The involvement of b2-agonists in asthma deaths

The involvement of b2-agonists in asthma deaths

Fiona Couper
Ph.D. Thesis 1996 (Monash University)

This thesis describes a series studies which were aimed at understanding the presence and significance of b2-agonists in asthma deaths.

A gas chromatographic/mass spectrometric method using solid phase extraction was developed to simultaneously measure salbutamol, terbutaline and fenoterol in clinical and postmortem specimens, with adequate precision, accuracy and sensitivity.

Eighty four asthma deaths were analysed for the presence of b2-agonists. The terbutaline concentrations detected were within reported therapeutic concentrations. In contrast, approximately half of the asthma deaths had salbutamol concentrations greater than the reported therapeutic concentration of salbutamol. Indeed, 13% of asthma deaths had potentially toxic levels of salbutamol.

The salbutamol concentrations detected in the asthma deaths were significantly higher than those measured in 81 asthmatics whose cause of death was unrelated to asthma, and in 223 patients who had been admitted to hospital for a severe asthma attack and survived. The elevated salbutamol concentrations observed could not be accounted for by postmortem processes such as drug stability and redistribution.

Through reviews of circumstances of death and questionnaire data, this thesis provided evidence that many asthmatics inappropriately use their inhaled bronchodilators during acute asthma attacks, and that such actions may have contributed to their deaths. Furthermore, it appeared that patients who had severe asthma attacks and survived were more likely to administer inhaled or oral preventative anti-asthmatic medications during the early stages of the attack, than those who had severe asthma attacks and died.

These studies will contribute to the understanding of b2-agonists and their involvement in deaths from asthma, and will lead to a more effective management of asthma.