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Do inhaled levalbuterol and racemic albuterol
have different cardiac effects?
Evidence-Based Answer
No consistent differences have been noted in the cardiac effects of levalbuterol and racemic albuterol when
given at equivalent doses and intervals. (SOR: A, based
on smaller RCTs.) Both agents are associated with
increased cardiovascular events when used in patients
with obstructive airway disease. (SOR: A, based on a
meta-analysis.)
Levalbuterol (LEV) is purified to contain only the metabolically active R-isomer, whereas racemic albuterol
(RAC) is composed of a 1:1 ratio of S- and R-isomers.
No clinical trials have demonstrated direct cardiac
effects of the S-isomer.
In 2004, a meta-analysis of 33 RCTs (n=6,855) evaluated the cardiovascular effects of beta-2-agonists. The
study population had either asthma or chronic obstructive pulmonary disease (COPD). Compared with placebo, beta-2-agonists were associated with a 2.5 relative
risk (95% CI, 1.69–4.1) for adverse cardiovascular
events (P<.001). While most of these events were sinus
tachycardia (RR=3.1; 95% CI, 1.7–5.5), there was a
trend for major cardiovascular events, such as heart
failure, myocardial infarction, ventricular tachycardia,
and death (RR=1.7; 95% CI, 0.76–3.6).1
One small, prospective, randomized crossover study
evaluated the cardiovascular differences between LEV
and RAC. The study used 20 ICU patients who were
treated every 4 hours with equivalent doses of either
LEV or RAC (1.25 vs 2.5 mg, respectively). Both drugs
caused a slight increase in heart rate (HR); however, no
statistical difference was noted between the 2 medications (3.6 bpm LEV vs 4.4 bpm RAC).2
In a pediatric RCT (n=81), patients with severe
asthma exacerbations were given either 10 mg/h of LEV
or 20 mg/h of RAC. Tachycardia occurred with a mean
HR of 130 to 137 bpm, but no statistically significant
difference was noted between the 2 treatment groups.3
In an RCT (n=49) of patients with asthma under good
control, researchers found the HR increased by an average of 3.5 bpm more in the RAC vs the LEV treatment
group (95% CI, 0.6–6.4).4
One large study (n=486) of adults with COPD
and asthma exacerbations did show a difference in the
subjective sensation of “rapid heartbeat” with RAC
(17.3% vs 6.1%; P<.001). No other cardiac data were
available from this study. This study used a protocol of
RAC every 1 to 4 hours and LEV every 8 hours.5
The 2007 National Heart, Lung, and Blood Institute guidelines for asthma exacerbation recommend
that the dosing interval for both LEV and RAC is every
1 to 4 hours as needed.6
Robert Grumbo, MD
Robert L. Gauer, MD
Womack FMR Clinic
Fort Bragg, NC
The opinions and assertions contained herein are the private views of the authors and
are not to be construed as official or as reflecting the views of the Medical Department
of the US Army or the US Army Service at large.
1.Salpeter SR, Ormiston TM, Salpeter EE. Cardiovascular effects of beta-agonists in
patients with asthma and COPD: a meta-analysis. Chest. 2004; 125(6):2309–2321.
[LOE 1a]
2.Lam S, Chen J. Changes in heart rate associated with nebulized racemic albuterol and
levalbuterol in intensive care patients. Am J Health Syst Pharm. 2003; 60(19):1971–
1975. [LOE 1b]
3.Andrews T, McGintee E, Mittal MK, et al. High-dose continuous nebulized levalbuterol
for pediatric status asthmaticus: a randomized trial. J Pediatr. 2009; 155(2):205–210.
[LOE 1b]
4.Tripp K, McVicar WK, Nair P, et al. A cumulative dose study of levalbuterol and racemic
albuterol administered by hydrofluoroalkane-134a metered-dose inhaler in asthmatic
subjects. J Allergy Clin Immunol. 2008; 122(3):544–549. [LOE 1b]
5.Donohue JF, Hanania NA, Ciubotaru RL, et al. Comparison of levalbuterol and racemic
albuterol in hospitalized patients with acute asthma or COPD: a 2-week, multicenter,
randomized, open-label study. Clin Ther. 2008; 30(Spec No):989–1002. [LOE 2b]
6.US Department of Health and Human Services, National Institutes of Health, National
Heart, Lung, and Blood Institute. Guidelines for the diagnosis and management of
asthma—summary report 2007. NIH publication 08-5846. http://www.nhlbi.nih.gov/
guidelines/asthma/asthsumm.htm. Updated October 2007. Accessed April 1, 2010.
[LOE 1a]
What’s in an HDA?
We've asked Dr. Robert Gauer, author of numerous HDAs,
What goes into writing an HDA?
I generally spend about 3 hours performing a literature
search. When I get the articles I want, I go over their
bibliographies and pull additional articles, spending about
8–10 hours of reading and processing.
From there, I am able to begin putting thoughts into words.
This process takes about 4 hours; then I spend another 2
hours after I’ve let it sit for a few days. After the external
peer review and a round or two of edits from Dr. Neher, it is
usually ready for print.
My favorite part is the actual writing and seeing how I can
take a mountain of information and make it into a molehill
that still has relevance for the reader.
I can’t tell you the countless times I have referred to an HDA
for a question asked by a student or resident. We find the
answer easily, and it takes less than 5 minutes to read.
Read more at: www.fpin.org/page/Gauer
Evidence-Based Practice / Vol. 13, No. 10
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