Do nebulised short-acting β₂ agonists cause transient blood glucose changes that impact asthma exacerbations?

Problem

β₂ agonists are a class of drug used to target specific receptors within the smooth airway muscle of asthma patients in exacerbation. Whilst the intention is to reduce constriction and inflammation through targeted action, a weak binding ability often results in stimulation of α1, α2 and β1 receptors resulting in adverse changes within the cardiovascular, respiratory and endocrine systems. As a result of α1 and α2 stimulation, transient changes within blood glucose levels are often referenced given the potential for increased levels to impact the ventilation/perfusion (V/Q) ratio and thus potentially magnify the exacerbation. Focusing on the emergency setting where exacerbations are often more severe, greater variables are involved and dosages are higher, the study sought to ascertain the effect nebulised β₂ agonists have on the blood glucose levels of asthma patients and how that correlates to their cardiorespiratory output.

Approach

Two phases of data collection undertaken within a single NHS ambulance Trust provided analysable data encompassing a 6-month timeframe. Phase 1 (P1) involved ambulance paramedics recruiting asthma patients at point of care, with Phase 2 (P2) being retrospective data collected from all patients receiving nebulised salbutamol across the 6 months. To reduce the level or variability and provide more consistent data sets for singular and joint analysis strict inclusion/exclusion criteria developed through consultation with different patient and public groups was used to recruit participants and filter P2 data. Primarily descriptive analysis was used to summarise and identify patterns within the data followed by inferential analysis to highlight relationships.

Findings

At the end of the timeframe data sets from 176 patients were analysed. Demographic showed 64% female, mean age 42 years and a largely white British ethnicity distribution. Findings from both phases are consistent. Post nebulisation measurements showed decreased heart rate (HR) in 62.5% (P1), 65% (P2) of patients; decreased respiratory rate (RR) in 87.5% (P1), 74% (P2) and an increased peripheral oxygen saturation (SpO2) in 75% (P1), 59% (P2). Phase 1 data further showed a post nebulisation capillary blood glucose (CBG) level increase in 87.5% of patients. A central tendency for RR and HR to reduce, and SpO2 to increase post treatment is seen. P1 subset data further shows a tendency for CBG levels to increase in circumstances when the RR reduces and the SpO2 level increases. Further research is needed to understand the dichotomy in pulse rates.

Consequences

A strong correlation seen between RR, SpO2 and CBG measurements during administration suggests the presence of actionable side effects amongst asthma patients. Due to the potential effect of increased glucose levels in both the short and long-term, clinical significance is shown for all asthma patients with or without existing diabetic markers.