**2. Assessment of muscle mass and nutritional status in intensive care**

Critically ill patients require a muscle mass assessment during their ICU stay. Unfortunately, the tools used to assess nutritional status are poor indicators of malnutrition in the critically ill population. A sarcopenic obesity, characterized by excess fat and fluid retention of 10–20% of the patient's body weight can mask the skeletal muscle wasting in the ICU [15]. Many ICU patients are edematous, and the measured weight, the BMI, and anthropometric measurements (mid-upper arm circumference and triceps skinfold thickness) may not reflect the real body muscle mass and could have limited results [16, 17]. In the ICU setting, albumin is also a poor marker of nutritional status not only due to changes in intravascular volume but also due to the impact of acute infection, inflammation, hepatic function, etc. [18]. Concerning the use of tools that assess muscle mass and nutrition, such as Nutrition Risk in Critically Ill Score [19], are difficult to perform and hence they cannot uniformly identify patients at risk of malnutrition. The bioelectrical impedance vector analysis is a useful method not only to evaluate tissue hydration but also to detect muscle mass variations in sarcopenic indictviduals, and it is able to discriminate sarcopenic individuals from sarcopenic obese individuals. However, the bioelectrical impedance vector analysis has some limitations: estimation of hydration status is related to fat-free mass, which basically means muscle mass (in the limbs). Whereas, the limbs contribute roughly 90% to whole body impedance, only 6–12% are contributed by the trunk which, however, provides roughly 50% of the body weight and stores most of the surplus volume [20]. A baseline muscle mass assessment in the acutely critically ill patient is challenging. Muscle ultrasound is an attractive emerging technique able to offer qualitative analysis [21], inexpensive, and readily available at bedside. Unlike computed tomography (CT), however, international consensus does not exist on methodology, with significant differences between the techniques [21]. Although CT scans provide a reliable measure of muscle mass in these medically ill populations, CT scans are not performed on every critically ill patient due to cost and radiation exposure [22].

#### **3. Muscle wasting and serum creatinine**

After 10 days from the intensive care unit (ICU) admission [23, 24], a dynamic clinical state characterizes a "cascade" of new clinical problems [25]. This transition point is defined as "persistent critical illness" based on the point "beyond which diagnosis and severity of illness at admission are no more predictive of in-hospital mortality than are simple premorbid patient characteristics" [23]. Characterized by persistent inflammation, neurohumoral alterations, and prolonged immobilization, this catabolic state is not suppressed by nutrition [26, 27]. Catabolism results in muscle wasting and associated weakness, which impairs outcome [26–28]. Currently, there is no routine biomarker available with acceptable sensitivity and specificity which is able to monitor catabolism. Accurate monitoring of nitrogen losses and balances is not easy, but the presence and severity of catabolism often becomes clear once muscle loss and weakness are established. SCr is a metabolite of creatine phosphate, an energy store found in skeletal muscle, and in normal subjects it is produced at a constant rate. Particularly, a prolonged immobilization could decrease the plasma volume, bone mass, and skeletal muscle mass [29, 30]. A decrease in muscle

mass could theoretically be associated with changes in the metabolism of urea and sCr. Indeed, a muscle mass reduction could increase the urea generation because the muscular tissue has a high protein content and urea is the final catabolite of endogenous protein breakdown [31]. Disorders associated with dehydration/hypovolemia or with hypercatabolism increase plasma urea [32, 33]. In addition, skeletal muscle mass is the main determining factor of creatinine generation since creatinine is the final catabolite of muscle energy metabolism [34]. A decrease in muscle mass could decrease SCr levels, and conversely, SCr may be falsely increased with higher muscle mass. In addition, creatinine generation is low among individuals who have more diminutive muscle mass, either constitutionally or disease-related [13]. Due to the correlation between SCr levels and muscle mass, SCr in the steady state has been used as a surrogate of muscle mass measurements [35].

#### **3.1 Muscle strength and sarcopenia index**

Sarcopenia is a skeletal muscle disorder that is characterized by the loss of strength and mass together with impairment in physical function [36]. Sarcopenia is a complex syndrome that is associated with muscle mass loss, alone or in conjunction with increased fat mass. Since 2018, sarcopenia is not only considered as a debilitating condition that involves loss of muscle mass and function but also as a muscle disease. However, challenges in understanding the current evidence of the role of nutrition is represented by the number of different aspects of muscle health that have been considered as outcomes, both in observational and interventional study. New guidelines, which aim to improve consistency in the identification of sarcopenia in clinical care, identify muscle strength as the key characteristic of sarcopenia. This new guidance may also offer a useful structure within which to evaluate the influences on muscle health, including the effects of differences in diet [37]. Thus, a low muscle strength leads to a diagnosis of probable sarcopenia [37]. Sarcopenia is associated with frailty, poor surgical outcomes, prolonged need for mechanical ventilation, increased hospital cost, depression, decreased quality of life, increased risk of fall, nursing home residence, and a higher risk of death [38]. Evaluation of patients with sarcopenia could be really difficult as often physical function assessment is not performed and the measurement of muscle mass requires expensive and complex radiologic technique [39]. In addition, BMI, serum albumin levels, prealbumin levels, and physical examination lack in sensitivity and specificity to be used as surrogates for muscle mass. As previously reported, a low baseline sCr value is associated with a worse outcome and has been proposed as an indicator of low muscle mass [recently, a method to estimate muscle mass, named sarcopenia index (SI), was developed using the differential origin of two molecules cleared by the kidney: sCr (skeletal muscle cells) and cystatin C (nucleated cells) [40, 41], assuming steady kidney function]. The SI was calculated as (sCr value/cystatin C value) × 100. The SI not only significantly correlates with imaging but also it has a superior performance compared with sCr alone in estimation of muscle mass, as reported by recent evidence [42].

#### **3.2 Urea:creatinine ratio**

The lack of validated and routinely available biomarkers of catabolism to some extent hampers the epidemiological and interventional studies on this topic. The initial decreases in sCr may be from altered metabolism and reflect bioenergetic failure. The subsequent continued fall in sCr reflected the length of ICU stay and length of hospitalization, and it is due to skeletal muscle loss (decreasing creatinine production) [43, 44]. Particularly, from 3 to 4 days after ICU admission, urea progressively rises, with a higher peak and greater duration of elevation in those patients remaining longer *Serum Creatinine, Muscle Mass, and Nutritional Status in Intensive Care DOI: http://dx.doi.org/10.5772/intechopen.93653*

**Figure 1.** *Urea:creatinine ratio in critical illness.*

in ICU. Recently, it was suggested that a persistent elevation in urea might reflect increased production from muscle catabolism, amino acid liberation, and metabolism. Based on the observed trajectory of urea, this catabolic state appears to persist throughout ICU admission [27]. For this reason, elevated urea:creatinine (UCR) may reflect a combination of muscle bioenergetic failure, muscle catabolism/altered protein homeostasis, and persistent muscle wasting, providing a metabolic signature of the effects of prolonged critical illness [27, 45, 46]. Although the potential role of UCR in future studies, clinical usability seem limited, as other factors such as the following may increase UCR independent of catabolism: decreased effective blood volume, protein intake or gastrointestinal bleeding, and acute kidney injury (**Figure 1**).

Particularly, despite altered tubular reabsorption of urea (normally 40–50%) can affect the serum urea:creatinine, classically increased urea retention occurs during severe dehydration with preserved tubular function. Conversely, tubular injury in AKI will lessen the concentrating capacity, thereby lessening urea:creatinine [47].
