Mechanical ventilation is a critical life-support intervention for many critically ill children. The VIDD is a common complication in patients with MV, and its pathogenesis involves a variety of pathophysiological changes, especially in pediatric patients. MV activates the ubiquitin-proteasome pathway through oxidative stress and promotes myosin heavy chain (MyHC) degradation, which is the core molecular mechanism of VIDD (
8). The diaphragm, as a continuously active muscle, is disused for passive ventilation during MV, resulting in rapid atrophy of muscle fibers (especially type II fast muscle fibers). Animal models have shown that just 12-24 hours of MV can lead to a 20 - 30% reduction in diaphragmatic cross-sectional area (
2). The proportion of type I slow muscle fibers in children's diaphragm is low (about 50% in adults and about 30% in children), while type II fibers are more likely to atrophy, and children's auxiliary respiratory muscles (such as intercostal muscles) are underdeveloped, making diaphragm dysfunction more likely to lead to weaning failure (
9). Data indicate (
10) that approximately one-third of children undergoing prolonged invasive respiratory support in PICUs develop VIDD. This leads to diaphragmatic atrophy and reduced muscle function, often resulting in weaning failure. Thus, timely and successful withdrawal from mechanical ventilation to minimize the occurrence of VIDD is of paramount importance for patient outcomes. The 2017 guidelines from the American Thoracic Society (
11) recommend that patients on MV for more than 24 hours should undergo a spontaneous breathing trial (SBT) to assess their readiness for weaning. Nonetheless, even after passing the SBT, about 13% - 26% of patients may require reintubation (
12). To enhance the probability of successful weaning, it is advisable to combine other indicators with the SBT for guidance. In recent years, numerous studies have reported on the predictive value of ultrasound-measured diaphragmatic parameters for weaning outcomes in mechanically ventilated patients (
13), predominantly in adults, with fewer studies focusing on children. This study aimed at pediatric patients, quantitatively assessing diaphragmatic function in mechanically ventilated children in PICUs using ultrasound and further analyzing the predictive value of diaphragmatic ultrasound parameters on weaning outcomes, thereby providing a reference for PICU physicians in making informed decisions about the timing of weaning.
DE represents the volume of gas inhaled into the lungs with each breath and serves as an indicator of the body’s ability to inhale sufficient volumes of air. The DTF reflects the contractile function of the diaphragm with respiration, akin to the principles of cardiac contraction and relaxation. Atrophied diaphragms have reduced contractile strength, leading to decreased DE. The study found that DE, Tei, Tee, and DTF were all lower in the MV group compared to the control group, while DE-RSBI and DTF-RSBI were higher. These findings indicate diaphragmatic atrophy and reduced contractility in the MV group. Literature suggests that muscles used frequently are more prone to inactivity-related fiber atrophy compared to less frequently used muscles (
14). Since the diaphragm operates 24 hours a day, it is more susceptible to atrophy and rapid loss of contractility when not contracting autonomously during mechanical ventilation. Diaphragmatic biopsies in MV patients have shown reduced cross-sectional area and contractile strength of diaphragmatic fibers (
15). The comparison of diaphragmatic parameters between the control and MV groups in this study aligns with these observations, further demonstrating that diaphragmatic ultrasound can provide a quantitative assessment of diaphragmatic function in MV patients.
This study found that the duration of MV and the total length of hospital stay were significantly longer in the failed weaning group than in the successful group, suggesting that an extended period of MV might exacerbate diaphragmatic atrophy, increase the difficulty of weaning, and create a vicious cycle. The total duration of hospitalization reflects the severity of the patients’ conditions to a certain extent. When comparing diaphragmatic ultrasound parameters between the successful and failed weaning groups (
Table 3), the DE and DTF were higher in the successful group, indicating that DE and DTF can serve as indicators of diaphragmatic contractility, with higher values indicating better diaphragmatic function and suggesting that normal diaphragmatic function is a prerequisite for successful weaning. This aligns with the conclusions of previous studies (
16). In the present study, the DE-RSBI and DTF-RSBI were higher in the failed weaning group, as these patients exhibited a faster respiratory rate and weaker diaphragmatic contractility, making it difficult for spontaneous breathing to meet the body’s demands after MV removal, thus leading to weaning failure.
The limitation of the traditional shallow RSBI, which is commonly used as a predictor of withdrawal, is that it reflects the overall respiratory muscle function rather than the specific diaphragm function. RSBI is calculated based on the ratio of respiratory rate to tidal volume (RR/VT), and the production of tidal volume depends on the synergistic action of all inspiratory muscle groups, including the diaphragm. When diaphragm function is impaired, auxiliary respiratory muscles (such as intercostal muscles, trapezius muscles, etc.) may maintain tidal volume through compensatory enhanced contractions, thus masking diaphragmatic dysfunction. This compensatory mechanism results in reduced sensitivity and specificity of RSBI in assessing diaphragm-specific dysfunction. In contrast, DE-RSBI and DTF-RSBI achieve a specific assessment of diaphragm function by replacing tidal volume in RSBI with ultrasound parameters that directly reflect diaphragm function (diaphragm displacement DE or diaphragm thickening fraction DTF). The DE-RSBI (RR/DE) is directly related to respiratory rate and diaphragm movement amplitude, eliminating the influence of auxiliary respiratory muscle compensation. The DTF-RSBI (RR/DTF) reflects the efficiency of diaphragmatic contraction through the change rate of diaphragmatic thickness, and directly evaluates diaphragmatic performance. Many studies have confirmed that the AUC is significantly higher than that of traditional RSBI (
17).
The results of this study showed that DE and DE-RSBI had the highest predictive power (AUC > 0.8), while DTF and DTF-RSBI had the second highest predictive power (AUC > 0.7). These findings are similar to those of previous studies in children or adults (
18,
19) regarding the predictive efficacy of ultrasound parameters for weaning outcomes, but with different cutoff values, possibly due to differences in the age groups of children included in this study compared to previous research. Therefore, future studies should expand the sample size and conduct age-specific predictions. Compared to adults, children have a faster RR and lower DE and DTF, hence the cutoff values for DE-RSBI and DTF-RSBI are higher in children.
There are still some shortcomings in this study. First, 60 patients with MV were included in this study, which met the previous sample size estimate, but the statistical power of subgroup analysis (such as different age groups or etiological groups) may be insufficient. The second is the inherent bias of retrospective design. Finally, this study only evaluated the diaphragm function during weaning, and did not track the recovery of diaphragm after weaning. Based on these limitations, we intend to conduct a multicenter prospective cohort study that includes children of different ages, etiologies, and complications to develop a more generalized prediction model. We look forward to measuring diaphragm parameters multiple times during MV and plotting trajectories of functional changes to identify high-risk time windows for VIDD.
In conclusion, diaphragm ultrasound can quantitatively evaluate diaphragm thickness and contractile function in children with MV, which is of great value in predicting the outcome of weaning. DE and DE-RSBI are superior to DTF and DTF-RSBI in predicting the outcome of withdrawal, and can provide reference for clinical withdrawal decision.