Safety and Feasibility Study of a Mechanical Ventilation Computerized Protocol: Intellivent
Condition: Mechanical Ventilation Weaning Phase in Children
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The present protocol will demonstrate the safety, feasibility and efficacy of a newly
      computerized protocol integrated into a ventilator: S1 ventilator (Hamilton Medical). During
      ventilation with S1 ventilator, the respiratory support including oxygenation and CO2 removal
      parameters are continuously adapted to patient respiratory status using science based rules.
      The present protocol is designed as a pilot evaluative study where the researchers will
      evaluate the safety, feasibility and efficacy of ventilating children during the weaning
      phase with the S1 ventilator for 5 hours, and compare to conventional ventilation.
    

Detailed description: 
      Research Design and Methods

      Aim: To demonstrate the safety, feasibility and efficacy of delivering ventilator support in
      intubated children during the weaning phase with S1 ventilator using CO2 removal and O2
      delivery explicit computerized protocol (ECP).

      Hypothesis: The computerized explicit protocol implemented in S1 ventilator will better
      maintain children in a normal oxygen saturation, respiratory rate and ETPCO2 range during the
      weaning phase when compared to usual care.

      Eligible patients: All critically ill children will be considered eligible for this research
      project if they fulfill all the following criteria :

        -  The patients should be PICU-hospitalized

        -  Child under mechanical ventilation with an endotracheal tube for at least 12 hours, as
           estimated by the attending intensivist.

        -  Child below 18 years of age, with a body weight ≥ 3 kg.

      Screening of eligible patients: The attending Pediatric Intensivist and a Research Nurse will
      check for candidates on a daily basis in the pediatric intensive care unit (PICU) of
      Sainte-Justine Hospital (HSJ). An eligibility screening log, documenting the subject's
      fulfillment of the entry criteria, will be completed for all eligible patients considered for
      the study, regardless of their subsequent inclusion or exclusion status ("Bookkeeping").
      Consent will be solicited from parents or legal guardians if a patient fulfils eligibility
      criteria and presents no exclusion criteria.

      Inclusion and exclusion Criteria (see below)

      Baseline data:

      All subjects included into this study will undergo routine examination upon admission to the
      hospital. These examinations include physical, medical/medication history (on the last year
      for medical history and the last 3 months for medication history (if available)), vital
      signs, radiologic data and laboratory tests. Assessment of these data will occur in potential
      candidates within 24 hours of their hospitalization. BMI (Body Mass Index) will be derived
      from the subjects' height and weight. PIM 2 and PELOD scores will be computed (the PIM 2
      score is a mortality risk score for children, and the PELOD score is a scale estimating the
      severity of cases of multiple organ).

      Measurements:

      Set and measured ventilatory parameters, SpO2 and ETPCO2 will be stored in the S1 ventilator.
      SpO2 will be measured via pulse oximetry placed on infant's extremities (in addition to usual
      monitoring) during the 5 hours of the study. End Tidal PCO2 measurements will also be made
      via probe placed on the Y piece of the respirator circuit (usual practice) during the 5 hours
      of the study.

      General protocol sequence:

        -  All patients in the PICU at HSJ screened daily for eligibility

        -  Eligible cases reviewed with attending team and study team

        -  Informed consent obtained from parents or guardian

        -  Pressure support test A pre-inclusion test (pressure support test) with a level of
           pressure support of ± 5 cmH2O of the previous level of positive inspiratroy pressure in
           the controlled mode (PCV for instance), but no greater than 30 cmH2O (pressure-support
           level plus positive end-expiratory pressure), is performed to evaluate if the patient's
           is ready to be weaned. The test could be stopped before 30 minutes if the patient showed
           evidence of respiratory distress (respiratory rate > 40 breaths per minute and FiO2 >
           60% in order to obtain pulse oxymetry ≥ 95%) or apnea. The test will be performed again
           the day after if he still reach inclusion/exclusion criteria. The test is considered
           positive when, after 30 minutes, the patient remained clinically stable with a
           respiratory rate between 10 and 40 breaths per minute and an expiratory tidal volume
           higher than 6 ml per kilogram of body weight within the authorized pressure-support
           range, with pulse oxymetry no lower than 95 percent when the fraction of inspired oxygen
           was no greater than 60 percent. When the pressure-support test is positive, the patient
           is included in the study.

        -  Data registered 1 hour in pressure support mode with the ventilator and settings of the
           pre-inclusion test.

        -  Ventilation is switched to S1 ventilator and the routine ventilator is kept in the
           patient room.

        -  Application of 3 hours with the S1 ventilator with the following initial settings:

      At the study beginning, the S1 ventilator will be implemented and the settings used will be:

        -  ASV mode with % minute volume (MV) set as compared to the mean patient's MV measured
           during the 1 hour pressure support before

        -  PEEP: same as in conventional ventilation

        -  FIO2: same as in conventional ventilation After 1 hour, the CO2 removal ECP is started
           and 1 hour later, the O2 delivery ECP is started for 1 hour (figure 3).

             -  Return to routine ventilator with the settings used at inclusion and registered
                during 1 hour A physician or respiratory therapist trained to use S1 ventilator
                will stay during the whole period (5 hours) next to the patient.

      Monitoring during conventional ventilation after discontinuation of S1 ventilator (1 hour):

      In order to compare S1 ventilator to conventional ventilation, monitoring will be continued
      with conventional settings on the usual ventilator for 1 hour. Following this, the study will
      be stopped and patient back to conventional ventilator unless attending physician decides to
      extubate the patient.

      Protocol termination criteria: If the child demonstrates a sustained change in any of the
      following, the protocol will be terminated and the child ventilated with the previous
      conventional ventilation:

        -  Sustained decrease in SaO2 < 92% requiring increase in FIO2 > 60%

        -  ETPCO2 > ETPCO2 at S1 start requiring increase of positive inspiratory pressure > 25
           cmH2O above PEEP,

        -  Sustained increase in heart rate > 180 bpm during 15 min,

        -  Sustained increase in respiratory rate > 60 bpm during 15 min,

        -  Uncontrolled agitation judged by the attending physician

      Management of protocol termination episodes:

      All protocol termination episodes will be analyzed by two pediatric intensivists non involved
      in the research project (François Proulx MD, France Gauvin MD). We do not expect any safety
      issue while performing this research project, but there is few experience with the S1
      ventilator under study, which explain why we will so closely watch for any problem
      attributable to S1 ventilator.

      Analysis and statistics Data will be described as n, mean, median, standard deviation,
      minimum and maximum for quantitative variables and frequencies for qualitative variables. The
      percentage of time in normal breathing range and normal saturation range will be compared
      between the last hour with S1 ventilator, and the first hour in conventional ventilation; and
      between the last hour with S1 ventilator and last hour in conventional ventilation 2 groups
      using a Wilcoxon's test.
    

Intervention name(s): S1 ventilation
Intervention type(s): Device
Intervention description(s): Ventilation with a O2 and CO2 controller
Other intervention name(s): Health Canada approval number: 155350
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Weaning; closed loop; mechanical ventilation; children