Short‐term effects of inhaled salbutamol on autonomic cardiovascular control in healthy subjects: a placebo‐controlled study

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Previous reports have demonstrated a link between inhaled β2‐agonist use and cardiovascular morbidity and mortality. • The underlying mechanism for this relationship, however, remains controversial. WHAT THIS STUDY ADDS • Inhalation of a therapeutic dose of salbutamol resulted in significant haemodynamic changes, which were accompanied by a shift in cardiovascular autonomic tone towards increased sympathetic outflow in the absence of baroreceptor activation. • The observed changes in cardiac autonomic function may contribute to an increased cardiac risk associated with inhaled β2‐agonist treatment. AIMS To investigate short‐term effects of inhaled salbutamol on haemodynamic changes and cardiovascular autonomic control. METHODS A randomized, single‐blinded, placebo‐controlled study of 0.2 mg of inhaled salbutamol was conducted on 12 healthy nonsmoking volunteers with a mean age of 24 ± 2 years at two different testing sessions. Non‐invasively obtained continuous haemodynamic measurements of cardiac output, beat‐to‐beat arterial blood pressure, and total peripheral resistance were recorded prior to and for a total of 120 min after inhalation of the respective study drug. Continuous cardiovascular autonomic tone was recorded using power spectral analysis of heart rate and blood pressure variability. Spontaneous baroreceptor activity was assessed by the sequence method. RESULTS There were no significant changes in any of the baseline parameters between the different testing sessions. Inhalation of salbutamol caused a significant increase in cardiac output from 6.7 ± 1.3 to 7.7 ± 1.4 l min−1 (P < 0.05), and a decrease in total peripheral resistance from 1076 ± 192 to 905 ± 172 dyne s−1 cm−5 (P < 0.05) within 15 min after inhalation. Moreover, salbutamol significantly increased sympathetically mediated low‐frequency heart rate variability (P < 0.01), whereas parasympathetically mediated high‐frequency heart rate variability decreased (P < 0.01). All changes persisted for approximately 30 min and were fully reversible at 120 min. There were no significant changes in systolic blood pressure variability or spontaneous baroreceptor activity. CONCLUSIONS Inhalation of therapeutic doses of salbutamol in healthy subjects resulted in significant haemodynamic changes and a shift of sympathovagal balance towards increased sympathetic tone in the absence of baroreceptor activation.

Efeito agudo do salbutamol no sistema cardiovascular durante o exercício físico em pacientes com asma moderada ou grave: estudo aleatorizado, duplo-cego e cruzado

“…In contrast, Eryonucu et al 19 found that 200mcg of salbutamol increased HR by 4 bpm in average in individuals with a recent diagnosis of asthma and without drug treatment. Similarly, Cekici et al 9 and Feitosa et al 15 showed a healthy increase in mean HR of 13 bpm and 8 bpm, respectively. These different results can be explained by the characteristics of the populations studied.…”

“…The ergometric treadmill Technogym Excite Run 700 (Technogym®, Cesena, Italy) was used according to the incremental stress protocol 15 . The predicted HR max (bpm) of each patient was calculated using the following formula [1] 16 : HR max =208-(0.7 x age) [1] The Power max (watts) during exercise was calculated using the following formula [2] 17 : Power max =weight(kg) x 9.81 x sine of angle of slope x speed(m/s) [2] Statistical analysis Considering a mean HR difference of 14 bpm with standard deviation of 11 bpm and considering the 10% follow-up attrition 9 , a sample of 13 patients was calculated. The normality of the data was checked by the Kolmogorov-Smirnov test.…”

“…To allow asthmatics to perform physical exercise with fewer symptoms, the prescription of short-acting β-2 agonists is common, salbutamol being the most frequently used agent 8 . The systemic absorption of the bronchodilator results in significant hemodynamic changes, such as increased heart rate (HR) and blood pressure (BP) 9 and may lead to side effects such as tachycardia, palpitations and anxiety 10 . These hemodynamic effects are well known during rest in subjects with mild asthma and a sedentary lifestyle 3,9 , but little is known about the effects of salbutamol on these variables during exercise and post exercise recovery in patients with moderate or severe asthma.…”

“…The systemic absorption of the bronchodilator results in significant hemodynamic changes, such as increased heart rate (HR) and blood pressure (BP) 9 and may lead to side effects such as tachycardia, palpitations and anxiety 10 . These hemodynamic effects are well known during rest in subjects with mild asthma and a sedentary lifestyle 3,9 , but little is known about the effects of salbutamol on these variables during exercise and post exercise recovery in patients with moderate or severe asthma. Considering that physical exercise is important for asthmatic individuals and that β 2 -agonist is often used to perform these activities, it is necessary to know the behavior of HR and BP with the bronchodilator during exercise and recovery for a correct prescription of training intensity and to minimize cardiovascular risks.…”

Effect of salbutamol on the cardiovascular response in healthy subjects at rest, during physical exercise, and in recovery phase: a randomized, double-blind, crossover study

“…Considering an average HR difference of 14 bpm with standard deviation of 11 bpm 25 and a loss of 10% of subjects during follow-up, the sample size calculated to be 13 patients. The normality of data was assessed using the Kolmogorov-Smirnov test.…”