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Original Research |

Effects of Nebulized Bronchodilator Therapy on Heart Rate and Arrhythmias in Critically Ill Adult PatientsNebulized Bronchodilator Therapy Effects FREE TO VIEW

Fahim M. Khorfan, MD, FCCP; Patricia Smith, RN, MSN; Sandra Watt, RN, MS; Kimberly R. Barber, PhD
Author and Funding Information

From the Pulmonary and Critical Care Medicine Department (Dr Khorfan) and Office of Research (Mss Smith and Watt and Dr Barber), Genesys Regional Medical Center, Grand Blanc, MI, and Michigan State University College of Human Medicine (Drs Khorfan and Barber), East Lansing, MI.

Correspondence to: Kimberly R. Barber, PhD, Genesys Regional Medical Center, One Genesys Pkwy, Grand Blanc, MI 48439; e-mail: kbarber@genesys.org

Fifty-five percent of patients had multiple conditions on admission. CABG = coronary artery bypass graft.

CAD = coronary artery disease; CHF = congestive heart failure; DM = diabetes mellitus; HTN = hypertension; K1 = potassium; Mg = magnesium; MI = myocardial infarction; PVC = premature ventricular contraction; WNL = within normal limits. See Table 1 legend for expansion of other abbreviation.

Funding/Support: The authors have reported to CHEST that no funding was received for this study.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


Funding/Support: The authors have reported to CHEST that no funding was received for this study.

Funding/Support: The authors have reported to CHEST that no funding was received for this study.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


Chest. 2011;140(6):1466-1472. doi:10.1378/chest.11-0525
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Background:  Tachycardia and tachyarrhythmias are associated with increased morbidity and mortality in adult patients in the ICU. This study examines the effects of nebulized bronchodilator therapy (albuterol and ipratropium) on heart rate and arrhythmias in this population and tests the proposition that levalbuterol is safer than albuterol in that regard.

Methods:  The design was a randomized, single-blind, crossover, prospective study in 70 critically ill adult patients treated with nebulized bronchodilators. Patients were randomized to nebulized albuterol alternating with levalbuterol every 4 to 6 h. Group A received albuterol 2.5 mg alternating with levalbuterol 0.63 mg. Group B received albuterol 2.5 mg alternating with levalbuterol 1.25 mg. All patients received nebulized ipratropium bromide with each treatment. Heart rate was recorded before and after each treatment. Cardiac rhythm was continuously monitored using electronic telemetry units.

Results:  In group A, mean ± SD change in heart rate after albuterol 2.5 mg (n = 303) was 0.89 ± 4.5 beats/min compared with 0.85 ± 5.3 beats/min after levalbuterol 0.63 mg (n = 301) (P = .89). In group B (n = 114), heart rate decreased 0.16 ± 5.1 beats/min after albuterol 2.5 mg compared with an increase of 1.4 ± 5.4 beats/min after levalbuterol 1.25 mg (n = 118) (P = .03). Five events of arrhythmias (0.6%) occurred during the course of 836 treatments. Four consisted of occasional premature ventricular contractions. Only one patient stopped treatment because of a 5-beat run of ventricular tachycardia (one in 70 patients [1.4%]).

Conclusions:  In critically ill adult patients, nebulized albuterol and ipratropium does not cause significant tachycardia or tachyarrhythmias. Substitution of levalbuterol for albuterol to avoid tachycardia and tachyarrhythmias is unwarranted.

Trial registry:  ClinicalTrials.gov; No.: NCT01151579; URL: www.clinicaltrials.gov

Figures in this Article

Nebulized, short-acting β2-agonists and short-acting anticholinergic medications are effective bronchodilator drugs and widely prescribed for the treatment of airflow obstruction. Although there is consensus on the benefit and effectiveness of albuterol and ipratropium in the treatment of airflow obstruction, there is considerable concern about their potential side effects, particularly pertaining to heart rate, arrhythmias, and cardiovascular morbidity and mortality. Tachycardia and tachyarrhythmias are very common in critically ill adult patients with various conditions.17 Pharmacologically, inhaled albuterol can result in significant changes of cardiac electrophysiological properties. Albuterol has been found to enhance atrioventricular nodal conduction and to decrease atrioventricular nodal, atrial, and ventricular refractoriness in addition to its positive chronotropic effects.8 β2-Agonists also increase QT dispersion.9 In healthy young adults, albuterol has caused increased cardiac output and decreased peripheral vascular resistance within 15 min.10 All these alterations theoretically could contribute to the generation of tachycardia and tachyarrhythmias. In addition, ipratropium inhalation may alter autonomic control of the heart rate in therapeutic doses during mild sympathetic stimulation in healthy subjects.11 The safety of short-acting anticholinergic drugs also has been questioned recently.12 The R-isomer albuterol (levalbuterol) is suggested to be associated with fewer side effects than the parent racemic albuterol.

The purpose of the present study is to prospectively determine the clinical significance of the nebulized combination β2-agonist albuterol and anticholinergic ipratropium in the recommended, commonly used clinical doses and frequencies on heart rate and arrhythmias specifically in critically ill adult patients. We also compared levalbuterol in the two commonly used strengths to the racemic albuterol in combination with the ipratropium in terms of heart rate and arrhythmia side effects.

The design was a 2:1 randomized, prospective, crossover, single-blind study of 70 critically ill adult patients treated with nebulized bronchodilator. Approval was obtained from the hospital institutional review board (ME07-0011). Patients were eligible for enrollment if they were aged ≥ 18 years. Patients were excluded if they had a known allergy or sensitivity to the study medications or their components and if their baseline heart rate was > 110 beats/min. Treating physicians determined the need for and frequency of treatment with bronchodilator therapy. All other medications were allowed, including steroids, β-blockers, vasopressors, theophylline, and others as determined by the treating physician. Hemodynamic instability, presence of a pacemaker, ventilator dependence, and preexisting atrial fibrillation were not exclusion criteria. Baseline characteristics, including age, sex, major reason for admission, indications for bronchodilator therapy, comorbid conditions, and concomitant medications were abstracted from the medical chart. All patients were evaluated in cardiac, medical, and surgical ICUs at a 410-bed teaching hospital.

Eighty-nine patients were screened. Five declined the study, 10 did not meet the study criteria, and four were excluded because of physician preference to not participate. Seventy patients were enrolled and randomized (Fig 1).13

Figure Jump LinkFigure 1. CONSORT (Consolidated Standards of Reporting Trials) 201013 flow diagram.Grahic Jump Location

After informed consent was obtained, patients were assigned to one of two groups. Group A received nebulized albuterol 2.5 mg alternated with levalbuterol 0.63 mg every 4 to 6 h. Group B received levalbuterol 1.25 mg alternated with albuterol 2.5 mg every 4 to 6 h. All patients received nebulized ipratropium bromide 500 μg with each treatment (Fig 2). Alternating study medications enabled each patient to act as his or her own control. Patients were blinded to which treatment they were receiving. Breathing treatments were administered by respiratory therapists per hospital standardized protocol. Heart rate was recorded prior to and 15 min after each treatment. (A 15-min interval is the time that baseline heart rate is associated with the highest increase after completion of treatment.)10 Cardiac rhythm was continuously recorded with computerized ECG ICU monitoring. Telemetry data on all patients were prospectively recorded after each treatment. Any rhythm abnormality was posted and further verified by an intensivist physician. Laboratory values were retrieved from the charts of patients who experienced arrhythmias or tachyarrhythmias.

Figure Jump LinkFigure 2. Randomization scheme. A = albuterol 2.5 mg; LH = levalbuterol 1.25 mg; LL = levalbuterol 0.63 mg.Grahic Jump Location

The primary outcome variable heart rate was measured in beats per minute and reported as mean ± SD. Change in heart rate per treatment was calculated by the difference between repeated pretreatment and posttreatment measures. Differences within drug treatments from preadministration to postadministration were tested for statistical significance using the paired Student t test. The independent effect of drug treatment with the effect of multiple treatments over time was analyzed by the repeated-measures mixed analysis of variance model. Pretreatment to posttreatment effect was estimated for a 1% difference between drugs. A total of 400 treatments or 65 patients overall was required to achieve 94% power to determine a 1% change by treatment or a 5% change between groups to be significant at a P value of .01 and .05, respectively.

Seventy patients were enrolled in this study and received a total of 836 treatments. There were 34 men (48.6%) and 36 women (51.4%). The mean age was 68.34 ± 13.3 years (range, 35-92 years).

Forty-six patients were randomized to group A (albuterol 2.5 mg alternating with levalbuterol 0.63 mg), and 24 patients were randomized to group B (levalbuterol 1.25 mg alternating with albuterol 2.5 mg). There were 604 treatments in group A and 232 treatments in group B. The median number of treatments per patient was 23 (mean, 22 ± 13; range, 1-45).

The patients’ clinical conditions are listed in Table 1. There were 37 ventilator-dependent patients (52.9%). More than one-half of the patients (55%) were admitted with multiple conditions (cardiac, respiratory, shock, sepsis, etc).

Table Graphic Jump Location
Table 1 —Most Common Medical Conditions

Fifty-five percent of patients had multiple conditions on admission. CABG = coronary artery bypass graft.

The average baseline heart rate for group A was 87.6 beats/min and, for group B, 87.2 beats/min (P = .74). The mean change in heart rate from baseline for the total 836 treatments was 0.81 ± 5.1 beats/min (effect magnitude, 1.5%). We examined prechange to postchange in heart rate for each drug regimen (Fig 3). Overall, there was no difference in heart rate changes by drug across five treatment periods (μ = 0.89 beats/min; effect size, 2.1%; F = 18; P = .99). In group A, we compared heart rate changes after albuterol 2.5 mg treatments (n = 303) vs levalbuterol 0.63 mg (n = 301). The heart rate increased an average of 0.89 ± 4.5 vs 0.85 ± 5.3 beats/min, respectively. The difference was not statistically significant (P = .89). In group B, the average heart rate after albuterol 2.5 mg (n = 114) decreased 0.16 ± 5.1 beats/min vs an increase of 1.4 ± 5.4 beats/min after levalbuterol 1.25 mg (n = 118). The difference was small, but statistically significant and favored the albuterol 2.5 mg (P = .03) (Fig 3). To confirm that these results were robust regarding a clinical washout period between treatments, we reran the analysis for measures with corresponding treatments of ≥ 5 h between administrations. Results showed a less dramatic difference between drugs for change in heart rate (albuterol, 0.74; levalbuterol 0.6 mg, −0.33; levalbuterol 2.5 mg, 1.46; P = .56) (e-Table 1).

Figure Jump LinkFigure 3. Mean changes in heart rate by drug treatment: (1) albuterol 2.5 mg (n = 303 treatments), +0.89 ± 4.5 beats/min; (2) levalbuterol 0.63 mg (n = 301 treatments), +0.85 ± 5.3 beats/min; (3) albuterol 2.5 mg (n = 114 treatments), −0.16 ± 5.1 beats/min; and (4) levalbuterol 1.25 mg (n = 118 treatments), +1.4 ± 5.4 beats/min. Vertical bars indicate ± 2 SD of the difference. NS = not significant.Grahic Jump Location

We also examined subsets of patients to compare those who were taking β-blockers to those who were not. The average change in heart rate after albuterol in patients taking β-blockers (n = 176) was 0.60 ± 4.6 beats/min compared with a change of 0.61 ± 4.7 beats/min in patients who were not taking β-blockers (n = 240). In patients who received levalbuterol 1.25 mg, the average heart rate increased 1.48 ± 5.7 beats/min in those taking β-blockers (n = 93) compared with an increase of 1.50 ± 4.8 beats/min in those not taking β-blockers (n = 26). In patients who received levalbuterol 0.63 mg, the average heart rate decreased 0.06 ± 6.1 beats/min in those taking β-blockers (n = 77) compared with an increase of 1.16 ± 4.9 beats/min in those not taking β-blockers (n = 224).

Five events of arrhythmias (0.6%) occurred during the course of the 836 treatments (Table 2). In group A, one patient had a short run of ventricular tachycardia after albuterol, necessitating discontinuation from the study (one of 70 patients [1.4%]). Another patient had premature ventricular contractions after levalbuterol 0.63 mg. In group B, two patients had occasional premature ventricular contractions after both albuterol and levalbuterol 1.25 mg. One patient had ventricular bigeminy after levalbuterol 1.25 mg.

Table Graphic Jump Location
Table 2 —Characteristics of Patients With Arrhythmias

CAD = coronary artery disease; CHF = congestive heart failure; DM = diabetes mellitus; HTN = hypertension; K1 = potassium; Mg = magnesium; MI = myocardial infarction; PVC = premature ventricular contraction; WNL = within normal limits. See Table 1 legend for expansion of other abbreviation.

The combination of inhaled short-acting β-agonists and short-acting anticholinergic medicine is an effective treatment of airflow obstruction.14 The risks and benefits of these drugs have been debated for > 30 years. In addition, the safety of short-acting anticholinergics was questioned recently.12 One of the concerns is that these medications cause tachycardia and promote arrhythmias. Elevated heart rate has been shown to be a strong independent risk factor for the development of cardiomyopathy, coronary artery disease, fatal myocardial infarction, sudden death, cardiovascular mortality, and total mortality.1517 For every 10-beat/min increase in heart rate, there is a 15% increased risk of atrial fibrillation.18

This prospective study shows that nebulized albuterol and ipratropium did not result in a clinically significant increase in mean heart rate after treatments, even in patients who were hemodynamically unstable, hypoxemic, or on ventilator support. Significant tachycardia necessitating discontinuation of treatment was not observed after any of the 836 treatments in 70 patients.

The data show that the incidence of cardiac arrhythmias after albuterol and ipratropium treatments in this population is low (five of 836 [0.6%]). They consisted of transient, benign, premature ventricular contractions (not altering treatment). Only one case resulted in discontinuation of the treatment (one of 70 patients [1.4%]) because of a 5-beat run of ventricular tachycardia after six doses of albuterol (Table 2).

The second goal of this study was to compare the effect of racemic albuterol with that of R-isomer albuterol (levalbuterol) on heart rate and rhythm. No significant difference was found between albuterol 2.5 mg and levalbuterol 0.63 mg (0.89 ± 4.4 beats/min vs 0.85 ± 5.3 beats/min, respectively). There was a significant difference between albuterol 2.5 mg and levalbuterol 1.25 mg, favoring the albuterol (an increase of 1.40 ± 5.4 beats/min vs a decrease of 0.16 ± 5.1 beats/min, respectively).

Some patients were already taking β-blockers as part of their usual treatment. The heart rate changes after albuterol 2.5 mg and levalbuterol 1.25 mg did not vary significantly whether patients were taking β-blockers or not. There was some blunting of the increase in heart rate in patients who received levalbuterol 0.63 mg if they were taking β-blockers compared with those who were not taking β-blockers (a decrease of 0.06 ± 6.1 beats/min vs an increase of 1.16 ± 4.9 beats/min, respectively). The difference is not clinically significant.

For years, there have been debates related to the side effects of the short-acting β-agonists on the heart. Robin and McCauley19 suggested that sudden cardiac death in bronchial asthma was caused by the inhalation of short-acting β-adrenergic agonist drugs. One editorial suggested that inhaled β-agonists should be used with caution in patients with hypoxemia due to COPD.20 Furthermore, it has been suggested that nebulized β-agonists should be avoided all together in patients with significant cardiac disease or a high risk for such diseases.21 There are case reports of cardiac side effects from inhaled β-adrenergic drugs on heart rate and rhythm.2225 Salpeter et al26 conducted a meta-analysis of the cardiovascular effects of β-agonists in patients with asthma and COPD and concluded that β-agonist use “in patients with obstructed airway disease increases the risk for adverse cardiovascular events.” They found that the majority of side effects were minor sinus tachycardia. Major adverse events (ventricular tachycardia, cardiac arrest, and sudden death) did not reach statistical significance.27 Most of the studies used long-acting β-agonists. It is important to note that long-acting β-agonists and short-acting β-agonists are not identical drugs, the former being under major scrutiny of late.2834

Other literature has reported no positive correlation between the use of short-acting β2-agonists and cardiac tachycardia and arrhythmias.3538 Braun et al36 used albuterol and ipratropium in patients with COPD aged 35 to 80 years and found that the incidence of adverse reactions on heart rate and BP was similar to placebo. In a cohort study of 12,090 subjects with COPD aged > 55 years treated with short-acting inhaled β-agonist, Suissa et al38 did not find an increased risk of fatal or nonfatal myocardial infarction.

With regard to racemic albuterol vs levalbuterol, albuterol is a 50/50 racemic mixture of R- and S-enantiomers. Bronchodilation is solely due to the R-isomer.39 The S-isomer is linked to contractile and proinflammatory activity.40 Experimental studies have suggested that accumulation of S-isomer occurs with frequent dosing and may oppose the action of R-isomer over time.41 Pure R-isomer levalbuterol was developed to avoid the proposed negative contributions of the S-isomer in racemic albuterol. The clinical significance of these findings has been debated in the literature.27,4244 The present study found no advantage of levalbuterol over racemic albuterol as far as heart rate and rhythm disturbances are concerned.

Nelson et al44 found that there were similar increases in heart rate with the use of levalbuterol 0.63 mg and albuterol 2.5 mg after the first dose in young patients with asthma. In a retrospective study in 537 hospitalized patients with COPD, Scott and Frazee45 found that the difference in the mean heart rate with albuterol vs levalbuterol 0.63 mg was 1.0 beat/min. They concluded that even the upper end of the CI range at 5.4 beats/min does not support a clinically significant difference in tachycardia with the R-isomer compared with the racemic-mixture drug in acute airflow obstruction. In 20 hemodynamically stable ICU patients treated with at least two consecutive doses of albuterol vs levalbuterol 1.25 mg, Lam and Chen46 concluded that the use of nebulized albuterol and levalbuterol was associated with a similar increase in patients with or without baseline tachycardia.

The present study is unique in that it involved sick patients at high risk for tachycardia and tachyarrhythmias. Hemodynamic instability and hypoxemia were not exclusion criteria. Many patients were taking multiple drugs, including vasoactive medications. More than 50% of patients were ventilator dependent. All medications were continued without exception. The study was prospective, patients were blinded to the study drugs, and the study medications were alternated. The crossover method was used to control for many daily variables in the patient’s clinical condition, so each patient served as his or her own control. Possible limitations to the study are its single-center site and that the design may not have adequately eliminated all carryover effects from the levalbuterol. However, the number of side effects due to cumulative treatment, without carryover, would be even less than we observed. The negative results on the heart rate and rhythm disturbances could be due to excessive sympathomimetic stimulation because of the patients’ underlying conditions. The frequent checking and correction of electrolyte imbalances, a practice common in the ICU, and the washout effect of alternating therapy could be other factors. It is conceivable that certain subpopulations may still be prone to arrhythmias secondary to the study drugs. Larger studies may be needed to investigate the effect of these drugs on specific subpopulations of critically ill patients.

This study suggests that in hospitalized critically ill adult patients, the use of the short-acting β-agonist albuterol and a short-acting anticholinergic in the recommended commonly used dose and frequency appear not to have a clinically significant detrimental effect on heart rate and rhythm. Substitution of the much more expensive levalbuterol ($2.16/treatment) for albuterol ($0.16/treatment) to avoid cardiac side effects is not justified. Since our study, the hospital eliminated levalbuterol from its formulary, saving $100,000/year.

Author contributions: Dr Khorfan had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Khorfan: contributed to the study conception and design; data acquisition, analysis, and interpretation; and drafting, critical revision for important intellectual content, and final approval of the submitted manuscript.

Ms Smith: contributed to the data acquisition and drafting and final approval of the submitted manuscript.

Ms Watt: contributed to the study conception and design; data acquisition and interpretation; and drafting, critical revision for important intellectual content, and final approval of the submitted manuscript.

Dr Barber: contributed to the study conception and design; data acquisition, analysis, and interpretation; and drafting, critical revision for important intellectual content, and final approval of the submitted manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Additional information: The e-Table can be found in the Online Supplement at http://chestjournal.chestpubs.org/content/140/6/1466/suppl/DC1.

Author contributions: Dr Khorfan had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Khorfan: contributed to the study conception and design; data acquisition, analysis, and interpretation; and drafting, critical revision for important intellectual content, and final approval of the submitted manuscript.

Ms Smith: contributed to the data acquisition and drafting and final approval of the submitted manuscript.

Ms Watt: contributed to the study conception and design; data acquisition and interpretation; and drafting, critical revision for important intellectual content, and final approval of the submitted manuscript.

Dr Barber: contributed to the study conception and design; data acquisition, analysis, and interpretation; and drafting, critical revision for important intellectual content, and final approval of the submitted manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Additional information: The e-Table can be found in the Online Supplement at http://chestjournal.chestpubs.org/content/140/6/1466/suppl/DC1.

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Andrade Capuchinho-Júnior G, Marques Dias R, Regina da Silva de Carvalho S. One hour effects of salbutamol and formoterol on blood pressure, heart rate and oxygen saturation in asthmatics. Rev Port Pneumol. 2008;143:353-361 [PubMed]
 
Braun SR, Levy SF, Grossman J. Comparison of ipratropium bromide and albuterol in chronic obstructive pulmonary disease: a three-center study. Am J Med. 1991;914suppl 1:S28-S32 [CrossRef]
 
Lee H, Evans HE. Lack of cardiac effect from repeated doses of albuterol aerosol. A margin of safety. Clin Pediatr (Phila). 1986;257:349-352 [PubMed] [CrossRef]
 
Suissa S, Assimes T, Ernst P. Inhaled short acting beta agonist use in COPD and the risk of acute myocardial infarction. Thorax. 2003;581:43-46 [PubMed] [CrossRef]
 
Page CP, Morley J. Contrasting properties of albuterol stereoisomers. J Allergy Clin Immunol. 1999;1042 pt 2:S31-S41 [PubMed] [CrossRef]
 
Rau JL. Introduction of a single isomer beta agonist. Respir Care. 2000;458:962-966 [PubMed]
 
Dhand R, Goode M, Reid R, Fink JB, Fahey PJ, Tobin MJ. Preferential pulmonary retention of (S)-albuterol after inhalation of racemic albuterol. Am J Respir Crit Care Med. 1999;1604:1136-1141 [PubMed]
 
Ameredes BT, Calhoun WJ. (R)-albuterol for asthma: pro [a.k.a. (S)-albuterol for asthma: con]. Am J Respir Crit Care Med. 2006;1749:965-969 [PubMed] [CrossRef]
 
Gawchik SM, Saccar CL, Noonan M, Reasner DS, DeGraw SS. The safety and efficacy of nebulized levalbuterol compared with racemic albuterol and placebo in the treatment of asthma in pediatric patients. J Allergy Clin Immunol. 1999;1034:615-621 [PubMed] [CrossRef]
 
Nelson HS, Bensch G, Pleskow WW, et al. Improved bronchodilation with levalbuterol compared with racemic albuterol in patients with asthma. J Allergy Clin Immunol. 1998;1026 pt 1:943-952 [PubMed] [CrossRef]
 
Scott VL, Frazee LA. Retrospective comparison of nebulized levalbuterol and albuterol for adverse events in patients with acute airflow obstruction. Am J Ther. 2003;105:341-347 [PubMed] [CrossRef]
 
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;6019:1971-1975 [PubMed]
 

Figures

Figure Jump LinkFigure 1. CONSORT (Consolidated Standards of Reporting Trials) 201013 flow diagram.Grahic Jump Location
Figure Jump LinkFigure 2. Randomization scheme. A = albuterol 2.5 mg; LH = levalbuterol 1.25 mg; LL = levalbuterol 0.63 mg.Grahic Jump Location
Figure Jump LinkFigure 3. Mean changes in heart rate by drug treatment: (1) albuterol 2.5 mg (n = 303 treatments), +0.89 ± 4.5 beats/min; (2) levalbuterol 0.63 mg (n = 301 treatments), +0.85 ± 5.3 beats/min; (3) albuterol 2.5 mg (n = 114 treatments), −0.16 ± 5.1 beats/min; and (4) levalbuterol 1.25 mg (n = 118 treatments), +1.4 ± 5.4 beats/min. Vertical bars indicate ± 2 SD of the difference. NS = not significant.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Most Common Medical Conditions

Fifty-five percent of patients had multiple conditions on admission. CABG = coronary artery bypass graft.

Table Graphic Jump Location
Table 2 —Characteristics of Patients With Arrhythmias

CAD = coronary artery disease; CHF = congestive heart failure; DM = diabetes mellitus; HTN = hypertension; K1 = potassium; Mg = magnesium; MI = myocardial infarction; PVC = premature ventricular contraction; WNL = within normal limits. See Table 1 legend for expansion of other abbreviation.

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Chowdhury BA, Dal Pan GD. The FDA and safe use of long-acting beta-agonists in the treatment of asthma. N Engl J Med. 2010;36213:1169-1171 [PubMed] [CrossRef]
 
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Andrade Capuchinho-Júnior G, Marques Dias R, Regina da Silva de Carvalho S. One hour effects of salbutamol and formoterol on blood pressure, heart rate and oxygen saturation in asthmatics. Rev Port Pneumol. 2008;143:353-361 [PubMed]
 
Braun SR, Levy SF, Grossman J. Comparison of ipratropium bromide and albuterol in chronic obstructive pulmonary disease: a three-center study. Am J Med. 1991;914suppl 1:S28-S32 [CrossRef]
 
Lee H, Evans HE. Lack of cardiac effect from repeated doses of albuterol aerosol. A margin of safety. Clin Pediatr (Phila). 1986;257:349-352 [PubMed] [CrossRef]
 
Suissa S, Assimes T, Ernst P. Inhaled short acting beta agonist use in COPD and the risk of acute myocardial infarction. Thorax. 2003;581:43-46 [PubMed] [CrossRef]
 
Page CP, Morley J. Contrasting properties of albuterol stereoisomers. J Allergy Clin Immunol. 1999;1042 pt 2:S31-S41 [PubMed] [CrossRef]
 
Rau JL. Introduction of a single isomer beta agonist. Respir Care. 2000;458:962-966 [PubMed]
 
Dhand R, Goode M, Reid R, Fink JB, Fahey PJ, Tobin MJ. Preferential pulmonary retention of (S)-albuterol after inhalation of racemic albuterol. Am J Respir Crit Care Med. 1999;1604:1136-1141 [PubMed]
 
Ameredes BT, Calhoun WJ. (R)-albuterol for asthma: pro [a.k.a. (S)-albuterol for asthma: con]. Am J Respir Crit Care Med. 2006;1749:965-969 [PubMed] [CrossRef]
 
Gawchik SM, Saccar CL, Noonan M, Reasner DS, DeGraw SS. The safety and efficacy of nebulized levalbuterol compared with racemic albuterol and placebo in the treatment of asthma in pediatric patients. J Allergy Clin Immunol. 1999;1034:615-621 [PubMed] [CrossRef]
 
Nelson HS, Bensch G, Pleskow WW, et al. Improved bronchodilation with levalbuterol compared with racemic albuterol in patients with asthma. J Allergy Clin Immunol. 1998;1026 pt 1:943-952 [PubMed] [CrossRef]
 
Scott VL, Frazee LA. Retrospective comparison of nebulized levalbuterol and albuterol for adverse events in patients with acute airflow obstruction. Am J Ther. 2003;105:341-347 [PubMed] [CrossRef]
 
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;6019:1971-1975 [PubMed]
 
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