Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03924232 |
| Other study ID # |
BUS |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
October 1, 2017 |
| Est. completion date |
December 1, 2019 |
Study information
| Verified date |
November 2020 |
| Source |
University of Milan |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Critically ill patients are characterized by wide variations in their carbohydrate, lipid,
and protein metabolism. Such variations can lead to increase in their energy requirement with
accelerated protein catabolism and ultimately alterations of their immune and
gastrointestinal systems, and in a variable frame time, it lead to a disruption of muscular
function that increased the ICU and hospital stay and mortality. There are multiple methods
to conduct these measurements. However, the accuracy of these measures could be very scares.
Skeletal muscle wasting in the critically ill is often masked by fluid retention. For these
reasons, in the last few decades, several different tools have been developed to integrate
the clinical and biochemical nutritional evaluations. Among these, the bioimpedance analysis
(BIA) and the muscular ultrasonography (MU) seem to be promising tools for this purpose.
The aim of this project is to compare and integrate the data collected by BIA and MU and the
routinely clinical used parameters of nutrition to define the nutritional status of
critically ill patients. The data from these tools and the biochemical and anthropometric
nutritional data (including the nutritional support) will be collected at the admission in
ICU and followed up within the first week of ICU stay.
Description:
the Bioelectrical impedance analysis and muscular Ultrasound in the detection of nutritional
Status in critically ill patients
Critically ill patients are characterized by wide variations in their carbohydrate, lipid,
and protein metabolism. Such variations can lead to increase in their energy requirement with
accelerated protein catabolism and ultimately alterations of their immune and
gastrointestinal systems, and in a variable frame time, it lead to a disruption of muscular
function that increased the ICU and hospital stay and mortality. It has been observed that
most of the critically ill patients who survive acute respiratory distress syndrome have to
deal with a wide variety of consequences, including muscular wasting and weakness, and these
conditions could last for at least one year. Intensive care unit acquired weakness has been
defined as generalized weakness that develops during critical illness and where no other
explanation than critical illness is present and is associated with long-term consequences
from the medical, human, and socioeconomic point of view. In the normal weight person, the
metabolic response to injury causes an increase in protein and energy requirements. As a
result, endogenous substrates serve as fuel sources and as precursors for protein synthesis.
From the nutrition perspective, one of the main challenges of providing nutritional support
to critically ill patients is to stop or slow lean mass losses. For these reasons, it is
fundamental for the nutritional support clinician to be able to measure and assess muscle
wasting during critical illness, using an easy and accessible technique.
There are multiple methods to conduct these measurements. Usually, admission weight and
height should be used to calculate the ideal body weight (IBW), the percentage of IBW, and
the Body Mass Index (BMI). However, the accuracy of these measures could be very scares.
Skeletal muscle wasting in the critically ill is often masked by fluid retention. In these
circumstances the normal anthropometric methods of assessing changes in body mass and
composition are not applicable, as the techniques all assume a normal state of hydration.
Thus, additional anthropometric data although useful in ambulatory patients, are not as
accurate measures of malnutrition in the critically ill patients. Moreover, some serum
proteins (such as albumin level and several other transport proteins) are commonly measured
as surrogates of visceral protein status. However, all of them are influenced by many factors
such as synthesis and degradation rates and vascular losses into the surrounding
interstitium, in addition to losses through the gut or kidney. As a result, their levels drop
by inflammation or sepsis where high levels of interleukin-6 stimulate acute phase protein
production as it inhibits transport protein production. Thus, they are a poor indicator of
critically ill patients' nutritional status as they serve as a marker of injury and metabolic
response to stress. For these reasons, in the last few decades, several different tools have
been developed to integrate the clinical and biochemical nutritional evaluations. Among
these, the bioimpedance analysis (BIA) and the muscular ultrasonography (MU) seem to be
promising tools for this purpose.
The aim of this project is to compare and integrate the data collected by BIA and MU and the
routinely clinical used parameters of nutrition to define the nutritional status of
critically ill patients. The data from these tools and the biochemical and anthropometric
nutritional data (including the nutritional support) will be collected at the admission in
ICU and followed up within the first week of ICU stay.
Bioimpedance analysis
Bioelectrical impedance analysis (BIA) is the collective term that describes the non-invasive
methods to measure the electrical body responses to the introduction of a low-level,
alternating current. Recently, advances in BIA technology gave rise to detailed and
sophisticated data analyses and targeted applications in clinical practice included the
critical care environment. The Bioelectric Impedance Vector Analysis (BIVA) is today a
commonly used approach for body composition measurements and assessment of clinical condition
and has recently been developed to assess both nutritional status and tissue hydration.
Basically, BIA measures the opposition of body tissues to the flow of a small alternating
current (i.e. the impedance). The classical BIA method consists of the use of four electrodes
attached to the hands, wrist, foots and ankles in which a painless electrical current at a
fixed or multiple frequency is introduced in the organism. Thus, BIA only measures the end
to-end voltage across the entire path between the voltage-sensing electrodes. This voltage is
the energy expended per unit of charge for the total current path and it does not provide any
direct information with respect to the amount of current traveling through intracellular
versus extracellular volumes, in blood versus muscle, or in fat versus fat-free media. The
impedance is a function of two components (or vectors): the "resistance" (R) of the tissues
themselves and the additional opposition or "reactance" (Xc).
Bioimpedance in the Nutritional assessment The metabolic response to critical illness is
characterized by increased energy expenditure, proteolysis, gluconeogenesis and myolysis with
an increment that exceeds 100% of predicted energy expenditure. This prediction can be
influenced by volume overload, since body weight is often used in equations to predict energy
needs. Increased proteolysis leads to accelerated protein loss, which occurs despite
provision of exogenous protein and non-protein intakes. Thus, muscle wasting often occurs due
to increased metabolic demands on the body, determining major losses of lean tissue due to
severity of illness and organ dysfunction, prolonged immobility, and malnutrition. The
variability of BIA measurements has often been cited as a major limitation for its clinical
use in evaluating nutritional status. Moreover, the oldest studies were performed using a
classical BIA to determine the body composition while the more recent studies focused the
attention on the use of BIVA and phase angle (PA) analysis.
Bedside muscular ultrasonography in critically ill patients With growing interest in
understanding muscle atrophy and function in critically ill patients and survivors,
ultrasound is emerging as a potentially powerful tool for skeletal muscle quantification. It
represents a simple, non-invasive method of quantification not only of central muscular (such
as the diaphragm) contractile activity, but also for the peripheral skeletal muscle atrophy.
This muscle quantification combined with metabolic, nutritional, and functional markers will
allow optimal patient assessment and prognosis. It is now well accepted how to assess the
diaphragm excursion and diaphragm thickening during breathing and the meaning of these
measurements under spontaneous or mechanical ventilation, as well as features of skeletal
muscle (including muscle quantity measures like mass and cross-sectional area and muscle
quality measures such as architecture and evidence of myonecrosis) may provide a more
feasible and objective approach to assessing muscle health in ICU patients. Moreover,
objective quantifications of muscle (which include, but are not limited to, muscle mass,
thickness, and cross-sectional area) that are sufficiently sensitive to detect small changes
over acute timeframes may ultimately facilitate evaluation of interventions to counter muscle
atrophy and weakness.
The diaphragmatic evaluation The relative contribution of patient effort during assisted
breathing is difficult to measure in clinical conditions. Moreover, the diaphragm is
inaccessible to direct clinical assessment. Bedside ultrasonography, which is already crucial
in several aspects of critically illness has recently been proposed as a simple, non-invasive
method of quantification of diaphragm contractile activity. Ultrasound can be used to
determine diaphragm excursion, which may help to identify patients with diaphragm
dysfunction.
Ultrasonographic examination can also allow for the direct visualization of diaphragm
thickness in its zone of apposition. Thickening during active breathing has been proposed to
reflect the magnitude of diaphragm effort, similarly to an ejection fraction of the heart.
A number of recent studies employed ultrasound to measure diaphragm thickness and inspiratory
thickening in ventilated patients. Some of them focused on the feasibility and
reproducibility of the technique, while other36 showed how with increasing levels of pressure
support (PSV), parallel reductions were found between diaphragm thickening and both diaphragm
and esophageal pressure-time product suggesting that diaphragm thickening is a reliable
indicator of respiratory effort.
Measurement of diaphragm thickness The right hemidiaphragm can be visualized in the zone of
apposition of the diaphragm to the rib cage with the probe placed in the midaxillary line,
between the 8th and 10th intercostal space, as a 3-layered structure consisting of pleural
and peritoneal (hyperechogenic) membranes and the hypoechogenic layer of muscle itself. This
site is ideal for ultrasonographic visualization, since the diaphragm is bounded by soft
tissue on either side and lies parallel to the skin surface and, therefore, the transducer
face. The diaphragm is additionally dynamically identified as the most superficial structure
that is obliterated by the leading edge of the lung upon inspiration. Eventually, it is
identified by direct visualization of its contraction at the beginning of the respiratory
cycle.
B-mode Using a 7.5-10 MHz linear probe, set in B-mode and placed parallel to a intercostal
space between the VIII and X, the inferior edge of costophrenic angle is identified by the
transient appearance of the lung artifact with breathing. Diaphragm thickness (Tdi) can be
measured both during tidal breathing and during a maximal inspiratory effort. Several studies
were performed to establish reference values of Tdi in supine healthy subjects, showing for
the right hemidiaphragm mean values of 0.3238 cm or 0.3339 cm, independently of sex, age or
body constitution.
M-mode The probe is placed with the same landmark previously described for B-mode with the
aim to identify pleural and peritoneal membranes around the diaphragm. Diaphragm thickness is
measured at end-expiration (Tdi,ee) and peak inspiration (Tdi,pi) as the distance between the
diaphragmatic pleura and the peritoneum using M-mode .
Peripheral muscular assessment It has been shown that muscle mass measurement by
ultrasonography (US) is a reliable technique in most of the patients even when oedema and
fluid retention are present. Muscle mass loss in critically ill patients has been assessed by
US, histological, and molecular biology techniques, showing a significant reduction of
approximately 10% of the rectus femoris (RF) cross-sectional area (CSA) measured by US
correlating with a decrease in muscle fibres CSA and less protein synthesis. US has become a
widely used research technique to quantify muscle wasting showing remarkable accuracy and
reliability with strong clinimetric properties and excellent intra- and interobserver
reliability in healthy people measured by clinicians with no previous experience in US45.
The lower limbs muscles are prone to early atrophy, showed by a greater decrease of thickness
within the first five days of admission to the intensive care unit compared with upper limbs,
making these muscles a good target for muscle mass assessment.
The quadriceps femoris is a group of muscles composed by three vastus muscles (medialis,
intermedius, and lateralis) and the RF. The latter one presents a proximal insertion in the
anterior inferior iliac spine (AIIS) and other insertion in the supra-acetabular sulcus. The
quadriceps femoris is distally inserted in the tibial tuberosity by a common ligament and is
a hip flexor and a knee extensor. Before starting, make sure the patient is in supine
position with extended knees and toes pointing to the ceiling. This is the most used position
in this kind of measurements. This position helps the practitioner to place the patient in
the AIIS Patella 1/2 AIIS Patella 1/2 1/3 1/3.
A specific technique technique has been proposed: using a non-stretchable measuring tape,
trace an imaginary line in the anterior part of the thigh from the AIIS to the midpoint of
the proximal border of the patella and mark the middle and one third point between these two
references which easily give us access to the RF and VI. The reason to use de AIIS and not
the anterior superior iliac spine is because using the exact middle point of the muscle helps
us to find its thickest part using as reference the insertion points of this muscle (RF) and
the reason to use a third of the distance will be discussed latter. To obtain a
cross-sectional image, the transducer must be oriented transversally to the longitudinal axis
(the imaginary line marked before) of the thigh forming a 90∘ angle in relation to the skin
surface. Tilting or moving the probe from its original position and angle will contribute to
obtaining an incorrect measurement.
Methodology The aim of the present study is to investigate and compare the diaphragmatic
thickness and the cross sectional area of the rectus assessed with ultrasound using the above
mentioned methodology and the data collected from BIVA as well as the nutritional and
anthropometrics parameters routinely used in clinical practice. The investigators will study
consecutive mechanically ventilated patients admitted in the ICU of our teaching hospital.
The investigators will screen each consecutive patient who required mechanical ventilation
for at least 72 hours. Non-inclusion criteria will be age <18 years, pregnancy, prevision of
ICU stays less than 7 days, history/diagnosis of neuromuscular disease. Within the first 24
hours of ICU admission (T1), patients will be evaluated with muscular ultrasonography
comprehensive of diaphragm thickness and rectus femoris (medial vastus) cross-sectional area.
At the same time, anthropometric measure will be collected (such as body height, ideal body
weight, real body weight declared, right arm circumference) as well as BIVA measure (Xc, R,
PA, lean body weight and % of extracellular body weight) and biochemical analysis (inclusive
albumin, pre-albumin, blood count, lymphocyte count, magnesium, phosphorus, reticulocytes,
renal and hepatic function test). The day after, the fluid balance will be calculated as well
as the nitrogen balance. All the same measures will be repeated at day 3 (T3) and 7 days
(T7).
The main outcome of the study is to evaluate the derived BIVA parameters, especially the
variation of PA, within the first week after ICU admission. The secondary outcomes are to
evaluate the BIVA parameters variations and the "central" and "peripheral" muscular
sonographic parameters as well as the anthropometric and biochemical nutritional indexes and
their eventually correlations.
Statistical Analysis
Data will be analyzed using Stata/SE 12.0 (StataCorp, College Station) statistical software
package. 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. Comparison between related variables will be performed by paired Student's t-test
or Wilcoxon sign-rank test, as needed. Two-tailed p values less than 0.05 will be considered
statistically significant. The computation of the study power is based on the primary
outcome. In a previous study, Kim and colleagues49 evaluated the variation of the PA in
critically illness patients and the mean PA value was 3.5±1.5. Assuming a variation of 20% of
the PA within the first week, a total sample size of 97 patients is calculated for 80% power
at a 5% significance level.
