Acute Exacerbation of COPD and Nebulized Magnesium Sulphate

Effect of Nebulized Magnesium Sulphate in Terms of In-hospital Outcome of Patients Admitted With Acute Exacerbation of Chronic Obstructive Pulmonary Disease

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.

Study Overview

• Status: Completed
• Conditions: Magnesium Sulfate; Chronic Obstructive Pulmonary Disease Exacerbation
• Intervention / Treatment: Drug: Nebulized Magnesium Sulphate

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.

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Pakistan
  • Punjab
    • Lahore, Punjab, Pakistan, 54000
      • Fawad Ahmad Randhawa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. The age of patient should between 30 to 70 years. 2. The patient could be male or female. 3. The duration of COPD must be less than 10 years. 4. Acute exacerbation of COPD requiring hospital admission and any two out of four criteria: I. Increase in the purulence or quantity of sputum II. Dyspnea grade 3, 4 or 5 according to MRC scale (Annexure attached) III. PEFR <200 L/min IV. Respiratory acidosis on arterial blood gas analysis

Exclusion Criteria:

- 1. Known case of other pulmonary parenchymal disease diagnosed by history, examination and previous medical records.

2. Bronchogenic carcinoma diagnosed by history and previous records. 3. Pulmonary edema diagnosed based on history, examination and investigations.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Magnesium Sulphate; Conventional treatment and 250mg of MgSO4 through nebulizer four times a day. 1 vial of injection MgSO4 was taken which contains 1gm of MgSO4 (each vial contains 10ml). It was divided into 4 equal parts, each contained 250mg MgSO4 i.e., 2.5 ml solution, which were used for nebulization 4 times a day.	Drug: Nebulized Magnesium Sulphate; 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.
No Intervention: Conventional; conventional treatment in the form of oxygen inhalation, anti-cholinergic and beta-2 agonist nebulization, intravenous steroids, as well as intravenous antibiotics.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In- Hospital Outcome	discharge or death or clinical improvement	5 days

Collaborators and Investigators

• Sponsor: King Edward Medical University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: December 15, 2021
• First Submitted That Met QC Criteria: January 22, 2023
• First Posted (Estimate): January 26, 2023

Study Record Updates

• Last Update Posted (Estimate): January 26, 2023
• Last Update Submitted That Met QC Criteria: January 22, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Disease Progression; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anticonvulsants; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Tocolytic Agents; Magnesium Sulfate
• Other Study ID Numbers: 7372/REG/KEMU2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No