What are reference values of the thickness and the thickening fraction of the diaphragm in children aged 0-8 years?

Critically ill children treated with invasive mechanical ventilation (iMV) in a
paediatric intensive care unit (PICU) may suffer from complications leading to
prolonged duration of ventilation and PICU stay. (6-8) These complications may
prolong the durations of iMV and PICU stay, which in turn could lead to a
cascade of extensive complications, such as ventilator associated pneumonia and
delirium, especially if deeper sedation is needed.(8-11)
Nevertheless, premature extubation should be prevented, as it may necessitate
re-intubation, with increased risk of morbidity and mortality. (12) The
consequences of a longer duration of iMV should be weighed agains those of too
early intubation.(13) Failure to wean of iMV is associated with haemodynamic
dysfunction, neuromuscular insufficiency, malnutrition, metabolic disorders and
diaphragmatic muscle weakness.(9, 13)
Studies in adult ICU patients support the existence of ventilator-induced
diaphragmatic dysfunction (VIDD), defined as iMV-induced loss of diaphragmatic
force-generating capacity, characterised by muscle fibre atrophy, myofibril
necrosis and disorganization.(14, 15) A study by Levine et al. (16) showed
atrophy of slow and fast fibers in ventilated adults. Diaphragm atrophy occurs
within as few as 18 hours of iMV, progresses at a rate between 4% and 7% per
day of iMV and is associated with extubation failure and increased
mortality.(17, 18) The progression of diaphragm atrophy was exacerbated by the
length of iMV, low spontaneous breathing fraction, use of neuromuscular
blockade, and exposure to corticosteroids
Diaphragm function or contractility can be assessed by measuring the
diaphragm thickening during inspiration and expressed as a thickening fraction
(TF) with ultrasound. Diaphragm TF correlates strongly with diaphragm
strength.(19) Absence of diaphragm thickening has been seen in patients with
diaphragm paralysis.(20, 21)
Goligher et al. showed in adult ventilated ICU patients that a low
diaphragm contractile activity was associated with rapid decreases in diaphragm
thickness, whereas high contractile activity was associated with increases in
diaphragm thickness (P=0.002). Contractile activity decreased with increasing
ventilator driving pressure (P=0.01) and controlled ventilator mode (P=0.002).
Maximal thickening fraction (a measure of diaphragm function) was lower in
patients with decreased or increased diaphragm thickness than in patients with
unchanged thickness (p=0.05).Titrating ventilatory support to maintain normal
levels of inspiratory effort may prevent changes in diaphragm configuration
associated with iMV.(4)
Dres et al. have showed a large difference in the diaphragm TF between patients
with or without diaphragm dysfunction (mean TF of 19 ± 9 % vs. 35 ± 12 %) under
the same pressure support values. This suggested a much lower contribution of
the diaphragm reflected by a lower tidal volume at VIDD. (22) Several adult
studies have provided evidence of more frequent reintubation if the diaphragm
cannot sufficiently thicken.(1, 3, 4, 17, 22-28)
Literature about diaphragm atrophy and VIDD in children is scarce. A recent
study showed that diaphragm atrophy is also present in critically ill children
receiving iMV for acute respiratory failure, like in adults. In that study, the
diaphragm contractility, measured as thickening fraction, was strongly
correlated with a spontaneous breathing fraction (beta coefficient 9.4 [95% CI,
4.2-14.7]; p=0.001).(24) Because diaphragm atrophy and less TF in adults have
been associated with a longer duration of iMV (caused by a longer weaning
period) it seems logical that diaphragm atrophy and VIDD also will negatively
affect the outcome of children with acute respiratory failure.(27)
There is no gold standard for the weaning off ventilation, and validated
extubation criteria are lacking.(29-31) A spontaneous breathing trial does not
provide sufficient information about the work of breathing that has to be
performed after extubation. This also depends on the sedation depth. A TF index
could be a predictor for successful extubation. So far, this has been confirmed
by one study in 31 ventilated children.(25) That study found that in the first
24 hours of iMV, the diaphragm thickness and TF substantially decreased and
thereafter gradually decreased. TF after attempted extubation was significantly
different between the children who were successful extubated and the children
in whom this failed (P<0.001). A TF value of < 17% was associated with
extubation failure. Ultrasound studies to measure the diaphragm thickness and
TF had been performed daily until the child*s discharge from the PICU. (25)
Glau et al. found in 56 ventilated children that diaphragm contractility
measured as TF is linearly correlated to a spontaneous respiratory fraction.
They did the first ultrasound within 36 hours and a final one just before
extubation. The study was underpowered, however, to measure daily atrophy for
different levels of respiratory support for extubation, and only two children
needed to be re-intubated. The clinical impact of diaphragm atrophy on
extubation success has therefore not yet been sufficiently demonstrated.
Failure of extubation occurs in approximately 6-8% of children and half of
these have upper airway obstruction due to airway damage through the tube.(29,
32, 33)
Diaphragmatic dysfunction is difficult to measure without knowing norm data for
normal diaphragmatic thickness and thickening fraction in infants and children.
Norm data is only available for healthy neonates (n=15) and from the age group
8-20 years (n=48).(34, 35)
The purpose of this study is to determine values of normal diaphragm thickness
and TF in children aged 0-8 years old by ultrasound. This age group represents
the largest patient group treated in the PICU. Once these values are known, the
clinical relevance of the measuring of the diaphragm thickness of ventilated
children by ultrasound can be further studied.

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Primary objective: To determine diaphragm thickness and thickening fraction in
healthy children below or equal to 8 years of age.
Secondary objective: To determine the interrater reliability of operators
performing the ultra-sound

prospective, cohort study.

A non-invasive ultrasound study does not carry any risks. A possible burden is
that the child is expected to lie still for ten minutes, but they may be
supported by the parents.
The necessity to lie still cannot be explained to children aged 0-2 years;
therefore we will we attempt to distract them.
It is important to know the normal thickness of the diaphragm in children and
there is no other way to get this. An ultrasound study is the least stressful
method and does not give radiation exposure, unlike a CT scan.