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 beta2 agonists may result in detrimental cardiovascular effects. A study was undertaken to investigate the effect of hypoxia on the systemic vascular effects of salbutamol in patients with asthma who are hypoxic by assessing forearm blood flow (FBF) as a measure of peripheral vasodilatation.


METHODS
Eight men with mild asthma underwent the following treatments: normoxia + 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 microg salbutamol was inhaled. The experiment was completed 30 minutes after the inhalation (t=60 minutes). For the hypoxia treatment the SpO2 level was 82%. Differences between treatments were sought using factorial ANOVA on percentage change from the pretreatment value.


RESULTS
There were no significant differences in blood pressure and potassium levels between the treatments. After 60 minutes the increase in FBF was 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 for 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).


CONCLUSIONS
Patients with asthma who are hypoxic and inhale beta2 agonists have serious systemic vascular side effects which may be an additional explanation for the association between asthma treatment and sudden death.
Burggraaf
J
J
Centre for Human Drug Research, Zernikedreef 10, 2333 CL Leiden, The Netherlands. kb@chdr.nl
Westendorp
R G
RG
in't Veen
J C
JC
Schoemaker
R C
RC
Sterk
P J
PJ
Cohen
A F
AF
Blauw
G J
GJ
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000009:adverse effects*; D000704:Analysis of Variance; D001249:Asthma / Q000150:complications / Q000188:drug therapy*; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005542:Forearm / Q000098:blood supply; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D000860:Hypoxia / Q000150:complications*; D008297:Male; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D000420:Albuterol