Introduction

Despite advancing knowledge of the pathophysiology and treatment of asthma, its morbidity and mortality are on the rise (₁,₂). To help avert this trend, clinicians and patients must focus their attention on the early identification and treatment of asthma exacerbation. Management of severe acute asthma attacks sometimes brings difficulty to the physician (₃). The goal of management of patients with respiratory failure is to restore then to a state of quiet breathing, without complication. This goal is often achieved by pharmacology alone (₄). Brnochodilator management of acute severe asthma has evolved considerably in recent years. Beta–2 agonists have emerged as the single most potent class of bronchodilator available, and the inhalational route of administration has proven to be the most effective and least toxic method of delivery except among apneic or highly uncooperative patients (₅). Some current treatment strategies have focused on intravenous (IV) magnesium sulfate (MgSO4) administration in some disease (3). Magnesium sulfate as IV form has been suggested as a treatment for certain emergence conditions for more than 60 years and it is currently proposed to be beneficial in treating asthma, preeclampsia, eclampsia, myocardial infarction and cardiac arrhythmia (₆). Intravenous magnesium sulfate has successfully been used in the treatment of acute asthma. There is some evidence that IV form of MgSO4 can provide additional bronchodilation when gives in conjunction with standard bronchodilating agent and corticosteroids (₇). One of the important problem for clinicians is managing of drug-resistant disease and non-responding patients. This study was conducted to determine whether IV MgSO4, when used as part of a standardized treatment protocol can improved pulmonary function in non- responding patients to therapy with beta-2 agonists and corticosteroids, presenting to the our pulmonary department with exacerbation of asthma.

Materials and Methods

This was a randomized, double –blind, controlled clinical trial. Asthmatics aged 12-85 years in acute exacerbation with a peak expiratory flow rate (PEFR) less than 200 (l/min) having taken bronchodilators, corticosteroids and requiring assisted ventilation were included. All patients, who had not responded to treatment during next 6 hr, were selected for this investigation. They were randomized to receive treatment with MgSO4 (25 mg/kg, as MgSO4 group) and saline (100 ml normal saline, as placebo group). Drugs were given as infusion over the 30-45 minutes. For all patients peak expiratory flow, arterial blood gas (ABG), vital signs, rate of cyanosis and diaphoresis, and using respiratory accessory muscles were monitored before starting treatment (as baseline findings). In the start of MgSO4 or placebo patients were monitored continuously for 6 hr. MgSO4 solution and normal saline were coded and dispensed in identical containers. Decoding was done at the completion of the study. All the patients reserved oxygen, neubolized salbutamol, IV aminophyllin and corticosteroids. PEFR was the main outcome variable. Frothy-eight patients (aged 12-85 years, 26 men, 22 women) as sulfate group and thirty three patients (aged 15-80 years, 17 men, 16 women) as control group were studied. Data collected from this investigation, were analyzed using x² and t-test and difference between data was considered significant at p<0.05.

Results

MgSO4 group showed early and significant improvement as compared to placebo group in PEFR at 30 min, and 3 hours after stopping the infusion (p= 0.00, 95%CI= 11.85, 27.77). The clinical asthma score also showed significant improvement in the MgSO4 group at 30 min and 3 hrs after stopping the infusion (p<0.0005). PEFR at baseline was similar in the two groups. 30 minutes after baseline (MgSO4 and saline) the mean (± SEM) increase in PEFR was greater in the MgSO4 group (62.81 ± 6.7) than in the normal saline group (46.52 ± 8.3). At 3hr, increase in peak flow was 82.6 ± 5.8 in the MgSO4 group compared with saline group (p<0.005, 95%CI= -55.8, -13.77). There was a significant difference in PEFR from initiation of the infusion to 30 min (p=0.00, 95%CI= -40.1, -22.55) and 3hrs later for the MgSO4 group (p=0.00, 95%CI= 11.85, 27.77). There was also a considerable decrease in number of breathing at base line, 30 min and 3hr in MgSO4 group (table 1). Patients in MgSo₄ group had been shown significant decrease in diaphoresis, cyanosis and using respiratory accessory muscles (table 2.)

Figure 1

Table 1. Mean ± SEM of peak expiratory flow rate and the number of breathing in MgSO4 and saline groups.

Figure 2

Table 2. Frequency (%) of some variables in MgSO4 in comparison with saline group.

Discussion

According to the results, it is suggested that MgSO4 can improve the respiratory function in the non-responding patients with acute severe asthma presenting to the our pulmonary department. It could improve and increase the peak expiratory flow rate and decreases the number of breathing. The increase of PEFR was statistically significant in MgSO4 to else (saline) group, then magnesium sulfate appears to be safe and beneficial in patients who present with severe acute asthma. This finding could be supported with other studies (1,3,4,7,₈). Inhaled beta-2 agonists, oxygen and systemic conticosteroids are main stays of acute care drug management, whereas other data support the use of inhaled steroids, ipratropium bromide, magnesium sulfate (₉,₁₀,₁₁) and theophyllin (4). Assisted ventilation by face mask or intubated patients, a ventilatory strategy that prolongs exhalation time and accepts hypercapnia minimizes lung hyperinflation and generally results in a good outcome. Non-responding asthmatic patients are the important clinical problem for clinicians. Some studies suggested that administration of systemic corticosteroids and beta-adrenergic agonists are useful for those patients (5, 10). Authors suggested that MgSO4 could be used as an adjunct agent in the treatment of acute asthma (10,₁₂). MgSO4 was used as inhalation dosage form and as a vehicle for nebulized beta-2 agonists in acute asthma. It had shown therapeutic effectiveness in those cases (9,11). Many reports has shown that magnesium sulfate has certainly a role as an adjunct to traditional therapy in asthma and asthma-like conditions and has been helpful in the treatment of acute exacerbation of asthma (10). Intravenous MgSO4 may be useful when conventional treatment has failed (12, ₁₃). It seems clear that IV MgSO4 also is effective for the suppression of bronchial smooth muscle contractions. Children who treated with IV MgSO4 for moderate to severe asthma had significantly greater improvement in short-term pulmonary function without, any considerable alteration in blood pressure (₁₄), suggesting a role for this agent as an adjunct in the treatment of such patients. Mg²⁺ is a natural calcium antagonist and intracellular Mg²⁺ is thought to modulate smooth muscle contractions and it is known to have a direct effect on calcium uptake, resulting in smooth muscle relaxation (10). Finally our data also supported previous studies (₁₅,₁₆) that MgSO4 is helpful for decrease of asthma complications. It seems that administration of MgSO4 in addition to improvement of pulmonary function and helpfulness in the treatment of our patients with acute non-responding asthma, can decrease admission rate in patients with acute severe asthma.

Acknowledgement

Correspondence to

Kh. Bijani, MD Pulmonary Ward Beheshti Hospital Sargord Ghasemi Street Keshvari Sq. Babol , Iran tel (+98)1112252071-2 E-mail : drbijani@altavista.com