Management of ARDS in Adults Michael D. Howell, MD, MPH; Andrew M. Davis, MD, MPH Summary of the Clinical Problem ARDS is an acute inflammatory lung injury that results in increased vascular permeability. Clinically, this leads to life-threatening acute hypoxemic respiratory failure with bilateral alveolar opacities on chest imaging that are not fully ex- plained by cardiogenic pulmo- nary edema, pleural effusions, or lung collapse. ARDS is associ- ated with many conditions, including sepsis, aspiration, pneumo- nia, severe trauma, and overdose. ARDS affects approximately 200 000 individuals and results in 74 500 deaths per year in the United States. 1 ARDS management remains largely supportive, with mechani- cal ventilation forming the cornerstone of therapy. Management of ARDS is clinically challenging because some approaches to mechani- cal ventilation exacerbate lung injury and increase mortality. 2 ARDS often is managed in community settings without easy access to in- tensive care specialists. Characteristics of the Guideline Source The guideline was developed by the ATS, ESICM, and SCCM with funding from the ATS and ESICM. 3 The committee included ex- perts in ARDS physiology and clinical trials as well as guideline meth- odologists, a medical librarian, and an ARDS survivor. A formal con- flict of interest management policy was followed. Evidence Base The guideline committee used Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods (Table). PICO (population, intervention, control, and outcomes) questions were constructed and a medical librarian assisted with systematic re- views. In some cases, new meta-analyses were performed. The com- mittee rated recommendations as strong or conditional and classi- fied the level of confidence in evidence of effect estimates. Benefits and Harms The guideline strongly recommends lung-protective ventilation for all patients with ARDS, defined as targeting a tidal volume of 4 to 8 mL/kg PBW and a plateau pressure of less than 30 cm H 2O. The ARDSNet trial supporting this recommendation enrolled 861 patients and found a 22% relative reduction in mortality with tidal volumes of 6 mL/kg PBW com- pared with 12 mL/kg PBW. 2 The guideline identified 8 other relevant trials. When all trials were included, the lung-protective approach was associated with lower mortality (risk ratio [RR], 0.80; 95% CI, 0.66- 0.98). Larger tidal volume differences between control and interven- tion groups were associated with larger improvements in mortality. The guideline makes 2 important recommendations for severe ARDS, defined as a Pa O2/FIO2 ratio of 100 or less. First, these pa- tients should be placed in the prone position for at least 12 hours per day. The recommendation is based largely on the PROSEVA trial, which found that prone positioning reduced 28-day mortality from 32.8% to 16.0% (P < .001) in 466 patients with severe ARDS. 4 This will be a practice change for many intensive care units (ICUs) and clinicians; moreover, implementing prone positioning can be logistically chal- lenging. In addition, prone positioning may carry additional risks, Related article page 698 and JAMA Patient Page page 732 Table. Guideline Rating Standard Rating Establishing transparency Good Management of conflict of interest in the guideline development group Fair Guideline development group composition Good Clinical practice guideline–systematic review intersection Good Establishing evidence foundations and rating strength for each of the guideline recommendations Good Articulation of recommendations Good External review Fair Updating Fair Implementation issues Fair GUIDELINE TITLE Mechanical Ventilation in Adult Patients With Acute Respiratory Distress Syndrome DEVELOPER American Thoracic Society (ATS)/European Society of Intensive Care Medicine (ESICM)/Society of Critical Care Medicine (SCCM) RELEASE DATE M a y1 ,2 0 1 7 TARGET POPULATION Hospitalized adults with acute respiratory distress syndrome (ARDS). SELECTED MAJOR RECOMMENDATIONS For all patients with ARDS: •Use lower tidal volumes of 4 to 8 mL/kg per breath, calculated using predicted body weight (PBW) (strong recommendation; moderate confidence in effect estimate). •Use lower inspiratory pressures, targeting a plateau pressure <30 cm H 2O (strong recommendation; moderate confidence). For patients with severe ARDS (PaO2/FIO2 ratio <100): •Use prone positioning for at least 12 h/d (strong recommendation; moderate confidence). •Do not routinely use high-frequency oscillatory ventilation (strong recommendation; high confidence). •Additional evidence is needed to recommend for or against the use of extracorporeal membrane oxygenation (ECMO) in severe ARDS. Clinical Review & Education JAMA Clinical Guidelines Synopsis jama.com (Reprinted) JAMA February 20, 2018 Volume 319, Number 7 711 © 2018 American Medical Association. All rights reserved. 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including endotracheal tube problems, requirements for increased sedation, less opportunity for early mobilization, and potentially more risk of pressure ulcers. Second, adult patients with moderate to se- vere ARDS should not routinely receive high-frequency oscillatory ven- tilation (HFOV). The OSCILLATE trial (N=548) used a higher positive end-expiratory pressure (PEEP) control group and found increased 28-day mortality with HFOV (RR, 1.41; 95% CI, 1.12-1.79) 5; other prag- matic trials have found no benefit. The guideline made 2 conditional recommendations for pa- tients with moderate to severe ARDS, suggesting using higher PEEP and recruitment maneuvers, which might in theory open collapsed lung and increase end-expiratory volume. H owever, shortly after the guideline was published, a large randomized trial found that a strategy of recruitment maneuvers with higher-PEEP titration (vs standard, lower-PEEP care) resulted in increased 28-day mor- tality (hazard ratio, 1.20; 95% CI, 1.01-1.42). 6 Discussion Perhaps the key challenge of ARDS management is that the same intervention that is immediately lifesaving—mechanical ventilation— can also worsen lung injury and increase mortality. Maneuvers that improve short-term parameters like oxygenation or tachypnea may paradoxically worsen survival. The most important recommendations in the guideline are for low tidal volumes and low inspiratory pressures. There are 2 practical points worth emphasizing. First, tidal volumes should be based on pre- dicted, not actual, body weight. Why? Obesity does not cause the lungs to increase in size, so using actual body weight often results in higher- than-desired tidal volumes and therefore higher mortality. Second, the plateau pressure is a potentially lifesaving parameter to follow in pa- tients with ARDS. This parameter measures the airway pressure af- ter a 0.5-second pause at the end of inspiration, and it reflects the in- teraction of respiratory system stiffness and the size of the tidal volume. It should be measured regularly in all ARDS patients, and the ventilator should be adjusted to target a plateau pressure of less than 30 cm H 2O. A pocket card summarizing the approach to tidal vol- ume and plateau pressure management used in the seminal ARDS- Net trial 2 is freely available and has practical value at the bedside. Management of sedation, analgesia, and strategies for liberation from mechanical ventilation are also crucial to outcomes. 7 For many clinicians, the strong recommendation for prone posi- tioning may be surprising. The benefit of prone positioning is patho- physiologically plausible: it changes ventilation-perfusion matching and more uniformly distributes tidal volume by changing chest wall (and abdominal) mechanics. While trials of prone positioning were con- ducted in selected expert centers, this guideline supports judicious dissemination of this practice to other ICUs in the community. Areas in Need of Future Study Numerous areas of ARDS management remain important areas for future research, including studies that guide the setting of tidal vol- ume and PEEP using physiology-based parameters such as driving pressure or esophageal pressure and that validate simple tools to guide safe lung recruitment. Even with current knowledge, in a 50- country study, only half of patients with ARDS (n = 3022) were rec- ognized clinically, 60% did not have a plateau pressure measured, and more than one-third received tidal volumes higher than 8 mL/kg PBW. 8 Development of quality measures and quality improvement programs in ARDS is therefore a priority. Whether spontaneous respiration in ARDS is helpful or harm- ful remains an area of debate. Most clinicians caring for a patient with severe ARDS must choose whether to initiate neuromuscular block- ade. The guideline is silent on this issue. A randomized multicenter trial (N=340) found that adjusted (but not unadjusted) 90-day sur- vival was higher in pharmacologically paralyzed patients with ARDS. 9 A multicenter confirmatory trial is under way suggesting that clini- cal equipoise remains for this issue. Finally, the guideline also re- viewed the evidence relating to ECMO for ARDS but withheld a rec- ommendation because of the rapid pace of technological evolution in extracorporeal techniques as well as numerous ongoing relevant randomized trials. ARTICLE INFORMATION Author Affiliations: Google Research, Google Inc, Mountain View, California (Howell); Section of General Internal Medicine, University of Chicago, Chicago, Illinois (Davis). Corresponding Author: Michael D. Howell, MD, MPH, Google Research, Google Inc, 1600 Amphitheater Pkwy, Mountain View, CA 94043 (mdh@uchicago.edu). Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Howell owns equity in Google Inc. No other disclosures were reported. REFERENCES 1. Rubenfeld GD, Caldwell E, Peabody E, et al. Incidence and outcomes of acute lung injury.N Engl J Med. 2005;353(16):1685-1693. 2. Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342(18):1301-1308. 3. Fan E, Del Sorbo L, Goligher EC, et al. An official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine clinical practice guideline: mechanical ventilation in adult patients with acute respiratory distress syndrome. Am J Respir Crit Care Med.2 0 1 7 ; 195(9):1253-1263. 4. Guerin C, Reignier J, Richard JC, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013;368(23):2159-2168. 5. Ferguson ND, Cook DJ, Guyatt GH, et al. High-frequency oscillation in early acute respiratory distress syndrome. N Engl J Med. 2013;368(9):795- 805. 6. Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial I; Cavalcanti AB, Suzumura EA, et al. Effect of lung recruitment and titrated positive end-expiratory pressure (PEEP) vs low PEEP on mortality in patients with acute respiratory distress syndrome. JAMA. 2017;318(14):1335-1345. 7. Ouelette DR, Patel S, Girard TD, et al. Liberation from mechanical ventilation in critically ill adults. Chest. 2017;151(1); 166-180. 8. Bellani G, Laffey JG, Pham T , et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016;315(8):788- 800. 9. Papazian L, Forel JM, Gacouin A, et al. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med . 2010;363(12): 1107-1116. Related guidelines and other resources Revised Berlin Definition of ARDS ARDSNet Tools ACCCM Guideline: Sedation and Analgesia in the ICU (Pain, Agitation, and Delirium Management) 2013 Clinical Review & Education JAMA Clinical Guidelines Synopsis 712 JAMA February 20, 2018 Volume 319, Number 7 (Reprinted) jama.com © 2018 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ by a Children's Hospital Medical Center User on 04/08/2020