Flow-cycled Ventilation in Preterm Infants
Condition: Neonatal Respiratory Distress Syndrome
MeSH terms: Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Hyaline Membrane Disease; Syndrome
Study type: Interventional

Summary: 
      This short pilot study is to assess the tolerance of preterm infants, born below 32 weeks
      gestation with respiratory distress syndrome, to flow-cycle ventilation, and see if infants
      require less overall pressure from the ventilator than the usual conventional settings used,
      with the aim of providing data to construct a larger trial looking at the longer term outcome
      of these infants using this type of ventilation in the future.

      Many preterm infants at these gestations require assistance from a ventilator due to the
      immaturity of their lungs. The lungs of preterm infants are susceptible to damage, especially
      if high pressures are needed or prolonged periods of ventilation. There is concern that if
      the infant's breathing pattern does not synchronise with the ventilator, this causes
      additional distress, longer duration of ventilation needed and increased risk of
      complications. Over the past 20 years, a different type of ventilation, known as flow-cycle
      ventilation, has been trialed, with limited use in preterm infants. This allows the baby to
      determine the duration of breathing in and out and how many breaths they require per minute.
      This would help babies to synchronise better with the ventilator, and consequently require
      less pressure from the ventilator.

      This pilot study is being conducted at St. Mary's Hospital, Manchester. All babies born under
      32 weeks gestation, with a stable respiratory effort, will be eligible for consideration for
      the study. The study will last no longer than 5 hours and involve the babies receiving
      different pressures from the ventilator in flow-cycle mode for 1-hour epochs. Blood gases
      after each epoch and continuous ventilator data will be downloaded to assess their tolerance
      on the different settings, before being returned to the usual conventional settings used on
      the unit. The babies will have continuous monitoring throughout as per standard neonatal
      intensive care.
    

Detailed description: 
      This study will be conducted as a short term, crossover study, where each infant will act as
      his or her own control and undertake all interventions within this study. The study is broken
      down into two parts in order to answer the two secondary research questions.

      The limited studies looking at flow-cycled ventilation in preterm babies have been set up in
      a similar manner. Making each infant its own control limits the number of infants needed for
      this pilot study.

        1. Prior preparations regarding protocol design

           The protocol has already been reviewed by the University of Leeds, by paper submission
           and viva to determine the suitability of the project from an educational point of view
           and suitability for the restricted time frame and resources available. Discussions with
           the neonatal unit technical support staff have already been undertaken to ensure that
           the study ventilators (an exact model to that used on the unit, but mobile) are
           configured with the required backup ventilation mode, to maintain the required level of
           breathing support, safety alarms and settings checked and the Eview box (device which
           allows the collection of data about the baby from the ventilator) installed as per
           manufacture guidelines.

           Training has also been given to the Principal investigator on the setup and maintenance
           of the study ventilator (the principal investigator is also a member of the clinical
           team who uses these ventilators on a daily basis and aware of how they are used).

        2. Prior clinical care given & assessment for eligibility

           Prior to the study, eligible babies would have had a breathing tube inserted and
           surfactant medication given due to concerns with underdeveloped / immature lungs,
           fitting with being born at an early gestation. They would be receiving breathing support
           from the Engstrom Carestation Version 5.X (GE Healthcare) ventilator, the same
           ventilator used for the study, and would have received a dose of caffeine citrate
           intravenously to aid the infant's breathing drive, in line with unit policy and
           international consensus on managing respiratory distress syndrome in preterm infants.
           The clinical team may have deemed it necessary for monitoring and blood sampling to have
           inserted a catheter into one of the infant's arteries (an arterial line), though this is
           not a requisite for the study, but would be used for monitoring and sampling during the
           study if the infant was suitable. As per routine practice, the infants will have two
           methods of monitoring at all times. This would monitor oxygen saturations and heart rate
           as well as having monitoring on for blood pressure, breathing rate and temperature where
           deemed necessary.

           As both of the Principal and Chief Investigators are members of the clinical team on the
           neonatal intensive care unit at St. Mary's Hospital, it is easy to highlight suitable
           infants for the study from the patient lists and admissions to the unit, though prior
           discussion will take place with the attending neonatal team to discuss suitability. For
           any infant deemed potentially suitable after discussion with the attending clinical
           team, a parent information leaflet will be given to the parents at the time of greeting
           & introducing the study, after they have received an update on their baby's progress to
           date. As much time as possible will be allowed between this introduction and any attempt
           to answer questions and obtain written consent (minimum one hour) to allow the parents
           uncoerced thinking time.

           During this time, the research team will corroborate with the attending nurse /
           clinician and review the clinical data on the infant, including the x-rays done up until
           this time, the nursing observations and blood gas results, in order to assess for the
           inclusion and exclusion criteria. An eligibility form will be completed and signed by
           both a member of the research team and clinical team to ensure an agreement of
           eligibility. If there are concerns, the infant will not be recruited at this time.

           At an appropriate time for the parents, they will be approached by the Principal or
           Chief Investigator and any questions answered about the study. The research team will
           have to be happy that the parents have understood the information, implications,
           alternatives and are free to make a choice (as well as being eligible to consent
           legally). If the infant is suitable, a consent form will be completed. Randomisation
           will then occur by taking a sealed study envelope from the study box to find out which
           order they will undertake the different parts of the trial, and will be allocated a
           study number, which will be used on all documentation pertaining to the study, to ensure
           anonymity. (The study box would already have been pre-made with sealed envelopes
           containing information that has been generated from a random number database. The
           process of randomisation prevents there from being any influence on the final results
           purely due to the order in which the study parts are undertaken, making the study more
           robust to analyse. This has been a previous concern with other studies in the
           literature).

           The study ventilator (an exact model of the ventilator used on the unit) will be set up
           and safety checks undertaken, as well as the Eview box (the box which allows the
           ventilator data to be extracted and analysed though has no interference with the working
           of the ventilator itself) installed, safety back-up modes enabled to ensure that the
           infant has sufficient breathing support from the ventilator in the event that they do
           not maintain a strong breathing pattern, and the study number and weight of the child be
           accurately entered into the ventilator by the research team.

           The researcher will then examine the infant to ensure that the time of commencing the
           study the infant still satisfies the criteria for inclusion and is deemed 'stable' and a
           blood gas sample will be taken from the baby (either from the pre-sited arterial line if
           available or from the capillaries in the foot according to standard practice; distress
           and amount of blood will be minimised and should not cause any instability). This sample
           will be analysed by the machines routinely used on the intensive care unit, and any
           other blood tests that the infant may need (e.g. blood sugar monitoring, which is
           usually done every 2-4 hours at this stage) will be performed at the same time / on the
           same sample of blood (if possible) to minimise distress and interventions. A special
           nursing observation chart will be commenced at this time by the attending nurse /
           research team, recording the routine observations that any ventilated infant would
           require. This first set of observations (on the pre-study ventilator settings) would be
           the baseline settings, allowing any deviation from this stability to be highlighted and
           acted upon early.

        3. First part of study

           The infant would be switched onto the study ventilator, a process which takes less than
           a second, and involves disconnecting the old ventilator tubing from the breathing tube
           reconnecting it to the new ventilator tubing. This is necessary in order for Eview box
           to work (the original ventilator would have to be turned off for a short period of time,
           which would not be ethical to leave the baby without controlled breathing support). Care
           would be taken not to dislodge the breathing tube whilst the infant was examined to
           ensure that the chest was rising and that the ventilator was receiving data from the
           infant. The time on the ventilator would be noted down on the observation chart to aid
           with data analysis later.

           Depending on randomisation, the infant would either receive a high pressure or low
           pressure from the study ventilator.

             -  All other settings would match those that the infant was on beforehand where
                possible. (The high and low pressures are pre-set based on what pressure the infant
                was requiring before the study with either 80% of this (low pressure) or 120% of
                this (high pressure) these limits are deemed to be safe and within acceptable
                clinical practice).

             -  The infant would remain on this setting for 1 hour.

             -  Their nursing observations will be recorded every 15 minutes, including a blood
                pressure if they did not have an arterial line to read it continuously (this is not
                unusual practice as the baby would receive this intensity of observation if they
                were having a blood transfusion).

           After the end of the hour, a blood gas would be taken, and the ventilator would be
           switched to the other setting (either low pressure, if the infant previously received
           high pressure, or vice versa). The same process would be repeated in terms of the
           timings and observations taken. The time on the ventilator would be noted for analysis
           purposes when the pressures were switched.

           After the second hour, the blood gas would be repeated and the infant placed back on the
           initial ventilator, on a setting appropriate for the condition of the infant at that
           time. This completes the first part of the study and the infant would resumed routine
           care for a least an hour. A blood gas would be taken after 1 hour as per usual
           convention to ensure that they are stable and settled back onto the initial ventilator.

        4. Second part of the study

           After 1 hour back on the standard ventilator, the infant would be reassessed to ensure
           that they were stable. If this is the case, as stated above, a blood gas would be taken
           and part two of the study commenced. The observations recorded would provide a baseline
           for the second part of the study. The infant would once again be switched back to the
           study ventilator and time noted.

           Depending on the initial randomisation, the infant would either receive time-cycled
           ventilation (the usual convention) or flow-cycled ventilation (as in part one of the
           study) from the study ventilator.

             -  All other settings would match those that the infant was on beforehand where
                possible.

             -  The infant would remain on this setting for 1 hour.

             -  Their nursing observations will be recorded every 15 minutes, including a blood
                pressure if they did not have an arterial line to read it continuously.

           After the end of the hour, a blood gas would be taken, and the ventilator would be
           switched to the other setting (either flow-cycled, if the infant previously received
           time-cycled, or vice versa). The same process would be repeated in terms of the timings
           and observations taken.

           The time on the ventilator would be noted for analysis purposes when the pressures were
           switched.

           After the second hour, the blood gas would be repeated and the infant placed back on the
           initial ventilator, on a setting appropriate for the condition of the infant at that
           time. This completes the second and final part of the study and the infant would resume
           routine care for the duration of their stay on the unit. A blood gas would be taken
           after 1 hour as per usual convention to ensure that they are stable and settled back
           onto the initial ventilator.

        5. After completion of study

           After the study had been completed, there would be a handover of care back to the
           attending clinical team with update to the clinical team and parents (if present)
           regarding the clinical condition of the baby.

           Regarding the data, the encrypted flash disk will be removed from the study ventilator
           and the data downloaded on an NHS computer on the unit. This data, along with the
           nursing observation charts and blood gas results, will then be reviewed by the
           independent consultant neonatologist for safety and quality assurance prior to a second
           baby undergoing the study.

           The researcher is responsible for ensuring that the study ventilator is cleaned
           appropriately in line with the manufactures and unit guidelines and is ready for any
           future participants.

        6. Safety interventions

      These have been highlighted in the main issues question where there is a break from protocol
      due to safety concerns. It is clear in the protocol what needs to be done if there are
      concerns. Only one baby will undergo the study at any one time and any concerns will be
      reviewed by the researchers.
    

Intervention name(s): Flow-cycle ventilation; Time-cycle ventilation mode
Intervention type(s): Other; Other
Intervention description(s): Pressure support level set as per previous pressure requirements to deliver a tidal volume of 5ml/kg (the same pressure amount used as the peak inspiratory pressure in the time-cycled mode); Peak inspiratory pressure set to deliver 5ml/kg tidal volume, Rate set as per previous requirements
Other intervention name(s): Pressure-support ventilation; Synchronised Intermittent Mandatory Ventilation
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Flow-cycled pressure-support ventilation