The Use of Apneic Oxygenation During Prolonged Intubation in Pediatric Patients: a Randomized Clinical Trial
Condition: Intubation of Pediatric Dental Surgery Patients
Study type: Interventional

Summary: 
      Patient demographics (age, height and weight) will be collected for 546 consecutive patients
      presenting for dental restoration under general anesthesia. The baseline saturation will be
      recorded. The induction of anesthesia will be standardized for all patients. All patients
      will undergo an inhalational induction administered by face mask. After inserting an
      intravenous (IV) line, rocuronium will be administered. Intravenous propofol and fentanyl
      could be added at the discretion of the anesthesiologist. The patients will be mask
      ventilated then be with a mixture of Air/Oxygen (O2) to achieve an FiO2 of 0.3 for 3 minutes
      after the administration of rocuronium.

      Patients will be randomly assigned to one of three groups for the purpose of airway
      management: 1) direct laryngoscopy for nasotracheal intubation without oxygen insufflation
      (DL group); 2) direct laryngoscopy for nasotracheal intubation with oxygen insufflation (DLO2
      Group); and 3) nasotracheal intubation using the Truview PCD video laryngoscope (VL Group).
      Computer-generated treatment allocations (using the PLAN procedure in SAS statistical
      software, using random-sized blocks) will be maintained in sequentially numbered sealed
      envelopes that will be opened after consent is obtained. The laryngoscopy and intubations
      will be performed by the study investigators who are faculty anesthesiologists or by the
      mid-level or resident or fellow working with them.

      The study will be stopped when:

        -  the patient will be intubated and a CO2 trace is obtained on the capnography or

        -  if the patient desaturates to 90%

        -  or if the patient shows signs of cardiac instability (ectopic beats, arrhythmia or
           hypotension)

      Randomized groups will be compared for balance on potentially confounding baseline variables
      using descriptive statistics. Primary outcome: In the primary hypothesis, desaturation will
      be characterized using both time to 1% saturation drop from the baseline and the rate (slope)
      of desaturation after an initial 1% drop. We will consider a given intubation technique (DLO2
      or VL) better than DL on controlling saturation if found noninferior (i.e., not worse) on
      both outcomes and superior on at least one of the outcomes. Thus our primary hypothesis will
      be assessed in a joint hypothesis testing framework described by Mascha and Turan. We
      a-priori define the non-inferiority delta for the outcome time to 1% drop as 5 seconds (or
      1.05 if using hazard ratio) and the slope delta as 0.05 percent per second.
    

Detailed description: 
      Secondary outcomes:

      Secondary-1. We will conduct tests for superiority to compare the Truview and DL with oxygen
      cannula methods on each of the two primary outcomes, and report the treatment effect
      estimates and adjusted confidence intervals. Notably, the study is not powered to be able to
      assess equivalence between these two oxygen techniques.

      Secondary-2. We will compare the three randomized groups on total desaturation slope (rate)
      using a random slope linear mixed effects model with repeated measures. This model will allow
      accounting for the variability of the saturation rate for the patients and possible
      correlation of the saturation measurements within a patient (autoregressive correlation). We
      only will use saturation data before it reaches 90%.

      Secondary-3. We will assess the relative efficacy of Truview and DL with oxygen cannula in
      preventing 90% saturation compared with DL alone using 2-tailed chi-square tests of
      proportions (for superiority), summarized with a relative risk and confidence interval.

      Secondary -4: We will assess the correlation between the rate of desaturation and both age
      and body mass index, independent of randomized group. This will be done in the context of a
      random slope model as in the primary aim, assessing the interaction between the mean
      desaturation slope and each of age and body mass index.

      To restrict overall Type I error of the secondary hypotheses at 5% we will apply Bonferroni
      correction for multiple inferences and adjustment for interim analyses.

      Interim analyses will be conducted every 25% of the maximum planned enrollment using a groups
      sequential design to test for efficacy and futility. We will use a gamma spending function
      (gamma = -4 for efficacy and -2 for futility) to maintain the significance level for the
      primary outcome at 2.5% and the power at 90% across the interim analyses. Significance
      criteria for all tests will be adjusted for interim analyses based on the above-mentioned
      gamma spending function and the corresponding z-statistic at teach interim look.
    

Intervention name(s): TrueView PCD Video Laryngoscope
Intervention type(s): Device
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other