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      Fundamentals of aerosol therapy in critical care

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          Abstract

          Drug dosing in critically ill patients is challenging due to the altered drug pharmacokinetics–pharmacodynamics associated with systemic therapies. For many drug therapies, there is potential to use the respiratory system as an alternative route for drug delivery. Aerosol drug delivery can provide many advantages over conventional therapy. Given that respiratory diseases are the commonest causes of critical illness, use of aerosol therapy to provide high local drug concentrations with minimal systemic side effects makes this route an attractive option. To date, limited evidence has restricted its wider application. The efficacy of aerosol drug therapy depends on drug-related factors (particle size, molecular weight), device factors, patient-related factors (airway anatomy, inhalation patterns) and mechanical ventilation-related factors (humidification, airway). This review identifies the relevant factors which require attention for optimization of aerosol drug delivery that can achieve better drug concentrations at the target sites and potentially improve clinical outcomes.

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          Most cited references133

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          Guidelines for the diagnosis and treatment of pulmonary hypertension.

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            What the pulmonary specialist should know about the new inhalation therapies.

            A collaboration of multidisciplinary experts on the delivery of pharmaceutical aerosols was facilitated by the European Respiratory Society (ERS) and the International Society for Aerosols in Medicine (ISAM), in order to draw up a consensus statement with clear, up-to-date recommendations that enable the pulmonary physician to choose the type of aerosol delivery device that is most suitable for their patient. The focus of the consensus statement is the patient-use aspect of the aerosol delivery devices that are currently available. The subject was divided into different topics, which were in turn assigned to at least two experts. The authors searched the literature according to their own strategies, with no central literature review being performed. To achieve consensus, draft reports and recommendations were reviewed and voted on by the entire panel. Specific recommendations for use of the devices can be found throughout the statement. Healthcare providers should ensure that their patients can and will use these devices correctly. This requires that the clinician: is aware of the devices that are currently available to deliver the prescribed drugs; knows the various techniques that are appropriate for each device; is able to evaluate the patient's inhalation technique to be sure they are using the devices properly; and ensures that the inhalation method is appropriate for each patient.
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              Randomized, placebo-controlled clinical trial of an aerosolized β₂-agonist for treatment of acute lung injury.

              β₂-Adrenergic receptor agonists accelerate resolution of pulmonary edema in experimental and clinical studies. This clinical trial was designed to test the hypothesis that an aerosolized β₂-agonist, albuterol, would improve clinical outcomes in patients with acute lung injury (ALI). We conducted a multicenter, randomized, placebo-controlled clinical trial in which 282 patients with ALI receiving mechanical ventilation were randomized to receive aerosolized albuterol (5 mg) or saline placebo every 4 hours for up to 10 days. The primary outcome variable for the trial was ventilator-free days. Ventilator-free days were not significantly different between the albuterol and placebo groups (means of 14.4 and 16.6 d, respectively; 95% confidence interval for the difference, -4.7 to 0.3 d; P = 0.087). Rates of death before hospital discharge were not significantly different between the albuterol and placebo groups (23.0 and 17.7%, respectively; 95%confidence interval for the difference,-4.0 to 14.7%;P = 0.30). In the subset of patients with shock before randomization, the number of ventilator-free days was lower with albuterol, although mortality was not different. Overall, heart rates were significantly higher in the albuterol group by approximately 4 beats/minute in the first 2 days after randomization, but rates of new atrial fibrillation (10% in both groups) and other cardiac dysrhythmias were not significantly different. These results suggest that aerosolized albuterol does not improve clinical outcomes in patients with ALI. Routine use of β₂-agonist therapy in mechanically ventilated patients with ALI cannot be recommended. Clinical trial registered with www.clinicaltrials.gov (NCT 00434993).
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                Author and article information

                Contributors
                +61 07 36364113 , Jayesh.Dhanani@health.qld.gov.au
                john.fraser@health.qld.gov.au
                kim.chan@sydney.edu.au
                jordialg@hotmail.com
                Jeremy.cohen@health.qld.gov.au
                j.roberts2@uq.edu.au
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                7 October 2016
                7 October 2016
                2016
                : 20
                : 269
                Affiliations
                [1 ]Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia
                [2 ]Department of Intensive Care Medicine, Royal Brisbane and Women’s Hospital, Level 3, Ned Hanlon Building, Herston, 4029 QLD Australia
                [3 ]Department of Intensive Care Medicine, The Prince Charles Hospital, Brisbane, Australia
                [4 ]Critical Care Research Group, The University of Queensland, Brisbane, Australia
                [5 ]Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Sydney, NSW Australia
                [6 ]Pharmacy Department, Royal Brisbane and Women’s Hospital, Herston, Brisbane, Australia
                [7 ]School of Pharmacy, The University of Queensland, Brisbane, Australia
                [8 ]Critical Care Department, Hospital Vall d’Hebron, Barcelona, Spain
                [9 ]CIBERES, Vall d’Hebron Institut of Research, Barcelona, Spain
                [10 ]Department of Medicine, Universitat Autonoma de Barcelona, Barcelona, Spain
                Author information
                http://orcid.org/0000-0001-9803-9701
                Article
                1448
                10.1186/s13054-016-1448-5
                5054555
                27716346
                ec1befd9-3f64-4621-803f-c98882a0b9f1
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;
                Award ID: APP1048652
                Award Recipient :
                Funded by: The Prince Charles Hospital Foundation Grant
                Award ID: MS2011-40
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001227, Office of Health and Medical Research;
                Award ID: Health Research Fellowship
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2016

                Emergency medicine & Trauma
                Emergency medicine & Trauma

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