Prior treatment with diuretic augments the hypokalemic and electrocardiographic effects of inhaled albuterol

Abstract

purpose: High doses of inhaled albuterol produce substantial improvements in bornchodilatation but are associated with dose-related systemic side effects including hypokalemia and hypomagnesemia. Concomitant diuretic therapy also produces these metabolic sequelae and may therefore precipitate cardiac arrhythmias in patients taking this combination of drugs. The purpose of this study was to investigate the electrocardiographic (ECG) effects of high-dose inhaled albuterol, and to evaluate whether potentiation occurs with bendrofluazide. patients and methods: Ten normal subjects (mean age [±SEM]: 29 ± 2 years, four women, six men) received seven days of treatment with either bendrofluazide 5 mg or identical placebo in a singel-blind, randomized, cross-over design, with a 10-day washout period. After each treatment period, responses (potassium, magnesium, ECG) to cumulative doubling doses of inhaled albuterol (100 μg to 2,000 μg) were measured. results: Baseline potassium levels (mean and 95% confidence intervals) were lower after pretreatment with bendrofluazide compared with placebo (3.07 mmol/L [2.89 to 3.25 mmol/L] versus 3.78 mmol/L [3.62 to 3.93 mmol/L]; p <0.001). The combination of bendrofluazide and albuterol produced a lower absolute level of potassium than did placebo and albuterol: (2.72 mmol/L [2.50 to 2.95 mmol/ L] versus 3.18 mmol/L [3.09 to 3.27 mmol/l]; P <0.001). Mean (± SEM) potassium fell to a lower level with bendrofluazide and albuterol in women than in men (2.45 ± 0.04 mmol/L versus 2.90 ± 0.13 mmol/L; p <0.005). Albuterol alone produced a small but significant fall in magnesium (0.842 mmol/L [0.815 to 0.869 mmol/L] to 0.789 mmol/L [0.757 to 0.820 mmol/L]; p <0.001), but no further change after bendrofluazide. Pretreatment with bendrofluazide increased the frequency (p <0.001) and amplitude (p <0.05) of U waves due to albuterol. Albuterol also attenuated T-wave amplitude (p <0.001) and prolonged the Q-Tc interval (p <0.001), with no additive effect from bendrofluazide. ST-segment depression (p <0.001) occurred in five subjects who inhaled albuterol. conclusion: These findings show that treatment with bendrofluazide augments the hypokalemic and ECG effects of high-dose inhaled albuterol. The Arrhythmogenic potential of this interaction may be important in patients with acute exacerbations of chronic airflow obstruction, who have concomitant hypoxemia and ischemic heart disease.