Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04864093 |
| Other study ID # |
Umilan@ |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 21, 2021 |
| Est. completion date |
October 21, 2021 |
Study information
| Verified date |
April 2022 |
| Source |
University of Milan |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Skeletal muscle weakness is a common complication of acute respiratory failure, shock and
other manifestations of critical illness or injury. ICU acquired weakness (ICUAW) - an entity
defined as a bundle of critically illness neuro-myopathy and disuse atrophy - is generally
diagnosed on the basis of a volitional, clinical strength evaluation, which however requires
patient cooperation and ability to comprehend the assessor's instructions. As patients are
often unconscious or uncooperative, due to sedation or delirium, such clinical diagnosis is
often not possible or is delayed. A further subclassification of critical illness
neuromyopathy can be achieved using detailed nonvolitional electrophysiological
investigations, which can be challenging in the ICU as they require skilled personnel for
both assessment and interpretation. An average Medical Research Council strength score
(MRC-SS) combined for 12 specified muscle groups lower than 48 has been widely used for
diagnosing ICUAW. Recent studies reported the clinical applicability of the MRC-SS in a
general ICU population, in particular its clinical usefulness in predicting ICU and
in-hospital patient outcomes . Moreover, interobserver agreement and clinical predictive
value have already been showed (8). However, ICU general population is less likely to be able
to cooperate with volitional strength assessment and more likely to have limited access to
their extremities because of trauma, burns and treatment involving medical devices. For these
reasons, MRC-SS may be confined to the later stages of ICU stay. Skeletal muscle ultrasound
is used for the evaluation of muscular, tendon and joint disorders. It allows the evaluation
of normal and pathological skeletal muscles through the measure of parameters reflecting
size, such as cross sectional area (CSA) , and architecture by calculating the pennation
angle, and it allows quick and repeated bedside evaluations. Despite such promising features,
to date, there are few published studies that have reported the clinical applicability of the
muscle ultrasound in prediction of ICUAW during the ICU stay. The principal aim of this study
is to evaluate the variation of peripheral muscle ultrasound characteristics (such as CSA and
pennation angle) during the ICU stay and its possible early predictive value of ICUAW as
compared to the MRC-SS performed when patients are able to cooperate.
Description:
Skeletal muscle weakness is a common complication of acute respiratory failure, shock and
other manifestations of critical illness or injury. ICU acquired weakness (ICUAW) - an entity
defined as a bundle of critically illness neuro-myopathy and disuse atrophy - is generally
diagnosed on the basis of a volitional, clinical strength evaluation, which however requires
patient cooperation and ability to comprehend the assessor's instructions. As patients are
often unconscious or uncooperative, due to sedation or delirium, such clinical diagnosis is
often not possible or is delayed. A further subclassification of critical illness
neuromyopathy can be achieved using detailed nonvolitional electrophysiological
investigations, which can be challenging in the ICU as they require skilled personnel for
both assessment and interpretation. An average Medical Research Council strength score
(MRC-SS) combined for 12 specified muscle groups lower than 48 has been widely used for
diagnosing ICUAW. Recent studies reported the clinical applicability of the MRC-SS in a
general ICU population, in particular its clinical usefulness in predicting ICU and
in-hospital patient outcomes . Moreover, interobserver agreement and clinical predictive
value have already been showed (8). However, ICU general population is less likely to be able
to cooperate with volitional strength assessment and more likely to have limited access to
their extremities because of trauma, burns and treatment involving medical devices. For these
reasons, MRC-SS may be confined to the later stages of ICU stay. Skeletal muscle ultrasound
is used for the evaluation of muscular, tendon and joint disorders. It allows the evaluation
of normal and pathological skeletal muscles through the measure of parameters reflecting
size, such as cross sectional area (CSA) , and architecture by calculating the pennation
angle, and it allows quick and repeated bedside evaluations. Despite such promising features,
to date, there are few published studies that have reported the clinical applicability of the
muscle ultrasound in prediction of ICUAW during the ICU stay. The principal aim of this study
is to evaluate the variation of peripheral muscle ultrasound characteristics (such as CSA and
pennation angle) during the ICU stay and its possible early predictive value of ICUAW as
compared to the MRC-SS performed when patients are able to cooperate.
Materials and methods
Study design and ethical approval
observational, single-center study in a mixed medical and surgical ICU in a university
teaching hospital. We will investigate the variation of CSA and pennation angle of rectus
femoris over the ICU stay. Moreover, we will examine the clinical predictive value of these
two variables as compared with MRC-SS at awakening. Patients 18 years of age and older who
had been invasively ventilated for 48 hours were eligible for inclusion. Exclusion criteria
included preexisting neurological weakness, pregnancy, malignancy, and those admitted for
routine overnight postoperative surgical recovery. A flow diagram of the study is showed in
figure 1.
Study protocol
At ICU admission (T1), patients underwent muscular ultrasound comprehensive of rectus femoris
cross sectional area (RFCSA) and pennation angle, diaphragm, and parasternal intercostal
end-expiratory thickness appraisal. At the same time, anthropometric data and biochemical
parameters necessary for the calculations of severity score (Sequential organ failure
assessment -SOFA (16); Simplified acute physiology score- SAPS II ; Acute Physiology and
Chronic Health Evaluation - APACHE II ) were collected. All the same measures were repeated
at day 3 (T3) and 7 (T7).
Anthropometric Assessment
Anthropometric measurements of body length and weight will be recorded at ICU admission. The
actual body weight as reported by the patients when able to do it was collected. From
anthropometric data, body mass index (BMI, kg/m2) will be calculated, while ideal body weight
was calculated using a standard formula as previously described .
Muscular ultrasound
RFCSA will bemeasured by B-mode ultrasonography using an 8 MHz, 5.6 cm linear transducer
array (MindRay TE-5 machine, Mindray Bio-Medical Electronics Co. Ltd. Shenzen, China),
similar to the method described elsewhere (11). The pennation angle, the angle of insertion
of muscle fascicles into the deep aponeurosis, of the rectus femoris will be measure on the
longitudinal view by rotating the probe parallel to either the lateral or medial head of the
muscle on the position where we measured CSA. To obtain precise measurements of muscle
parameters, all measurements will be performed by the same sonographer (PF) with 5 years of
experience . All data will be measure three times, and the average value will be used for
further analysis.
Diaphragm end-expiratory thickness will be measure in the right hemi-diaphragm in the zone of
apposition as described elsewhere . All ultrasound examinations will be performe using a
10-15 MHz linear transducer in B mode (MindRay TE-5 machine, Mindray Bio-Medical Electronics
Co. Ltd. Shenzen, China) by the same trained operators (PF). The inferior border of the
costophrenic sinus will be identifiy as the zone of transition from the artefactual
representation of the lung to the visualization of diaphragm and liver. The expiratory
thickening of the parasternal intercostal muscles will be assesse with a linear probe placed
3 cm laterally from the sternum, and oriented along the sagittal plane, between the 2nd and
the 3rd ribs (22). Muscle thickness will be measure just above the pleural line between the
inner and outermost hyperechogenic layers of the muscle fascial borders. Images will be
recorde for a subsequent computer-assisted quantitative analysis performed by a trained
investigator (MU), unaware of the ventilatory condition.
MRC-SS
The consciousness level of patients will be determine using the Richmond Agitation Sedation
Scale, with a score from -1 to +1 being indicative of wakefulness. Awake patients will then
required to demonstrate a positive response to simple one-stage commands. Successful
completion of commands was followed by muscle strength assessment using the MRC-SS - a
six-point grading scale ranging from 0 (no visible contraction) to 5 (normal power) applied
to six upper- and lower-limb muscle groups bilaterally (25). The day upon which MRC-SS will
be performe will be recorded. ICUAW is defined as an MRC-SS less than 48 out of a possible
score of 60. A standardized protocol for performing the MRC-SS will be always followed during
testing. Given the volitional nature of manual muscle testing, strong verbal encouragement
will be provided during all strength assessments.
statistical analysis
The computation of the study power isbased on the primary outcome (prediction of ICU-acquired
weakness). A previous study found a correlation between diaphragm ultrasound and the
development of ICU-acquired weakness of r=0.3. Since the current study also assesses
peripheral muscle ultrasound, we hypothesized that a stronger correlation (about twice that
found in the cited study) could be found with 80% power at a 5% significance level by
enrolling 47 patients.
Data will be analyzed using Stata/SE 12.0 (StataCorp, College Station, TX USA) statistical
software package. Two-tailed P-values <0.05 will be considered statistically significant.
Normality will be assessed by the Shapiro-Francia test. Results will be reported as mean ±
standard deviation if normally distributed, or median [25-75th percentiles] otherwise, and
differences will be tested with a two-sided t test or the MannWhitney U test. Categorical
variables are expressed as counts and percentage and the Chi-square or Fischer exact test
will be used for analysis.
