This was a single center study, conducted retrospectively from January 2010 to December 2012 in the PICU of the National Center for Children and Mothers (Tokyo, Japan). This PICU has 20 beds and admits an average of 1000 children each year, which is the largest number of critically ill children treated at a single center in Japan.

The inclusion criteria for this study were (1) an age < 16 years and (2) patients requiring tracheal intubation and mechanical ventilation for > 48 hours. Patients admitted to PICU after tracheotomy, patients intubated because of upper airway obstruction, patients transferred before extubation, and patients who died in PICU were excluded from this study. Accordingly, 463 patients were enrolled and were divided into a derivation cohort (n = 294) admitted to PICU from January 2010 to December 2011 and a validation cohort (n = 169) admitted to PICU from January 2012 to December 2012 (Fig 1).

We used the Newport^TM 3260 ventilator. Patients were usually placed on intermittent mandatory ventilation or synchronized intermittent mandatory ventilation in the pressure-control mode. The PICU attending physician weaned patients who fulfilled these criteria: (1) resolution of the primary reason for intubation; (2) no pneumonia, pulmonary atelectasis, or pleural effusion on X-ray films; and (3) the following mechanical ventilation parameters: F_IO2 ≤ 0.40, peak inspiratory pressure (PIP) ≤ 25 cmH₂O, pressure support (PS) ≤ 8 cmH₂O, positive end expiratory pressure (PEEP) ≤ 5 cmH₂O, and ventilation frequency ≤ 10 /min.

The timing of extubation was determined by the PICU attending physician based on mechanical ventilation parameters, the respiratory rate during spontaneous breathing, and the results of respiratory function evaluation before extubation. The following respiratory function parameters were evaluated with the Aivision respiratory function laboratory (Aivision Corporation, Tokyo, Japan): (1) crying vital capacity (CVC); (2) peak inspiratory flow rate (PIFR); and (3) maximum inspiratory pressure (MIP). We defined failure of extubation as the need for re-intubation and mechanical ventilation within 72 hours after extubation.

We retrospectively validated the predictors of successful extubation using split-sample validation. Therefore, the attending physicians only knew the values of the respiratory function parameters and were blinded to the results of the "all-3-tests" to determine whether extubation should be performed or not.

The following data were collected for each patient: demographic variables [age in months], clinical characteristics [predicted mortality calculated according to the pediatric mortality index2, origin of the patient, primary reason for admission, CVC, PIFR, MIP, and duration of mechanical ventilation before extubation], and outcome information [failed extubation rate, time to re-intubation, duration of mechanical ventilation and PICU stay].

Results are expressed as the median and interquartile range (25^th–75^th percentile) for continuous variables or as percentages for categorical variables. The Mann-Whitney U test was used for analysis of continuous variables and Fisher’s exact test was employed for categorical variables.

The accuracy of using respiratory function parameters to predict successful extubation was evaluated in the derivation and validation cohorts by calculating the area under the receiver operating characteristics curve (AUC) for each parameter. The optimal cut-off value for predicting successful extubation was defined as that achieving the maximum combination of sensitivity and specificity.

Patients were divided into three groups based on the number of respiratory function tests performed successfully: (1) all 3 tests; (2) at least one test; and (3) no tests. Then we calculated the successful extubation rate for each of these groups in the derivation and validation cohorts.

All statistical tests were two-sided and an α value of 0.05 was defined as indicating significance. All statistical analyses were performed using STATA software, version 12.1 (College Station, Texas, USA).

The National Medical Center for Children and Mothers Ethics Committee provided consent for the medical record to be used in this study. Data are available from the National Nation Medical Center for Children and Mothers Ethics Committee or researchers who meet the criteria for access to confidential data. The ethics committee waived the requirement for informed consent in individual patients.

There are ethical restrictions on sharing a de-identified data set, because all data including the patient information are owned by the National Medical Center for children and Mothers and the Ethics Committee imposed them.

Among 3,270 patients admitted to our PICU from 2010 to 2012, 463 patients met the inclusion criteria and their characteristics are shown in Table 1. The primary reasons for admission and total duration of mechanical ventilation differed between the derivation and validation cohorts, but other characteristics did not differ between them. The incidence rate of failed extubation was 5% and 9% in the derivation and validation cohorts, respectively.

The optimal cut-off values of the respiratory function parameters were as follows: 17 ml/kg for CVC, 3.5 ml/sec/cm for PIFR, and 50 cmH₂O for MIP. Patients with values of CVC, PIFR, and MIP higher than the optimal cut-off value were classified as passing each test. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CVC, PIFR, and MIP are shown in Table 2. Pass rates for CVC, PIFR, and MIP were 54.2%, 92.7%, and 55.5%, respectively.

We classified the patients into three groups according to the number of respiratory tests they passed and we compared the successful extubation rate among these groups. In the validation cohort, the successful extubation rate was 97.9% in the group that passed all 3 tests, 88.8% in the group that passed at least one test, and 66.7% in the group that failed all of the tests (Table 3). The PPV and NPV for the “all-3-test” was 97.9% and 12.3%, in the validation dataset.

The AUC of each functional parameter and the “all-3-test” in validation dataset was as follows: the AUC of CVC was 0.58, the AUC of PIFR was 0.54, the AUC of MIP was 0.57, and the AUC of the “all-3-test” was 0.62 (Fig 2).

In the group passing all 3 tests from the derivation and validation cohorts, extubation failed in only 5 patients. The clinical characteristics of these 5 patients are listed in Table 4. Four patients were in PICU after surgery and one patient was admitted after cardiac arrest. The reason for re-intubation was respiratory muscle fatigue and deterioration of the respiratory status in 3 patients (Patients 1–3), while 2 patients (Patients 4 and5) had upper airway problems.