A double-blind, randomized clinical trial of methylprednisolone in status asthmaticus. Intravenous methylprednisolone in adults in status asthmaticus. Comparison of two dosages. Methylprednisolone pulse therapy in severe acute asthma. Controlled trial of intravenous corticosteroids in severe acute asthma. High-dose and low-dose systemic corticosteroids are equally efficient in acute severe asthma. Corticosteroids in acute severe asthma: effectiveness of low doses. Are intravenous corticosteroids required in status asthmaticus? Methylprednisolone pulse therapy in acute severe asthma. A randomized, double-blind study.
Twenty-five consecutive patients admitted with status asthmaticus were blindly randomized to receive intravenous (IV) methylprednisolone every six hours for three days at one of the following dosages: (1) low, 15 mg; (2) medium, 40 mg; or (3) high, 125 mg. All other therapy, including IV and inhaled bronchodilators, was kept constant. We measured forced expiratory volume in 1 s (FEV1) to quantitate response. The high-dose group improved significantly by the end of the first day, the medium-dose group improved by the middle of the second day, but the low-dose group did not improve significantly in three days. Together, the high- and medium-dose groups were significantly improved (FEV1 greater than 50% of predicted) compared with the low-dose group. No serious steroid side effects were encountered. We conclude that the greater benefit of higher doses of steroids, such as 125 mg of methylprednisolone every six hours, justifies their use in severe asthma. nan In a group comparative double blind pilot study six asthmatic patients with an acute exacerbation of their disease were randomly treated with either methylprednisolone pulse therapy (MPPT) (1000 mg daily for 3 days) (n = 2) followed by placebo tablets, or standard doses of methylprednisolone (MP) (50 mg daily gradually decreased to zero over 3 weeks) (n = 4). The results showed that the effect of MPPT did not differ from that of standard doses of MP. MPPT has, however, the potential of being preferable to standard treatment with MP, because of easy administration and optimal patient compliance. The value of corticosteroids in severe acute asthma continues to be debated.
                Ninety consecutive patients admitted to the emergency room with severe acute asthma were studied in a randomised, double blind, controlled trial to determine the efficacy of corticosteroids. Eighty two patients completed the study. All received oxygen therapy and intensive bronchodilator treatment. The patients were divided into three groups for steroid treatment, receiving intravenous methylprednisolone 10 mg/kg every four hours for 48 hours (29 patients, group A); intravenous methylprednisolone 2 mg/kg every 4 hours for 48 hours (27 patients, group B); or no intravenous corticosteroids (26 patients, group C).
                There were no differences on admission among the three groups in forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), or arterial oxygen or carbon dioxide tension; and the rates of recovery in FEV1, FVC, and PEF were similar.
                Corticosteroids given with bronchodilators have not shown a beneficial effect in the first 48 hours of recovery of severe acute asthma. Only in those patients who failed to respond by the third hour of treatment, and in those who were previously taking oral corticosteroids, does a favourable, though not statistically significant, effect appear to occur. The optimal amount of systemic corticosteroids to be used in acute severe asthma remains an unresolved issue. In this double-blind, randomized study we compared two doses of methylprednisolone (1 vs 6 mg.kg-1 q.d.) in asthmatics presenting with an acute severe asthma attack, unresponsive to an intensive beta 2-agonist regimen administered during a run-in period. Concurrent therapy, including oxygen, inhaled and intravenous salbutamol, and aminophylline was strictly standardized. The response was assessed by serial bedside spirometry. The primary outcome measurement was forced expiratory volume in one second (FEV1) (expressed as percentage of predicted values) at 24 and 44 h. The trial was designed in order to achieve a statistical power of 90%. Twenty three patients were included in the low-dose group and 24 in the high-dose group. Both groups were comparable in terms of demographic profiles, history of asthma, and severity of the current attack. Improvement in pulmonary function was similar in both groups. At 44 h, the mean (+/- SD) FEV1 values were 53 +/- 22 and 45 +/- 14% in the low and in the high-dose group respectively (NS). We conclude that high dose systemic corticosteroids offer no further benefit over low-doses in the treatment of severe acute asthma. Although the need for corticosteroids in acute severe asthma is well established the appropriate dose is not known.
                The response to intravenous hydrocortisone 50 mg (low dose), 100 mg (medium dose), and 500 mg (high dose), administered every six hours for 48 hours and followed by oral prednisone, was compared in patients with acute asthma in a double blind randomised study. After initial emergency treatment with bronchodilators subjects received oral theophylline or intravenous aminophylline and nebulised salbutamol four hourly. Patients were given low, medium, or high doses of intravenous hydrocortisone and then 20, 40, or 60 mg/day respectively of oral prednisone with a reducing regimen over the following 12 days. Beclomethasone dipropionate, 400 micrograms twice daily by metered dose inhaler, was also started. Peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), and visual analogue dyspnoea scores (VAS) were recorded daily in hospital and PEF and VAS twice daily after discharge for a total of 12 days.
                The 66 subjects (40 female) who completed the study had a mean (SD) age of 31(14) years. On presentation mean (SD) FEV1% predicted in the low (n = 22), medium (n = 20), and high dose (n = 24) groups was 17(13), 19(12), and 19(11) and after emergency bronchodilator treatment 32(20), 30(12), and 36(13). After 24 hours of treatment the respective post-bronchodilator FEV1% predicted values were 62(22), 62(23), and 65(28) compared with 71(24), 69(22), and 71(24) after 48 hours. No significant difference between the groups was detected. PEF and VAS improved with treatment over the 12 days but was not influenced by steroid dose.
                Hydrocortisone 50 mg intravenously four times a day for two days followed by low dose oral prednisone is as effective in resolving acute severe asthma as 200 or 500 mg of hydrocortisone followed by higher doses of prednisone. Seventy-seven patients with status asthmaticus were prospectively studied to compare oral with intravenous methylprednisolone. Patients were given methylprednisolone, either 160 or 320 mg orally or 500 or 1000 mg intravenously, daily in equally divided doses. They were randomly assigned to either group on a daily sequential basis. Spirometry was performed within one hour of the initial dose of steroids. The mean presenting forced expiratory volume in 1 s was 26% of the predicted value. Spirometry was then repeated every six hours for the first 24 hours and then every eight to 12 hours until discharge or 72 hours, whichever occurred first. There were no significant differences in the incidence of respiratory failure, forced expiratory volume in 1 s, days of hospitalization, rate of improvement in pulmonary function, or side effects. No patient who went into respiratory failure did so more than three hours after receiving the initial dose of steroids. We conclude that oral methylprednisolone is safe and effective in the treatment of status asthmaticus. Methylprednisolone pulse therapy (MPPT) has been shown to possess a long-lasting effect in other immune-inflammatory diseases without the well-known side effects caused by long-term treatment with glucocorticosteroids. In an attempt to reduce the long-term use of oral steroids in asthmatics, we conducted this double-blind, double-dummy study to compare the use of MPPT (1 g of methylprednisolone intravenously) (8 patients) with a short course of oral prednisolone (10 patients) in asthmatics presenting with acute severe asthma. Both treatments were effective in relieving the acute attack of asthma. The MPPT-treated patients did not show a faster resolution than did the orally treated group. No patients needed assisted ventilation, and no deaths occurred. One week after the treatment FEV1 tended to decrease in the methylprednisolone group compared with the oral prednisolone group (P = 0.06). The patients initially receiving MPPT needed supplementary prednisolone earlier and in higher doses than did the patients receiving oral prednisolone as initial treatment. At the end of the 12 weeks' study period, the groups reached identical FEV1. In conclusion, we did not find intravenous methylprednisolone superior to oral prednisolone in the treatment of acute attacks of severe asthma, but methylprednisolone pulse therapy had a shorter duration as regards protection against future asthma attacks.
No differences were identified among the different doses of corticosteroids in acute asthma requiring hospital admission. Low dose corticosteroids (< or = 80 mg/day of methylprednisolone or < or = 400 mg/day of hydrocortisone) appear to be adequate in the initial management of these adult patients. Higher doses do not appear to offer a therapeutic advantage.