Cardiovascular side effects of inhaled salbutamol in hypoxic asthmatic patients

Background - Beta-2 adrenoceptor agonists have been associated with sudden death in asthma patients but the cause and underlying mechanism are unclear . Animal experiments indicate that the combination of hypoxia and PZ agonis ts may result in detrimental cardiovascular effects. A study was undertaken to investigate the effect of hypoxia on the systemic vascular effects of s albutamol in patients with asthma who are hypoxic by assessing forearm bloo d flow (FBF) as a measure of peripheral vasodilatation. Methods - Eight men with mild asthma underwent the following treatments :no rmoxia + placebo (NP), normoxia + salbutamol (NS), hypoxia + placebo (HP), and hypoxia + salbutamol (HS). The period of mask breathing started at t=0 minutes, lasted for 60 minutes, and at 30 minutes 800 mug salbutamol was in haled. The experiment was completed 30 minutes after the inhalation (t=60 m inutes). For the hypoxia treatment the Spo(2) level was 82%. Differences be tween treatments were sought using factorial ANOVA on percentage change fro m the pretreatment value. Results - There were no significant differences in blood pressure and potas sium levels between the treatments. After 60 minutes the increase in FBF wa s 13% (95% CI -12 to 39) more for HP treatment than for NP, 21% (95% CI -5 to 46) more for NS than for NP, and 32% (95% CI 7 to 58) more for HS than f or HP (p=0.016). The inhalation of salbutamol during hypoxia resulted in a significant increase in FBF of 45% (95% CI 20 to 71) compared with NP (p=0. 001). Conclusion - Patients with asthma who are hypoxic and inhale beta (2) agoni sts have serious systemic vascular side effects which may be an additional explanation for the association between asthma treatment and sudden death.