CLINICAL REVIEW CLINICIAN’S CORNER Ventilatory Management of Acute Lung Injury and Acute Respiratory Distress Syndrome Eddy Fan, MD Context The acute lung injury and acute respiratory distress syndrome are critical Dale M. Needham, MD, PhD illnesses associated with significant morbidity and mortality. Mechanical ventilation is Thomas E. Stewart, MD the cornerstone of supportive therapy. However, despite several important advances, the optimal strategy for ventilation and adjunctive therapies for patients with acute OR NEARLY 4 DECADES SINCE THE lung injury and acute respiratory distress syndrome is still evolving. acute respiratory distress syn- Evidence Acquisition To identify reports of invasive ventilatory and adjunctive thera- drome (ARDS) was first de- pies in adult patients with acute lung injury and acute respiratory distress syndrome, scribed,1 research has been on- we performed a systematic English-language literature search of MEDLINE (1966- Fgoing in an effort to improve the 2005) using the Medical Subject Heading respiratory distress syndrome, adult, and outcome of this critical illness. Acute related text words, with emphasis on randomized controlled trials and meta-analyses. EMBASE and the Cochrane Central Register of Controlled Trials were similarly searched. respiratory distress syndrome is char- The search yielded 1357 potential articles of which 53 were relevant to the study ob- acterized by the acute onset of hypox- jectives and considered in this review. emia and bilateral infiltrates on chest Evidence Synthesis There is strong evidence to support the use of volume- and radiography in the absence of left atrial pressure-limited lung-protective ventilation in adult patients with acute lung injury and hypertension. Various pulmonary (eg, acute respiratory distress syndrome. The benefit of increased levels of positive end- pneumonia) and nonpulmonary (eg, expiratory pressure and recruitment maneuvers is uncertain and is being further evalu- pancreatitis) risk factors are associ- ated in ongoing trials. Existing randomized controlled trials of alternative ventilation ated with ARDS.2 Mortality rates range modes, such as high-frequency oscillation and adjunctive therapies, including inhaled from 26% to 74%, with most deaths at- nitric oxide and prone positioning demonstrate no significant survival advantage. How- tributed to associated conditions, such ever, they may have a role as rescue therapy for patients with acute respiratory dis- as sepsis and multisystem organ fail- tress syndrome with refractory life-threatening hypoxemia. ure, rather than hypoxemia alone.2-6 Conclusions Volume- and pressure-limited ventilation strategies should be used in Some survivors of ARDS have reduced managing adult acute lung injury and acute respiratory distress syndrome patients. quality of life with physical, neurocog- Further research is needed to identify barriers to widespread adoption of this strategy, nitive, and emotional morbidity.7-10 as well as the role of alternative ventilation modes and adjunctive therapies. The original ARDS case series1 out- JAMA. 2005;294:2889-2896 www.jama.com lined a number of clinical features that Ͻ were later incorporated into more for- 300), while ARDS represents the sub- though necessary to preserve life, can po- mal definitions of this syndrome set of ALI patients with the most se- tentiate or directly injure the lungs Ͻ (TABLE 1).11-13 In 1994, the American- vere lung injury (PaO2/FIO2 ratio 200). through a variety of mechanisms col- European Consensus Conference Using these definitions, ALI and ARDS (AECC) definition was developed and are relatively common with annual in- Author Affiliations: Interdepartmental Division of Criti- is used widely by clinicians and re- cidences estimated at 20 to 50 and 15 cal Care Medicine and Department of Medicine, Uni- versity of Toronto and University Health Network and 13 searchers. Under this definition, acute to 30 cases per 100 000 persons, re- Mount Sinai Hospital, Toronto, Ontario, (Drs Fan and 2,3 lung injury (ALI) is designated for pa- spectively. Stewart) and Division of Pulmonary and Critical Care No specific pharmacologic therapy Medicine, Johns Hopkins University, Baltimore, Md (Dr tients with significant hypoxemia (par- Needham). tial pressure of arterial oxygen to frac- has proved effective for ALI or ARDS, Corresponding Author: Thomas E. Stewart, MD, Uni- and therapy is largely supportive with versity Health Network/Mount Sinai Hospital, 600 Uni- tion of inspired oxygen [PaO2/FIO2] ratio 11 versity Ave, Suite 18-206, Toronto, Ontario, Canada the use of mechanical ventilation. Per- M5G 1X5 ([email protected]). haps the most important advance in ALI Clinical Review Section Editor: Michael S. Lauer, MD. CME available online at and ARDS research has been the recog- We encourage authors to submit papers for consid- www.jama.com eration as a “Clinical Review.” Please contact Mi- nition that mechanical ventilation, al- chael S. Lauer, MD, at [email protected]. ©2005 American Medical Association. All rights reserved. (Reprinted) JAMA, December 14, 2005—Vol 294, No. 22 2889 Downloaded from www.jama.com at K C Library Svs 142d, on January 28, 2006 MANAGEMENT OF ACUTE LUNG INJURY AND ARDS lectively referred to as ventilator- tomography studies (FIGURE).20 As a re- quently, mechanical ventilation can re- associated lung injury.14-16 These mecha- sult, some areas of the lung (often de- sult in barotrauma or volutrauma when nisms include exposure to high inflation pendent regions) are atelectatic, con- volumes and pressures meant for the pressures or overdistention (baro- solidated, less compliant, and thus less entire lung are forced into only a small trauma or volutrauma),17 repetitive op- available for ventilation while other portion of functional lung. In addi- ening and closing of alveoli (atelec- areas (usually nondependent regions) tion, shear forces at the interface be- trauma),18 and mechanotransduction appear and behave normally. Under- tween the open and closed lung units resulting in up-regulated cytokine re- standing this heterogeneity has led to result in atelectrauma. Both of these lease and a systemic inflammatory re- the “baby lung” concept, which sug- types of injury also can lead to release sponse (biotrauma).19 The lungs of pa- gests that, overall, a markedly re- of cytokines from the lung and have ad- tients with ALI or ARDS are particularly duced volume of lung is available for verse systemic effects, contributing to prone to ventilator-associated lung in- ventilation in ALI or ARDS, effec- the development of multisystem or- jury because they are heterogeneously tively, a functionally baby-sized lung gan failure.18,19 affected, as demonstrated in computed within an adult-sized body.21,22 Conse- This improved understanding of ALI and ARDS and ventilator-associated Table 1. Diagnostic Criteria for ARDS lung injury has been important in de- Source Oxygenation Chest Radiograph Other Criteria signing lung protective mechanical ven- Petty and Cyanosis refractory Diffuse alveolar Impaired pulmonary tilation strategies aimed at attenuat- Ashbaugh,11 to oxygen therapy infiltrates on frontal compliance ing ventilator-associated lung injury and 1971 chest radiograph Marked difference in inspired vs arterial improving outcomes. Such strategies for oxygen tensions the invasive ventilatory management of 12 Murray et al, Hypoxemia (PaO2/FIO2), No. of quadrants PEEP and respiratory adult ALI and ARDS have recently been 1988 by quintiles of alveolar system compliance consolidation (by quintiles) tested in a number of important clini- on frontal chest Preexisting direct or cal trials, which we review in this ar- radiograph indirect lung injury ticle. In addition, we discuss alterna- Nonpulmonary organ dysfunction tive invasive ventilatory modes and 13 Bernard et al, ALI, PaO2/FIO2 Յ300, Bilateral infiltrates on PCWP Յ18 mm Hg adjunctive therapies, with a focus on 1994 regardless of PEEP level frontal chest if measured or those that we believe are widely avail- ARDS, PaO2/FIO2 Յ200, radiography no clinical evidence regardless of PEEP level of left atrial able for clinical use in adults at the hypertension present time. We also highlight recent Abbreviations: ALI, acute lung injury; ARDS, acute respiratory distress syndrome; PaO2/FIO2, ratio of partial pressure of controversies and suggest areas for arterial oxygen to fraction of inspired oxygen; PCWP, pulmonary capillary wedge pressure; PEEP, positive end- expiratory pressure. future research. Figure. Typical Chest Radiograph and Computed Tomographic Scan of a Patient With Acute Respiratory Distress Syndrome A B A, The chest radiograph shows bilateral pulmonary infiltrates that appear to be diffuse. B, A computed tomographic scan of the thorax from the same patient dem- onstrates that the distribution of the bilateral infiltrates is predominantly in dependent regions with more normal-appearing lung in nondependent regions. 2890 JAMA, December 14, 2005—Vol 294, No. 22 (Reprinted) ©2005 American Medical Association. All rights reserved. Downloaded from www.jama.com at K C Library Svs 142d, on January 28, 2006 MANAGEMENT OF ACUTE LUNG INJURY AND ARDS EVIDENCE ACQUISITION corporeal membrane oxygenation). A charge, and a high mortality rate (71%) To assist with this review, we system- total of 53 articles met our criteria and in the control group may have ac- atically searched MEDLINE (1966 to were considered in this review. counted for the survival difference. Nev- September 2005), using