The Use of Milrinone Versus Conventional Treatment for the Management of Life-Threatening Bronchial Asthma

Abstract

Background and Aims: In our study, we investigated the effectiveness of intravenous milrinone in life-threatening bronchial asthma as compared to conventional treatment. Methods: Fifty patients aged 18-50 years, presenting with life-threatening asthma were enrolled in a Randomised Controlled Trial (RCT). They were randomly allocated into Group C (25 patients): who received the standard pharmacotherapy and placebo, and Group M (25 patients): who in addition to the standard therapy, received 25 μg milrinone as an initial slow IV bolus diluted in 10 ml of normal saline. The following data were recorded: PEFR (Peak Expiratory Flow Rate) expressed as a percentage of the patient’s previous value, Respiratory Rate (RR), MABP (Mean Arterial Blood Pressure), arterial blood gases, and the number of patients requiring mechanical ventilation. Differences between groups were tested using Analysis of Variance (ANOVA) for quantitative variables with post hoc using the Least Significant Difference (LSD) test, and Chi square test for categorical variables. Results: Group M showed marked improvement in PEFR that was highly significant (P < 0.001) 10 min after injection and significant after one hour from the start of treatment in comparison to Group C. There was also an improvement in RR and PO2 that was significant in group M. Milrinone was associated with a reduction in MABP only after 10 min from injection, and showed a statistically significant decrease in the number of patients requiring mechanical ventilator support (P ˂ 0.05). Conclusion: Milronine is a promising agent as a rescue drug in the treatment of life-threatening bronchial asthma.

(Oral) enoximone in asthma

“…Recently, S obhy et al . [ 3 ] confirmed our case series with a successful clinical trial, which was performed in Egypt, using the phosphodiesterase (PDE)-3 inhibitor milrinone. We would like to report we are currently treating 12 children and 51 adults (outpatients) with oral enoximone (Perfan) in addition to standard therapy, in the context of investigational use, in search of effectiveness [ 4 ].…”

PDE3-inhibitor enoximone prevented mechanical ventilation in patients with SARS-CoV-2 pneumonia

“…4 A major consideration is that several of the pro-inflammatory mediators released by effector cells in COVID-19 act on airway smooth muscle cells and induce bronchoconstriction, 4,27,28 which can be relieved by (combined) PDE3-inhibitors producing (potent and sustained) bronchodilation. 5,[7][8][9][10]21 Recently, based on their broad anti-inflammatory activity, systemic corticosteroids have been advocated in severe COVID-19 patients requiring supplemental oxygen (i.e., with a similar indication as our COVID-19 cases) in line with the preliminary findings in the RECOVERY study. 29 However, high-dosed (systemic) corticosteroids may also induce deleterious effects and impose health risks, especially in vulnerable patients.…”

“…Selective phosphodiesterase (PDE)3-inhibitors enoximone and milrinone previously showed clinical effectiveness in patients with CAS. [5][6][7] PDE3-inhibitors relax airway smooth muscle, 8,9 possess anti-inflammatory properties, [9][10][11] improve mucosal barrier function and prevent endothelial leakage caused by vaso-active mediators (e.g. bradykinin, histamine and leukotrienes).…”

PDE3 Inhibition Reduces Epithelial Mast Cell Numbers in Allergic Airway Inflammation and Attenuates Degranulation of Basophils and Mast Cells

“…Clinical trials are underway to confirm these observation in asthma patients. PDE3 inhibition is not only a smooth muscle relaxant being beneficial in obstructive lung disease (Leeman et al, 1987), but also improve mucosal barrier function (Kern et al, 2001) and is in use as a rescue medication in severe asthma (Leeman et al, 1987;Kern et al, 2001;Beute, 2014;Sobhy et al, 2019). In conclusion, the present work has established that the small molecule PDE3 inhibitor enoximone is important in preventing basophil and mast cell degranulation.…”

“…The initial effect of PDE3 inhibition is smooth muscle relaxation in humans. This effect is already noticeable within 30 s after IV treatment (Beute, 2014;Sobhy et al, 2019). In smooth muscle cells, increased cAMP inhibits myosin light chain kinase (MLCK), preventing Ca 2+ binding, thereby reducing MLC phosphorylation, and hence relaxing the vascular smooth muscle (Prakash, 2016).…”