Pediatric Acute Respiratory Distress Syndrome: Much More Than Little Acute Respiratory Distress Syndrome* Alexandre T. Rotta, MD, FCCM, FAAP Division of Pediatric Critical Care Medicine UH Rainbow Babies & Children’s Hospital Case Western Reserve University School of Medicine Cleveland, OH Jefferson P. Piva, MD, PhD Department of Pediatric Emergency Medicine and Intensive Care Hospital de Clinicas de Porto Alegre UFRGS School of Medicine Porto Alegre, Brazil

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ore than 47 years have passed since the original report of the acute respiratory distress syndrome (ARDS) (1). Initially described as “acute respiratory distress in adults,” so as to differentiate it from the already established respiratory distress syndrome of the newborn, that report is remarkable in its characterization of a heterogeneous group of patients sharing unique features from multifactorial etiologies (1). This adult-centric definition (2) is peculiar, considering children not only are known to have ARDS but an 11-year old and four teenagers were among the 12 patients featured in the first report (1). Nearly three decades passed before a multinational task force developed a more precise and widely accepted definition: the American-European Consensus Conference (AECC) on ARDS (3). The AECC definition immediately became the standard by which patients were diagnosed, classified, and enrolled into clinical trials. It had, however, significant shortcomings, such as not considering the effect of respiratory support on oxygenation (4), radiographic inclusion criterion open to interobserver variability (5), and no definition for the term “acute,” thus creating arbitrary definitions within the definition.

*See also p. 428. Key Words: acute respiratory distress syndrome; children; mechanical ventilation; pediatric intensive care unit; respiratory failure Dr. Rotta is a member of the scientific advisory board of and has been a speaker for Vapotherm. He consulted for Vapotherm (provide consultation as part of a scientific advisory board), lectured for Vapotherm (give lectures in events sponsored by the company), received royalties from Elsevier (royalties relative to participation as associate editor in a pediatric critical care textbook), and received support for the development of educational presentations from Vapotherm (develop educational materials for the company). Dr. Piva has disclosed that he does not have any potential conflicts of interest. Copyright © 2015 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies DOI: 10.1097/PCC.0000000000000359

Pediatric Critical Care Medicine

Recently, a more robust characterization of ARDS was developed: the Berlin definition (6). The Berlin definition addressed several shortcomings of the AECC definition, including the creation of three severity-of-illness categories based on hypoxemia measured as the arterial partial pressure of oxygen to fraction of inspired oxygen (Pao2/Fio2) ratio subjected to a minimum positive end-expiratory pressure (PEEP) level (6). It also clarified the chest radiograph criteria to decrease interrater variability, defined the acute onset time frame as occurring within 1 week of a known insult, and provided guidance on how to address pulmonary infiltrates resulting from fluid overload or cardiac failure (6). The Berlin definition became the new standard for ARDS in the adult population, but its applicability to children remained unclear (7). It was created by adult critical care specialists for adult patients and validated using data from adult clinical trials. Over nearly five decades, pediatric intensivists have gained significant cumulative experience treating patients with ARDS and have consistently reported improving outcomes (7–9) despite the lack of a pediatric-specific definition of ARDS and a paucity of high-grade clinical trials in this population. In this issue of Pediatric Critical Care Medicine, the Pediatric Acute Lung Injury Consensus Conference (10) group introduces the long overdue and much needed first pediatric-specific definition of ARDS, consensus recommendations regarding management of pediatric acute respiratory distress syndrome (PARDS), and future research directions. This work was developed over the span of 2 years by 27 renowned experts representing 21 academic institutions from eight countries and truly represents a turning point in the history of PARDS (10). We congratulate the expert panel for producing a precise definition of PARDS based on the best available evidence and fashioned through unanimous agreement. This definition provides a framework that will allow for comparisons across multiple institutions, will clarify the role of various treatments and their impact on outcome, and will help delineate the real prevalence of this condition throughout the world. The experts deliberately chose not to specify age criteria for PARDS, but it should be understood that the definition is intended to cover patients generally cared for by pediatric intensivists, excluding neonates with perinatal-related lung disease. The presence of bilateral pulmonary infiltrates is no longer a requirement. There is also a definition of PARDS in special populations, including children with cyanotic congenital heart disease, left ventricular dysfunction, or chronic lung disease. Like in the Berlin definition, the onset of PARDS must occur within 7 days of a known clinical insult and respiratory failure must not be fully explained by cardiac failure or fluid overload. A significant departure from the Berlin definition comes www.pccmjournal.org

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Editorials

by abandoning the Pao2/Fio2 ratio to grade disease severity in favor of the oxygenation index (OI) or the oxygen saturation index (OSI). Using the OI or the OSI allows for a much more informed appreciation of the role of positive pressure ventilation on oxygenation, since it is well known that differences in the ventilator management can “attenuate or exacerbate” the degree of observed hypoxemia (4), thus influencing the true prevalence and severity-of-illness classification. In a field marked by individuals with strong convictions and a paucity of data, we find it remarkable that a pediatric critical care expert panel reached strong (unanimous) agreement in 132 of 151 recommendations. Unanimous agreement was reached in important topics, such as sedation, neuromuscular blockers, nutrition, and fluid management strategies, probably as a reflection of how the judicious use of minimal sedation and paralysis, emphasis on optimal nutrition, and goal-directed fluid titration are common sense practices that have been incorporated into the pediatric critical care zeitgeist. It was interesting to note that experts tended to diverge (weak agreement) on relevant topics related to specific management and mechanical ventilation strategies (e.g., choice of tidal volume, plateau pressure, PEEP, recruitment maneuvers, high-frequency ventilation, and oxygenation and ventilation targets). The lack of expert consensus on these important topics is emblematic of a specialty that is no longer content in simply applying an adult paradigm to children. Every pediatric intensivist is keenly aware of the definitive clinical trials showing improved outcomes associated with reduced tidal volumes in adults with ARDS (11, 12), yet there is a wide gap between what we believe we do and what we actually do while caring for children with ARDS (9, 13–15). Where pediatric-specific data lack, opinions abound. In this regard, the document is quite realistic, indicating a proposed direction, while emphasizing through the “weak agreement” level that these are not definitive recommendations. In other words, the art of ventilation was considered and preserved to some extent in this document; at least until higher quality evidence germane to PARDS becomes available. The expert panel should be commended for not limiting their recommendations to areas where robust evidence and consensus already exist. Aside from a clear and objective definition for PARDS and grading of the available evidence, perhaps the most important contribution made by the panel was in identifying areas necessitating further research and creating a roadmap for future progress. The 19 topics where a consensus was not obtained represent a remarkable opportunity: 19 hot topics in PARDS awaiting definitive answers. The experts fulfilled their obligation by identifying areas of controversy, and it is now up to the pediatric critical care community worldwide to produce answers to those open questions.

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Welcome, PARDS! We have been expecting you for nearly half a century!

REFERENCES

1. Ashbaugh DG, Bigelow DB, Petty TL, et al: Acute respiratory distress in adults. Lancet 1967; 2:319–323 2. Petty TL, Ashbaugh DG: The adult respiratory distress syndrome. Clinical features, factors influencing prognosis and principles of management. Chest 1971; 60:233–239 3. Bernard GR, Artigas A, Brigham KL, et al: The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994; 149:818–824 4. Ferguson ND, Kacmarek RM, Chiche JD, et al: Screening of ARDS patients using standardized ventilator settings: Influence on enrollment in a clinical trial. Intensive Care Med 2004; 30:1111–1116 5. Rubenfeld GD, Caldwell E, Granton J, et al: Interobserver variability in applying a radiographic definition for ARDS. Chest 1999; 116:1347–1353 6. Ranieri VM, Rubenfeld GD, Thompson BT, et al: Acute respiratory distress syndrome: The Berlin Definition. JAMA 2012; 307:2526–2233 7. De Luca D, Piastra M, Chidini G, et al; Respiratory Section of the European Society for Pediatric Neonatal Intensive Care (ESPNIC): The use of the Berlin definition for acute respiratory distress syndrome during infancy and early childhood: Multicenter evaluation and expert consensus. Intensive Care Med 2013; 39:2083–2091 8. López-Fernández Y, Azagra AM, de la Oliva P, et al; Pediatric Acute Lung Injury Epidemiology and Natural History (PED-ALIEN) Network: Pediatric Acute Lung Injury Epidemiology and Natural History study: Incidence and outcome of the acute respiratory distress syndrome in children. Crit Care Med 2012; 40:3238–3245 9. Khemani RG, Conti D, Alonzo TA, et al: Effect of tidal volume in children with acute hypoxemic respiratory failure. Intensive Care Med 2009; 35:1428–1437 10. The Pediatric Acute Lung Injury Consensus Conference Group; Thomas NJ: Pediatric Acute Respiratory Distress Syndrome: Consensus Recommendations From the Pediatric Acute Lung Injury Consensus Conference. Pediatr Crit Care Med 2015; 16:428–439 11. Amato MB, Barbas CS, Medeiros DM, et al: Effect of a protectiveventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 1998; 338:347–354 12. The 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; 342:1301–1308 13. Santschi M, Jouvet P, Leclerc F, et al; PALIVE Investigators; Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI); European Society of Pediatric and Neonatal Intensive Care (ESPNIC): Acute lung injury in children: Therapeutic practice and feasibility of international clinical trials. Pediatr Crit Care Med 2010; 11:681–689 14. Santschi M, Randolph AG, Rimensberger PC, et al; Pediatric Acute Lung Injury Mechanical Ventilation Investigators; Pediatric Acute Lung Injury and Sepsis Investigators Network; European Society of Pediatric and Neonatal Intensive Care: Mechanical ventilation strategies in children with acute lung injury: A survey on stated practice pattern. Pediatr Crit Care Med 2013; 14:e332–e337 15. Piva JP, Garcia PC, Fiori H: Mechanical ventilation in children with acute respiratory distress syndrome: A huge gap between what we know and our practice! Pediatr Crit Care Med 2013; 14:732–733

June 2014 • Volume 16 • Number 5

Copyright © 2015 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. Unauthorized reproduction of this article is prohibited

Pediatric acute respiratory distress syndrome: much more than little acute respiratory distress syndrome.

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