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      Inhaled beta-2 agonist salbutamol and acute lung injury: an association with improvement in acute lung injury

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          Abstract

          Introduction

          β2 agonists have several properties that could be beneficial in acute lung injury (ALI). We therefore chose to study the effect of inhaled β2 agonist use (salbutamol) on duration and severity of ALI.

          Methods

          We undertook a retrospective chart review of 86 consecutive mechanically ventilated patients with ALI, who had varying exposure to inhaled salbutamol. The cohort was divided into two groups according to the average daily dose of inhaled salbutamol they received ('high dose' ≥ 2.2 mg/day and 'low dose' <2.2 mg/day). Severity of ALI and non-pulmonary organ dysfunction was compared between the groups by calculating the days alive and free of ALI and other organ dysfunctions.

          Results

          The high dose and low dose groups received a mean of 3.72 mg and 0.64 mg salbutamol per day, respectively. The high dose salbutamol group had significantly more days alive and free of ALI than the low dose group (12.2 ± 4.4 days versus 7.6 ± 1.9 days, p = 0.02). There were no associations between dose of β agonist and non-pulmonary organ dysfunctions. High dose salbutamol ( p = 0.04), APACHE II score ( p = 0.02), and cause of ALI ( p = 0.02) were independent variables associated with number of days alive and free of ALI in a multivariate linear regression model.

          Conclusion

          Our retrospective study suggests that salbutamol, an inhaled β2 agonist, is associated with a shorter duration and lower severity of ALI. A dose greater than 2.2 mg/day of inhaled salbutamol could be a minimal effective dose to evaluate in a randomized controlled trial.

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          Most cited references42

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          The APACHE III prognostic system. Risk prediction of hospital mortality for critically ill hospitalized adults.

          The objective of this study was to refine the APACHE (Acute Physiology, Age, Chronic Health Evaluation) methodology in order to more accurately predict hospital mortality risk for critically ill hospitalized adults. We prospectively collected data on 17,440 unselected adult medical/surgical intensive care unit (ICU) admissions at 40 US hospitals (14 volunteer tertiary-care institutions and 26 hospitals randomly chosen to represent intensive care services nationwide). We analyzed the relationship between the patient's likelihood of surviving to hospital discharge and the following predictive variables: major medical and surgical disease categories, acute physiologic abnormalities, age, preexisting functional limitations, major comorbidities, and treatment location immediately prior to ICU admission. The APACHE III prognostic system consists of two options: (1) an APACHE III score, which can provide initial risk stratification for severely ill hospitalized patients within independently defined patient groups; and (2) an APACHE III predictive equation, which uses APACHE III score and reference data on major disease categories and treatment location immediately prior to ICU admission to provide risk estimates for hospital mortality for individual ICU patients. A five-point increase in APACHE III score (range, 0 to 299) is independently associated with a statistically significant increase in the relative risk of hospital death (odds ratio, 1.10 to 1.78) within each of 78 major medical and surgical disease categories. The overall predictive accuracy of the first-day APACHE III equation was such that, within 24 h of ICU admission, 95 percent of ICU admissions could be given a risk estimate for hospital death that was within 3 percent of that actually observed (r2 = 0.41; receiver operating characteristic = 0.90). Recording changes in the APACHE III score on each subsequent day of ICU therapy provided daily updates in these risk estimates. When applied across the individual ICUs, the first-day APACHE III equation accounted for the majority of variation in observed death rates (r2 = 0.90, p less than 0.0001).
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            Report of the American-European consensus conference on ARDS: definitions, mechanisms, relevant outcomes and clinical trial coordination. The Consensus Committee.

            The acute respiratory distress syndrome (ARDS), a process of non-hydrostatic pulmonary edema and hypoxemia associated with a variety of etiologies carries a high morbidity, mortality (10-90%) and financial cost. The reported annual incidence in the United States is 150,000 cases, but this figure has been challenged and may be different in Europe. Part of the reason for these uncertainties is the heterogeneity of diseases underlying ARDS and the lack of uniform definitions for ARDS. Thus, those whose wish to know the true incidence and outcome on this clinical syndrome are stymied. The European American Consensus Committee on ARDS was formed to focus on these issues and on the pathophysiologic mechanisms of the process. It was felt that international coordination between North America and Europe in clinical studies of ARDS was becoming increasingly important in order to address the recent plethora of potential therapeutic agents for the prevention and treatment of ARDS.
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              Epinephrine inhibits tumor necrosis factor-alpha and potentiates interleukin 10 production during human endotoxemia.

              Short-term preexposure of mononuclear cells to epinephrine inhibits LPS-induced production of TNF, whereas preexposure for 24 h results in increased TNF production. To assess the effects of epinephrine infusions of varying duration on in vivo responses to LPS, the following experiments were performed: (a) Blood obtained from eight subjects at 4-24 h after the start of a 24-h infusion of epinephrine (30 ng/kg per min) produced less TNF after ex vivo stimulation with LPS compared with blood drawn before the start of the infusion, and (b) 17 healthy men who were receiving a continuous infusion of epinephrine (30 ng/kg per min) started either 3 h (EPI-3; n = 5) or 24 h (EPI-24; n = 6) were studied after intravenous injection of LPS (2 ng/kg, lot EC-5). EPI-3 inhibited LPS-induced in vivo TNF appearance and also increased IL-10 release (both P < 0.005 versus LPS), whereas EPI-24 only attenuated TNF secretion (P = 0.05). In separate in vitro experiments in whole blood, epinephrine increased LPS-induced IL-10 release by a combined effect on alpha and beta adrenergic receptors. Further, in LPS-stimulated blood, the increase on IL-10 levels caused by epinephrine only marginally contributed to concurrent inhibition of TNF production. Epinephrine, either endogenously produced or administered as a component of sepsis treatment, may have a net antiinflammatory effect on the cytokine network early in the course of systemic infection.
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                Author and article information

                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                2006
                11 January 2006
                : 10
                : 1
                : R12
                Affiliations
                [1 ]Clinical/Research Fellow, Critical Care Research Laboratories, Centre for Cardiovascular and Pulmonary Research, University of British Columbia, Vancouver, BC, Canada
                [2 ]Clinical/Research Fellow, Critical Care Research Laboratories, Centre for Cardiovascular and Pulmonary Research, University of British Columbia, Vancouver, BC, Canada
                [3 ]Pharmacist, Critical Care Research Laboratories, Centre for Cardiovascular and Pulmonary Research, University of British Columbia, Vancouver, BC, Canada
                [4 ]Research Assistant, Critical Care Research Laboratories, Centre for Cardiovascular and Pulmonary Research, University of British Columbia, Vancouver, BC, Canada
                [5 ]Professor of Medicine, Critical Care Research Laboratories, Centre for Cardiovascular and Pulmonary Research, University of British Columbia, Vancouver, BC, Canada
                [6 ]Professor of Medicine, Critical Care Research Laboratories, Centre for Cardiovascular and Pulmonary Research, University of British Columbia, Vancouver, BC, Canada
                Article
                cc3971
                10.1186/cc3971
                1550825
                16420663
                86257e32-2758-4d24-ab89-a3bc30979e28
                Copyright © 2006 Manocha et al., licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is cited.

                History
                : 13 October 2005
                : 15 December 2005
                Categories
                Research

                Emergency medicine & Trauma
                Emergency medicine & Trauma

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