The transient effect of nebulised β₂ agonists on blood glucose levels and the impact on objectively measured health outcomes amongst asthma patients experiencing an acute exacerbation

Asthma affects approximately 339.4 million people globally and is primarily managed with bronchodilator drugs (β₂ agonists) during acute exacerbations. These drugs target specific receptors in the body to relax airway muscles, reduce inflammation and alleviate bronchoconstriction. However, their weak binding ability often leads to unintended stimulation of other receptors (α1, α2, β1) causing adverse effects across the cardiovascular, respiratory, and endocrine systems. This 'off-target' stimulation can trigger a complex cascade of internal processes, intensifying inflammatory responses and prolonging of exacerbations. One significant yet underreported effect is the elevation of blood glucose levels which can induce a transient diabetic state, further complicating the exacerbation by impairing the ventilation/perfusion (V/Q) ratio. This research investigates the impact of nebulised salbutamol on blood glucose levels and its correlation with V/Q in acute emergency settings, where higher doses are used, and exacerbations are more severe. Understanding these effects may help clarify how β₂ agonists complicate the usual asthma pathway, potentially leading to more severe and prolonged outcomes for patients.

To effectively examine this area, three interconnected studies were conducted, each employing distinct methods. The first was a systematic review assessing the effects of nebulised β₂ agonists on clinical outcomes in asthma patients during exacerbations. Following the review, eight studies were synthesised and despite varying quality, the data consistently supported the therapeutic benefits of nebulised β₂ agonists in treating exacerbations. However, it concluded that adverse effects, particularly on the cardiovascular and endocrine systems are common. Although, their precise impact on patients remained unclear, the review highlighted the need for further investigation, especially regarding interactions with comorbidities and the level of impact healthcare professionals have on these changes.

Next, a qualitative study within a single NHS ambulance service explored paramedics' clinical decision making through semi-structured interviews. Data from fifteen interviews highlighted the heterogeneous nature of asthma and the critical role of paramedics in adapting management guidelines to respond to its complexities. While comorbidities, side effects and fluctuating clinical observations were acknowledged, they were often overlooked unless they overshadowed the presenting exacerbation.

Finally, a single-arm observational study, using both retrospective and prospective data examined the relationship between blood glucose levels and cardiorespiratory output during nebulised salbutamol administration. Retrospective data (n=100) revealed statistically significant cardiorespiratory changes in asthma patients, with oxygen saturation levels increasing despite fluctuating heart and respiratory rates. Although, the expected increase in heart rate due to the pharmacological effects of β₂ agonists was less pronounced than anticipated. Prospective data, though limited by a smaller sample size (n=8) also demonstrated a statistically significant difference in capillary blood glucose levels before and after nebulisation.

Overall, the research suggests that asthma patients receiving nebulised salbutamol tend to present with elevated peripheral blood oxygenation and capillary blood glucose levels post-nebulisation. However, the influence of additional variables such as stress, anxiety and comorbidities remain unclear. Further investigation is required to fully understand the interplay of these variables and the dichotomy observed in pulse rate and glucose fluctuations.