Despite the ubiquitous use of POCUS in PICUs for echocardiograph and lung examinations, its use for investigating muscle changes over time is relatively novel. Our results indicate that POCUS is a valuable non-invasive tool for assessing and monitoring muscle loss during IMV. In critically ill adults, the decrease in muscle mass has been reported to range from 8.6–25% over a period of 5 to 7 days (10, 12, 13). Parry et al. (12) found a large (30%) reduction in vastus intermedius thickness and rectus femoris thickness within 10 days of admission whereas Puthucheary et al. (13) found that the rectus femoris cross-sectional area decreased significantly by day 7 of an ICU stay (-12.5% [95% CI, − 35.4 to 24.1%]; p = 0.002) and continued to decrease to day 10 (-17.7% [95% CI, -25.9 to 8.1%]; p < 0.001).
In line with a recent landmark study (4), our PICU muscle mass monitoring investigation demonstrates that muscle atrophy (> 10% decrease in thickness) occurs promptly and early in this population. In addition, the age of critically ailing children appears to influence muscle atrophy. Banwell et al. (14) found that 11 of 14 patients with muscle impairment in their cohort were older than 10 years, and none were younger than 18 months. Likewise, age-related decreases in growth factors and resistance to anabolic agents are thought to be responsible for the slowing of muscle protein synthesis that occurs with age (15). Growth hormones such as growth hormone (GH) and insulin-like growth factor-1 (IGF-1) may also account for age-related changes in muscle protein turnover. Another important thing is the fact that muscular protein synthesis is downregulated in young adults due to inactivity, while muscular protein degradation is unaffected (16). Therefore, supine lying may suddenly reduce limb muscle demands in older children but not in infants or neonates during mechanical breathing (4)
Muscle disuse and starvation are often associated with a catabolic response leading to a dramatic loss of skeletal muscle mass. Nutrition is essential for preserving muscle mass, as shown by feeding and starving studies in animals (17). In our work, a cumulative energy deficit predicted greater decrease in QFMT (r = 0.4, CI 95%, 0.021–1.44, p = 0.010). These results are in accordance with the current evidence from studies involving critically ill children (8, 18). Intake of at least two-thirds of the estimated energy goal in a large multicenter prospective cohort and > 80% of the estimated energy goal in a smaller single-center retrospective cohort was significantly associated with reduced mortality in critically ill children receiving mechanical ventilation (19–20). For this reason, we also analyzed which patients achieved delivery of at least two-thirds of the prescribed energy requirements by the end of the first week, and we found differences between these two groups in terms of QFMT [-8.5% (IQR − 18 to 0%) vs -22.5% (IQR − 24 to -15%) p = 0.020]
Hulst et al. demonstrated that cumulative protein deficits are associated with a decline in mid-arm circumference (21). Mehta et al., in a study involving 1245 children from 59 PICUs, reported that a greater delivery (> 60%) of the prescribed protein intake was associated with lower mortality rates in mechanically ventilated children (22). Protein is the main source of energy substrate during the catabolic stress phase of critical illness and muscle wasting seems to be negatively associated with total protein delivery (13, 23). Furthermore, Ferry et al., assessing 119 critically ill patients, compared amino-acid intakes of 0.8 g/kg/day and 1.2 g/kg/day delivered by parenteral nutrition and also demonstrated that greater amino acid provision was associated with significantly greater forearm muscle thickness evaluated by ultrasound (24). In our study, protein deficit intake was also associated with a greater decrease in QFMT (r = 0.38, p = 0.015)
The extent of inflammation may also impact muscle metabolism shifts in critical illness. Orellana et al., demonstrated that sepsis decreases muscle protein synthesis due to reduced mRNA translation of anabolic signaling (25). Dysregulation of the GH/IGF-1 axis has also been observed in children with sepsis. It was hypothesized that the elevated GH levels that occurred during critical illness resulted from a combination of elevated inflammatory cytokine production and a lack of feedback inhibition from reduced IGF-1 levels, leads to a GH-resistant condition. Our PICU muscle mass monitoring study demonstrates that muscle atrophy is greater in children who have the highest values of CRP (r = 0.44, p = 0.004)
In animal models, prolonged immobilization and pharmacological denervation (neuromuscular blockade) of muscle result in myosin thick filament loss, consistent with acute quadriplegic myopathy. A higher level of atrophy was found in children who were infused with NMB compared to children in the same cohort who did not receive these drugs: [-24% (IQR = -32.5 to -15%) vs. -6.25% (IQR = -16.25 to 0%); p = 0.001], as well as an increase in the daily atrophy rate [-1.85% (IQR = -4 .9 to 0.91%)] compared to unexposed patients [− 0.89% (IQR = − 2.3 to 0%); p = 0.031]. This agrees with previous findings suggesting that NMB infusion can exacerbate muscle atrophy (5).
The strength of the present study lies in the precise measurement of muscle parameters. The smaller anatomical dimensions of children make it more challenging to reliably identify ultrasonographic muscle changes compared to adults. It is also important that, while measuring thickness, the authors tried to eliminate the error by defining the margins of muscles; standardizing the position of leg, level of sedation, and site of measurement; and avoiding compression. Previous studies have excluded neonates less than 1 week old (4) and infants aged less than 12 months (8, 9); one of the key strengths of this review is, therefore, that we included these patients in our analysis. The limitations of the study include the fact that it involved a single center and relatively small sample, which may hamper generalization to other centers. One of the inclusion criteria, requiring patients to be expected to remain intubated for at least 48 hours after enrollment, resulted in the selection of a cohort of ill patients than the general PICU population. Another limitation is the lack of a long-term follow-up, which prevents the characterization of functional deficits and/or recovery; however it wasn't the point of the study, which was to look at how often kids in the NICU lose muscle and what causes it.