Outcomes of mechanical ventilation according to WIND classification in pediatric patients

Mechanical ventilation (MV) is a widely used form of respiratory support in pediatric intensive care units (ICUs). However, prolonged use of MV causes complications [1‐3]. The weaning period may comprise up to 40% of MV days [4, 5]. Weaning from MV is difficult for 30% of patients, and such patients showed a higher mortality rate [6]. Therefore, previous studies have assessed the relationships between weaning classifications and clinical outcomes.

The weaning process was classified by the International Consensus Conference on weaning from MV according to difficulty and duration of the weaning process: simple weaning, difficult weaning, and prolonged weaning [7]. Patients with prolonged weaning have higher mortality than other groups [8‐11]. However, the International Consensus Conference classification excludes patients who were not weaned from MV or who were weaned from MV without a spontaneous breathing test (SBT). In 2017, a new pragmatic classification of weaning, the Weaning according to a New Definition (WIND) classification, was proposed to overcome these limitations and was associated with survival to discharge in adult ICU patients [12].

Studies of the weaning processes and patient outcomes in pediatric ICU patients are rare. There are some data indicating an association between extubation failure and mortality rate [13], but weaning is more complex than single extubation and requires more time. In this study, we evaluate the relationship between weaning process as categorized by WIND classification and ICU mortality in pediatric ICU patients.

During the study period, 313 patients were admitted to the pediatric ICU and required MV for more than 24 h. Among these patients, 89 were excluded according to exclusion criteria: 14 patients had been on home ventilators at admission, 40 admissions were other than the first ICU admission, 32 patients were transferred from other hospitals with intubation, two patients were extubated on extracorporeal membrane oxygenation, and one patient was transferred to another hospital before ready to wean. Therefore, 224 patients were included in the final analysis (Fig. 1).

For baseline characteristics, the median age of the 224 enrolled patients was 2.1 (interquartile range 0.5–6.6) years (Table 1). The median-predicted mortality rate at admission was 4.6% (interquartile range [IQR] 1.4–15.0) with right-skewed distribution. The mean predicted mortality rate was 15.5%, and the actual mortality rate was 20.5% (46/224). The standardized mortality ratio calculated by observed/predicted (PIM 3) mortality was 1.32 (95% confidence interval [CI] 0.75–1.89). Thirty-seven (16.5%) patients were admitted for postoperative care, and 187 (83.5%) patients were admitted for medical organ dysfunctions or problems. The most common underlying condition was oncologic disease (21.9%), followed by cardiologic (21.0%) and neurologic disease (21.0%) (Table 1).

For the characteristics of weaning, SBT was applied in 157 patients (70.1% of 224 enrolled patients and 87.2% of 180 patients with SA), and post-extubation support was applied in 36 (16.1%) patients. The median duration of mechanical ventilation was 7 (IQR 4–14) days, and ventilator-free days were 19 (IQR 0–24) days. The median duration after intubation to the first SA was 4 (range 0–36) days. The first SA was performed within 7 days after intubation in 76.7% of patients (138/180), within 14 days in 92.8% of patients (167/180), and within 28 days in 99.4% (179/180) of patients. The median duration after the first SA to successful weaning was 0.83 (IQR 0.1–2.14) days. Weaning was done with tracheostomy in 22 patients (9.8%), although 12 patients (5.4%) with tracheostomy could not wean mechanical ventilation.

In the WIND classification, 99 (44.2%) completed the weaning process within 24 h and were classified as group 1. All patients in group 1 were successfully weaned. Fifty-three patients (23.7%) completed the weaning process from 1 to 7 days (group 2), and all were successfully weaned. Twenty-eight patients (12.5%) had weaning processes lasting more than 7 days (group 3). Thirteen patients in group 3 were weaned, but 15 were not. Finally, 44 (19.6%) patients who had never undergone SA were classified in the no-SA group (Fig. 1).

We compared the characteristics and clinical outcomes of the weaning groups (Table 2). The mortality rate predicted by PIM 3 score at ICU admission tended to increase from group 1 to group 3, but the difference was not significant. Age and underlying oncologic disease also tended to increase from group 1 to group 3, but the difference was not significant. As the duration of the weaning process increased in groups 1, 2, and 3, the total duration of MV, reintubation rate, time to reintubation after the first extubation, tracheostomy rate, rate of post-extubation support application, and length of stay in ICU were significantly different (Table 2). However, the duration from intubation to the first SA was shorter in group 3 than in groups 1 and 2, and application of SBT was not significantly different across groups (p = 0.175). Reintubation rate after the first extubation trial was high in group 3 (92.8%). Poor lung parenchymal was the most common cause (50.0%) followed by airway problem (15.4%) and problem of breathing control (15.4%), and statistical difference among groups 1, 2, and 3 was not found (p value = 0.106) (Additional file 1: Supplementary Table 1). ICU mortality occurred only in group 3 patients with SA (p value < 0.001), but group 3 was not associated with mortality in adjusted analysis conducted in SA group with variables of age, sex, PIM 3 score (p value = 0.996).

In comparison of the SA groups and the no-SA group, the no-SA group was older (p = 0.001). The no-SA group had a higher predicted mortality rate at admission (22.3% vs. 3%, p < 0.001), more medical admissions (95.5% vs. 80.6%, p = 0.009), and a higher incidence of underlying oncologic disease (50.0% vs. 15.0%, p = 0/001) than the SA group. The clinical outcomes of the no-SA group included fewer ICU-free days (0 vs. 16 days, p < 0.001) and higher ICU mortality (93.2% vs. 2.8%, p < 0.001) than the SA group (Table 1). The causes of mortality were sepsis/multiorgan failure (34.8%), central nervous system failure (29.3%), respiratory failure (22.4%), and cardiac failure (7.3%) in no-SA group, and there was statistically difference between SA and no-SA groups (p value = 0.032) (Additional file 2: Supplementary Table 2). In a multivariate logistic regression test, the presence of underlying oncologic disease was 7.341 times higher (95% CI 3.008–17.916) in the no-SA group, and a 1% increase in PIM 3 score at admission was 1.036 times more frequent (95% CI 1.022–1.055) in the no-SA group (Table 3).

In this study, WIND classification according to weaning process was associated with mortality rate in pediatric patients (Additional file 3: Supplementary Fig 1). Weaning processes lasting more than 7 days were associated with increased mortality rate. About 20% of patients had never undergone SA during MV, and most deaths (89%) occurred among those patients. We demonstrated that high admission severity score and underlying oncologic disease were independent risk factors for lack of SA.

The clinical significance of the presence of SA during invasive MV was not well understood. Previous studies of weaning classifications or extubation failure enrolled only patients who underwent weaning process [3, 9, 10, 14, 15]. However, in this study, 89% mortality among mechanically ventilated patients occurred in patients who had never undergone SA. The high mortality rate in the absence of SA was similar to the results of a previous study of adults [12]. In adults, the mortality rate of the no-SA group was 86%, and the mortality of the no-SA group comprised 73.4% of total mortality. Therefore, the description of mortality rates according to WIND classification represents a comprehensive view of mortality and has pragmatic importance.

Considering the high mortality rates of no-SA group, the risk factors associated with lack of SA are clinically important. There are various causes of applying mechanical ventilation, such as acute respiratory problem, heart failure, sepsis, coma, neuromuscular problems [16]. Also, there are many reasons for weaning failures, such as airway/lung problems, brain dysfunction, cardiac dysfunction, diaphragmatic weakness, and endocrine problems [17]. There are predictive markers associated with each weaning problem in the respiratory ICU, such as weaning-induced pulmonary edema in cardiac dysfunction, thickening fraction of the diaphragm in diaphragmatic weakness, and hypercapnia [11, 18, 19]. However, these physiologic markers are not applicable to other weaning problems. In this study, severity at admission as assessed by PIM 3 score and underlying oncologic disease were independent risk factors for lack of SA. When we consider our causes of deaths and weaning criteria, our hypothesis is that the absence of SA is an indicator of uncontrolled underlying problems such as hemodynamic instability, altered mentation, or progressive respiratory failure which may inhibit weaning process and also cause death directly or indirectly. Patients with underlying oncologic disease or high PIM 3 score might be more likely to have uncontrolled underlying problems [20, 21].

Among patients who underwent SA, only group 3 (no successful weaning within 7 days) showed a significantly different mortality rate in an unadjusted analysis. According to the International Consensus Conference classification (only applying to 70% of our study population), the adjusted mortality rate in previous studies was higher in the prolonged weaning group (weaning duration longer than 7 days) than in other weaning groups, but the mortality rate was not different between simple weaning (weaning on the first attempt) and difficult weaning (weaning within 7 days) [9, 11]. Our results were similar, although we did not detect a significant difference in mortality rate in a severity-adjusted analysis.

Prolonged weaning was associated with prolonged total duration of MV in our study. In a previous study, complications such as ventilator-associated pneumonia are known to increase over time [22]. However, we did not evaluate the incidence of complications. Further studies are required to understand the association between prolonged weaning and cause of mortality.

Prolonged mechanical ventilation before weaning trial was associated with prolonged weaning in previous studies [10, 14, 23] and was also reported as a risk factor for extubation failure [15]. The results were different in our study, in which group 3 was not associated with the delayed first SA (Table 2). In the previous adult studies, T-piece or continuous positive airway pressure was common methods used for SBT, and the incidence of SBT showed a decreasing trend as weaning became more difficult [10, 14]. However, in our study, pressure support (< 8 cm H₂O) was a common method used for SBT, and the incidence of SBT did not show any trends of increase or decrease. The different results might be caused by different study populations or different methods of SBT.

In this retrospective study design, we did not define the cutoff duration after intubation to the first SA. The duration of mechanical ventilation (range 0—36 days) before weaning trials showed a right-skewed distribution, and 99.4% (except 1 out of 180) patients tried their first SA within 28 days after intubation. Therefore, clinicians may need to consider that a patient is likely to be in the no-SA group in the absence of improvement to tolerate SA until 28 days after intubation.

We included only patients who received mechanical ventilation for more than 24 h, although there was no mention of duration in the previous WIND classification [12]. In the studying pediatric ICU, some patients applied mechanical ventilation only for several hours during a short procedure or postoperative periods. We tried to exclude them because our weaning protocol did not concern them before 24 h of mechanical ventilation. The different inclusion criteria might change the number of short weaning group (group 1).

There are several limitations to this study. First, this study was a retrospective cohort study and did not include data such as ventilator pressure settings or physiologic parameters. Second, we did not collect data about use of sedatives or neuromuscular blockers or about incidence of delirium, factors that may affect the weaning process. Third, this study was conducted in a single tertiary hospital with daily weaning assessments, and it may not apply to hospitals with low severity or different weaning characteristics. Fourth, the results of analysis using predicted mortality might be different in ICUs with a deviated standardized mortality ratio or ICUs using different severity tools. Therefore, the results may need cautions in the interpretation.

Despite these limitations, this was the first study to elucidate the outcomes of MV in pediatric patients using WIND classification. We included patients without SA or SBT, who were excluded from the previous weaning studies. Furthermore, we demonstrated the importance of the excluded population and the presence of SA as a prognostic indicator of mechanical ventilation. In addition to prognosis, development of weaning classification which describes weaning process better is clinically important, since the weaning process is also associated with ICU occupancy and healthcare cost [24]. Weaning studies based on the WIND classification might help to understand weaning process better and facilitate further research, trying to identify which population to target and which interventions to test to improve weaning protocols or policies.

In conclusion, the WIND classification of weaning from MV is associated with ICU mortality in pediatric patients. Further studies of this association are required to improve protocols associated with the weaning process and clinical outcomes.