Full materials and methods of the pediatric pilot randomized trial on
mechanical ventilation weaning with a computerized protocol versus
usual care
Patients
Eligible patients were children between 2 and 18 years with body weight (BW) ≥ 15 kg
admitted to the pediatric intensive care unit (PICU) of Sainte-Justine Hospital for any
reason, except cardiac surgery, between September 2007 and June 2009, for whom
mechanical ventilation for at least 12 hours was expected. Children were included if the
Evita XL respirator with SmartCare/PS™ was available and if they fulfilled the following
weaning criteria during the screening periods (Monday to Friday mornings): patient able
to breath spontaneously, no vasopressor or inotrope medication (other than digoxin or
low dose dopamine (< 5 µg/kg/min)), FiO2 ≤ 60% with oxygen saturation ≥ 95%,
positive end expiratory pressure (PEEP) ≤ 8 cmH2O, plateau pressure ≤ 25 cmH2O,
PaCO2 < 70 mmHg on most recent blood gas, endotracheal tube leak ≤ 20%. Patients
were excluded if: they had severe chronic respiratory insufficiency due to neurological,
neuromuscular or lung diseases prior to PICU admission, primary pulmonary
hypertension or cyanotic congenital heart disease. Children expected to be extubated on
the day of inclusion, not expected to survive, with a decision to withdraw care or with no
parental consent were also excluded. The study protocol was approved by the
institutional review board of Sainte-Justine Hospital.
Pilot trial design
This was a single centre, pilot randomized study. After inclusion, a pressure support (PS)
test was performed (ventilation in PS mode at a level of ± 5 cmH2O of the pre-inclusion
plateau pressure). The test was considered positive when, after 30 minutes, the patient
remained with a respiratory rate (RR) between 10 and 40 breaths per minute (bpm), an
expiratory tidal volume (Vt) ≥ 6 ml/kg and a SpO2 ≥ 95% with FiO2 ≤ 60%. The test was
stopped before 30 minutes if the patient showed evidence of respiratory distress (RR > 40
bpm or FiO2 > 60% with SpO2 ≥ 95%). The test was repeated daily until positive. When
the PS test was positive, the patient was ventilated with an Evita XL respirator in PS
mode and was allocated randomly to wean via SmartCare/PS™ (SmartCare group) or
usual methods through a sequential opaque envelope technique.
In the usual care group, physicians were instructed to wean according to their practice, in
the absence of formal guidelines in the PICU, including modification of ventilation
mode if required. In the SmartCare group, the SmartCare/PS™ option of the Evita XL
was switched on after adjusting for BW. SmartCare/PS™ is an explicit computerized
protocol that manages the weaning phase with modification of pressure support level in
closed loop. Its functioning for children has already been described in a previous study
(17). In addition, PEEP was adjusted using a written protocol including the following
two guidelines: (1) decrease of PEEP level by 1 cmH2O per 8 hours to a minimum of 5
cmH2O, if FiO2 ≤ 50% with SpO2 ≥ 95%; (2) if FiO2 ≥ 60% to maintain a SpO2 ≥ 95%
during 1 hour, the attending physician could decide if an increase in PEEP was
necessary. If the patient required heavy sedation, or if his clinical status deteriorated,
with a RR ≥ 40 bpm, clinical discomfort, and/or hypoxemia (need for FiO2 ≥ 60% and
need for PEEP ≥ 8 cmH2O with SpO2 ≥ 95%), or PS level reached the upper limit of 27
cmH2O, ventilation was switched back to assist control ventilation. The patient was then
retested with PS test daily and SmartCare/PS™ was restarted when the test was positive.
The decision to extubate was made by the attending clinicians in both groups. In the
SmartCare group, if the extubation was performed later than 30min after a ‘‘separation
recommendation’’ from SmartCare/PS™, this was considered to be a delayed extubation.
The reason for this delay was collected prospectively. In accordance with current
mechanical ventilation practice in this pediatric intensive care unit, no recommendation
of separation from the respirator was provided by the SmartCare/PS™ between 8:00 pm
and 6:00 am.
The primary endpoint studied was the time from randomization to the first extubation.
Secondary endpoints included: (1) weaning failure: resuming mechanical ventilation (non
invasive or invasive) within 48 hours after extubation or failure to wean within 28 days of
randomization. Non-invasive ventilation was considered as weaning failure if used more
than 12 hours a day. Causes of failure were documented (lower respiratory tract
problems, upper airway obstruction, apnea, cardiovascular insufficiency, others); (2) total
duration of mechanical ventilation: duration of ventilatory support from first intubation
until extubation. If a patient was reintubated within 48 hours after extubation, both
mechanical ventilation episodes were considered as the same episode; (3) length of PICU
stay; (4) length of hospital stay; (5) Ventilator free days at 28 days: number of days
between successful weaning from invasive mechanical ventilation and day 28 after study
enrollment.
Power & sample size calculations
This pilot study included 30 patients (15 in each group), which corresponded to 10% of
the sample size that we expect to include in a multicentrer randomized clinical trial that
we plan to conduct after this pilot study. Our preliminary study had suggested a 20%
difference in length of weaning between usual care vs SmartCare/PS™ (17). A study led
by A. Randolph et al. (13) reported that the duration of weaning was 3.22.5 days in a
similar population. A 20% reduction of this period would have resulted in a difference of
0.70.5 days. Therefore, to detect a statistically significant difference in the length of
weaning at 90% power and at a 2-sided alpha=0.05 using the “Paired t-test for sample
size calculations” and considering 5 PICUs with 3 stratification levels (ie acute lung
injury, surgical procedure, others) and an attrition rate of 10%, the calculated sample size
for the multicenter randomized clinical trial was 296 patients.
Data analysis
Analysis was done using the intention to treat principle. As the primary outcome did not
have a normal distribution, a non-parametric statistical test was used (Mann-Whitney U
test) to assess for statistical significance. Levels of statistical significance were set at
P<0.05. Statistical analysis was performed with SPSS software, version 13.0. The
probability of remaining on mechanical ventilation was analyzed by the Kaplan-Meier
method, and a log-rank test was used to assess differences. Cox proportional hazards
modelling was performed to estimate the adjusted effect of selected variables (close to
statistical significance at baseline between the two groups) on the primary end point.