USE OF BETA-AGONIST THERAPY PRIOR TO HOSPITAL ATTENDANCE FOR SEVERE ASTHMA EXACERBATIONS

Supplementary Material

Mitesh Patel, BMBS, Janine Pilcher, MBChB, Robert Hancox, MD, Davitt Sheahan, MBChB, Alison Pritchard, Irene Braithwaite, MBChB, Dominick Shaw, MD, Peter Black, MBChB (deceased), Mark Weatherall, MBChB, Richard Beasley, DSc, for the SMART Study Group.

Methods

Randomised controlled trial key exclusion criteria

Key exclusion criteria included a diagnosis of chronic obstructive pulmonary disease or an onset of respiratory symptoms after the age of 40 in current or ex-smokers with a ≥10 pack year smoking history.

Data collection

The following definitions were used:

Emergency Department (ED) visit: Discharge after attendance to ED for asthma, without an in-patient stay.

Hospital admission: In-patient admission for asthma.

Attendance time: Triage time after attendance to ED. Medication use data was extracted for the 14 24-hour periods from the attendance time for each patient, so that the period of observation would be identical for all patients.

Heart rate (HR), blood pressure (BP), respiratory rate (RR), and oxygen saturation (SpO2) were the first recorded values.

First QTc interval (ms): The first 12-lead ECG recorded after the attendance time was reviewed and the QTc interval was calculated using the following linear regression formula:[1, 2] QTc interval = QT + 0.154(1-RR).

First serum potassium level (mmol/L): The first laboratory serum potassium value performed after the attendance time.

Peak expiratory flow rate (PEFR) measurements: the first PEFR recorded was used. The patient’s usual best value was used for the calculation of % best values. Where this was not recorded, a predicted best value was calculated from age, height and gender.

Results

Medical therapy

All patients received oral corticosteroids for their severe exacerbation. 4/9 Standard patients also received treatment with intravenous (IV) corticosteroids. Two Standard patients were treated with pre-hospital intramuscular adrenaline by attending paramedics. One SMART patient received IV magnesium therapy. No patients required non-invasive ventilation/assisted ventilation and there were no intensive care unit admissions, or intubations, for asthma.

There was no association between the serum potassium and the total number of budesonide/formoterol or salbutamol actuations in the 24 hours, or seven days, preceding initial hospital attendance for SMART and Standard patients respectively (Figure OS1).

ECG parameters

Other than sinus tachycardia, there were ECG rhythm abnormalities in two SMART patients. One patient, with a pre-study history of paroxysmal atrial fibrillation (PAF), was in AF (at a ventricular rate of 80 beats/min). Another patient, who was subsequently diagnosed with idiopathic hypertrophic cardiomyopathy, had left bundle branch block and a QTc interval of 456ms. Both of these abnormalities were considered by the treating physicians to be unrelated to study medication.

Beta agonist dose and serum potassium

Figure OS1: Correlation between beta agonist doses in the 24 hours or 7 days preceding hospital attendance and initial serum potassium.

A Number of doses of budesonide/formoterol in the 24 hours preceding attendance and serum potassium for SMART (n=6)
Correlation coefficient -0.12, p=0.82 / B Number of doses of budesonide/formoterol in the 7 days preceding attendance and serum potassium for SMART (n=6)

Correlation coefficient 0.001, p=0.99
C Number of doses of salbutamol in the 24 hours preceding attendance and serum potassium for Standard (n=6)

Correlation coefficient 0.57, p=0.24 / D Number of doses of salbutamol in the 7 days preceding attendance and serum potassium for Standard (n=6)

Correlation coefficient 0.65, p=0.16

References

1.Rautaharju PM, Surawicz B, Gettes LS, et al. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part IV: the ST segment, T and U waves, and the QT interval: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society. Endorsed by the International Society for Computerized Electrocardiology. J Am Coll Cardiol 2009; 53: 982–91.

2.Sagie A, Larson MG, Goldberg RJ, Bengtson JR, Levy D. An improved method for adjusting the QT interval for heart rate (the Framingham Heart Study). Am J Cardiol 1992; 70: 797–801.