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

NCT01959009 | Unknown

• 1 other identifier: H-2-2012-167
• 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. 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.

Conditions

Respiratory Distress Syndrome, Newborn; Bronchopulmonary Dysplasia; Ventilator Induced Lung Injury

Keywords

newborn, lung disease, mechanical ventilation, lung recruitment, high frequency ventilation

Outcome Measures

Primary Outcomes (2)

• Delta-a/A-ratio

  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.

  on study day

• stability of oxygen saturation

  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).

  on study day

Secondary Outcomes (4)

• FiO2

  on study day

• Partial pressure of CO2

  on study day

• heart rate

  on study date

• Partial pressure of O2

  on study date

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

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

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:

• 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.

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (1)

Department of Neonatology, Rigshospitalet

Copenhagen, 2100, Denmark

Location

MeSH Terms

Conditions

Respiratory Distress Syndrome, Newborn; Bronchopulmonary Dysplasia; Ventilator-Induced Lung Injury; Lung Diseases

Condition Hierarchy (Ancestors)

Respiratory Distress Syndrome; Respiratory Tract Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lung Injury

Study Officials

• Christian Heiring, md

  Rigshospitalet, Denmark

  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 7, 2013
• First Posted: October 9, 2013
• Study Start: August 1, 2014
• Primary Completion: June 1, 2022
• Study Completion: June 1, 2022
• Last Updated: October 20, 2020

Record last verified: 2020-10

Locations

DK (1)