Infants With Severe Acute Respiratory Distress Syndrome: The Prone Trial

Official title

Short-Term Effect of Prone Positioning in Infants With Severe Acute Respiratory Distress Syndrome

Overview

The main objective is to determine the short-term effect of prone positioning in infants with infection-associated severe acute respiratory distress syndrome. The investigators compare oxygenation parameters and measurements from electrical impedance tomography (EIT) and lung ultrasonography (LUS) in mechanically ventilated infants in prone position versus supine position after surfactant administration.

Detailed description

The acute respiratory distress syndrome (ARDS) is an acute lung injury that can be triggered by pulmonary (direct lung injury) and extrapulmonary (indirect lung injury) etiologies. Pediatric ARDS (pARDS) occurs in approximately 3% of children admitted to intensive care units (ICUs) and is associated with approximately 17% mortality. The primary etiologies of pARDS have been summarized as pneumonia (35%), aspiration (15%), sepsis (13%), near-drowning (9%), cardiac disease (7%), and other clinical conditions (21%). ARDS manifests as pulmonary inflammation, alveolar edema, and hypoxemic respiratory failure. Mechanical ventilation remains an essential component in the care of patients with ARDS. Many adjunctive treatments rely on pathophysiological considerations. The pathophysiology of ARDS is characterized by inflammatory, proliferative, and fibrotic phases. The different phases induce a ventilation-perfusion mismatch. Inflammation causes surfactant inactivation and depletion. A number of clinical studies have reported clinical benefits following the instillation of exogenous surfactant in pediatric patients with acute respiratory failure. On the other side, prone positioning seem to be a promising intervention in critically ill infants and children with infection-associated acute lung injury. However, data conflict on the use of prone positioning in pediatric patients with acute lung injury.

Turning patients with moderate to severe lung disease into prone position has shown many positive effects. Prolonged intervals of prone positioning have been associated with a decrease in mortality in adult patients with acute respiratory failure. An increase in partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) has been described after 4 hours in prone position in adult patients with severe acute respiratory failure. Similarly, a decrease of the oxygenation index has been found after 8 hours of prone positioning in adult patients with respiratory failure from coronavirus disease of 2019 (COVID-19) associated acute respiratory distress syndrome. The process of prone positioning appeared safe also in critically ill infants and children. In a randomized control trial, it has been shown that in 90% of prone positioning oxygenation index decreased of more than 10% in children with acute lung injury.

Electrical impedance tomography (EIT) and lung ultrasound (LUS) are two non-invasive methods to monitor aeration and lung function parameters. EIT can quantify regional distribution of ventilation as well as improvement in end-expiratory air content. EIT has been used at bedside in critically ill adult patients to measure effects of prone position and also in infants with respiratory distress syndrome. On the other side, LUS has become an increasingly popular diagnostic bedside tool for lung examination. It is considered reliable and fast to detect various lung-related pathologies, such as pneumonia, atelectasis, pneumothorax, and interstitial syndrome.

The main objective is to determine the short-term effect of prone positioning in infants with infection-associated severe acute respiratory distress syndrome. To accomplish this, oxygenation parameters and measurements from EIT and LUS will be compared in mechanically ventilated infants in prone position versus supine position after surfactant administration.

Interventions

• Other Prone positioning
  Turn patient in prone position after surfactant administration.

Primary outcome measures

• Change in Oxygenation saturation index [Time frame: Change from baseline oxygenation saturation index at 6 hours]

Secondary outcome measures (3)

• Chang in Lung Ultrasound [Time frame: Change from baseline LUS score at 6 hours]
• Change in the Distribution of the End-Expiratory Lung Volume [Time frame: Change from baseline EELV at 6 hours]
• Change in the Distribution of the Tidal Volume [Time frame: Change from baseline tidal volume at 6 hours]

Eligibility criteria

Inclusion criteria

• Patients hospitalized at Pediatric Intensive Care Unit (PICU) or Neonatal Intensive Care Unit (NICU) of the Medical University Vienna.
• Patients aged >36 weeks (corrected gestational age) and <24 months.
• Patient intubated and mechanically ventilated for at least 6 hours, with an expected requirement of invasive ventilatory support for at least 12 hours.
• Clinical picture strongly suggestive for acute bronchiolitis or pneumonia (fever, fine crackles, prolonged expiration, lung hyperinflation and/or findings of new infiltrates consistent with acute pulmonary parenchymal disease on chest X-ray).
• Severe pediatric acute respiratory distress syndrome (ARDS), defined by OSI ≥12.3 (wean FIO2 to maintain SpO2 ≤ 97% to calculate oxygen saturation index).
• Written informed consent obtained from parents.

Exclusion criteria

• Clinical context

• Need for O2 supplementation to maintain SpO2>94% in the 4 weeks preceding hospitalization in the PICU/NICU
• Cyanotic congenital heart disease Cardiogenic pulmonary edema
• Severe pulmonary hypertension
• Untreated pneumothorax
• Severe neurological abnormalities
• Other severe congenital anomalies such as congenital diaphragmatic hernia
• Ongoing cardiopulmonary resuscitation or limitation of life support
• Contradictions for prone positioning (adapted from Guerin, C., et al., Prone positioning in severe acute respiratory distress syndrome. N Engl J Med, 2013. 368(23): p. 2159-68):

• Intracranial pressure >30 millimeters of mercury (mmHg) in supine position or cerebral perfusion pressure <60 mmHg
• Massive hemoptysis requiring an immediate surgical or interventional radiology procedure
• Tracheal surgery or sternotomy during the previous 15 days
• Serious facial trauma or facial surgery during the previous 15 days
• Deep venous thrombosis treated for less than 2 days
• Cardiac pacemaker inserted in the last 2 days
• Unstable spine, femur, or pelvic fractures
• Use of extracorporeal membrane oxygenation (ECMO) before inclusion
• Lung transplantation
• Burns on more than 20% of the body surface
• Other non-inclusion criteria

• Indication not to attempt resuscitation
• Patient already recruited for other clinical studies
• Patients who already received surfactant in the last 4 weeks
• Thoracic skin lesions or wounds on the thorax, where the EIT-electrode-belt would be placed

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Austria · 1 center

• Medical University of Vienna — Vienna

Publications

• Cheifetz IM. Pediatric ARDS. Respir Care. 2017 Jun;62(6):718-731. doi: 10.4187/respcare.05591. PMID 28546374
• Khemani RG, Smith L, Lopez-Fernandez YM, Kwok J, Morzov R, Klein MJ, Yehya N, Willson D, Kneyber MCJ, Lillie J, Fernandez A, Newth CJL, Jouvet P, Thomas NJ; Pediatric Acute Respiratory Distress syndrome Incidence and Epidemiology (PARDIE) Investigators; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Paediatric acute respiratory distress syndrome incidence and epidemiology ( PMID 30361119
• Santschi M, Randolph AG, Rimensberger PC, Jouvet P; 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 Sep;14(7):e332-7. doi: 10 PMID 23842587
• Orloff KE, Turner DA, Rehder KJ. The Current State of Pediatric Acute Respiratory Distress Syndrome. Pediatr Allergy Immunol Pulmonol. 2019 Jun 1;32(2):35-44. doi: 10.1089/ped.2019.0999. Epub 2019 Jun 17. PMID 31236307
• Mok YH, Lee JH, Rehder KJ, Turner DA. Adjunctive treatments in pediatric acute respiratory distress syndrome. Expert Rev Respir Med. 2014 Dec;8(6):703-16. doi: 10.1586/17476348.2014.948854. Epub 2014 Aug 13. PMID 25119574
• Gattinoni L, Taccone P, Carlesso E, Marini JJ. Prone position in acute respiratory distress syndrome. Rationale, indications, and limits. Am J Respir Crit Care Med. 2013 Dec 1;188(11):1286-93. doi: 10.1164/rccm.201308-1532CI. PMID 24134414
• De Luca D, Cogo P, Kneyber MC, Biban P, Semple MG, Perez-Gil J, Conti G, Tissieres P, Rimensberger PC. Surfactant therapies for pediatric and neonatal ARDS: ESPNIC expert consensus opinion for future research steps. Crit Care. 2021 Feb 22;25(1):75. doi: 10.1186/s13054-021-03489-6. PMID 33618742
• Amigoni A, Pettenazzo A, Stritoni V, Circelli M. Erratum to: Surfactants in Acute Respiratory Distress Syndrome in Infants and Children: Past, Present and Future. Clin Drug Investig. 2017 Jul;37(7):711. doi: 10.1007/s40261-017-0544-x. No abstract available. PMID 28589372

Identifiers

NCT: NCT05002478 · 1426/2021

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗