode of administration, and lesser side effects.
    

Intervention name(s): Nebulized Magnesium Sulphate
Intervention type(s): Drug
Intervention description(s): Group A received 250mg of MgSO4 /dose given through nebulizer four times a day, while group B did not. The groups will be followed for five days to see the results in terms of in-hospital outcome, whether the patient is discharged after fulfilling the set criteria or needing assisted ventilation.
Intervention MeSH terms: Magnesium Sulfate
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment