Chest
Volume 127, Issue 6, June 2005, Pages 2057-2063
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Clinical Investigations
Acute Electrophysiologic Effects of Inhaled Salbutamol in Humans

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Study objectives

Although inhaled β2-agonists are in widespread use, several reports question their potential arrhythmogenic effects. The purpose of this study was to evaluate the cardiac electrophysiologic effects of a single, regular dose of an inhaled β2-agonist in humans.

Design

Prospective study.

Setting

Tertiary referral center.

Patients

Six patients with bronchial asthma and 12 patients with mild COPD.

Interventions

All patients underwent an electrophysiologic study before and after the administration of salbutamol solution (5 mg in a single dose).

Measurements and results

Sinus cycle length, sinus node recovery time (SNRT), interval from the earliest reproducible rapid deflection of the atrial electrogram in the His bundle recording to the onset of the His deflection (AH), interval from the His deflection to the onset of ventricular depolarization (HV), Wenckebach cycle length (WCL), atrial effective refractory period (AERP), and ventricular effective refractory period (VERP) were evaluated just before and 30 min after the scheduled intervention. Salbutamol, a selective β2-agonist, administered by nebulizer had significant electrophysiologic effects on the atrium, nodes, and ventricle. The AH length decreased from 86.1 ± 19.5 ms at baseline to 78.8 ± 18.4 ms (p < 0.001), and the WCL decreased from 354.4 ± 44.2 to 336.6 ± 41.7 ms (p = 0.001). Salbutamol significantly decreased the AERP and VERP too while leaving the HV unchanged. Additionally, inhaled salbutamol increased heart rate (from 75.5 ± 12.8 beats/min at baseline to 93.1 ± 16 beats/min, p < 0.001) and shortened the SNRT (from 1,073.5 ± 178.7 to 925.2 ± 204.9 ms, p = 0.001).

Conclusion

Inhaled salbutamol results in significant changes of cardiac electrophysiologic properties. Salbutamol enhances atrioventricular (AV) nodal conduction and decreases AV nodal, atrial, and ventricular refractoriness in addition to its positive chronotropic effects. These alterations could contribute to the generation of spontaneous arrhythmias.

Section snippets

Patient Selection

The ethics committee of our institution approved the study. This investigation conforms to the principles outlined in the Declaration of Helsinki. Signed informed written consent was obtained from all subjects before their participation in the study.

In the present study, 18 patients were enrolled. All patients had mild COPD with postbronchodilator FEV1/FVC ratio ≤ 70% and FEV1 ≥ 80% of predicted normal value, or mild persistent bronchial asthma with FEV1 ≥ 80% of the predicted normal value and

Patients

The patient population included 11 men and 7 women between 44 years and 71 years of age (mean, 57 ± 4 years). Six patients had bronchial asthma, and the remaining 12 patients had mild COPD. Nine patients also had arterial hypertension and were receiving an angiotensin-converting enzyme inhibitor drug regimen. No patients were receiving administered β-blockers. All patients were evaluated with lung function tests at the beginning of the study. All subjects had normal left ventricular function as

Discussion

Despite the widespread use of β2-agonists, their safety has been questioned. Several studies9101112131415 have reported an increased incidence of cardiac arrhythmias in patients treated with these agents, and other studies131415 found an increased cardiovascular death with the use of oral and nebulized β2-agonists.9101112131415 Although no causal relationship has been demonstrated, the possible arrhythmogenic effects of these drugs place them under considerable suspicion. Clarifying the effects

Conclusion

We have demonstrated that inhaled salbutamol results in significant changes in cardiac electrophysiologic properties. These effects seem to be due to β2-adrenergic stimulation and could explain the increased incidence of arrhythmias in some patients treated with these agents, especially in certain clinical conditions, such as heart failure. Care must be taken before extrapolating our findings to all human subjects, and further studies are required to clarify to what extent the

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