Short paper
Cardiovascular side effects of inhaled salbutamol in hypoxic
asthmatic patients
J Burggraafa, R G J Westendorpc, J C C M in`t Veenb, R C Schoemakera, P J Sterkb, A F Cohena, G J Blauwc
a Centre for
Human Drug Research, Zernikedreef 10, 2333 CL Leiden, The Netherlands, b Department of Pulmonology, Leiden University
Medical Center, c Department of General Internal Medicine, Leiden
University Medical Center
Correspondence to: Dr J Burggraaf kb{at}chdr.nl
Received 6 April 2000; Returned to authors 18 September 2000; Revised version received 4 December 2000; Accepted for publication 19 March 2001
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
2 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.
METHODSEight
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 µg
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.
RESULTSThere 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).
CONCLUSIONPatients
with asthma who are hypoxic and inhale 2 agonists have
serious systemic vascular side effects which may be an additional explanation for the association between asthma treatment and sudden death.
Keywords: asthma; hypoxia;
2
agonists
© 2001 by Thorax
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