Skip to main content
Clinical Trials/NCT01959009
NCT01959009UnknownNot Applicable

Does High Frequency Oscillatory Ventilation Combined With Intermittent Sigh Breaths Improve Oxygenation Compared to High Frequency Oscillatory Ventilation Without Sigh Breaths in Neonates?

Rigshospitalet, Denmark2 sites in 1 country16 target enrollmentStarted: August 2014Last updated:
Conditions

Trial Snapshot

Phase
Not Applicable
Enrollment
16
Locations
2
Primary Endpoint
Delta-a/A-ratio

Study Overview

Brief Summary

Background:

Ventilator induced lung injury (VILI) remains a problem in neonatology. High frequency oscillatory ventilation (HFOV) provides effective gas exchange with minimal pressure fluctuation around a continuous distending pressure and therefore small tidal volume. Animal studies showed that recruitment and maintenance of functional residual capacity (FRC) during HFOV ("open lung concept") could reduce lung injury.

"Open lung HFOV" is achieved by delivering a moderate high mean airway pressure (MAP) using oxygenation as a guide of lung recruitment. Some neonatologists suggest combining HFOV with recurrent sigh-breaths (HFOV-sigh) delivered as modified conventional ventilator-breaths at a rate of 3/min. The clinical observation is that HFOV-sigh leads to more stable oxygenation, quicker weaning and shorter ventilation. This may be related to improved lung recruitment. This has however to our knowledge not been tested in a clinical trial using modern ventilators.

Purpose, aims:

  • To compare HFOV-sigh with HFOV-only and determine if there is a difference in oxygenation expressed as a/A-ratio and/or stability of oxygenation expressed as percentage time with oxygen saturation outside the reference range.
  • To provide information on feasibility and treatment effect of HFOV-sigh to assist planning larger studies. We hypothesize that oxygenation is better during HFOV-sigh.

Methods:

Infants at 24-36 weeks corrected gestational age already on HFOV are eligible. Patients will be randomly assigned to HFOV-sigh (3 breaths/min) followed by HFOV-only or vice versa for 4 alternating 1-hours periods (2-treatment, double crossover design, each patient being its own control). During HFOV-sigh set-pressure will be reduced to keep MAP constant, otherwise HFOV will remain at pretrial settings. Outcome will be calculated from normal clinical parameters including pulx-oximetry and transcutaneous monitoring of oxygen and carbon-dioxide partial pressures.

Detailed Description

High frequency oscillatory ventilation (HFOV) has been used in neonatal respiratory care for more than three decades. HFOV provides effective gas exchange with minimal pressure fluctuation around a set mean airway pressure (MAP) functioning as a continuous distending pressure (CDP), and low tidal volume compared to conventional ventilation (CV). HFOV was therefore thought to be able to reduce the risk of bronchopulmonary dysplasia in ventilated preterm babies. However results from randomized controlled trials comparing HFOV with conventional ventilation have been conflicting and meta-analyses have not shown clear evidence that HFOV is safer or more effective than conventional ventilation neither when used as initial strategy nor as rescue strategy in preterm babies with respiratory distress syndrome (RDS). Consequently there are no absolute indications for HFOV in preterm babies and most neonatologists today use HFOV as a rescue mode when conventional ventilation is failing in the acute setting of RDS as well as in the baby with bronchopulmonary dysplasia.

Maintaining adequate functional residual capacity (FRC) together with the fraction of inspired oxygen FiO2 are the main determinants of oxygenation. The larger the FRC, the larger is the volume of available oxygen in the alveoli for gas transport. Adequate oxygen saturation (SAT) of the blood in room air or an improvement in oxygen-saturation without changing the fraction of inspired oxygen can be seen as an indirect indicator of normal or normalized FRC, and most neonatologists use oxygenation as an indirect marker for lung volume during HFOV.

The CDP or set-MAP is the main determinant of lung-aeration during HFOV. A too low MAP may cause non-homogenous aeration and atelectasis leading to atelectotrauma and redirection of airflow to more compliant alveoli leading to localized hyperinflation.

Accordingly, early animal studies showed that recruitment and maintenance of FRC during HFOV could reduce lung injury. Lung recruitment was initially achieved by superimposing conventional ventilation (CV) breaths on top of HFOV with lower MAP than used today, either as recurrent sustained inflations lasting 15-20 seconds about every 20 minute, as intermittent sigh breaths (3-5 tidal breaths pr minute) delivered as normal conventional breaths or as conventional ventilation at normal rate combined with HFOV.

Today most neonatologists perform this so-called "open lung" concept by adjusting the set-MAP using oxygenation as an indirect guide of lung recruitment. Different approaches are used explained by difficulties in direct bedside monitoring of FRC. Some initiate HFOV with MAP 2-3 cm H2O above the MAP needed during conventional ventilation subsequently adjusting MAP until the fraction of inspired O2 (FiO2) <0.25-0.6 providing no signs of over inflation of the lungs on x-ray. Others go through a more complex step-wise increase in MAP till FiO2 cannot be reduced further, and then gradually decrease MAP until FiO2 again needs to be increased to maintain a predefined SAT and then continues ventilations with a MAP set at 2 cm H2O above this point, thereby placing ventilation on the more compliant deflation limb of the pressure-volume relationship of the lung.

Study Design

Study Type
Interventional
Allocation
Randomized
Intervention Model
Crossover
Primary Purpose
Treatment
Masking
None

Eligibility Criteria

Ages
24 Weeks to 44 Weeks (Child)
Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Infants at 24-36 weeks corrected gestational age
  • Already ventilated with high frequency ventilation
  • Requiring FiO2=21%-70% to maintain adequate oxygen saturation.
  • Clinical stable
  • o i.e. ventilated on current settings for more than just a few hours with stable but not necessarily normalized blood gases or transcutaneous values and oxygen requirement.
  • Parent(s) or guardian able and willing to provide informed consent

Exclusion Criteria

  • Major congenital cardiovascular or respiratory abnormalities.
  • The attending neonatologist responsible for the baby considers one of the ventilation modes unsuitable for the infant.
  • Poor skin integrity precluding use of transcutaneous monitoring.
  • Lack of parental signed written informed consent.
  • Parents under 18 years of age.

Outcomes

Primary Outcomes

Delta-a/A-ratio

Time Frame: on study day

a/A-ratio calculated as a/A-ratio= TcPO2/(0,95\*FiO2- TcPCO2) By delta-a/A-ratio means the difference in a/A-ratio between the two modes of ventilation, as an indirect measure of lung recruitment.

stability of oxygen saturation

Time Frame: on study day

The difference in area-under-the-curve for "out of range" for oxygen saturation (based on accepted general reference ranges for the given gestational age).

Secondary Outcomes

  • Partial pressure of CO2(on study day)
  • heart rate(on study date)
  • FiO2(on study day)
  • Partial pressure of O2(on study date)

Investigators

Sponsor Class
Other
Responsible Party
Principal Investigator
Principal Investigator

Christian Heiring

Neonatologist

Rigshospitalet, Denmark

Study Sites (2)

Loading locations...

Similar Trials