Optimising HFO&VTV in Newborn Infants

Mechanical ventilation (MV) is life saving for infants requiring respiratory support in the newborn period but its use has been associated with complications. High frequency oscillation (HFO) is a type of MV that delivers small volumes of gas across the lungs at fast frequencies. HFO is a lung protective strategy but it has also been linked to brain injury due to low carbon dioxide tensions. High-frequency oscillation with volume-targeted ventilation (HFO\&VTV) is a new mode of HFO in which the clinician sets a target volume of gas to be delivered to the lungs at fast rates to decrease the lung injury related to the ventilator. Further, HFO\&VTV achieves better control of carbon dioxide levels and may therefore protect against brain injury. Currently, there are no written guidelines about the use of HFO\&VTV. This study aim to determine the safety profile of HFO\&VTV compared to HFO by comparing the velocity of blood flow to the brain in term born infants and the cardiac output in term and preterm infants during the two modes. The investigators will also determine the optimum starting value of the target tidal volume during HFOV\&VTV. Infants will be studied at three different target tidal volumes for a period of 10-20 minutes each. A cranial ultrasound (for term infants only) and bedside echocardiogram will be performed at the end of each period.

This is a single centre, randomised cross-over trial in newborn infants requiring high-frequency oscillatory ventilation (HFOV) at any postnatal age. Infants with known intracerebral pathology (stroke, hydrocephalus, intracerebral haemorrhage, severe HIE) and congenital cardiac abnormalities will be excluded from the study. In preterm infants cerebral blood flow will not be studied as there is no clear evidence for the significance of the resistive index (RI) in the cerebral arteries to predict brain injury and neurodevelopmental outcomes.

The research team will identify infants based on the inclusion criteria and approach parents to discuss the study and provide information leaflets.

The investigators aim to recruit a minimum of 25 infants (13 preterm and 12 term infants) over 18 months.

Informed written consent will be requested from the parents or legal guardians of the infants and the attending Neonatal Consultant will be requested to verbally assent to the study.

All infants will be oscillated using SLE6000 ventilators. Ventilation settings will be adjusted by the clinical team as per unit's protocol.

Infants will be studied when clinically stable and a blood gas confirms that the carbon dioxide (CO2) levels are in the target range (4.5 to 6.5 kPa). Participants will receive HFO\&VTV at targeted tidal volumes of 1.5, 2.0 and 2.5 ml/kg in random order for a period of 10-20 minutes each. Additionally, there will be a control period of 20 minutes between each tidal volume when infants will be switched to HFOV without volume-guarantee at the settings applied prior to the study. The order in which they receive the different levels of tidal volumes will be randomised using an excel random number generator.

Transcutaneous CO2 monitoring will be applied to the infants during the study. The resistive index (RI) as an indicator of cerebral blood flow in term infants and the cardiac output of all paticipants will be assessed at the last five minutes of each twenty-minute period. Measurements of the RI and the cardiac output will also be made during the last five minutes of the control periods and the results will be averaged.

The nurse to patient ration will be according to the unit's protocol that is determined on the patient's acuity.

The investigators will also record basic epidemiologic parameters such as sex, gestational age, birth weight, mode of delivery, Apgar scores, administration of surfactant, day of life at study, mechanical ventilation starting time and HFO starting time, and initial diagnosis.

Eligibility Criteria:
Inclusion Criteria:

-Newborn infants of any gestation receiving high frequency oscillatory ventilation

Exclusion Criteria:

* Infants with known intracerebral pathology (stroke, hydrocephalus, intracerebral hemorrhage, severe hypoxic ischemic encephalopathy).
* Infants with congenital cardiac abnormalities.