High Frequency Oscillatory Ventilation Combined With Intermittent Sigh Breaths: Effects on Lung Volume Monitored by Electric Tomography Impedance.

NCT01962818 | Completed

• 1 other identifier: 1936M
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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. Electric Impedance Tomography (EIT) enables measurement and mapping of regional ventilation distribution and end-expiratory lung volume (EELV). EIT generates cross-sectional images of the subject based on measurement of surface electrical potentials resulting from an excitation with small electrical currents and has been shown to be a valid and safe tool in neonates. Purpose, aims:

• To compare HFOV-sigh with HFOV-only and determine if there is a difference in global and regional EELV (primary endpoints) and spatial distribution of ventilation measured by EIT
• To provide information on feasibility and treatment effect of HFOV-sigh to assist planning larger studies. We hypothesize that EELV during HFOV-sigh is higher, and that regional ventilation distribution is more homogenous. 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. 16 ECG-electrodes for EIT recording will be placed around the chest at study start. Each recording will last 180s, and will be done at baseline and at 30 and 50 minutes after each change in ventilator modus. Feasibility No information of EIT-measured EELV in babies on HFOV-sigh exists. This study is a pilot-trial. In a similar study-protocol of lung recruitment during HFOV-sigh using "a/A-ratio" as outcome, 16 patients was estimated to be sufficient to show an improvement by 25%. This assumption was based on clinical experience in a unit using HFOV-sigh routinely. As the present study examines the same intervention we assume that N=16 patients will be a sufficient sample size. We estimate to include this number in 6 months.

Conditions

Respiratory Distress Syndrome In Premature Infants; Bronchopulmonary Dysplasia; Ventilator-Induced Lung Injury; Functional Residual Capacity

Keywords

Respiratory Distress Syndrome In Premature Infants; Bronchopulmonary Dysplasia; Ventilator-Induced Lung Injury; Functional Residual Capacity; Electric impedance tomography

Outcome Measures

Primary Outcomes (2)

• Global changes in end expiratory lung volume (EELV)

  Relative difference in EELV expressed as difference in end-expiratory lung impedance during HFOV-only and HFOV-sigh

  all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.

• Regional ventilation distribution

  Relative difference in regional EELV during HFOV-sigh vs HFOV-only expressed as change in regional end-expiratory lung impedance in predefined regions of interests (ROI), such as e.g. ventral, mid-ventral, mid-dorsal and dorsal lung areas.

  all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.

Secondary Outcomes (6)

• Global changes in oscillatory volume (Vosv):

  all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.

• Regional difference in oscillatory volume

  all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.

• Regional distribution of sigh-breaths volume

  all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.

• Global inhomogeneity index

  all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.

• Phase angle analyses

  all data for the outcome is collected on the study day. Calculations and analyses will be done within 6 months from the study day.

Study Arms (2)

HFOV-sigh at start

EXPERIMENTAL

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

HFOV-only at start

EXPERIMENTAL

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

Interventions

HFOV combined with sigh breaths OTHER

It is planned 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

HFOV-only at start; HFOV-sigh at start

Eligibility Criteria

• Age: 24 Weeks - 44 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• Poor skin integrity precluding use of adhesive ECG electrodes used for EIT monitoring.
• The physician responsible for the baby considers one of the ventilation modes unsuitable for the infant or the patient unsuitable for EIT monitoring.
• Lack of parental signed written informed consent or if both parents are under 18 years of age (due to complexities of obtaining consent).

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (1)

Department of Neonatology, Mater Mothers Hospital

Brisbane, Queensland, 4101, Australia

Location

MeSH Terms

Conditions

Respiratory Distress Syndrome In Premature Infants; Bronchopulmonary Dysplasia; Ventilator-Induced Lung Injury

Condition Hierarchy (Ancestors)

Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Christian Heiring, neonatologist

  Department of Neonatology, Rigshospitalet, Copenhagen

  PRINCIPAL INVESTIGATOR

• Luke Jardine, neonatologist

  Department of Neonatology, Mater Mothers Hospital, Brisbane, Australia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Neonatologist

Study Record Dates

• First Submitted: October 9, 2013
• First Posted: October 14, 2013
• Study Start: January 1, 2014
• Primary Completion: July 1, 2018
• Study Completion: January 1, 2023
• Last Updated: March 22, 2023

Record last verified: 2023-03

Locations

AU (1)