A prospective observational study on critically ill children with diaphragmatic dysfunction: clinical outcomes and risk factors

As the primary muscle for respiration, the diaphragm generates nearly three- to four-fifths of the inspiratory capacity [1]. A remarkably negative effect of diaphragmatic dysfunction or DD is exerted on the respiratory ability, a general complication in critically ill adult patients, particularly among those on mechanical ventilation (MV) [2]. The study conducted by Goligher et al. reveals that in about 50% of patients on MV, there is a rapid decrease in the thickness of the diaphragm after intubation [3]. The primary reason for DD is MV, with significant atrophy of the diaphragm in 18–69 h in absolutely controlled ventilation [4]. In children with a critical illness, MV is widely used as a conventional treatment process of pediatric intensive care unit (PICU); a significant number of children (30%) in the PICU were given the support of MV [5], and nearly two-fifth (38%) of them suffered from DD [6]. There is a high risk for difficult, delayed weaning and failed extubation, in DD patients, besides the increased possibility of poor functional outcomes, a longer stay in the PICU, and death [7‐9].

There are several reports on the causes of DD and associated clinical outcomes in adult patients with a critical illness. However, there are not many studies on DD in pediatric patients with a critical illness, the associated risk factors, with limited information on its impact on clinical outcomes in children [10‐12]. Therefore, there is little experience in clinical identification, proper intervention and prognostic improvement of children in such cases.

In this study, risk factors in relation to DD were identified, short-term clinical outcomes and the role of DD were assessed in patients below 18 years of age, and the suggestion of any possible association of DD with poor clinical outcomes was evaluated among seriously ill pediatric patients in the PICU.

This study is the first, as per our knowledge, to evaluate factors related to the DD development and clinical outcomes in severely ill pediatric population. We observed a 34.3% DD incidence rate in children, as well as the association between the time for ventilatory treatment and the period of elevated CRP in the occurrence of DD. Thus, these outcomes implicate MV as not the exclusive cause of DD, with multiple factors playing a role in DD development in seriously ill children. For the first time in studies done to date, we report a relationship between elevated CRP duration and DD in children with a critical illness, indicating an important risk factor in the form of the body’s inflammatory response. We also found that pediatric patients with DD exhibit poorer outcomes, such as a longer period of stay in PICU, enhanced rates of extubation failure or weaning and increased mortality.

The outcomes of our analyses are in accordance with those obtained after assessing DD in hospitalized adult patients. In these patients, we observed a longer time of total ventilation, increased rates of failed extubation or weaning and mortality than in children who did not have DD [6, 19, 20]. Few reports on DD in severely ill children observed an independent association of respiratory weakness with longer time of ventilation and reintubation [9, 21]. In our previous study, we observed worsened diaphragmatic function in patients with failed weaning [22]. This suggests a close association of poorer clinical outcomes with DD in both children and adults. In mechanically ventilated adults, there was a 40–60% prevalence of dysfunction of the diaphragm diagnosed through ultrasound [8, 23, 24]. These values are higher than those observed in the current study. The primary cause for these may be, yet immaturely developed auxiliary inspiratory muscles in children; in adults, a greater role is played by the diaphragm [25]. Thus, a higher diaphragm baseline function is seen in children than in adults. The second cause may be that majority of adult patients suffered from chronic obstructive pulmonary disorder (COPD), where muscle fibers of the diaphragm undergo chronic oxidative remodeling, resulting in weakness in the ability of diaphragm compensation [26]. Third, the average time for ventilatory treatment was more the elderly than that in the children with DD [576 (374–850) hrs vs 360 (168–528)] [6, 22]. In addition, in critically ill children, we observed that the time of ventilation is a risk factor independent of DD, similar to that observed in adult studies [2, 27]. Further, the association of elevated CRP with DD development is another important observation in this study. In the diseases implicated in skeletal muscle dysfunction, an important contributor to the pathology is inflammation [28]; few studies on adults revealed that the risk factor with most significant impact for ICU-acquired weakness(ICU-AW) is systemic inflammation [18, 29]. Even post-critical illness, inflammation is prevalent and is not related to good recovery physically [30]. Nevertheless, the function of respiratory muscle imflammation remains unexplored largely, particularly in children with critical illnesses. In this study, we observed that the main risk factor of DD may be the period of the inflammatory response, although the rate of casualties cannot be estimated through our findings, and a randomized control trial (RCT) can demonstrate the same.

There were a few limitations to this study. First, the sample size was relatively small and may constrain the validity. The second limitation is the establishment of the criterion of ultrasound diagnosis (DTF < 20%) for DD from studies in adults and further study is needed in the pediatric population to ascertain the use of this reference value in children. Third, here, only CRP was used to represent patient inflammatory response, thus limiting the accuracy of our findings. Hence, more inflammatory factors like IL-6 (interleukin 6), IL-8 (interleukin 8), and TGF (transforming growth factor) must be included for a better indication of, to confirm our findings. Fourth, due to the small sample size in our study, a few crucial components in adult research like sepsis did not yield positive outcomes. While this does not directly associate sepsis with DD, the sample size must be expanded and the RCT must be conducted. Finally, the clinical outcomes of only the children with DD in the period of their stay at the hospital were investigated, and the patients post-discharge were not followed up. Dres et al. [4] showed that the frequency of DD is two times as that of weakness of the limb muscle, which associates significantly with post-discharge mediocre physical function [31‐33]. Thus, the assessment of the effect of DD on the long-term prognosis of the pediatric population with critical illness is imperative.

The clinical outcomes are remarkably affected by DD in children with critical illnesses, including a longer stay at the PICU, an enhanced rate of failed extubation and weaning, and a higher rate of mortality. The duration and time of ventilation of increased CRP are primary risk factors of DD development in children with critical illness. Particularly, an earlier DD identification in pediatric population with critical illnesses is vital to protect the functions of the diaphragm. However, research in children has been relatively inadequate, and more studies on the pediatric population with DD are needed for better respiratory and clinical rehabilitation.