The Montreux definition of neonatal ARDS: biological and clinical background behind the description of a new entity

doi:10.1016/S2213-2600(17)30214-X

The Lancet Respiratory Medicine

Volume 5, Issue 8, August 2017, Pages 657-666

https://doi.org/10.1016/S2213-2600(17)30214-X Get rights and content

Summary

Acute respiratory distress syndrome (ARDS) is undefined in neonates, despite the long-standing existing formal recognition of ARDS syndrome in later life. We describe the Neonatal ARDS Project: an international, collaborative, multicentre, and multidisciplinary project which aimed to produce an ARDS consensus definition for neonates that is applicable from the perinatal period. The definition was created through discussions between five expert members of the European Society for Paediatric and Neonatal Intensive Care; four experts of the European Society for Paediatric Research; two independent experts from the USA and two from Australia. This Position Paper provides the first consensus definition for neonatal ARDS (called the Montreux definition). We also provide expert consensus that mechanisms causing ARDS in adults and older children—namely complex surfactant dysfunction, lung tissue inflammation, loss of lung volume, increased shunt, and diffuse alveolar damage—are also present in several critical neonatal respiratory disorders.

Introduction

Acute respiratory distress syndrome (ARDS) is undefined in neonates, despite the longstanding recognition of ARDS in later life. We describe the Neonatal ARDS Project: an international, collaborative, multicentre, and multidisciplinary project which aimed to produce an ARDS consensus definition for neonates that is applicable from the perinatal period. This project is an initiative endorsed by the European Society for Pediatric and Neonatal Intensive Care (ESPNIC) and the European Society for Pediatric Research (ESPR). The Steering Committee of the Neonatal ARDS Project first reviewed the literature on the biological, pathophysiological, and histological features of ARDS in neonates compared with other age groups, and on the current definitions of ARDS in older children and adults. The consensus definition was then developed from this literature analysis. This paper also presents the rationale for issuing a specific definition of ARDS in neonates.

Section snippets

Age and evolution of the ARDS definition

ARDS was originally reported in 12 patients (including an 11-year-old) by Ashbaugh and colleagues¹ in The Lancet in 1967. They characterised ARDS as “dyspnoea, tachypnoea, cyanosis resistant to oxygen therapy, loss of lung compliance, and diffuse alveolar infiltration” and “areas of atelectasis, alveolar oedema, and haemorrhage” at necropsy. The clinical and histological similarities with respiratory distress syndrome (RDS) in neonates due to primary surfactant deficiency2, 3 were recognised

Why do we need a definition of neonatal ARDS?

The first month of life (ie, the neonatal period) is a unique life-stage characterised by a high risk of mortality.¹⁹ The American Academy of Pediatrics recommends that causes of mortality would be specifically defined for the first month of life and include perinatal events and the degree of fetal maturation.²⁰ The PALICC definition¹⁷ specifically excludes causes of acute hypoxaemia that are unique to the perinatal period. Primary RDS related to prematurity is clearly different from paediatric

Does neonatal ARDS really exist?

From our search strategy we retrieved 32 publications that used the term neonatal ARDS: 23 clinical (mainly case series) and nine translational neonatal animal model studies (see appendix). The first use of the term neonatal ARDS in 1989 described 11 term neonates with ARDS associated with perinatal asphyxia and meconium or blood aspiration.²⁸ Faix and colleagues²⁸ concluded that “ARDS can and does occur in newborn infants. We see no reason why this syndrome could not be superimposed on some of

Biological, pathophysiological, and histological rationale for neonatal ARDS

ARDS is biologically characterised by qualitative or quantitative surfactant dysfunction affecting both proteins and phospholipids, and extensive lung tissue inflammation.31, 32 These biological processes share commonality with a number of neonatal respiratory disorders characterised by variable secondary impairment of surfactant function or surfactant amount, rather than primary surfactant deficiency. For instance, meconium aspiration syndrome, biliary pneumonia, and respiratory failure

Methods used in the Neonatal ARDS Project

An international multidisciplinary collaborative project commenced in January, 2014, with the aim to draft and test a definition for neonatal ARDS. The project method is summarised in figure 3. Experts in respiratory critical care from neonatal and paediatric intensive care units representing ESPNIC, ESPR, and independent expert colleagues, were contacted to create a Steering Committee composed of 12 members. Experts were selected after discussion in ESPNIC and ESPR Councils, on the basis of

The Montreux definition of neonatal ARDS

The Committee maintained consistency in ARDS¹² and paediatric ARDS¹⁷ definitions where possible. Table 2 shows the final Montreux definition of neonatal ARDS, which was approved by consensus of the Steering Committee at a meeting in Montreux (Switzerland). The following ten points addressed in this Committee meeting should be highlighted. First, the definition of neonatal ARDS applies to infants from birth until 44 weeks, post-menstrual age or until 4 weeks, postnatal age (for neonates born

Next steps

The Neonatal ARDS Project is divided into two main phases (figure 3). The first phase aimed to review the available literature to create a definition of neonatal ARDS based on an expert consensus of the available scientific knowledge: this phase led to the Montreux definition. This definition has now been or is being presented at ESPNIC, ESPR, and local congresses in order to identify health-care professionals from neonatal and paediatric intensive care units who are willing to participate in

Conclusions

With the dissemination of the Montreux definition of neonatal ARDS, we expect an increase in the clinical attention to the entity of the disorder. The Montreux definition might foster neonatal ARDS research, which will facilitate the investigation of new therapeutic approaches, such as larger or multiple dosing of exogenous surfactants and anti-inflammatory or surfactant protective agents.93, 94 The knowledge that will be acquired in this area might also be useful in the clinical care and

Search strategy and selection criteria

We searched the authors' personal files and references, PubMed, and Google Scholar for the terms (“infant, newborn”[MeSH Terms] OR (“infant”[All Fields] AND “newborn”[All Fields]) OR “newborn infant”[All Fields] OR “neonate”[All Fields]) AND “ARDS”[All Fields] OR “acute respiratory distress syndrome” or “acute lung injury”[All Fields]), with no restriction on language or date. This search was last done on Sept 12, 2016. We also searched the Pediatric Academic Societies meetings' abstracts'

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Position PaperThe Montreux definition of neonatal ARDS: biological and clinical background behind the description of a new entity

Summary

Introduction

Section snippets

Age and evolution of the ARDS definition

Why do we need a definition of neonatal ARDS?

Does neonatal ARDS really exist?

Biological, pathophysiological, and histological rationale for neonatal ARDS

Methods used in the Neonatal ARDS Project

The Montreux definition of neonatal ARDS

Next steps

Conclusions

Search strategy and selection criteria

Lancet

Lancet

J Pediatr

Am J Med

Am J Surg

Crit Care

Mol Med Today

J Pediatr

Crit Care Clin

Respir Med

J Pediatr

J Pediatr

J Pediatr Surg

Semin Perinatol

Transfus Sci

Optimum end-expiratory airway pressure in patients with acute pulmonary failure

N Engl J Med

An expanded definition of the adult respiratory distress syndrome

Am Rev Respir Dis

Assessment of pulmonary function in the early phase of ARDS in pediatric patients

Pediatr Pulmonol

Comparison of SpO2 to PaO2 based markers of lung disease severity for children with acute lung injury

Crit Care Med

Effect of tidal volume in children with acute hypoxemic respiratory failure

Intensive Care Med

The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination

Am J Respir Crit Care Med

Acute respiratory distress syndrome: the Berlin definition

JAMA

The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material

Intensive Care Med

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

Evaluating the performance of the pediatric acute lung injury consensus conference definition of acute respiratory distress syndrome

Pediatr Crit Care Med

Epidemiology and outcomes of acute respiratory distress syndrome in children according to the Berlin definition: a multicenter prospective study

Crit Care Med

Pediatric acute respiratory distress syndrome: definition, incidence, and epidemiology: proceedings from the Pediatric Acute Lung Injury Consensus Conference

Pediatr Crit Care Med

Evaluating the performance of the Pediatric Acute Lung Injury Consensus Conference definition of acute respiratory distress syndrome

Pediatr Crit Care Med

Infant, Newborn

Standard terminology for fetal, infant, and perinatal deaths

Pediatrics

Daily practice of mechanical ventilation in Italian pediatric intensive care units: a prospective survey

Pediatr Crit Care Med

Impact of retrieval, distance traveled, and referral center on outcomes in unplanned admissions to a national PICU

Pediatr Crit Care Med

The postnatal decline of hemoglobin F synthesis in normal full-term infants

J Clin Invest

Postnatal fetal and adult hemoglobin synthesis in early preterm newborn infants

J Clin Invest

Neonatal non-invasive respiratory support: synchronised NIPPV, non-synchronised NIPPV or bi-level CPAP: what is the evidence in 2013?

Neonatology

Elective high frequency oscillatory ventilation versus conventional ventilation for acute pulmonary dysfunction in preterm infants

Cochrane Database Syst Rev

Adult respiratory distress syndrome in full-term newborns

Pediatrics

Innate immune deficiency of extremely premature neonates can be reversed by interferon-γ

PLoS One

Management of acute lung injury and acute respiratory distress syndrome in children

Crit Care Med

Surfactant alteration and replacement in acute respiratory distress syndrome

Respir Res

Role of distinct phospholipases A2 and their modulators in meconium aspiration syndrome in human neonates

Intensive Care Med

Secretory phospholipase A2 and neonatal respiratory distress: pilot study on broncho-alveolar lavage

Position Paper
The Montreux definition of neonatal ARDS: biological and clinical background behind the description of a new entity

Comparison of SpO₂ to PaO₂ based markers of lung disease severity for children with acute lung injury