ORIGINAL ARTICLE

Open Access

Safety outcomes of salbutamol: A systematic review and meta-analysis

Lan-Hong Ma

Department of Respiratory, Digestive, and Cardiology, Children's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China

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Li Jia,

Li Jia

Department of Pharmacy, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China

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Ling Bai,

Corresponding Author

Ling Bai

[email protected]

orcid.org/0000-0003-3778-610X

Department of Nephrorheumatology, Children's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China

Correspondence

Ling Bai, Department of Nephrorheumatology, Children's Hospital of Xinjiang Uygur Autonomous Region, 39 Xicheng Street, Shayibuck District, Urumqi, Xinjiang Uygur Autonomous Region, China.

Email: [email protected]

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Lan-Hong Ma,

Lan-Hong Ma

Department of Respiratory, Digestive, and Cardiology, Children's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China

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Li Jia,

Li Jia

Department of Pharmacy, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China

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Ling Bai,

Corresponding Author

Ling Bai

[email protected]

orcid.org/0000-0003-3778-610X

Department of Nephrorheumatology, Children's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China

Correspondence

Ling Bai, Department of Nephrorheumatology, Children's Hospital of Xinjiang Uygur Autonomous Region, 39 Xicheng Street, Shayibuck District, Urumqi, Xinjiang Uygur Autonomous Region, China.

Email: [email protected]

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First published: 16 October 2023

https://doi.org/10.1111/crj.13711

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Abstract

Purpose

Salbutamol has been used to alleviate bronchospasm in airway disease for decades, while its potential risks have not been systematically investigated yet. The risk of any potential adverse events (AEs) in patients treated with salbutamol was assessed through systematic review and meta-analysis.

Methods

A systematic search of the literature was conducted, using EMBASE, PubMed and Cochrane library, until 3 April 2023. Once the AE incidence was evaluated, randomized controlled trials (RCTs) were eligible for review. The endpoints included the incidence of total AEs, severe AEs, treatment discontinuation and specific AEs. The pooled AEs incidence was analysed via random-effects model in a single-arm meta-analysis. A subgroup study was carried out to examine whether the pooled incidence of AE differed by indications or formulations.

Results

Of the 8912 studies that were identified, 58 RCTs met the inclusion criteria and involved 12 961 participants. The analysis showed the pooled incidences of total AEs, severe AEs and treatment discontinuation in patients treated with salbutamol were 34%, 2% and 3%, respectively. Subgroup analysis indicated that premature labour users and intravenous salbutamol users were more likely associated with total AEs. The most frequently observed specific AEs were palpitations or tachycardia.

Conclusion

This meta-analysis indicated that salbutamol was associated with a very common risk of palpitations or tachycardia. Clinical vigilance and research efforts are needed to optimize the safe use of salbutamol.

1 INTRODUCTION

Salbutamol is the first choice to relieve acute airflow obstruction and symptoms and widely used for asthma, chronic obstructive pulmonary disease (COPD) and other bronchospasm reactions.^{1, 2} In the past, numerous studies concluded that the long-term use of salbutamol was well tolerated.^3-7 However, Global Initiative for Asthma (GINA) indicated higher use of short-acting β₂ agonists (SABA) is associated with higher risk of adverse clinical outcomes, including emergency department presentation⁸ and death.⁹ Although most adverse events (AEs) are manageable and not life-threatening, they can have a considerable impact on patients' psychological function (such as nervousness and anxiety) or physical function (including palpitation or tachycardia, tremors and headache).^10-12 Furthermore, the safety profiles of salbutamol varied among trials.

To our knowledge, no systematic meta-analysis focused on the AEs profile of salbutamol has been conducted. To investigate the AE profiles of salbutamol users, we conducted a comprehensive search and meta-analysis of randomized controlled trials (RCTs).

2 METHODS

2.1 Data sources, search strategy and selection criteria

The study was carried out and reported in accordance with the Statement of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA).¹³ RCTs reported the risks of AEs for patients treated with salbutamol were eligible in our study, without any restriction on language. From the beginning to 3 April 2023, a comprehensive search of EmBase, PubMed and the Cochrane library was conducted using the following search terms: ‘salbutamol’, ‘albuterol’, ‘adverse event’, ‘adverse effect’, ‘side effect’, ‘toxicity’, ‘clinical trial’, ‘controlled clinical trial’ and ‘randomized controlled trial’. Only human RCTs were included. When numerous publications of the same clinical trials were identified, only the most comprehensive and latest trial report was included.

Two reviewers worked separately on the literature search and study selection, and any disagreements were resolved through group discussion until a consensus was established. Trials that met the following criteria were included: (a) randomized controlled trials, (b) salbutamol (without restrictions of formulation) was used as the unique medication in the experimental arm, and (c) data on AEs were available. The detail of literature search strategy was shown in Data S1.

2.2 Data collection and clinical outcomes

The following data were extracted from each study that met inclusion criteria: the first author's name, publication year, country, number of patients in the salbutamol cohort, mean age, indication, formulation of salbutamol, numbers of patients with total AEs, severe AEs, treatment discontinuation and specific AEs (including tremor, palpitations or tachycardia, headache, nervousness, anxiety, cough, dyspnoea, nausea and vomiting) in the salbutamol cohort and incidence of above AEs in the salbutamol cohort. Two reviewers extracted data separately, and any discrepancies were resolved through consensus.

2.3 Quality assessment

Two reviewers independently assessed the methodological quality of the included studies using the Newcastle-Ottawa Scale (NOS),¹⁴ by evaluating the following three subscales: (a) selection (four items), (b) comparability (one item) and (c) outcome (three items). Items that are judged as adequate receive a star and 1 point. Responses are summed (range 0 to 9). Studies scoring 7 or over are considered of good quality, 5 or 6 of fair quality and 0 to 4 of poor quality. Any disagreements were settled through consensus.

2.4 Statistical analysis

The pooled incidence of total AEs, severe AEs, treatment discontinuation and specific AEs (including tremor, palpitations or tachycardia, headache, nervousness, anxiety, cough, dyspnoea, nausea and vomiting) after salbutamol treatment were the endpoint of this meta-analysis. The number of total AEs, severe AEs, treatment discontinuations and specific AEs from the salbutamol treated group in each study were extracted to calculate the incidence. A random-effects model was used to generate the pooled incidence and the corresponding 95% confidence interval (CI).^{15, 16} The I² and Q statistic were used to measure heterogeneity. The I² > 50.0% or the P_{Q statistic} < 0.10 was used to characterize significant heterogeneity.^{17, 18} The potential impact of a single trial on pooled incidences of total AEs, severe AEs and treatment discontinuation was assessed by sensitivity analysis.¹⁹ The researchers used subgroup analysis to evaluate whether the pooled incidences of total AEs, severe AEs and treatment discontinuation varied by indications (premature labour, asthma or COPD) and the formulations of salbutamol (inhaled, oral or intravenous). The interaction P test was used to assess the subgroup analysis.²⁰ A two-sided P value lower than 0.05 was considered statistically significant. Publication bias was conducted using funnel plots, Egger's test and Begg's test.^21-23 All analyses were performed by STATA 10.0 (Stata Corporation, College Station, TX, USA).

3 RESULTS

3.1 Literature search

The initial search yielded 8912 potentially relevant trails. After duplicate publications were removed, 5287 trails were included. After checking the titles and abstracts, 5136 records were eliminated, leaving 151 possibly relevant articles to be reviewed in full text. Based on the full-text review, 93 articles were ruled out for one or more of the following reasons: reviews, duplicated cohorts, commentaries, non-randomized trials, non-human trials or without AEs outcomes. Ultimately, 58 RCTs with a total of 12 961 patients were included in this meta-analysis.^24-81 The selection procedure is depicted in Figure 1.

Details are in the caption following the image — **FIGURE 1**
Open in figure viewer PowerPoint

The flow chart of study selection.

3.2 Study characteristics

Summary of the main characteristics of the included studies was displayed in Table S1. Of the included 58 trials, the number of salbutamol users ranged from 11 to 8393, which were published from 1978 to 2020,^24-81 and 38 (65.5%), seven (12.1%), five (8.6%) and eight (13.8%) focused on asthma, COPD, premature labour and other bronchoconstriction indications, respectively. Inhaled salbutamol was used in 75.9% of trails (44/58), while oral salbutamol was used in seven trails, and intravenous salbutamol was used in the rest seven trails. Salbutamol's dosage ranged from 200 μg to 30 mg per day, with treatment duration ranging from 1 day to 52 weeks.

3.3 Quality of the studies and publication bias

Table S2 indicates the methodological quality of the included studies. Thirty-one studies reported six stars and the remaining 27 studies with five stars. Furthermore, visual inspection of the funnel plots and Egger's test revealed no indication of publication bias for severe AEs (Figures S1–S12). Similar to the Egger's test, the Begg's test also presented no evidence of asymmetry.

3.4 Incidences of Total AEs

A total of 30 trails reported the risk of total AEs for patients treated with salbutamol,^{24, 26, 29, 31, 32, 34, 35, 38, 40-42, 45, 49, 50, 54-59, 63-66, 69, 72, 76, 77, 79, 81} and the pooled incidence of total AEs was 34% (95% CI: 25%–43%, I² = 98.4%, P < 0.001; Figure 2). The incidences of total AEs varied in different indication subgroups and formulation subgroups (Table 1). As for indication subgroups, there were three studies,^{24, 42, 69} 19 studies^{26, 29, 31, 32, 34, 38, 41, 45, 50, 54, 56-58, 63, 65, 76, 77, 79, 81} and five studies^{35, 40, 49, 64, 66} reported total AEs in premature labour subgroup, asthma subgroup and COPD subgroup, and the pooled incidence was highest in premature labour subgroup (pooled incidence: 57%, 95% CI: 0.33–0.80, I² = 90.4%, P < 0.001). As for formulation subgroups, total AEs were reported in 24 studies,^{26, 31, 32, 34, 35, 38, 40, 41, 45, 49, 50, 54, 56, 58, 59, 63-66, 72, 76, 77, 79, 81} four studies^{24, 42, 57, 69} and two studies^{29, 55} in inhaled, intravenous and oral subgroup, while the pooled incidence was highest in intravenous subgroup (pooled incidence: 51%, 95% CI: 0.21–0.81, I² = 92.9%, P < 0.001).

TABLE 1. Subgroup analyses for adverse events.

Outcomes	Subgroup		No. of studies	Incidence (95% CI)	I² (%)	P_{Q statistic}	P value between subgroups
Total AEs	Different indications	Premature labour	3	0.57 (0.33–0.80)	90.4	<0.001	<0.001
		Asthma	19	0.30 (0.20–0.40)	98.4	<0.001
		COPD	5	0.38 (0.16–0.60)	98.1	<0.001
	Different formulations	Inhaled	24	0.33 (0.24–0.43)	98.5	<0.001	<0.001
		Oral	2	0.22 (0.08–0.36)	90.6	<0.001
		Intravenous	4	0.51 (0.21–0.81)	92.9	<0.001
Severe AEs	Different indications	Premature labour	0	-	-	-	0.004
		Asthma	5	0.02 (0.01–0.03)	59.2	0.023
		COPD	1	0.06 (0.03–0.09)	-	-
	Different formulations	Inhaled	6	0.02 (0.01–0.03)	67.6	0.003	0.004
		Oral	0	-	-	-
		Intravenous	1	0.06 (0.02–0.09)	-	-
Treatment discontinuations	Different indications	Premature labour	0	-	-	-	0.001
		Asthma	7	0.01 (0.01–0.02)	0	0.436
		COPD	3	0.13 (0.02–0.23)	88.7	<0.001
	Different formulations	Inhaled	11	0.03 (0.01–0.04)	70.1	<0.001	0.108
		Oral	1	0.05 (−0.01–0.12)	-	-
		Intravenous	0	-	-	-

Abbreviations: AEs, adverse events; CI, confidence interval; COPD, chronic obstructive pulmonary disease.

3.5 Incidences of severe AEs

Seven trials reported the risk of severe AEs in salbutamol users,^{26, 33, 50, 66, 73, 77, 81} and the pooled incidence was 2% (95% CI: 1%–3%, I² = 68.9%, P < 0.001; Figure 3). The incidences of severe AEs varied in different indication subgroups and formulation subgroups (Table 1). Compared with COPD subgroup (pooled incidence: 6%, 95% CI: 3%–9%),⁶⁶ the risk of severe AEs in asthma subgroup was slightly lower (pooled incidence: 2%, 95% CI: 1%–3%, I² = 59.2%, P = 0.004),^{26, 33, 50, 77, 81} while inhaled salbutamol subgroup (pooled incidence: 2%, 95% CI: 1%–3%, I² = 67.6%, P = 0.004)^{26, 33, 50, 66, 77, 81} was with a lower risk of severe AEs than intravenous subgroup (pooled incidence: 6%, 95% CI: 2%–9%, P = 0.038).⁷³ No studies reported severe AEs either in premature labour subgroup or oral subgroup.

3.6 Incidences of treatment discontinuations

Twelve trials reported the risk of treatment discontinuations in salbutamol users,^{34, 35, 39, 41, 44, 45, 50, 54, 64, 66, 72, 77} and the pooled incidence of treatment discontinuations was 3% (95%CI: 2%–5%, I² = 69.8%, P < 0.001; Figure 4). There was a higher risk of treatment discontinuation in COPD subgroup (pooled incidence: 13%, 95% CI: 2%–23%, I² = 88.7%)^{35, 64, 66} than asthma subgroup (pooled incidence: 1%, 95% CI: 1%–2%, I² = 0%, P < 0.001).^{34, 39, 41, 45, 50, 54, 77} There are no significant differences between oral subgroup and inhaled subgroup (P = 0.108, Table 1). No studies reported treatment discontinuations in either premature labour subgroup or intravenous subgroup.

3.7 Incidences of specific AEs

3.7.1 Cardiovascular system

The pooled incidence of palpitations or tachycardia was 16% (95%CI: 11%–22%, I² = 98.7%, P < 0.001; Figure S13).

3.7.2 Nervous system

The pooled incidences of tremor, headache, nervousness and anxiety were 9% (95%CI: 7%–11%, I² = 87%, P < 0.001), 8% (95%CI: 6%–10%, I² = 88.2%, P < 0.001), 5% (95%CI: 3%–7%, I² = 44.1%, P = 0.057) and 13% (95%CI: 6%–21%, I² = 92.3%, P < 0.001), respectively (Figures S14–S17).

3.7.3 Respiratory system

The pooled incidences of cough and dyspnoea were 3% (95%CI: 2%–5%, I² = 51.5%, P = 0.036) and 7% (95%CI: 2%–12%, I² = 86.7%, P < 0.001), respectively (Figures S18 and S19).

3.7.4 Digestive system

The pooled incidences of nausea and vomiting were 5% (95%CI: 3%–8%, I² = 81.7%, P < 0.001) and 7% (95%CI: 3%–11%, I² = 78.8%, P < 0.001), respectively (Figures S20 and S21).

3.8 Sensitivity analysis

A sensitivity analysis was conducted if any AE outcome with significant heterogeneity in the reported results. All the results (total AEs, severe AEs, treatment discontinuation and all specific AEs) were not significantly altered by sequentially omitting each study in the meta-analysis (Figures S22–S24).

4 DISCUSSION

Nowadays, numerous studies have already illustrated the treatment effectiveness of salbutamol for patients undergoing various conditions,^82-84 while no study systematically assessed the pooled effect estimates for AEs. This meta-analysis involved 12 961 patients treated with salbutamol from 58 RCTs across different indications and different salbutamol formulations. The risk of total AEs was very common (≥1/10) as 34 per 100 patients in salbutamol users, while the risk of severe AEs and treatment discontinuation were common (2% and 3%, respectively). The most frequent specific AEs were palpitations or tachycardia (16%).

As for different indications, premature labour users (57%) were more likely to be associated with total AEs. Compared with inhaled salbutamol users, intravenous users were more likely to be associated with total AEs (51% vs. 33%, P < 0.001) and severe AEs (6% vs. 2%, P = 0.004), while the rates of treatment discontinuation were 3% and 5% in inhaled users and oral salbutamol users, with no significant differences (P = 0.108). Sriprasart et al.⁸⁵ conducted a meta-analysis in asthmatic patients (aged ≥12 years old) in inhaled SABA users, which reported the rates of treatment discontinuation, and severe AEs were 3.9% and 1.8%, respectively. Our results were consistent with previous systematic reviews. Therefore, additional effective treatment strategies should be applied to these salbutamol users to prevent further AEs risk.

Palpitations or tachycardia is the highest incidence in our study. It is also a common adverse reaction in clinical practice, which could be explained by the following reason: (1) Hypokalaemia or prolonged QT interval could cause arrhythmogenic effects; (2) the increased heart rate could cause by shortened diastole; (3) increased sympathetic outflow are significantly associated with poor prognosis of cardiovascular disease and COPD.^86-89 In a retrospective study involving 64 patients with asthma treated with salbutamol, 95% of the patients developed tachycardia.⁹⁰ The results of another retrospective database analysis showed that the incidence of supraventricular tachycardia caused by salbutamol treatment in children with asthma from 0 to 18 years old from 2006 to 2015 was 0.39‰.⁹¹ Previous studies and our meta-analysis indicated the use of salbutamol in patients with cardiovascular disease should be more carefully.

As for other specific AEs, salbutamol seems to have a greater effect on the nervous system, while the pooled incidence of anxiety and tremor was 13% and 9%, respectively. It is worth noting that not all the labels for salbutamol suggest the adverse effects on anxiety. A prospective study reported that anxiety has been associated with increased asthma-related exacerbations.⁹² However, whether the anxiety caused by the use of salbutamol affects the disease state needs further analysis. In addition, salbutamol could induce skeletal muscle tremor, irrespective of short- or long-term use of salbutamol.^{93, 94} Tremor is usually transient, that is, disappears after stopping the use of salbutamol, and usually does not require additional treatment. Considering that patients often feel worried or fearful, it is suggested that clinicians can provide appropriate emotional comfort when patients experience such adverse events.

These results are important because the overprescription of SABA continues to increase worldwide especially in asthmatic patients, which is associated with an increased risk of asthma exacerbations, mortality and incremental health care resource utilization.^{95, 96} However, it is important to note that this meta-analysis has limitations, mainly due to the variation in study design features (such as duration of follow-up), features of the population (such as severity of illness, age and gender) and intervention factors (such as dosage, timing or duration of treatment). These may be the determinant reasons for the high heterogeneity of results we observed in all of the quantitative analyses, which could not be interpreted by sensitivity and subgroup analyses. And we performed the risk of bias assessment and revealed all of the included studies with fair quality. What is more, our study mainly focuses on mono-therapy with salbutamol. Furthermore, some of the included RCTs had small sample sizes and varied study duration. More studies with sufficient methodological quality are needed to monitor the safety of salbutamol. Because of the mentioned considerations, our pooled estimate of incidence might be underestimated.

5 CONCLUSION

In conclusion, the risk of total AEs may be quite common in the clinical use of salbutamol. Incidences of severe AEs and treatment discontinuation are also considered common. When using salbutamol in clinical practice, more attention is needed to be paid to palpitation or tachycardia, which might occur more frequently. Moreover, premature labour users or intravenous salbutamol users might have a higher risk of AEs, which should be cautious in clinical practice. For the safe use of salbutamol, further research is needed, particularly large-scale intensive monitoring studies.

AUTHOR CONTRIBUTIONS

We declare that this work was done by the authors named in this article, and all liabilities pertaining to claims relating to the content of this article will be borne by the authors. Ling Bai conceived and designed the study; Lanhong Ma, Li Jia and Ling Bai performed the study; Lanhong Ma analysed the data; Ling Bai contributed to reagents/materials/analysis tools; Lanhong Ma wrote the manuscript.

ACKNOWLEDGEMENTS

The authors would like to thank Canghong Zhi, Honglin Li and Dandan Zhao for providing medical writing support.

This work was supported by the Technology and Innovation Project of Xinjiang Uygur Autonomous Region People's Hospital (No. 20180311) and the Natural Science Foundation of Xinjiang Uygur Autonomous Region (No. 2021D01A136).

CONFLICT OF INTEREST STATEMENT

No conflict of interest was associated with this work.

ETHICS STATEMENT

No ethical approval was required for this systematic review and meta-analysis.

Open Research

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Supporting Information

REFERENCES

1Barnes PJ. Drugs for the treatment of asthma and COPD. In: FP Nijkamp, MJ Parnham, eds. Principles of Immunopharmacology. Birkhäuser Basel; 2005.
10.1007/3-7643-7408-X_19
Google Scholar
2Price OJ, Hull JH, Backer V, Hostrup M, Ansley L. The impact of exercise-induced bronchoconstriction on athletic performance: a systematic review. Sports Med. 2014; 44(12): 1749-1761. doi:10.1007/s40279-014-0238-y
10.1007/s40279-014-0238-y
PubMed Web of Science® Google Scholar
3Bondesson E, Friberg K, Soliman S, Löfdahl CG. Safety and efficacy of a high cumulative dose of salbutamol inhaled via Turbuhaler or via a pressurized metered-dose inhaler in patients with asthma. Respir Med. 1998; 92(2): 325-330. doi:10.1016/S0954-6111(98)90116-0
10.1016/S0954-6111(98)90116-0
CAS PubMed Web of Science® Google Scholar
4Golish J, Curtis-McCarthy P, McCarthy K, et al. Albuterol delivered by metered-dose inhaler (MDI), MDI with spacer, and RotahalerTMDevice-A comparison of efficacy and safety. J Asthma. 1998; 35(4): 373-379. doi:10.3109/02770909809075671
10.3109/02770909809075671
CAS PubMed Web of Science® Google Scholar
5Tinkelman DG, Bleecker ER, Ramsdell J, et al. Proventil HFA and ventolin have similar safety profiles during regular use. Chest. 1998; 113(2): 290-296. doi:10.1378/chest.113.2.290
10.1378/chest.113.2.290
CAS PubMed Web of Science® Google Scholar
6Geoffroy P, Lalonde RL, Ahrens R, et al. Clinical comparability of albuterol delivered by the breath-actuated inhaler (Spiros) and albuterol by MDI in patients with asthma. Ann Allergy Asthma Immunol. 1999; 82(4): 377-382. doi:10.1016/S1081-1206(10)63287-5
10.1016/S1081-1206(10)63287-5
CAS PubMed Web of Science® Google Scholar
7Ramsdell JW, Klinger NM, Ekholm BP, Colice GL. Safety of long-term treatment with HFA albuterol. Chest. 1999; 115(4): 945-951. doi:10.1378/chest.115.4.945
10.1378/chest.115.4.945
CAS PubMed Web of Science® Google Scholar
8Stanford RH, Shah MB, D'Souza AO, Dhamane AD, Schatz M. Short-acting beta-agonist use and its ability to predict future asthma-related outcomes. Ann Allergy Asthma Immunol. 2012; 109(6): 403-407. doi:10.1016/j.anai.2012.08.014
10.1016/j.anai.2012.08.014
CAS PubMed Web of Science® Google Scholar
9Suissa S, Ernst P, Boivin JF, et al. A cohort analysis of excess mortality in asthma and the use of inhaled beta-agonists. Am J Respir Crit Care Med. 1994; 149(3 Pt 1): 604-610. doi:10.1164/ajrccm.149.3.8118625
10.1164/ajrccm.149.3.8118625
CAS PubMed Web of Science® Google Scholar
10Ng G, da Silva O, Ohlsson A. Bronchodilators for the prevention and treatment of chronic lung disease in preterm infants. Cochrane Database Syst Rev. 2016; 12(1):CD003214. doi:10.1002/14651858.CD003214.pub3
10.1002/14651858.CD003214.pub3
PubMed Google Scholar
11Bio LL, Willey VJ, Poon CY. Comparison of levalbuterol and racemic albuterol based on cardiac adverse effects in children. J Pediatr Pharmacol Ther. 2011; 16(3): 191-198. doi:10.5863/1551-6776-16.3.191
10.5863/1551?6776?16.3.191
PubMed Google Scholar
12Khorfan FM, Smith P, Watt S, Barber KR. Effects of nebulized bronchodilator therapy on heart rate and arrhythmias in critically ill adult patients. Chest. 2011; 140(6): 1466-1472. doi:10.1378/chest.11-0525
10.1378/chest.11-0525
PubMed Web of Science® Google Scholar
13Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009; 6(7):e1000097. doi:10.1371/journal.pmed.1000097
10.1371/journal.pmed.1000097
PubMed Web of Science® Google Scholar
14Wells G, Shea B, O'Connell D. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Hospital Research Institute; 2009.
Google Scholar
15DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986; 7(3): 177-188. doi:10.1016/0197-2456(86)90046-2
10.1016/0197-2456(86)90046-2
CAS PubMed Google Scholar
16Ades AE, Lu G, Higgins JP. The interpretation of random-effects meta-analysis in decision models. Med Decis Making. 2005; 25(6): 646-654. doi:10.1177/0272989X05282643
10.1177/0272989X05282643
CAS PubMed Web of Science® Google Scholar
17Deeks JJ, Higgins JP, Altman DG. Analysing data and undertaking meta-analyses. In: Cochrane Handbook for Systematic Reviews of Interventions; 2008.
10.1002/9780470712184.ch9
Google Scholar
18Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003; 327(7414): 557-560. doi:10.1136/bmj.327.7414.557
10.1136/bmj.327.7414.557
PubMed Google Scholar
19Tobias A. Assessing the influence of a single study in the meta-analysis estimate. Stata Technical Bulletin. 1999; 8(47):15.
Google Scholar
20Altman DG, Bland JM. Interaction revisited: the difference between two estimates. BMJ. 2003; 326(7382): 219. doi:10.1136/bmj.326.7382.219
10.1136/bmj.326.7382.219
PubMed Web of Science® Google Scholar
21Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994; 50(4): 1088-1101. doi:10.2307/2533446
10.2307/2533446
CAS PubMed Web of Science® Google Scholar
22Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997; 315(7109): 629-634. doi:10.1136/bmj.315.7109.629
10.1136/bmj.315.7109.629
CAS PubMed Web of Science® Google Scholar
23Duval S, Tweedie R. A nonparametric “trim and fill” method of accounting for publication bias in meta-analysis. J am Stat Assoc. 2000; 95(449): 89-98.
10.1080/01621459.2000.10473905
Web of Science® Google Scholar
24Sims CD, Chamberlain GVP, Boyd IE, Lewis PJ. A comparison of salbutamol and ethanol in the treatment of preterm labour. Br J Obstet Gynaecol. 1978; 85(10): 761-766. doi:10.1111/j.1471-0528.1978.tb15598.x
10.1111/j.1471-0528.1978.tb15598.x
CAS PubMed Google Scholar
25Prime FJ. A clinical trial of choline theophyllinate versus salbutamol with placebo control. J Int Med Res. 1979; 7(5): 428-433. doi:10.1177/030006057900700517
10.1177/030006057900700517
CAS PubMed Web of Science® Google Scholar
26Bronsky E, Bucholtz GA, Busse WW, et al. Comparison of inhaled albuterol powder and aerosol in asthma. J Allergy Clin Immunol. 1987; 79(5): 741-747. doi:10.1016/0091-6749(87)90205-3
10.1016/0091-6749(87)90205-3
CAS PubMed Web of Science® Google Scholar
27Assoufi BK, Hodson ME. High dose salbutamol in chronic airflow obstruction: comparison of nebulizer with Rotacaps. Respir Med. 1989; 83(5): 415-420. doi:10.1016/S0954-6111(89)80073-3
10.1016/S0954-6111(89)80073-3
CAS PubMed Web of Science® Google Scholar
28Colacone A, Wolkove N, Stern E, Afilalo M, Rosenthal TM, Kreisman H. Continuous nebulization of albuterol (salbutamol) in acute asthma. Chest. 1990; 97(3): 693-697. doi:10.1378/chest.97.3.693
10.1378/chest.97.3.693
CAS PubMed Web of Science® Google Scholar
29Pierson WE et al. Long-term, double-blind comparison of controlled-release albuterol versus sustained-release theophylline in adolescents and adults with asthma. J Allergy Clin Immunol. 1990; 85(3): 618-626. doi:10.1016/0091-6749(90)90102-A
10.1016/0091-6749(90)90102-A
CAS PubMed Web of Science® Google Scholar
30Emerman CL, Cydulka RK, Effron D, Lukens TW, Gershman H, Boehm SP. A randomized, controlled comparison of isoetharine and albuterol in the treatment of acute asthma. Ann Emerg Med. 1991; 20(10): 1090-1093. doi:10.1016/S0196-0644(05)81381-2
10.1016/S0196-0644(05)81381-2
CAS PubMed Web of Science® Google Scholar
31Liippo K, Silvasti M, Tukiainen H. Inhaled procaterol versus salbutamol in bronchial asthma. Eur J Clin Pharmacol. 1991; 40(4): 417-418. doi:10.1007/BF00265855
10.1007/BF00265855
CAS PubMed Web of Science® Google Scholar
32Pearlman DS, Chervinsky P, LaForce C, et al. A comparison of salmeterol with albuterol in the treatment of mild-to-moderate asthma. N Engl J Med. 1992; 327(20): 1420-1425. doi:10.1056/NEJM199211123272004
10.1056/NEJM199211123272004
CAS PubMed Web of Science® Google Scholar
33Castle W, Fuller R, Hall J, Palmer J. Serevent nationwide surveillance study: comparison of salmeterol with salbutamol in asthmatic patients who require regular bronchodilator treatment. BMJ. 1993; 306(6884): 1034-1037. doi:10.1136/bmj.306.6884.1034
10.1136/bmj.306.6884.1034
CAS PubMed Web of Science® Google Scholar
34D'Alonzo GE, Nathan RA, Henochowicz S, et al. Salmeterol xinafoate as maintenance therapy compared with albuterol in patients with asthma. Jama. 1994; 271(18): 1412-1416. doi:10.1001/jama.1994.03510420044032
10.1001/jama.1994.03510420044032
PubMed Web of Science® Google Scholar
35Steffensen I, Faurschou P, Riska H, Rostrup J, Wegener T. Inhaled formoterol dry powder in the treatment of patients with reversible obstructive airway disease. A 3-month, placebo-controlled comparison of the efficacy and safety of formoterol and salbutamol, followed by a 12-month trial with formoterol. Allergy. 1995; 50(8): 657-663. doi:10.1111/j.1398-9995.1995.tb02582.x
10.1111/j.1398-9995.1995.tb02582.x
CAS PubMed Web of Science® Google Scholar
36Karpel JP, Schacter EN, Levey D, et al. A comparison of ipratropium and albuterol vs albuterol alone for the treatment of acute asthma. Chest. 1996; 110(3): 611-616. doi:10.1378/chest.110.3.611
10.1378/chest.110.3.611
CAS PubMed Web of Science® Google Scholar
37Khine H, Fuchs SM, Saville AL. Continuous vs intermittent nebulized albuterol for emergency management of asthma. Acad Emerg Med. 1996; 3(11): 1019-1024. doi:10.1111/j.1553-2712.1996.tb03346.x
10.1111/j.1553-2712.1996.tb03346.x
CAS PubMed Web of Science® Google Scholar
38Shrestha M, Gourlay S, Robertson S, Bidadi K, Wainscott M, Hayes J. Isoetharine versus albuterol for acute asthma: greater immediate effect, but more side effects. Am J Med. 1996; 100(3): 323-327. doi:10.1016/S0002-9343(97)89491-0
10.1016/S0002-9343(97)89491-0
CAS PubMed Web of Science® Google Scholar
39Skoner DP, Boltansky H, Kobayashi RH, et al. Extended-release albuterol in the treatment of 6- to 12-year-old asthmatic children. Ann Allergy Asthma Immunol. 1996; 76(5): 462-468. doi:10.1016/S1081-1206(10)63464-3
10.1016/S1081-1206(10)63464-3
CAS PubMed Web of Science® Google Scholar
40Routine nebulized ipratropium and albuterol together are better than either alone in COPD. The COMBIVENT Inhalation Solution Study Group. Chest. 1997; 112(6): 1514-1521.
10.1378/chest.112.6.1514
PubMed Web of Science® Google Scholar
41Boulet LP, Laviolette M, Boucher S, Knight A, Hébert J, Chapman KR. A twelve-week comparison of salmeterol and salbutamol in the treatment of mild-to-moderate asthma: a Canadian multicenter study. J Allergy Clin Immunol. 1997; 99(1 Pt 1): 13-21. doi:10.1016/S0091-6749(97)70295-1
10.1016/S0091-6749(97)70295-1
CAS PubMed Web of Science® Google Scholar
42Jannet D, Abankwa A, Guyard B, Carbonne B, Marpeau L, Milliez J. Nicardipine versus salbutamol in the treatment of premature labor. A prospective randomized study. Eur J Obstet Gynecol Reprod Biol. 1997; 73(1): 11-16. doi:10.1016/S0301-2115(97)02701-2
10.1016/S0301-2115(97)02701-2
CAS PubMed Web of Science® Google Scholar
43Bisits A, Madsen G, McLean M, O'Callaghan S, Smith R, Giles W. Corticotropin-releasing hormone: a biochemical predictor of preterm delivery in a pilot randomized trial of the treatment of preterm labor. Am J Obstet Gynecol. 1998; 178(4): 862-866. doi:10.1016/S0002-9378(98)60503-2
10.1016/S0002-9378(98)60503-2
CAS PubMed Web of Science® Google Scholar
44Dobson JV, Stephens-Groff SM, McMahon SR, Stemmler MM, Brallier SL, Bay C. The use of albuterol in hospitalized infants with bronchiolitis. Pediatrics. 1998; 101(3 Pt 1): 361-368. doi:10.1542/peds.101.3.361
10.1542/peds.101.3.361
CAS PubMed Web of Science® Google Scholar
45Kemp J, Wolfe J, Grady J, et al. Salmeterol powder compared with albuterol aerosol as maintenance therapy for asthma in adolescent and adult patients. Clin Ther. 1998; 20(2): 270-282. doi:10.1016/S0149-2918(98)80090-8
10.1016/S0149-2918(98)80090-8
CAS PubMed Web of Science® Google Scholar
46Rodrigo C, Rodrigo G. Salbutamol treatment of acute severe asthma in the ED: MDI versus hand-held nebulizer. Am J Emerg Med. 1998; 16(7): 637-642. doi:10.1016/S0735-6757(98)90164-4
10.1016/S0735-6757(98)90164-4
CAS PubMed Web of Science® Google Scholar
47Wenzel SE, Lumry W, Manning M, et al. Efficacy, safety, and effects on quality of life of salmeterol versus albuterol in patients with mild to moderate persistent asthma. Ann Allergy Asthma Immunol. 1998; 80(6): 463-470. doi:10.1016/S1081-1206(10)63068-2
10.1016/S1081-1206(10)63068-2
CAS PubMed Web of Science® Google Scholar
48Bradding P, Rushby I, Scullion J, Morgan MD. As-required versus regular nebulized salbutamol for the treatment of acute severe asthma. Eur Respir J. 1999; 13(2): 290-294. doi:10.1034/j.1399-3003.1999.13b12.x
10.1034/j.1399-3003.1999.13b12.x
CAS PubMed Web of Science® Google Scholar
49Campbell S. For COPD a combination of ipratropium bromide and albuterol sulfate is more effective than albuterol base. Arch Intern Med. 1999; 159(2): 156-160. doi:10.1001/archinte.159.2.156
10.1001/archinte.159.2.156
CAS PubMed Google Scholar
50Nelson H, Kemp JP, Bieler S, Vaughan LM, Hill MR. Comparative efficacy and safety of albuterol sulfate Spiros inhaler and albuterol metered-dose inhaler in asthma. Chest. 1999; 115(2): 329-335. doi:10.1378/chest.115.2.329
10.1378/chest.115.2.329
CAS PubMed Web of Science® Google Scholar
51Bensch G, Lapidus RJ, Levine BE, et al. A randomized, 12-week, double-blind, placebo-controlled study comparing formoterol dry powder inhaler with albuterol metered-dose inhaler. Ann Allergy Asthma Immunol. 2001; 86(1): 19-27. doi:10.1016/S1081-1206(10)62351-4
10.1016/S1081-1206(10)62351-4
CAS PubMed Web of Science® Google Scholar
52 French/Australian Atosiban Investigators, G. Treatment of preterm labor with the oxytocin antagonist atosiban: a double-blind, randomized, controlled comparison with salbutamol. Eur J Obstet Gynecol Reprod Biol. 2001; 98(2): 177-185. doi:10.1016/S0301-2115(01)00331-1
10.1016/S0301-2115(01)00331-1
PubMed Web of Science® Google Scholar
53Kissel JT, McDermott M, Mendell JR, et al. Randomized, double-blind, placebo-controlled trial of albuterol in facioscapulohumeral dystrophy. Neurology. 2001; 57(8): 1434-1440. doi:10.1212/WNL.57.8.1434
10.1212/WNL.57.8.1434
CAS PubMed Web of Science® Google Scholar
54Molimard M, Bourcereau J, le Gros V, et al. Comparison between formoterol 12 microg b.i.d. and on-demand salbutamol in moderate persistent asthma. Respir Med. 2001; 95(1): 64-70. doi:10.1053/rmed.2000.0972
10.1053/rmed.2000.0972
CAS PubMed Web of Science® Google Scholar
55Rasul CH, Khan MA. Salbutamol versus theophylline for wheezy infant. J Pak Med Assoc. 2001; 51(5): 187-189.
CAS PubMed Google Scholar
56Cydulka RK, McFadden ER, Sarver JH, Emerman CL. Comparison of single 7.5-mg dose treatment vs sequential multidose 2.5-mg treatments with nebulized albuterol in the treatment of acute asthma. Chest. 2002; 122(6): 1982-1987. doi:10.1378/chest.122.6.1982
10.1378/chest.122.6.1982
CAS PubMed Web of Science® Google Scholar
57Roberts G, Newsom D, Gomez K, et al. Intravenous salbutamol bolus compared with an aminophylline infusion in children with severe asthma: a randomised controlled trial. Thorax. 2003; 58(4): 306-310. doi:10.1136/thorax.58.4.306
10.1136/thorax.58.4.306
CAS PubMed Web of Science® Google Scholar
58Busse W, Levine B, Andriano K, Lavecchia C, Yegen U. Efficacy, tolerability, and effect on asthma-related quality of life of formoterol bid via multidose dry powder inhaler and albuterol QID via metered dose inhaler in patients with persistent asthma: a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group study. Clin Ther. 2004; 26(10): 1587-1598. doi:10.1016/j.clinthera.2004.10.004
10.1016/j.clinthera.2004.10.004
CAS PubMed Web of Science® Google Scholar
59Mull CC, Scarfone RJ, Ferri LR, et al. A randomized trial of nebulized epinephrine vs albuterol in the emergency department treatment of bronchiolitis. Arch Pediatr Adolesc Med. 2004; 158(2): 113-118. doi:10.1001/archpedi.158.2.113
10.1001/archpedi.158.2.113
PubMed Web of Science® Google Scholar
60Kruse M, Rosenkranz B, Dobson C, Ayre G, Horowitz A. Safety and tolerability of high-dose formoterol (Aerolizer) and salbutamol (pMDI) in patients with mild/moderate, persistent asthma. Pulm Pharmacol Ther. 2005; 18(3): 229-234. doi:10.1016/j.pupt.2004.12.011
10.1016/j.pupt.2004.12.011
CAS PubMed Web of Science® Google Scholar
61Langley JM, Smith MB, LeBlanc JC, Joudrey H, Ojah CR, Pianosi P. Racemic epinephrine compared to salbutamol in hospitalized young children with bronchiolitis; a randomized controlled clinical trial [ISRCTN46561076]. BMC Pediatr. 2005; 5(1): 7. doi:10.1186/1471-2431-5-7
10.1186/1471-2431-5-7
CAS PubMed Google Scholar
62Aggarwal P, Sharad S, Handa R, Dwiwedi SN, Irshad M. Comparison of nebulised magnesium sulphate and salbutamol combined with salbutamol alone in the treatment of acute bronchial asthma: a randomised study. Emerg Med J. 2006; 23(5): 358-362. doi:10.1136/emj.2005.026203
10.1136/emj.2005.026203
CAS PubMed Web of Science® Google Scholar
63Balanag VM, Yunus F, Yang PC, Jorup C. Efficacy and safety of budesonide/formoterol compared with salbutamol in the treatment of acute asthma. Pulm Pharmacol Ther. 2006; 19(2): 139-147. doi:10.1016/j.pupt.2005.04.009
10.1016/j.pupt.2005.04.009
CAS PubMed Web of Science® Google Scholar
64Donohue JF, Parsey MV, Andrews C, et al. Evaluation of the efficacy and safety of levalbuterol in subjects with COPD. COPD. 2006; 3(3): 125-132.
10.1080/15412550600829190
PubMed Google Scholar
65Kemp J, Turck CJ, York JM. Evaluation of albuterol 1.25 mg and 0.62 mg for nebulization in 6- to 12-year-old children with moderately severe asthma. Adv Ther. 2007; 24(3): 463-477. doi:10.1007/BF02848768
10.1007/BF02848768
CAS PubMed Web of Science® Google Scholar
66Donohue 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; 30: 989-1002. doi:10.1016/j.clinthera.2008.06.010
10.1016/j.clinthera.2008.06.010
CAS PubMed Web of Science® Google Scholar
67Gupta P, Aggarwal A, Gupta P, Sharma KK. Oral salbutamol for symptomatic relief in mild bronchiolitis a double blind randomized placebo controlled trial. Indian Pediatr. 2008; 45(7): 547-553.
PubMed Web of Science® Google Scholar
68Bigham MT, Jacobs BR, Monaco MA, et al. Helium/oxygen-driven albuterol nebulization in the management of children with status asthmaticus: a randomized, placebo-controlled trial. Pediatr Crit Care Med. 2010; 11(3): 356-361.
PubMed Web of Science® Google Scholar
69Motazedian S, Ghaffarpasand F, Mojtahedi K, Asadi N. Terbutaline versus salbutamol for suppression of preterm labor: a randomized clinical trial. Ann Saudi Med. 2010; 30(5): 370-375. doi:10.4103/0256-4947.67079
10.4103/0256-4947.67079
PubMed Web of Science® Google Scholar
70Direkwatanachai C, Teeratakulpisarn J, Suntornlohanakul S, et al. Comparison of salbutamol efficacy in children—via the metered-dose inhaler (MDI) with Volumatic spacer and via the dry powder inhaler, Easyhaler, with the nebulizer—in mild to moderate asthma exacerbation: a multicenter, randomized study. Asian Pac J Allergy Immunol. 2011; 29(1): 25-33.
CAS PubMed Web of Science® Google Scholar
71Mangunnegoro H, Novariska F, Wiyono WH, Setiawati A, Louisa M. The efficacy of nebulized procaterol versus nebulized salbutamol for the treatment of moderate acute asthma: a randomized, double-blind, parallel group study. Int J Clin Pharmacol Ther. 2011; 49(10): 614-621. doi:10.5414/CP201513
10.5414/CP201513
CAS PubMed Web of Science® Google Scholar
72 National Heart, L., Matthay MA, Brower RG, et al. Randomized, placebo-controlled clinical trial of an aerosolized beta(2)-agonist for treatment of acute lung injury. Am J Respir Crit Care Med. 2011; 184(5): 561-568. doi:10.1164/rccm.201012-2090OC
10.1164/rccm.201012-2090OC
PubMed Web of Science® Google Scholar
73Gao Smith F, Perkins GD, Gates S, et al. Effect of intravenous beta-2 agonist treatment on clinical outcomes in acute respiratory distress syndrome (BALTI-2): a multicentre, randomised controlled trial. Lancet. 2012; 379(9812): 229-235. doi:10.1016/S0140-6736(11)61623-1
10.1016/S0140-6736(11)61623-1
PubMed Web of Science® Google Scholar
74Singh D, Corradi M, Bindi E, Baronio R, Petruzzelli S, Paggiaro P. Relief of methacholine-induced bronchospasm with extrafine beclomethasone dipropionate/formoterol in comparison with salbutamol in asthma. Pulm Pharmacol Ther. 2012; 25(5): 392-398. doi:10.1016/j.pupt.2012.07.004
10.1016/j.pupt.2012.07.004
CAS PubMed Web of Science® Google Scholar
75Lin Q, Liu QH, Bao YX. Efficacy and safety of tulobuterol patch versus oral salbutamol sulfate in children with mild or moderate acute attack of bronchial asthma: a comparative study. Zhongguo Dang Dai Er Ke Za Zhi. 2013; 15(6): 462-465.
PubMed Google Scholar
76Liu CT, Sun XZ, Luo Z, Hao QL, Han XW, Huang YJ. A multi-center, randomized, double-blind, positive controlled clinical trial of salbutamol sulfate MDI without CFC in the treatment of asthma. Sichuan Da Xue Xue Bao Yi Xue Ban. 2014; 45(2): 266-269.
PubMed Google Scholar
77Raphael G, Taveras H, Iverson H, O'Brien C, Miller D. Twelve- and 52-week safety of albuterol multidose dry powder inhaler in patients with persistent asthma. J Asthma. 2016; 53(2): 187-193. doi:10.3109/02770903.2015.1070862
10.3109/02770903.2015.1070862
CAS PubMed Web of Science® Google Scholar
78LaForce C, Taveras H, Iverson H, Shore P. Albuterol multidose dry powder inhaler efficacy and safety versus placebo in children with asthma. Allergy Asthma Proc. 2017; 38(1): 28-37. doi:10.2500/aap.2017.38.4015
10.2500/aap.2017.38.4015
CAS PubMed Web of Science® Google Scholar
79Beasley R, Holliday M, Reddel HK, et al. Controlled trial of budesonide-formoterol as needed for mild asthma. N Engl J Med. 2019; 380(21): 2020-2030. doi:10.1056/NEJMoa1901963
10.1056/NEJMoa1901963
PubMed Web of Science® Google Scholar
80Katsunuma T, Fujisawa T, Maekawa T, et al. Low-dose l-isoproterenol versus salbutamol in hospitalized pediatric patients with severe acute exacerbation of asthma: a double-blind, randomized controlled trial. Allergol Int. 2019; 68(3): 335-341. doi:10.1016/j.alit.2019.02.001
10.1016/j.alit.2019.02.001
CAS PubMed Web of Science® Google Scholar
81Schuh S, Sweeney J, Rumantir M, et al. Effect of nebulized magnesium vs placebo added to albuterol on hospitalization among children with refractory acute asthma treated in the emergency department: a randomized clinical trial. Jama. 2020; 324(20): 2038-2047. doi:10.1001/jama.2020.19839
10.1001/jama.2020.19839
CAS PubMed Web of Science® Google Scholar
82Jat KR, Khairwa A. Levalbuterol versus albuterol for acute asthma: a systematic review and meta-analysis. Pulm Pharmacol Ther. 2013; 26(2): 239-248. doi:10.1016/j.pupt.2012.11.003
10.1016/j.pupt.2012.11.003
CAS PubMed Web of Science® Google Scholar
83Moresco L, Calevo MG, Baldi F, Cohen A, Bruschettini M, Cochrane Neonatal Group. Salbutamol for transient tachypnea of the newborn. Cochrane Database Syst Rev. 2016; 5(5):CD011878. doi:10.1002/14651858.CD011877.pub2
10.1002/14651858.CD011877.pub2
Google Scholar
84Cai Z, Lin Y, Liang J. Efficacy of salbutamol in the treatment of infants with bronchiolitis: a meta-analysis of 13 studies. Medicine (Baltimore). 2020; 99(4):e18657. doi:10.1097/MD.0000000000018657
10.1097/MD.0000000000018657
PubMed Web of Science® Google Scholar
85Sriprasart T, Waterer G, Garcia G, et al. Safety of SABA monotherapy in asthma management: a systematic review and meta-analysis. Adv Ther. 2023; 40(1): 133-158. doi:10.1007/s12325-022-02356-2
10.1007/s12325-022-02356-2
PubMed Web of Science® Google Scholar
86Cekici L, Valipour A, Kohansal R, Burghuber OC. Short-term effects of inhaled salbutamol on autonomic cardiovascular control in healthy subjects: a placebo-controlled study. Br J Clin Pharmacol. 2009; 67(4): 394-402. doi:10.1111/j.1365-2125.2009.03377.x
10.1111/j.1365-2125.2009.03377.x
CAS PubMed Web of Science® Google Scholar
87Snyder EM, Wong EC, Foxx-Lupo WT, Wheatley CM, Cassuto NA, Patanwala AE. Effects of an inhaled beta2-agonist on cardiovascular function and sympathetic activity in healthy subjects. Pharmacotherapy. 2011; 31(8): 748-756. doi:10.1592/phco.31.8.748
10.1592/phco.31.8.748
PubMed Web of Science® Google Scholar
88Iribarren C, Tolstykh IV, Miller MK, Sobel E, Eisner MD. Adult asthma and risk of coronary heart disease, cerebrovascular disease, and heart failure: a prospective study of 2 matched cohorts. Am J Epidemiol. 2012; 176(11): 1014-1024. doi:10.1093/aje/kws181
10.1093/aje/kws181
PubMed Web of Science® Google Scholar
89Andreas S, Haarmann H, Klarner S, Hasenfuß G, Raupach T. Increased sympathetic nerve activity in COPD is associated with morbidity and mortality. Lung. 2014; 192(2): 235-241. doi:10.1007/s00408-013-9544-7
10.1007/s00408-013-9544-7
CAS PubMed Web of Science® Google Scholar
90Sarnaik SM, Saladino RA, Manole M, et al. Diastolic hypotension is an unrecognized risk factor for beta-agonist-associated myocardial injury in children with asthma. Pediatr Crit Care Med. 2013; 14(6): e273-e279. doi:10.1097/PCC.0b013e31828a7677
10.1097/PCC.0b013e31828a7677
PubMed Web of Science® Google Scholar
91Woodward S, Mundorff M, Weng C, Gamboa DG, Johnson MD. Incidence of supraventricular tachycardia after inhaled short-acting beta agonist treatment in children. J Asthma. 2021; 58(4): 471-480. doi:10.1080/02770903.2019.1709867
10.1080/02770903.2019.1709867
PubMed Web of Science® Google Scholar
92Ahmedani BK, Peterson EL, Wells KE, Williams LK. Examining the relationship between depression and asthma exacerbations in a prospective follow-up study. Psychosom Med. 2013; 75(3): 305-310. doi:10.1097/PSY.0b013e3182864ee3
10.1097/PSY.0b013e3182864ee3
PubMed Web of Science® Google Scholar
93Thiringer G, Svedmyr N. Evaluation of skeletal muscle tremor due to bronchodilator agents. Scand J Respir Dis. 1975; 56(2): 93-102.
CAS PubMed Google Scholar
94Larsson S, Svedmyr N. Tremor caused by sympathomimetics is mediated by beta2-adrenoreceptors. Scand J Respir Dis. 1977; 58(1): 5-10.
CAS PubMed Google Scholar
95Bloom C, Cabrera C, Arnetorp S, et al. Asthma-related health outcomes associated with short-acting β2-agonist inhaler use: an observational UK study as part of the SABINA global program. Adv Ther. 2020; 37(10): 4190-4208. doi:10.1007/s12325-020-01444-5
10.1007/s12325-020-01444-5
CAS PubMed Web of Science® Google Scholar
96Nwaru B, Ekström M, Hasvold P, et al. Overuse of short-acting β₂-agonists in asthma is associated with increased risk of exacerbation and mortality: a nationwide cohort study of the global SABINA programme. Eur Respir J. 2020; 55(4):1901872. doi:10.1183/13993003.01872-2019
10.1183/13993003.01872-2019
CAS PubMed Web of Science® Google Scholar

Volume17, Issue12

December 2023

Pages 1254-1264

Filename	Description
crj13711-sup-0001-Supplemental Figure 1..tifTIFF image, 6.5 MB	Figure S1. Funnel plot for the incidence of total AEs.
crj13711-sup-0002-Supplemental Figure 2.tifTIFF image, 6.4 MB	Figure S2. Funnel plot for the incidence of severe AEs.
crj13711-sup-0003-Supplemental Figure 3.tifTIFF image, 10.5 MB	Figure S3. Funnel plot for the incidence of treatment discontinuation.
crj13711-sup-0004-Supplemental Figure 4.tifTIFF image, 10.5 MB	Figure S4. Funnel plot for the incidence of tremor.
crj13711-sup-0005-Supplemental Figure 5.tifTIFF image, 10.5 MB	Figure S5. Funnel plot for the incidence of palpitations or tachycardia.
crj13711-sup-0006-Supplemental Figure 6.tifTIFF image, 6.3 MB	Figure S6. Funnel plot for the incidence of headache.
crj13711-sup-0007-Supplemental Figure 7.tifTIFF image, 10.5 MB	Figure S7. Funnel plot for the incidence of nervousness.
crj13711-sup-0008-Supplemental Figure 8.tifTIFF image, 10.5 MB	Figure S8. Funnel plot for the incidence of anxiety.
crj13711-sup-0009-Supplemental Figure 9.tifTIFF image, 10.5 MB	Figure S9. Funnel plot for the incidence of cough.
crj13711-sup-0010-Supplemental Figure 10.tifTIFF image, 10.5 MB	Figure S10. Funnel plot for the incidence of dyspnoea.
crj13711-sup-0011-Supplemental Figure 11.tifTIFF image, 10.5 MB	Figure S11. Funnel plot for the incidence of nausea.
crj13711-sup-0012-Supplemental Figure 12.tifTIFF image, 10.5 MB	Figure S12. Funnel plot for the incidence of vomiting.
crj13711-sup-0013-Supplemental Figure 13.tifTIFF image, 10.5 MB	Figure S13. Forest plot for the incidence of palpitations or tachycardia.
crj13711-sup-0014-Supplemental Figure 14.tifTIFF image, 10.5 MB	Figure S14. Forest plot for the incidence of tremor.
crj13711-sup-0015-Supplemental Figure 15.tifTIFF image, 17.1 MB	Figure S15. Forest plot for the incidence of headache.
crj13711-sup-0016-Supplemental Figure 16.tifTIFF image, 10.5 MB	Figure S16. Forest plot for the incidence of nervousness.
crj13711-sup-0017-Supplemental Figure 17.tifTIFF image, 10.5 MB	Figure S17. Forest plot for the incidence of anxiety.
crj13711-sup-0018-Supplemental Figure 18.tifTIFF image, 10.5 MB	Figure S18. Forest plot for the incidence of cough.
crj13711-sup-0019-Supplemental Figure 19.tifTIFF image, 10.5 MB	Figure S19. Forest plot for the incidence of dyspnoea.
crj13711-sup-0020-Supplemental Figure 20.tifTIFF image, 10.5 MB	Figure S20. Forest plot for the incidence of nausea.
crj13711-sup-0021-Supplemental Figure 21.tifTIFF image, 10.5 MB	Figure S21. Forest plot for the incidence of vomiting.
crj13711-sup-0022-Supplemental Figure 22.tifTIFF image, 13.5 MB	Figure S22. Sensitivity analysis for the incidence of total AEs.
crj13711-sup-0023-Supplemental Figure 23.tifTIFF image, 6.3 MB	Figure S23. Sensitivity analysis for the incidence of severe AEs.
crj13711-sup-0024-Supplemental Figure 24.tifTIFF image, 10.5 MB	Figure S24. Sensitivity analysis for the incidence of treatment discontinuation.
crj13711-sup-0025-Supplemental Material 1.docxWord 2007 document , 10.8 KB	Data S1. Supporting Information.
crj13711-sup-0026-Supplemental Table 1.docxWord 2007 document , 27 KB	Table S1. The baseline characteristics of identified trials and patients.
crj13711-sup-0027-Supplemental Table 2.docxWord 2007 document , 27.6 KB	Table S2. Risk of bias of the included trials.

Safety outcomes of salbutamol: A systematic review and meta-analysis

Abstract

Purpose

Methods

Results

Conclusion

1 INTRODUCTION

2 METHODS

2.1 Data sources, search strategy and selection criteria

2.2 Data collection and clinical outcomes

2.3 Quality assessment

2.4 Statistical analysis

3 RESULTS

3.1 Literature search

3.2 Study characteristics

3.3 Quality of the studies and publication bias

3.4 Incidences of Total AEs

3.5 Incidences of severe AEs

3.6 Incidences of treatment discontinuations

3.7 Incidences of specific AEs

3.7.1 Cardiovascular system

3.7.2 Nervous system

3.7.3 Respiratory system

3.7.4 Digestive system

3.8 Sensitivity analysis

4 DISCUSSION

5 CONCLUSION

AUTHOR CONTRIBUTIONS

ACKNOWLEDGEMENTS

CONFLICT OF INTEREST STATEMENT

ETHICS STATEMENT

Open Research

DATA AVAILABILITY STATEMENT

Supporting Information

REFERENCES

Figures

References

Related

Information