The BIA and MUS in the Detection of Nutritional Status in Critically Ill Patients
The BIA and MUS 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. 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.
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.
Inclusion Criteria:

 -  All patients aged 18 or older and with a recent (<48h) ICU entry requiring mechanical
 ventilation for at least 3 days will be considered for enrolment

 Exclusion Criteria:

 -  not intubated patients

 -  patients with an ICU prevision of stay less than 3 days