Nebulised magnesium sulphate as an adjuvant to the treatment of acute exacerbation of COPD: A systematic review and meta-analysis of randomised controlled trials with trial sequential analysis

Abstract

The purpose of this meta-analysis was to evaluate the efficacy of nebulised magnesium in the treatment of acute exacerbation of COPD. PubMed and Embase databases were searched for randomised controlled trials comparing any dose of nebulised magnesium sulphate with placebo for treatment of acute exacerbation of COPD, published from database inception till 30 June 2022. Bibliographic mining of relevant results was performed to identify any additional studies. Data extraction and analyses were done independently by review authors and any disagreements were resolved through consensus. Meta-analysis was done using a fixed-effect model at clinically significant congruent time points reported across maximum studies to ensure comparability of treatment effect. Four studies met the inclusion criteria, randomly assigning 433 patients to the comparisons of interest in this review. Pooled analysis showed that nebulised magnesium sulphate improved pulmonary expiratory flow function at 60 minutes after initiation of intervention compared to placebo [median difference (MD) 9.17%, 95% confidence interval (CI) 2.94 to 15.41]. Analysis of expiratory function in terms of standardised mean differences (SMD) revealed a small yet significant positive effect size (SMD 0.24, 95% CI 0.04 to 0.43). Among the secondary outcomes, nebulised magnesium sulphate reduced the need for ICU admission (risk ratio 0.52, 95% CI 0.28 to 0.95), amounting to 61 fewer ICU admissions per 1000 patients. No difference was noted in the need for hospital admission, need for ventilatory support, or mortality. No adverse events were reported. Nebulised magnesium sulphate improves pulmonary expiratory flow function and reduces the need for ICU admission in patients with acute exacerbation of COPD.

Keywords: Bronchial asthma; COPD; intensive care; magnesium; mechanical ventilation; nebulizer.

Figure 1

PRISMA flow diagram showing the process of selection of studies

Figure 2

Risk of bias summary (green—low risk of bias, yellow—unclear risk of bias, red—high risk of bias)

Figure 3

Forest plots: (a) Expiratory flow function as a percentage of baseline (b) Expiratory flow function as reported (c) Peak expiratory flow rate (sensitivity analysis) [NS = normal saline; SD = standard deviation; IV = inverse variance; CI = confidence intervals]

Figure 4

Funnel plot: pulmonary expiratory flow function as a percentage of baseline [MD = mean difference; SE (MD) = standard error of mean difference]

Figure 5

Progression of expiratory flow function with time (pooled weighted means from all 4 studies as a percentage of baseline flow; error bars denote proportional standard deviation; (P = 0.001 at 30 mins, P = 0.004 at 60 min, P = 0.008 at 90 min, two-sample t-test)

Figure 6

Trial sequential analysis of expiratory flow function as a percentage of baseline. The uppermost and lowermost curves represent trial sequential monitoring boundary lines for harm and benefit, respectively. Horizontal lines represent the traditional boundaries for statistical significance. Triangular lines represent the futility boundary. The cumulative Z curve represents the trial data

Figure 7

Forest plot—a meta-analysis of different qualitative outcomes : (a) Need for ICU admission (b)Need for ventilatory support (c) Mortality (NS = normal saline; SD = standard deviation; M-H = Mantel–Haenszel; CI = confidence intervals)