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      Clinical review: Early treatment of acute lung injury - paradigm shift toward prevention and treatment prior to respiratory failure

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      Author(s): 1 , , 2
      Publication date (Electronic):
      Journal: Critical Care
      Publisher: BioMed Central

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          Abstract

          Acute lung injury (ALI) remains a major cause of morbidity and mortality in critically ill patients. Despite improved understanding of the pathogenesis of ALI, supportive care with a lung protective strategy of mechanical ventilation remains the only treatment with a proven survival advantage. Most clinical trials in ALI have targeted mechanically ventilated patients. Past trials of pharmacologic agents may have failed to demonstrate efficacy in part due to the resultant delay in initiation of therapy until several days after the onset of lung injury. Improved early identification of at-risk patients provides new opportunities for risk factor modification to prevent the development of ALI and novel patient groups to target for early treatment of ALI before progression to the need for mechanical ventilation. This review will discuss current strategies that target prevention of ALI and some of the most promising pharmacologic agents for early treatment of ALI prior to the onset of respiratory failure that requires mechanical ventilation.

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          Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial.

          Maureen Meade, Deborah Cook, Gordon Guyatt … (2008)
          Low-tidal-volume ventilation reduces mortality in critically ill patients with acute lung injury and acute respiratory distress syndrome. Instituting additional strategies to open collapsed lung tissue may further reduce mortality. To compare an established low-tidal-volume ventilation strategy with an experimental strategy based on the original "open-lung approach," combining low tidal volume, lung recruitment maneuvers, and high positive-end-expiratory pressure. Randomized controlled trial with concealed allocation and blinded data analysis conducted between August 2000 and March 2006 in 30 intensive care units in Canada, Australia, and Saudi Arabia. Nine hundred eighty-three consecutive patients with acute lung injury and a ratio of arterial oxygen tension to inspired oxygen fraction not exceeding 250. The control strategy included target tidal volumes of 6 mL/kg of predicted body weight, plateau airway pressures not exceeding 30 cm H2O, and conventional levels of positive end-expiratory pressure (n = 508). The experimental strategy included target tidal volumes of 6 mL/kg of predicted body weight, plateau pressures not exceeding 40 cm H2O, recruitment maneuvers, and higher positive end-expiratory pressures (n = 475). All-cause hospital mortality. Eighty-five percent of the 983 study patients met criteria for acute respiratory distress syndrome at enrollment. Tidal volumes remained similar in the 2 groups, and mean positive end-expiratory pressures were 14.6 (SD, 3.4) cm H2O in the experimental group vs 9.8 (SD, 2.7) cm H2O among controls during the first 72 hours (P < .001). All-cause hospital mortality rates were 36.4% and 40.4%, respectively (relative risk [RR], 0.90; 95% confidence interval [CI], 0.77-1.05; P = .19). Barotrauma rates were 11.2% and 9.1% (RR, 1.21; 95% CI, 0.83-1.75; P = .33). The experimental group had lower rates of refractory hypoxemia (4.6% vs 10.2%; RR, 0.54; 95% CI, 0.34-0.86; P = .01), death with refractory hypoxemia (4.2% vs 8.9%; RR, 0.56; 95% CI, 0.34-0.93; P = .03), and previously defined eligible use of rescue therapies (5.1% vs 9.3%; RR, 0.61; 95% CI, 0.38-0.99; P = .045). For patients with acute lung injury and acute respiratory distress syndrome, a multifaceted protocolized ventilation strategy designed to recruit and open the lung resulted in no significant difference in all-cause hospital mortality or barotrauma compared with an established low-tidal-volume protocolized ventilation strategy. This "open-lung" strategy did appear to improve secondary end points related to hypoxemia and use of rescue therapies. clinicaltrials.gov Identifier: NCT00182195.
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            Prone positioning in patients with moderate and severe acute respiratory distress syndrome: a randomized controlled trial.

            Gianni Tognoni, Roberto Latini, Claude Guerin … (2009)
            Post hoc analysis of a previous trial has suggested that prone positioning may improve survival in patients with severe hypoxemia and with acute respiratory distress syndrome (ARDS). To assess possible outcome benefits of prone positioning in patients with moderate and severe hypoxemia who are affected by ARDS. The Prone-Supine II Study, a multicenter, unblinded, randomized controlled trial conducted in 23 centers in Italy and 2 in Spain. Patients were 342 adults with ARDS receiving mechanical ventilation, enrolled from February 2004 through June 2008 and prospectively stratified into subgroups with moderate (n = 192) and severe (n = 150) hypoxemia. Patients were randomized to undergo supine (n = 174) or prone (20 hours per day; n = 168) positioning during ventilation. The primary outcome was 28-day all-cause mortality. Secondary outcomes were 6-month mortality and mortality at intensive care unit discharge, organ dysfunctions, and the complication rate related to prone positioning. Prone and supine patients from the entire study population had similar 28-day (31.0% vs 32.8%; relative risk [RR], 0.97; 95% confidence interval [CI], 0.84-1.13; P = .72) and 6-month (47.0% vs 52.3%; RR, 0.90; 95% CI, 0.73-1.11; P = .33) mortality rates, despite significantly higher complication rates in the prone group. Outcomes were also similar for patients with moderate hypoxemia in the prone and supine groups at 28 days (25.5% vs 22.5%; RR, 1.04; 95% CI, 0.89-1.22; P = .62) and at 6 months (42.6% vs 43.9%; RR, 0.98; 95% CI, 0.76-1.25; P = .85). The 28-day mortality of patients with severe hypoxemia was 37.8% in the prone and 46.1% in the supine group (RR, 0.87; 95% CI, 0.66-1.14; P = .31), while their 6-month mortality was 52.7% and 63.2%, respectively (RR, 0.78; 95% CI, 0.53-1.14; P = .19). Data from this study indicate that prone positioning does not provide significant survival benefit in patients with ARDS or in subgroups of patients with moderate and severe hypoxemia. clinicaltrials.gov Identifier: NCT00159939.
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              Randomized, placebo-controlled clinical trial of an aerosolized β₂-agonist for treatment of acute lung injury.

              Michael Matthay, Roy Brower, Shannon Ryan Carson … (2011)
              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
                Joseph E Levitt
                Michael A Matthay
                Journal
                Journal ID (nlm-ta): Crit Care
                Journal ID (iso-abbrev): Crit Care
                Title: Critical Care
                Publisher: BioMed Central
                ISSN (Print): 1364-8535
                ISSN (Electronic): 1466-609X
                Publication date (Print): 2012
                Publication date (Electronic): 19 June 2012
                Publication date PMC-release: 19 June 2013
                Volume: 16
                Issue: 3
                Page: 223
                Affiliations
                [1 ]Division of Pulmonary/Critical Care, Stanford University, 300 Pasteur Drive, MC 5236 Stanford, CA 94305, USA
                [2 ]Departments of Medicine and Anesthesia, Cardiovascular Research Institute, University of California, San Francisco, Moffitt Hospital, 505 Parnasssus Ave, M-917, San Francisco, CA 94143, USA
                Article
                Publisher ID: cc11144
                DOI: 10.1186/cc11144
                PMC ID: 3580596
                PubMed ID: 22713281
                SO-VID: debbaa28-9a4d-4088-a69b-a024ce1db2a9
                Copyright © Copyright ©2012 BioMed Central Ltd
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                Subject: Review

                ScienceOpen disciplines: Emergency medicine & Trauma
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                ScienceOpen disciplines: Emergency medicine & Trauma

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