Markers of Inflammation and Lung Recovery in ECMO Patients for PPHN

The primary hypothesis is that damage to red blood cells by the exposure to the ECMO circuit will result in inflammatory responses that mitigate against successful weaning from Extra-Corporeal Membrane Oxygenation (ECMO) for Persistent Pulmonary Hypertension of the Newborn (PPHN).

The secondary hypothesis are:

• Damage to red cells will result in platelet, leukocyte and endothelial activation.
• Markers of platelet, endothelial and leukocyte activation are indicators of lung inflammation and injury severity and hence lung recovery.
• Markers of platelet, endothelial and leukocyte activation are indicators of kidney injury severity and hence acute kidney injury.
• The level of oxidative stress will correlate with type shifts in pulmonary macrophages, tissue iron deposition and organ injury.
• Ability to raise anti-oxidative response, measured by Heme Oxigenase-1 (HMOX 1) expression, will correlate with shorter intubation times and less severe kidney and lung injury.
• Granulocyte and platelets activation are secondary to rising redox potential and the levels of activation will correlate with longer intubation times and more severe organ injury.
• Markers of anti-oxidative response, platelet, endothelial and leukocyte activation, as well as oxidative stress levels have diagnostic and prognostic utility for the prediction of key clinical events including delayed time to recovery, acute kidney injury in paediatric patients undergoing Extra-Corporeal Membrane Oxygenation (ECMO) for Persistent Pulmonary Hypertension of the Newborn (PPHN).

This is a pilot feasibility study that will establish the following:

• Recruitment rates and patient flows for 24 patients specified as the target population for the feasibility study
• Withdrawal rate, and completeness of follow-up and data collection in a paediatric population at high risk for death and major morbidity
• The proportions (categorical data) and variance (continuous data) for the primary and secondary outcomes of interest. These will be used to model the sample sizes and outcomes that may be used in a definitive study
• Perceptions of family members whose children participate in the study as to the appropriateness of the screening and consent process

Inclusion criteria

• Patients with a diagnosis of PPHN
• Patients that require ECMO support as determined by the ECMO team
• Patients aged less than 30 days
• Emergency consent obtained within 12 hours from cannulation, and ultimately full consent

Exclusion criteria

• PPHN is caused by a congenital heart pathology
• ECMO is required for a congenital heart disease
• Lack of consent