High Frequency Oscillatory Ventilation Combined With Intermittent Sigh Breaths: Effects on Blood Oxygenation and Stability of Oxygenation

This study is not yet open for participant recruitment.
Verified October 2013 by Rigshospitalet, Denmark
Sponsor:
Information provided by (Responsible Party):
Christian Heiring, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT01959009
First received: October 7, 2013
Last updated: October 8, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention
Respiratory Distress Syndrome, Newborn
Bronchopulmonary Dysplasia
Ventilator Induced Lung Injury
Other: HFOV combined with sigh breaths

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Does High Frequency Oscillatory Ventilation Combined With Intermittent Sigh Breaths Improve Oxygenation Compared to High Frequency Oscillatory Ventilation Without Sigh Breaths in Neonates?

Resource links provided by NLM:


Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • Delta-a/A-ratio [ Time Frame: on study day ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • FiO2 [ Time Frame: on study day ] [ Designated as safety issue: No ]
    Difference in fraction of inspired oxygen between the two ventilator modes

  • Partial pressure of CO2 [ Time Frame: on study day ] [ Designated as safety issue: No ]
    Difference in transcutaneous pCO2 between the two ventilator modes

  • heart rate [ Time Frame: on study date ] [ Designated as safety issue: No ]
    Difference in heart rate between the two ventilator modes

  • Partial pressure of O2 [ Time Frame: on study date ] [ Designated as safety issue: No ]
    Difference in partial pressure of oxygen measured transcuteneously between the two ventilator modes


Estimated Enrollment: 16
Study Start Date: November 2013
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HFOV-sigh at start

Each patient will be exposed to either HFOV alone (HFOV-only) or HFOV combined with sigh breaths (HFOV-sigh), but in different order.

MAP=mean airway pressure.

DURING HFOV-SIGH:

  • Frequency 3 breaths/min
  • Ti = 1s
  • Peak inspiratory pressure (PIP) = 30 cm H2O

For patients already on HFOV-sigh at study start:

• MAP-set will be left unchanged at pre-trial settings.

For patients on HFOV-only at study start:

• During periods with superimposed sigh breaths, MAP-set will be reduced in accordance with a calculation of MAP aiming to keep average mean airway-pressure (MAP) unchanged. (MAP=(PIP*Tinsp+PEEP*Texp)/(Tinsp+Texp)

DURING HFOV-ONLY

For patients on HFOV-sigh at study start:

• During HFOV-only, the MAP-set will be increased in accordance with a calculation of MAP, aiming to keep average mean airway-pressure (MAP) unchanged.

For patients on HFOV-only at study start:

• MAP-set will be left unchanged at pre-trial settings.

Other: HFOV combined with sigh breaths

We plan only to investigate infants already ventilated on the HFOV-modus on high frequency oscillators, where the HFOV modus can be superimposed on conventional modes of ventilation. This gives the opportunity to combine HFOV with intermittent sigh breaths with a pre-set frequency and pre-set peak inspiratory pressure (PIP) and thus comparing HFOV combined with sigh breaths (HFOV-sigh) with conventional HFOV (HFOV-only).

All included participants will be exposed to the two different ventilator strategies tested in this trial, albeit in alternating and different order.

Each patient will serve, as it's own control. The trial will involve four alternating 1-hours periods allowing a sufficient "wash-out" period, as it has been shown that alveolar recruitment and derecruitment may take up to 25 min after changes to ventilator pressures At study start the patients will randomly be assigned to either starting with HFOV-only or HFOV-sigh

Experimental: HFOV-only at start

Each patient will be exposed to either HFOV alone (HFOV-only) or HFOV combined with sigh breaths (HFOV-sigh), but in different order.

MAP=mean airway pressure.

DURING HFOV-SIGH:

  • Frequency 3 breaths/min
  • Ti = 1s
  • Peak inspiratory pressure (PIP) = 30 cm H2O

For patients already on HFOV-sigh at study start:

• MAP-set will be left unchanged at pre-trial settings.

For patients on HFOV-only at study start:

• During periods with superimposed sigh breaths, MAP-set will be reduced in accordance with a calculation of MAP aiming to keep average mean airway-pressure (MAP) unchanged. (MAP=(PIP*Tinsp+PEEP*Texp)/(Tinsp+Texp)

DURING HFOV-ONLY

For patients on HFOV-sigh at study start:

• During HFOV-only, the MAP-set will be increased in accordance with a calculation of MAP, aiming to keep average mean airway-pressure (MAP) unchanged.

For patients on HFOV-only at study start:

• MAP-set will be left unchanged at pre-trial settings.

Other: HFOV combined with sigh breaths

We plan only to investigate infants already ventilated on the HFOV-modus on high frequency oscillators, where the HFOV modus can be superimposed on conventional modes of ventilation. This gives the opportunity to combine HFOV with intermittent sigh breaths with a pre-set frequency and pre-set peak inspiratory pressure (PIP) and thus comparing HFOV combined with sigh breaths (HFOV-sigh) with conventional HFOV (HFOV-only).

All included participants will be exposed to the two different ventilator strategies tested in this trial, albeit in alternating and different order.

Each patient will serve, as it's own control. The trial will involve four alternating 1-hours periods allowing a sufficient "wash-out" period, as it has been shown that alveolar recruitment and derecruitment may take up to 25 min after changes to ventilator pressures At study start the patients will randomly be assigned to either starting with HFOV-only or HFOV-sigh


  Show Detailed Description

  Eligibility

Ages Eligible for Study:   24 Weeks to 44 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01959009

Contacts
Contact: Christian Heiring, MD +4522174087 cheiring@gmail.com
Contact: Gorm Greisen, professor +4535451326 greisen@regionh.dk

Locations
Denmark
Department of Neonatology, Rigshospitalet Not yet recruiting
Copenhagen, Denmark, 2100
Contact: Christian Heiring, md    +4522174087    cheiring@gmail.com   
Principal Investigator: Christian Heiring, md         
Sponsors and Collaborators
Rigshospitalet, Denmark
Investigators
Principal Investigator: Christian Heiring, md Rigshospitalet, Denmark
  More Information

No publications provided

Responsible Party: Christian Heiring, Neonatologist, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT01959009     History of Changes
Other Study ID Numbers: H-2-2012-167
Study First Received: October 7, 2013
Last Updated: October 8, 2013
Health Authority: Denmark: The Regional Committee on Biomedical Research Ethics

Keywords provided by Rigshospitalet, Denmark:
newborn, lung disease, mechanical ventilation, lung recruitment, high frequency ventilation

Additional relevant MeSH terms:
Thoracic Injuries
Bronchopulmonary Dysplasia
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Lung Injury
Wounds and Injuries
Ventilator-Induced Lung Injury
Lung Diseases
Respiratory Tract Diseases
Infant, Premature, Diseases
Infant, Newborn, Diseases
Respiration Disorders

ClinicalTrials.gov processed this record on April 16, 2014