In-line Mechanical Insufflation-Exsufflation in the Management of Ventilated Patients
Condition: Ventilation Therapy; Complications; Airway Clearance Impairment
Study type: Interventional

Summary: 
      Catheter suction (CS), the standard method for airway secretion management during mechanical
      ventilation, is invasive and has significant hemodynamic and traumatic side effects. In-line
      mechanical insufflation-exsufflation (IL-MIE) is a new, noninvasive technology that clears
      secretions by cough-simulation, without interrupting ongoing ventilation. It is not known
      whether IL-MIE can be safely and effectively used as an alternative to CS in ventilated
      patients. Methods: A randomized, controlled, non-inferiority study comparing a standard
      protocol of CS, with automatic IL-MIE (CoughSync, Ruxin Medical Systems, Beijing) performed
      every 30 minutes, with CS added only if needed, in post-operative ventilated patients.
    

Detailed description: 
      The study was designed as a randomized, open-label, parallel, non-inferiority, controlled
      trial. The study was carried out in two Intensive Care Units - the Cardiac Surgery ICU at
      Anzhen Hospital, and the Critical Care Medicine ICU at Tian Tan Hospital - both in Beijing,
      China, over a 36 month period between July 2015 and July 2018. The study group included
      patients aged 18 to 75 years undergoing mechanical ventilation during the immediate recovery
      period following a cardiac or neuro-surgical procedure.

      Subjects were randomized to either a control group, managed for 8 hours with CS whenever the
      subject showed signs of airway secretion accumulation, as per standard clinical practice for
      those ICU's, or a study group, managed for 8 hours with automatic IL-MIE treatments
      (CoughSync, Ruxin Medical Systems Company Ltd, Beijing, China) performed automatically every
      30 minutes, and with CS performed only if signs of airway secretion accumulation manifested
      despite ongoing IL-MIE. IL-MIE was performed using standard IL-MIE parameters (exsufflation
      pressure = -60 cm H2O, with flutter, 10 coughs/treatment).

      Before each CS treatment, 100% oxygen was administered for one minute, regardless of the
      patient's baseline oxygen requirement, as per standard operating protocol in that ICU. Before
      IL-MIE treatments, no additional oxygen was administered beyond the patient's baseline oxygen
      requirement.

      Pharmacological management in both groups included analgesia and sedation as routinely used
      postoperatively in those ICU's.

      Demographic information and vital signs were recorded for all subjects. Arterial partial
      pressure of oxygen (PaO2), arterial oxygen saturation (SaO2 ) and oxygenation index
      (PaO2/FiO2) were defined as the primary end points of the study, and arterial partial
      pressure of carbon dioxide (PaCO2), pulseoximetry (SpO2), heart rate (HR), and ventilator
      parameters (inspired oxygen, tidal volume [Vt], peak inspiratory pressure [PIP], airway
      plateau pressure [Pplat], and PEEP) as secondary end points.

      All primary and secondary end-point data were recorded at baseline (2 minutes prior to
      starting the trial), and at 5 minutes, 4 hours and 8 hours after commencement of the trial.
      The number of CS treatments performed on each subject was recorded throughout the trial.
      Follow up for adverse events was performed during, and 48 hours after completion of, the
      trial.

      Statistical Analysis:

      The minimum sample size required to demonstrate non-inferiority, was calculated to be 49 in
      each cohort, or a total of 98 subjects in total.

      Collected data were analyzed with a mixed model with repeated measures (MMRM) considering all
      observations (2 minutes before commencement of the trial protocol, and at 5 minutes, 4 hours
      and 8 hours thereafter) and accounting for the baseline value of oxygenation. For the indices
      of oxygenation derived from blood gas measurements (PaO2, SaO2 , and oxygenation index),
      non-inferiority was evaluated by comparison to the two-sided 95% confidence interval of the
      treatment effect in the MMRM model, with non-inferiority between the IL-MIE and control
      cohorts established if the lower limit of the 95% confidence interval for the intergroup
      difference in least squares mean for a measured index was found to be higher than the
      pre-determined non-inferiority margin for that index. For comparison of other quantitative
      data between groups, a two-sample t-test or Wilcoxon rank sum test was used, based on the
      data distribution. For between-group comparison of subjects with significant adverse events,
      a chi-square test was used. The number of CS treatments performed in each cohort was analyzed
      post-hoc as an exploratory analysis.
    

Intervention name(s): Mechanical In-Line Inexsufflation; catheter suction
Intervention type(s): Device; Procedure
Intervention description(s): In-line mechanical inexsufflation (IL-MIE) is a new method for performing MIE in intubated patients, which overcomes the drawbacks of MIE for ICU use . IL-MIE devices are integrated in-line with the patient's ventilator circuit, and do not themselves perform insufflations. Rather, the regular inspiration provided by the ventilator serves as the insufflation phase of each simulated cough, and the IL-MIE device performs only exsufflation, timing the onset of each exsufflation to the beginning of passive exhalation. Figure 1 demonstrates the setup and mode of operation of an IL-MIE device. The concept of IL-MIE was first developed by one of the authors (EB) in the Department of Respiratory Rehabilitation of ALYN Hospital in Jerusalem, Israel.; catheter suction is the standard, routine method for clearing secretions from the airway of a ventilated subject, by means of inserting a catheter into the endotracheal tube.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The study was designed as a randomized, open-label, parallel, non-inferiority, controlled trial.
Masking: None (Open Label)
Primary purpose: Treatment