Comparison of Automated Oxygen Control With and Without Automated Pressure Control in Preterm Ventilated Infants.
Condition: Oxygen Saturation Targetting in Preterm Ventilated Infants
MeSH terms: Premature Birth
Study type: Interventional

Summary: 
      This is a cross-over randomized study. Eligible participants are preterm infants born at less
      than 37 weeks gestation (23+0 to 36+6 weeks), who are receiving conventional mechanical
      ventilation through an endotracheal tube and have a need for supplemental oxygen at the time
      of enrolment. The planned sample size is 19 subjects completing the study with both arms (38
      study periods). The objective of this crossover study is to evaluate the efficacy of the
      automatic oxygen control function with or without Volume Guarantee®(automatic control of
      ventilator pressure to deliver the set volume) mode of ventilation in keeping oxygen levels
      in the safe target range (90 to 95%) in ventilated preterm infants requiring oxygen therapy.
    

Detailed description: 
      Supplemental oxygen remains by far the most commonly used 'drug' in neonatal intensive care
      units. The goal of oxygen therapy is to maintain normal oxygenation while minimizing
      hyperoxaemia and hypoxemia. Preterm infants are particularly vulnerable to oxygen toxicity
      and oxidative stress leading to retinopathy of prematurity (ROP), bronchopulmonary dysplasia
      (BPD), and periventricular leukomalacia (PVL)[1]. Similarly, exposure to hypoxemic episodes
      can lead to increased mortality [2, 3]. Traditionally oxygen saturation (SpO2) targeting is
      carried out by manual adjustment of fraction of inspired oxygen (FiO2) by the caregiver.
      However, in practice this is only partially achieved during routine care[4]. Hagadorn et al
      conducted a study in 14 centres and showed that preterm infants under 28 weeks' gestation
      receiving oxygen spent on average only 48% of the time with SpO2 within the prescribed target
      range, about 36% of the time above and 16% of the time with SpO2 below the target range There
      was a wide and significant variation in SpO2 target range compliance between the
      participating centres[5].

      Preterm infants have frequent fluctuations in SpO2 due to their respiratory instability
      requiring frequent adjustments of FiO2 [6]. Consequently, these particularly vulnerable
      infants spend significant time with SpO2 outside intended range and are often exposed to
      extremes of hypoxemia and hyperoxaemia. To this end, it is now possible to have automated
      control of inspired oxygen using a device (CLiO2™) incorporated in Avea® ventilator. The
      safety, feasibility and efficacy of this device have already been established [7-12]. There
      has been further improvement in the algorithm of the pulse oximeter incorporated in Avea®
      ventilator to achieve a better normative distribution around the median SpO2 value[13].
      Automated control of FiO2 significantly improves compliance of oxygen saturation targeting
      and significantly reduces exposure to hypoxemia as well as hyperoxaemia [7-12, 14].

      Another mechanism of respiratory instability and hypoxemia is wide fluctuation in tidal
      volume in ventilated preterm infants. Volume-targeted modes of ventilation have been used for
      several years to aim to more accurately control the tidal volumes delivered to ventilated
      infants. Jain et al showed a reduction in duration of hypoxaemic events when using volume
      targeted ventilation as compared to pressure controlled ventilation[15]. Avea ventilators can
      deliver several types of volume-targeted ventilation, including Volume Guarantee® (VG) and
      volume controlled ventilation (VCV). VCV aims to deliver a set volume of gas irrespective of
      the lung compliance whereas VG® uses a servo-controlled feedback loop to automatically adjust
      inspiratory pressures to aim to control tidal volume delivery.

      There is no data available currently on whether automatic control algorithm adjustment of
      inspired oxygen and tidal volume together leads to further improvements in maintaining SpO2
      profile within prescribed target range and more importantly to reduce episodes of prolonged
      hypoxemia and hyperoxaemia in preterm ventilated infants. Hence the investigators propose
      this study.

      The aim of this study is to examine whether automatic control of inspired oxygen and tidal
      volume together leads to further improvements in maintaining SpO2 profile within the
      prescribed target range in preterm, ventilated infants.

      The objective is to evaluate the efficacy of the automatic oxygen control function with or
      without VG® (automatic control of ventilator pressure to deliver the set volume) mode of
      ventilation in keeping oxygen levels in the safe target range (90 to 95%) in ventilated
      preterm infants requiring oxygen therapy.

      This study will be conducted in a tertiary neonatal intensive care unit at the James Cook
      University Hospital, Middlesbrough, United Kingdom after approval by the Local Research
      Ethics Committee and the Institutional Review Board.

      This study will be completed over 2 consecutive 12-hour periods in randomly assigned sequence
      of automatic FiO2 control (CLiO2™) with VG® and automatic FiO2 control without VG®.

      The Automated FiO2 system CLiO2™ is integral to the Avea® infant ventilator (CareFusion,
      Yorba Linda, CA) and allows automated FiO2 adjustment aiming to maintain SpO2 within assigned
      target range using Radical neonatal pulse oximeter (Masimo, Irvine, CA). When first started
      it adopts the FiO2 previously set by the clinician as the initial 'Baseline FiO2' level.
      Thereafter, the changes to the FiO2 and their frequency depend on whether SpO2 is below,
      above or within the target range, the trend in SpO2 and all changes are proportionate to the
      'Baseline FiO2' level. FiO2 is reduced in a step wise fashion when SpO2 exceeds the target
      range. The step decrements in FiO2 result in a gradual reduction in the FiO2. When SpO2 falls
      below the target range the increments in FiO2 are generally larger and more frequent. These
      are proportionate to the difference between SpO2 and the target range and the declining or
      increasing trend in SpO2. The changes in FiO2 generally range between 0.01 and 0.05. Their
      frequency increases to achieve a faster rate of change of FiO2 and can be as frequent as one
      per second. The Baseline FiO2 level is gradually adjusted to changes in the infant's needs
      for FiO2 to keep SpO2 in range. The pulse oximeter default settings are normal sensitivity, 8
      second averaging time, 20 second alarm delay, and a tight alarm limit of 90% and 95% SpO2.
      Masimo neonatal probe (LNOP Neo-L) will be applied to the right wrist whenever possible. In
      the event of SpO2 signal loss (saturation 'dropouts') the fail-safe mechanism adjusts the
      backup FiO2 at the median level in the preceding 15 seconds, or to the baseline if higher.

      Volume Guarantee ventilation (VG)® is a volume-targeted mode of ventilation aimed at
      delivering the set tidal volume of gas by automatically adjusting the peak inspiratory
      pressure (PIP) on a breath-by-breath basis. Theoretically this should minimise variation in
      tidal volume delivery as lung compliance and the infant's condition changes. This function is
      achieved by an automated servo-controlled mechanism. The upper PIP limit can be set by the
      clinician as a safety mechanism. There is lack of data on VG® but it is thought to achieve
      comparable gas exchange at lower mean PIP levels[15].

      Volume-Controlled ventilation (VCV) is a type of 'volume targeted' mode. It aims to target be
      supported the desired tidal volume by delivering a set volume (chosen by the clinician)
      irrespective of the underlying lung mechanics. The ventilator will generate whatever peak
      inspiratory pressure is necessary to deliver this volume. There is constant inspiratory flow
      pattern (a square flow waveform) and peak volume and inspiratory pressure delivery are
      achieved at the end of inspiration. During 'control period' of 12 hours without VG, infants
      will using VCV A/C (assist control) as is our current clinical standard.

      Both VG® and VCV can be delivered to infants using the ventilators currently in use in our
      unit, the AVEA® ventilators (Carefusion, Yorba Linda, CA). All devices and equipment used for
      infants in either arm of the trial will be the same as those currently used on our unit. They
      will be used in line with Carefusion AVEA® ventilator systems operator's manual, L2786,
      revision M, July 2011.

      Verbal and written information (in the form of the Participant Information Sheet) about the
      trial will be offered to parents at the earliest opportunity after the infant has been
      intubated. It will only be offered after all other information about the medical care of
      their infant and the progress has been discussed with them and only if they wish to receive
      trial information at that time. Consent will not be obtained before any infant is born.

      After the infant has been intubated and ventilated, parents will be approached for
      participation consent only after relevant information about their infant's medical care and
      progress has been discussed. Parents will be offered written and verbal information about the
      trial. Parents giving consent for their baby to participate in the trial will be asked to
      sign a written consent form. Infants will only be randomised to either Volume Guarantee® or
      Volume-Controlled ventilation cross-over periods after obtaining written consent from
      parents.

      If the infants' respiratory care is escalated to non-conventional mode of ventilation for
      clinical reasons, the time spent in the 12 hour cross over would be determined. If the infant
      has spent at least 50% of the time in a cross-over, this would be considered acceptable and
      data used for analysis. If the infant has spent less than 50%, then parents will be
      approached again to revalidate the consent for the study when the infant is ready for
      conventional ventilation.

      When commencing Volume Guarantee® mode a setting of 5ml/kg will be the initial starting
      setting, with the option of decreasing to 4ml/kg or increasing to 6ml/kg as the clinical
      condition dictates. This is standard neonatal practice. Nursing allocation will remain at 1:1
      (one nurse caring for 1 intensive care infant) as is our standard clinical practice during
      the study period. Target SpO2 range of 90 to 95% will be applicable to both study periods as
      is our current clinical practice. All elective / planned procedures will be performed before
      starting the study. All 'routine patient care and procedures' such as endotracheal tube
      suction, chest physiotherapy, oral care, change of position, kangaroo care, insertion of
      lines / cannula and catheters, blood sampling will be recorded during the study period. All
      babies will receive a loading dose of caffeine citrate (20mg/kg intravenously) followed by
      5mg/kg once daily, as per standard practice.

      Statistical Analysis:

      Intention-to-treat analysis will apply for both 12-hour periods. Statistical analysis will
      consist of within-patient comparisons with paired t tests for normally distributed data or
      nonparametric Wilcoxon signed rank tests. Shapiro-Wilk test for normality will be used.
      Results will be presented as mean ± standard deviation (SD) or median and interquartile
      range. P values of less than 0.05 will be considered statistically significant. Descriptive
      statistics will be used for summarising the questionnaire responses. Stata® data analysis and
      statistical software version 11, Stata Corp LP Texas, USA will be used for all statistics.
    

Intervention name(s): Mode of ventilation (Volume Guarantee)®; Mode of ventilation (Volume control Ventilation)
Intervention type(s): Other; Other
Intervention description(s): This is a volume-targeted mode of ventilation aimed at delivering the set tidal volume of gas by automatically adjusting the peak inspiratory pressure (PIP) on a breath-by-breath basis. Theoretically this should minimise variation in tidal volume delivery as lung compliance and the infant's condition changes. This function is achieved by an automated servo-controlled mechanism. The upper PIP limit can be set by the clinician as a safety mechanism.; Volume-Controlled ventilation (VCV) is a type of 'volume targeted' mode. It aims to target be supported the desired tidal volume by delivering a set volume (chosen by the clinician) irrespective of the underlying lung mechanics. The ventilator will generate whatever peak inspiratory pressure is necessary to deliver this volume. There is constant inspiratory flow pattern (a square flow waveform) and peak volume and inspiratory pressure delivery are achieved at the end of inspiration. During the 'control period' of 12 hours without VG, infants will using VCV A/C (assist control) as is our current clinical standard.
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This study will be completed over 2 consecutive 12-hour periods in randomly assigned sequence of automatic oxygen control with Volume Guarantee ventilation (VG) ® and automatic FiO2 control without VG®.Once consent has been obtained, the team will complete the trial registration/randomisation form and access the web based randomisation service at http://www.sealedenvelope.com to obtain unique trial number and assignment of intervention. Before logging onto the website to randomise the following information must be available: Infant's gestation age, Oxygen requirement (Yes/No), Ventilated(Yes/No).
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: automated oxygen control; automated pressure control; CLIO; Volume guarantee; preterm; ventilated infants