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Respiratory Medicine Aug 2019Asthmatics are at increased cardiovascular disease risk, which has been linked to beta2(β)-agonist use. Inhalation of β-agonists increases sympathetic nerve activity...
BACKGROUND
Asthmatics are at increased cardiovascular disease risk, which has been linked to beta2(β)-agonist use. Inhalation of β-agonists increases sympathetic nerve activity (SNA) in healthy individuals, however the systemic impact of salbutamol in asthmatics using β-agonists regularly is unknown.
OBJECTIVES
This study compared the systemic vascular responses to a clinical dose of salbutamol (Phase I) and following an acute increase in SNA (Phase II) in asthmatics and controls.
METHODS
Fourteen controls and 14 asthmatics were recruited for Phase I. On separate days, flow-mediated dilation (FMD) and peripheral arterial stiffness (pPWV) were evaluated at baseline and following either 400 μg inhaled salbutamol or a placebo inhaler. For Phase II, heart rate, blood pressure, vascular conductance, pPWV, and central (c)PWV were evaluated in response to a large increase in SNA brought on by cold-water hand immersion (i.e. cold-pressor test) or body-temperature water hand immersion (i.e. control) in 10 controls and 10 asthmatics.
RESULTS
Following salbutamol, asthmatics demonstrated reduced FMD (-3.0%, p < 0.05) and increased pPWV (+0.7 m/s, p < 0.05); however, salbutamol had no effect in controls. The cold-pressor test resulted in similar increases in blood pressure, vascular flow rates and conductance, pPWV, and cPWV in both asthmatics and controls, suggesting similar neurovascular transduction in asthmatics and controls.
CONCLUSION
Inhaled Salbutamol leads to increased arterial stiffness and reduced FMD in asthmatics. As asthmatics and controls had similar vascular responses to an increase in SNA, these findings suggest asthmatics have heightened sympathetic responses to β-agonists which may contribute to the increased cardiovascular risk in asthma.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Albuterol; Asthma; Blood Pressure; Cardiovascular Diseases; Female; Humans; Male; Risk; Vascular Stiffness; Young Adult
PubMed: 31349187
DOI: 10.1016/j.rmed.2019.07.018 -
The Clinical Respiratory Journal Dec 2023Salbutamol has been used to alleviate bronchospasm in airway disease for decades, while its potential risks have not been systematically investigated yet. The risk of... (Meta-Analysis)
Meta-Analysis
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.
Topics: Humans; Albuterol; Tachycardia
PubMed: 37844914
DOI: 10.1111/crj.13711 -
Tuberkuloz Ve Toraks 2012Breath relieving and protective drugs in asthma treatment are applied through pressurized metered dose inhaler (pMDI), nebulizer or dry powder inhaler. The short acting... (Review)
Review
Breath relieving and protective drugs in asthma treatment are applied through pressurized metered dose inhaler (pMDI), nebulizer or dry powder inhaler. The short acting beta-2 agonist salbutamol used in acute asthma exacerbation is found in the forms of nebule or pMDI in Turkey. Nebule form is used more frequently in emergency services. The aim of this review is to compare these two routes of administration through clinical efficacy, the amount of drug reaching to the lungs and adverse events comprehensively by way of looking through the studies. Additionally effect of different inhalation techniques through chambers, different methods used in cleaning of them and different types of nebulizers, to the efficacy are investigated. As a result, asthma exacerbation can be treated with pMDIs used through holding chambers in emergency room successfully when applied with dosing scheme appropriate for the patient's age, weight and severity of exacerbation (usually 1/4th of nebule dosing) on the contrary to ordinary method of nebulizers.
Topics: Adrenergic beta-2 Receptor Agonists; Albuterol; Asthma; Bronchodilator Agents; Drug Delivery Systems; Dry Powder Inhalers; Humans; Nebulizers and Vaporizers; Treatment Outcome
PubMed: 22779944
DOI: 10.5578/tt.3413 -
Emergency Medicine Journal : EMJ May 2005A short cut review was carried out to establish whether nebulised levalbuterol is better than or equivalent to albuterol for lowering serum potassium. Seven papers were... (Review)
Review
A short cut review was carried out to establish whether nebulised levalbuterol is better than or equivalent to albuterol for lowering serum potassium. Seven papers were found using the reported search, of which three presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. A clinical bottom line is stated.
Topics: Adrenergic beta-Agonists; Albuterol; Emergencies; Evidence-Based Medicine; Humans; Hyperkalemia; Nebulizers and Vaporizers
PubMed: 15843710
DOI: 10.1136/emj.2005.024414 -
Thorax Nov 1994
Topics: Albuterol; Biological Availability; Humans; Lung; Nebulizers and Vaporizers
PubMed: 7831646
DOI: 10.1136/thx.49.11.1183 -
Respiratory Care Nov 2018Predosing patients with COPD with salbutamol by using a pressurized metered-dose-inhaler (pMDI) as a bronchodilator was hypothesized to improve the distribution of the... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Predosing patients with COPD with salbutamol by using a pressurized metered-dose-inhaler (pMDI) as a bronchodilator was hypothesized to improve the distribution of the subsequent nebulized dose. This study determined the effect of a pMDI preliminary bronchodilator dose on the aerosol delivered by a mesh nebulizer during single-limb noninvasive ventilation.
METHODS
Twelve subjects with COPD who received noninvasive ventilation were enrolled in a randomized, open-label, urinary pharmacokinetic study. A bi-level ventilator with a dry single-limb circuit and the fixed expiratory port was set in the spontaneous mode, with initial inspiratory and expiratory pressures of 20 and 5 cm HO respectively, a 1:3 inspiratory-expiratory ratio, and 15 breaths/min. Salbutamol was administered via a mesh nebulizer with a large spacer or T-piece placed between the fixed-orifice expiratory valve and the oronasal mask. In vivo dosing methods were randomized for days 1, 3, and 5 of the study. On each day, a 1-mL respirable solution that contained 5,000 μg salbutamol was nebulized by using a mesh nebulizer with 3 setting: (1) T-piece, (2) large spacer, and (3) large spacer plus pMDI. Only with the large spacer plus pMDI setting, 2 pMDI doses, which contained 100 μg salbutamol each, were actuated before nebulization. Urine samples were collected at 0.5 h (as an index of pulmonary bioavailability) and pooled up to 24 h after dosing (as an index of systemic absorption). On day 2, ex vivo studies were performed for the 3 setting with salbutamol collected onto filters placed before the mask. The drug was eluted from the filters and analyzed to determine the inhaled dose.
RESULTS
A large spacer plus pMDI showed a trend to deliver a higher fraction (percentage of nominal dose) of both ex vivo filters and 0.5-h urinary salbutamol. The 0.5-h urinary salbutamol excreted with a large spacer plus pMDI (1.99%) was larger than with the T-piece (1.73%) and large spacer (1.78%). This trend did not extend to the 24-h levels, in which bioavailability with the large spacer plus pMDI (49.9%) was lower than with the T-piece (52.8%) and with the large spacer (54.3%). However, no differences were significant.
CONCLUSIONS
The T-piece and large spacer were equally efficient for salbutamol delivery from the mesh nebulizer in patients with COPD and on single-limb noninvasive ventilation. Adding a preliminary bronchodilator dose by pMDI prenebulization showed a trend toward greater pulmonary bioavailability of nebulized salbutamol and may be worth considering to maximize delivery of salbutamol to patients who are severely ill.
Topics: Aged; Albuterol; Biological Availability; Bronchodilator Agents; Cross-Over Studies; Female; Humans; Inhalation Spacers; Male; Middle Aged; Noninvasive Ventilation; Pulmonary Disease, Chronic Obstructive
PubMed: 30087193
DOI: 10.4187/respcare.05976 -
The Cochrane Database of Systematic... 2002Selective beta-adrenergic agonists for use in asthma are: short acting (2-6 hours) and long acting (>12 hours). There has been little controversy about using short... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Selective beta-adrenergic agonists for use in asthma are: short acting (2-6 hours) and long acting (>12 hours). There has been little controversy about using short acting beta-agonists intermittently, but long acting beta-agonists are used regularly, and their regular use has been controversial.
OBJECTIVES
To determine the benefit or detriment of treatment with regular short- or long acting inhaled beta-agonists in chronic asthma.
SEARCH STRATEGY
A search was carried out using the Cochrane Airways Group register. Bibliographies of identified RCTs were searched for additional relevant RCTs. Authors of identified RCTs were contacted for other published and unpublished studies.
SELECTION CRITERIA
All randomised studies of at least two weeks duration, comparing a long acting inhaled beta-agonist given twice daily with any short acting inhaled beta-agonist of equivalent bronchodilator effectiveness given regularly in chronic asthma.
DATA COLLECTION AND ANALYSIS
Two reviewers performed data extraction and study quality assessment independently. Authors of studies were contacted for missing data.
MAIN RESULTS
31 studies met the inclusion criteria, 24 of parallel group and 7 cross over design. Salmeterol xinafoate was used as long acting agent in 22 studies and formoterol fumarate in 9. Salbutamol was the short acting agent used in 27 studies and terbutaline in 5. The treatment period was over 2 weeks in 29 studies, and at least 12 weeks in 20. 25 studies permitted a variety of co-intervention treatments, usually inhaled corticosteroid or cromones. One study did not permit inhaled corticosteroid. Long acting beta-agonists were significantly better than short acting for a variety of lung function measurements including morning PEF (Weighted Mean Difference (WMD) 33 l/min 95% CI 25, 42) or evening PEF (WMD 26 l/min 95% CI 18, 33); and had significantly lower scores for day and night time asthma symptom scores and percentage of days and nights without symptoms. They were also associated with a significantly lower use of rescue medication both during the day and night. Risk of exacerbations was not different between the two types of agent, but most studies were of short duration which limits the power to test for such differences.
REVIEWER'S CONCLUSIONS
Long acting inhaled beta-agonists have advantages across a wide range of physiological and clinical outcomes for regular treatment.
Topics: Adrenergic beta-Agonists; Adult; Albuterol; Asthma; Bronchodilator Agents; Child; Ethanolamines; Formoterol Fumarate; Humans; Randomized Controlled Trials as Topic; Salmeterol Xinafoate
PubMed: 12519616
DOI: 10.1002/14651858.CD003901 -
Respiratory Care Sep 2018A new holding chamber was designed to be used with the Aerogen Solo nebulizer to increase the aerosol emitted that reach the patient. The aim of this study was to...
BACKGROUND
A new holding chamber was designed to be used with the Aerogen Solo nebulizer to increase the aerosol emitted that reach the patient. The aim of this study was to evaluate the efficacy of this holding chamber with the nebulizer and determine its usability with other nebulizers.
METHODS
The study was divided into 2 parts. In the first part, aerosol emitted of 1 mL respirable solution (nominal dose of 5000 μg salbutamol), delivered by using the mesh nebulizer, Pro nebulizer, and jet nebulizer, connected to a T-piece or a holding chamber, was determined by using a breathing simulator set to provide a tidal volume of 500 mL, frequency of 15 breaths/min, and the inspiratory-expiratory ratio of 1:1 for adults as the quiet breathing pattern. Aerodynamic particle size characterizations were determined by using a cooled cascade impactor at an inhalation flow of 15 L/min. In the second part of the study, 12 healthy nonsmoking subjects (6 females) >18 y, with an FEV1 > 90% were enrolled. Inhaled aerosol of 1 mL respirable solution (5,000 μg salbutamol) was delivered through the mesh nebulizer-holding chamber and an mesh nebulizer-T-piece using normal tidal breathing. The subjects provided urine samples 30 min after dosing and cumulatively collected their urine for 24 h. The samples were analyzed for salbutamol content.
RESULTS
The holding chamber significantly increased aerosol emitted by the 3 nebulizers compared with the T-piece ( < .01) and relatively decreased the mass median aerodynamic diameter but with no significant difference. The mesh nebulizer-holding chamber resulted in significantly higher aerosol emitted compared with any other delivery method tested ( < .01). The mesh nebulizer-holding chamber resulted in higher urine samples 30 min after dosing (as an index of lung deposition) and cumulatively collected urine for 24 h (as an index of systemic absorption) compared with the nebulizer-T-piece ( < .05).
CONCLUSIONS
The use of the holding chamber with a jet nebulizer, Pro nebulizer, and the Solo nebulizer significantly increased the aerosol delivery. The Solo nebulizer-holding chamber had the highest aerosol emitted compared with all nebulizer-adapter combinations and higher urine samples 30 min after dosing and cumulatively collected urine for 24 h compared with the nebulizer-T-piece.
Topics: Administration, Inhalation; Adult; Aerosols; Albuterol; Bronchodilator Agents; Drug Delivery Systems; Equipment Design; Female; Forced Expiratory Volume; Healthy Volunteers; Humans; Inhalation Spacers; Male; Nebulizers and Vaporizers; Tidal Volume
PubMed: 29789412
DOI: 10.4187/respcare.06061 -
Archives of Disease in Childhood Jan 1986The bronchodilator response after five different modes of salbutamol inhalation by rotahaler was assessed in 15 asthmatic children in a double blind cross over study.... (Clinical Trial)
Clinical Trial
The bronchodilator response after five different modes of salbutamol inhalation by rotahaler was assessed in 15 asthmatic children in a double blind cross over study. Inspiratory flow rates lower than 50 litres/minute were associated with a significant reduction in response compared with flow rates higher than 60 litres/minute, but tilting the head back during inhalation and holding the breath for 10 seconds had no significant effect on bronchodilation. Peak inspiratory flow rates measured in 150 normal children and 13 asthmatic children with acute wheeze showed that many young children and many children with severe bronchoconstriction were unable to generate a sufficiently high inspiratory flow rate to obtain maximum benefit from rotahaler treatment. Children using a rotahaler should be taught to inhale as quickly as possible and not with a quiet deep breath as recommended in the instruction leaflets.
Topics: Acute Disease; Adolescent; Aerosols; Age Factors; Albuterol; Asthma; Child; Clinical Trials as Topic; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Respiration
PubMed: 3513714
DOI: 10.1136/adc.61.1.11 -
Lung Aug 2022In patients with chronic obstructive pulmonary disease (COPD), bronchial responsiveness after acute administration of short acting bronchodilators is conventionally...
PURPOSE
In patients with chronic obstructive pulmonary disease (COPD), bronchial responsiveness after acute administration of short acting bronchodilators is conventionally assessed by measuring the improvement of forced expiratory volume in the first second (FEV) during a maximal forced expiratory maneuver. This study aimed to measure the variation of intrathoracic airway wall compliance (AWC) after acute administration of short acting beta-2 agonist in COPD patients since this might influence the final modification of airway caliber during maximal expiratory effort and the resulting bronchodilation as inferred by FEV changes.
METHODS
In a group of 10 patients suffering from COPD, intrathoracic AWC was measured at middle (50% of Forced Vital Capacity (FVC) and low (75% of FVC) lung volumes using the interrupter method during forced expiratory maneuver in basal conditions and after acute inhalation of albuterol (salbutamol) (400 mcg by MDI). Ten healthy subjects were examined similarly as a control group.
RESULTS
Lower values of baseline intrathoracic AWC at both lung volumes were found in COPD patients (1.72 ± 0.20 ml/cmHO and 1.08 ± 0.20 ml/cmHO, respectively) as compared to controls (2.28 ± 0.27 ml/cmHO and 1.44 ± 0.22 ml/cmHO, respectively) (p < 0.001). In COPD patients, AWC increased significantly at both lung volumes after salbutamol, amounting to 1.81 ± 0.38 ml/cmHO and 1.31 ± 0.39 ml/cmHO, respectively (p < 0.01), but the relative change was not different from that observed in controls.
CONCLUSION
In COPD patients, AWC is reduced compared to controls, but after bronchodilator, the intrathoracic airways become more compliant. The consequent increased collapsibility under high positive pleural pressure could limit the airway caliber improvement seen after bronchodilator, as assessed by the FEV changes during the forced expiratory maneuver, underestimating the effective bronchodilation achieved in these patients.
Topics: Administration, Inhalation; Albuterol; Bronchodilator Agents; Forced Expiratory Volume; Humans; Pulmonary Disease, Chronic Obstructive; Vital Capacity
PubMed: 35851429
DOI: 10.1007/s00408-022-00556-9