The Evaluation of Acute Sarcopenia in Hospitalized Elderly: Muscle Characteristics Assessment Through Ultrasound
Conditions: Sarcopenia
Sponsor: Universiteit Antwerpen

 
 
 
 
 
 
SARCUS2 
Acute sarcopenia in hospitalized elderly - 
assessment through ultrasound 
 
 
 
NCT ID: not yet assigned 
 
 
Date:  23rd of October2018 
 
 
 
 
 
 
 
 
 

 
Acute sarcopenia in hospitalized elderly: 
assessment through ultrasound 
 
Sophie Bastijns a, Jürgen Bauer b, Alfonso J. Cruz-Jentoft c, Anne-Marie De Cock a, Evelien 
Gielen d, Agnieszka Kasiukiewicz e, Francesco Landi f, Ester Marco g, Anna Maria Martone f, 
Ana Merello c, Karolina Piotrowicz h, Elisabet Sanchez c, Dolores Sanchez-Rodriguez i, 
Maurits Vandewoude a,j, Stany Perkisas a,j. 
 
a University of Antwerp, Antwerp, Belgium.  
b Department of Geriatric Medicine, Klinikum, Carl von Ossietzky University, Oldenburg, Germany. 
c Servicio de Geriatría, Hospital Universitario Ramón y Cajal (IRYCIS), Madrid, Spain. 
d Department of Geriatric Medicine, University Hospitals Leuven, Leuven, Belgium. 
e Department of Geriatrics, Medical University in Bialystok, Poland. 
f Department of Geriatrics, Neuroscience and Orthopedics, Teaching Hospital "Agostino Gemelli", Catholic University of the 
Sacred Heart School of Medicine, Rome, Italy. 
g Physical & Rehabilitation Medicine, Parc de Salut Mar; Rehabilitation Research Group, Hospital del Mar Research Institute; 
Universitat Autònoma de Barcelona, Barcelona, Spain. 
h Department of Internal Medicine and Gerontology, Faculty of Medicine, Jagiellonian University Medical College, Kraków, 
Poland. 
i Geriatrics Dpt. Parc Salut Mar. Institut Hospital Del Mar d’Investigacions Mèdiques (IMIM). Universitat Autònoma de 
Barcelona. Universitat Pompeu Fabra. Barcelona, Spain. 
j Belgian Ageing Muscle Society, Belgium. 
 
 
Corresponding author: 
Stany Perkisas, MD 
Address: Leopoldstraat 26, 2000 Antwerp, Belgium 
E-mail: stany.perkisas@zna.be 
Telephone number: 0032-3-280-35-39 
 
 

Highlights 
 
Sarcopenia is known as a decline in muscle function and muscle mass. It is often seen in 
increasing age in otherwise healthy individuals and also in those with multimorbidity. 
Moreover, recent studies highlight that sarcopenia can establish rapidly; this is named acute 
sarcopenia. In this condition acute illnesses, stressors or hospitalisation lead to a decrease in 
muscle mass and function because the acute stress reaction.  
Traditionally, muscle mass – a part of the concept of sarcopenia – is measured by computed 
tomography (CT) or dual-energy X-ray absorptiometry (DEXA) scan. These devices are not 
always easily available in clinical practice and cannot be used bedside. An innovation in 
sarcopenia is the assessment of muscle mass and quality with ultrasound. Because this 
device is much more available and applicable in all patients, diagnosis of acute sarcopenia 
would be much easier with ultrasound. Moreover, if other factors that contribute to 
accelerated decline in muscle mass and function can be determinated, we can screen for 
acute sarcopenia in those individuals and hopefully reverse this mechanism. 
This is the first multicenter study that will investigate the role of acute illness on sarcopenia 
during hospitalisation, assessed through ultrasound. 
 

Abstract 
Sarcopenia is a geriatric syndrome defined as progressive and generalized age-related 
muscle loss with decline in muscle mass and muscle function (either strength or 
performance). It is closely related to adverse outcomes such as frailty, reduced quality of life, 
increased risk of falling, more frequent hospitalisations and higher mortality. Acute 
sarcopenia is the decline of muscle mass and function following acute disease or 
hospitalisation, sufficiently to meet the criteria of sarcopenia.  
Objectives: To assess the effect of hospitalisation and acute illness on muscle mass and 
function, and to assess which other factors contribute to the development of acute 
sarcopenia. 
Study design and main outcome measures: This study is a prospective multicenter 
observational study. Patients admitted to acute geriatric wards of different European centers 
and hospitalised for at least 5 days will be included. Measurements of muscle mass will be 
performed via ultrasound. Measurements of muscle function will be done by hand grip 
strength using Jamar dynamometer and by gait speed using the 4-meter walking test, when 
feasible. Other parameters will be measured via file study, laboratory investigations or 
validated questionnaires. Activity levels during hospitalisation will be measured through 
pedometers. 
Anticipated results: Decline of muscle mass and muscle characteristics secondary to 
hospitalisation. We also expect an association with reasons of hospitalisation, pre-existing 
conditions, laboratory results and nutritional status prior to hospitalisation on the decline in 
muscle parameters. 
Conclusions: This study seeks to gain knowledge of the development of acute sarcopenia 
and its contributing factors. 
Keywords 
 
Acute sarcopenia, assessment, ultrasound, older people, skeletal muscle 
Clinical trial registration number 
???? 
Abbreviations 
CT, Computed Tomography; DEXA, Dual-energy X-ray absorptiometry; EWGSOP, European 
Working Group on Sarcopenia in Older People; BIA, bio-impedance analysis; MRI, magnetic 
resonance imaging; CIRS-G, Cumulative Illness Rating Scale for Geriatrics; CRP, C-reactive 
protein; 25-OH-vitamin D, 25-hydroxyvitamin D; MNA-SF, Mini-Nutritional Assessment – 
Short Form; GLIM, Global Leadership Initiative on Malnutrition; PASE, Physical Activity Scale 
of the Elderly; SDPAR, Seven Day Physical Activity Recall; NMES, Neuromuscular electrical 
stimulation; CRM, Calorie Restriction Mimetics; EM, Exercise Mimetics. 
 
 

1. Introduction 
Sarcopenia is a well-known concept in geriatric medicine, although the definition has 
changed somewhat in recent years. Currently, it is defined by the second meeting of the 
European Working Group on Sarcopenia in Older People (EWGSOP) as a muscle disease 
(muscle failure), with low muscle strength as principal determinant [1].  
 
In a review report from the International Sarcopenia Initiative, the prevalence of sarcopenia 
was reported according to care setting. There was a prevalence of 1-29% in community-
dwelling older people, 10% in older patients in acute hospital care and 14-33% in older 
residents in long-term care [2]. The variability of prevalence is mostly due to the difference in 
assessment methods and cut-off points used. Screening for sarcopenia is very relevant in all 
these settings because it is correlated with mortality, functional decline, a higher rate of falls 
and a higher incidence of hospitalization and institutionalization [3].  
 
A hospitalization poses an extra risk factor for older adults in terms of physical decline. Bed 
rest has a negative effect on muscle mass and muscle function [4-6], more pronounced in 
older people than in young individuals [7]. Acute illness and/or acute stress can lead to 
reduced muscle mass and function because of hypercortisolism and increased 
cortisol/dihydroepiandrosteron ratio [8], oxidative stress and inflammation processes [9, 10]. 
Although some data exist on acute muscle changes [6, 7, 11, 12], this concept of an acute 
component of sarcopenia was only first mentioned in 2016 [13].  
 
Acute sarcopenia, secondary to an acute stressful event followed by hospitalisation, might 
not always recover completely and may lead to development of chronic sarcopenia [6]. 
Patients who have already met the criteria of sarcopenia may also develop an acute-on-
chronic sarcopenia syndrome [8]. Furthermore, sarcopenia is associated with an increased 
length of hospital stay [14, 15], which can create a negative health spiral.  
 
In order to prevent sarcopenia, diagnosis is paramount. There are different methods to 
diagnose sarcopenia [16]. Cut-off points are available for bio-impedance analysis (BIA) and 
dual X-ray absorptiometry (DEXA) but both lack qualitative data on muscle. Computed 
tomography (CT) and magnetic resonance imaging (MRI) provide both qualitative and 
quantitative data [16, 17], but lack cut-off points and are usually not feasible in daily practice. 
Ultrasound can also offer an objective and standardized measure of muscle quantity and 
quality, and is suitable for use on an acute ward since it is easy to perform, cheap, 
reproducible and can be used bedside. Previous reviews concluded that ultrasound 
technique is valid for measuring muscle size compared with measurement instruments such 
as CT and MRI [18]. Although standardization for ultrasound muscle muss measurements in 
older adults have been a major problem, recent efforts have tried to nullify this problem [19]. 
 
1.1. Objective 
The aim of this study is to investigate the effect of hospitalisation due to acute illness on 
muscle mass characteristics, assessed in older adults through ultrasound. The primary 
endpoint is the change of characteristics of muscle mass in function of time since admission. 
The secondary endpoint of the study is to identify health related parameters associated with 
the development of acute sarcopenia. Relevant determinants of the evolution of muscle 

mass and muscle strength since admission (reason of hospitalisation, comorbidities and 
laboratory data) will therefore also be investigated. 
 
1.2. Hypothesis 
Hospitalisation and acute illnesses will negatively affect both muscle mass and muscle 
function and will hereby contribute to the development of acute sarcopenia. We hypothesize 
that hospitalisation due to an elevated degree of inflammation will lead to more severe 
decrease of muscle mass and muscle function than hospitalisation due to non-inflammatory 
reasons. Furthermore, certain pre-existing conditions are supposed to increase the risk of 
acute sarcopenia.  
 
2. Methods 
2.1. Study design 
A prospective, multicenter, international observational study will be conducted. The study is 
designed to determine the effect of hospitalisation due to acute illness on the changes in 
muscle mass and muscle function. The secondary endpoint of the study is to identify health 
related parameters associated with the development of acute sarcopenia. 
 
2.2. Subjects  
2.2.1. Inclusion criteria 
Patients admitted between the 1st of November 2018 until the 31th of October 2019 will be 
eligible for inclusion. Included wards for admission are: internal medicine, acute geriatrics, 
orthogeriatrics and rehabilitation. Age limit will be set on 65 years and older.  
2.2.2. Exclusion criteria 
Patients on dialysis will be excluded because of possible metabolic features. Individuals with 
paresis of the lower limbs or hemiparesis due to a stroke will be excluded because of 
neurological involvement that can influence the results. Hypo-or hyperthyroid patients will be 
excluded because of the role of thyroid hormones in muscle homeostasis. Pitting oedema of 
the legs (due to heart failure, anasarca oedema, renal failure or liver cirrhosis) or severely 
dehydrated patients will be excluded because fluid shifts could influence the ultrasound 
measurement results. Because of possible previous changes in muscle mass, architecture 
and function, patients with systemic connective tissue disorders, myositis, calcification and 
ossification of muscle, systemic atrophies primarily affecting the central nervous system and 
demyelinating diseases of the central nervous system will be excluded. Patients using 
chronic oral corticosteroids will be excluded.  
2.2.3. Settings and locations 
The study will be a multicenter study held in different university and tertiary teaching 
hospitals throughout Europe. 
 

2.3. Measurements 
 
2.3.1. Patient characteristics 
Date of birth, gender, height and weight will be registered. If the patient is bedridden, weight 
can be measured through either weight chairs or weight measuring lifts. Height will be 
estimated using the ulna length or knee height [20]. Date of admission and discharge will be 
noted. The home care setting of the patient will be registered. The main reason of hospital 
admission will be registered. 
Comorbidities on admission will be registered through the Cumulative Illness Rating Scale for 
Geriatrics (CIRS-G) [21]. The CIRS-G was designed to estimate the survival of elderly 
persons, assessing disease severity using a score from 0 to 4 in 14 different categories of 
organ systems: cardiac, vascular, hematological, respiratory, ophthalmological and 
otorhinolaryngological, upper gastro-intestinal, lower gastro-intestinal, hepatic and 
pancreatic, renal, genito-urinary, musculoskeletal and tegumental, neurological, 
endocrine/metabolic/breast and psychiatric [22]. Score ‘0’ stands for ‘no problem affecting 
that system’, score ‘1’ stands for ‘current mild problem or past significant problem’, score ‘2’ 
stands for ‘moderate disability or morbidity’, score ‘3’ stands for ‘severe problem’ and score 
‘4’ stands for ‘extremely severe problem’. 
Laboratory values that will be checked are either nutritional through albumin and prealbumin, 
inflammatory through C-reactive protein (CRP) and white blood cell count, and the 
measurement of 25-hydroxyvitamin D (25-OH-vitamin D). Blood samples will be collected on 
day of admission. Laboratory values that are not expected to fluctuate strongly (albumin, pre-
albumin, 25-OH-vitamin D) will be taken within the first 5 days of admission.  
2.3.2. Muscle mass 
In order to obtain reliable and consistent measurements, all ultrasonography will be done by 
an ultrasonographist that is trained to perform the measurements proposed. For the 
measurements, a linear probe of 5 cm width will be used. Frequency of the beam will be set 
on 12 MHz.  
 
Patients should not have had any physical exercise in the 30 minutes before the 
measurement. Muscles should be completely relaxed and patients should be placed in the 
supine position, with hips in neutral position and knees fully extended. The dominant leg will 
be taken for the measurements. To calculate the relative muscle thickness values, the total 
length of muscle will be noted. 
 
Ultrasonographic data of the four bellies of the quadriceps muscle (rectus femoris, vastus 
lateralis, vastus medialis, vastus intermedius) will be taken. Measuring points will be 
specified according to the propositions of the SARCUS-working group [19]. Muscle 
thickness, fascicle length, pennation angle, muscle cross-sectional area and echo-intensity of 
all muscles listed will be taken.  
 
The first measurement will be taken as early as possible within 48 hours after admission at 
the latest. Follow-up measurements will be taken according to the type of ward the patient is 
admitted to. For patients that are expected to be hospitalized for a limited time (<5 days), the 
follow-up measurement will be done 3 days after initial measurement. For patients that are 
expected to be hospitalized for a longer time (>7 days), measurements will be repeated 7 

days after initial measurement, to be repeated after another 7 days as long as the patient is 
hospitalized. 
2.3.3. Muscle strength and function 
Muscle strength will be measured through hand grip strength using a Jamar dynamometer, 
using the Southampton protocol [23]. The first measurement will be taken as early as 
possible within 48 hours after admission at the latest. Follow-up measurements will be taken 
according to the type of ward the patient is admitted to. For patients that are expected to be 
hospitalized for a limited time (<5 days), the follow-up measurement will be done 3 days after 
initial measurement. For patients that are expected to be hospitalized for a longer time (>7 
days), measurements will be repeated 7 days after initial measurement, to be repeated after 
another 7 days as long as the patient is hospitalized. Measurement will be done directly after 
the ultrasonographic assessment. If feasible, muscle function will be measured through gait 
speed, using the 4-meter walking test at usual gait speed [24]. In case of those bedridden, 
gait speed will not be measured. 
2.3.4. In-hospital activity 
Registration of activity level during hospitalisation will be performed by means of pedometers 
in those centers that have access to these devices. Both amount of steps and step length will 
be noted, and total walked distance per day can hereby be calculated. 
2.3.5. Nutritional status 
Nutritional state of the patient will be registered through the Mini-Nutritional Assessment – 
Short Form (MNA-SF) [25]. For diagnosis of malnutrition, the new Global Leadership 
Initiative on Malnutrition (GLIM)-criteria will be used [26]. 
2.3.6. Questionnaires 
The SARC-F [27] and FRAIL-scale [28] will be completed as routine screening 
questionnaires for sarcopenia and frailty, respectively. The SAR-QOL questionnaire will be 
used to evaluate the self-reported quality of life [29].  
 
2.4. Statistical analysis 
Databases will be kept up in a Microsoft Access database. 
Statistical analysis will be done by using SPSS Statistics version 24. Descriptive analyses 
will be used for determining the clinical and demographic characteristics. A Kolmogorov-
Smirnov test will be used to verify the normal distribution of the different variables. Further 
statistical analyses will be performed by Chi Square test, Fisher exact, Mann-Whitney U test 
or Fisher exact test, depending on the distribution and the nature of the variables analysed. 
P-values of ≤0.05 will be considered statistically significant. 
 
2.5. Ethics 
We will comply with both international and country specific guidelines concerning research 
ethics. We will also adhere to the World Medical Association Declaration of Helsinki. A 
written information flyer will be given to all patients and/or their family, and a written informed 
consent will be registered in the medical file. In patients with cognitive disorders, informed 
consent will be taken from the family or the main representative (proxy signature). The local 

ethical committee agreement of all participating study sites will be obtained before the start of 
the study. 
 
3. Discussion 
This protocol has been designed to check whether acute illnesses or stressors followed by 
hospitalisation will promote the development of acute sarcopenia. This is a study protocol, 
and at this point no data are already available.  
Although there are very few studies about the existence of acute sarcopenia, we hypothesize 
a relation between acute illnesses and acute sarcopenia [8]. We also hope to foresee health 
related parameters playing a crucial role in the accelerated development of sarcopenia, such 
as poor nutritional status before hospitalisation, acute inflammation and having a frail or 
sarcopenic status before the acute event. Certain pre-existing diseases are also believed to 
have an effect in worsening muscle parameters in acute illness or bedrest. It is important to 
identify risk factors for acute sarcopenia, so that strategies can be undertaken to prevent or 
at least delay the development of acute sarcopenia. Previous studies showed reduced intake 
of protein, reduced physical activity, inflammation, oxidative stress and low vitamin D as 
contributing factors to the development of (chronic) sarcopenia [9, 10, 30-32]. For acute 
sarcopenia, proposed risk factors include acute inflammation, reduced mobility, delirium, 
sleep disturbances, cognitive impairment, psychological stress and malnutrition [33-37]. 
A negative effect of bed rest on muscle mass has been already reported, and this effect is 
greater in older patients [7]. Also hypercortisolemia, as seen in acute stress and 
inflammatory conditions, was shown to decrease muscle mass in a study in which young 
adults were given hydrocortisone and bed rest [30]. Because of very fluctuating cortisol 
levels during the day, we chose not to measure cortisol in our study patients routinely.  
Activity levels before the acute stressor occurrence, and then during hospitalisation could 
also be an influencing factor for acute sarcopenia. Determining activity prior to hospitalisation 
is however difficult. Possible tools are questionnaires like the Physical Activity Scale of the 
Elderly (PASE) [38] or the Seven Day Physical Activity Recall (SDPAR) [39], but those 
questionnaires are rather extensive and time-consuming. It could be a suggestion for further 
studies to examine the effect of activity pre-hospitalisation on acute sarcopenia. Activity 
levels during hospitalisation will be measured by use of pedometers in patients who are not 
bed-or chair bound.  
Nutritional status at admission will be noted via the MNA-SF questionnaire [25], 
complementary with selected laboratory values. Although aware that malnutrition or 
starvation during hospitalisation will probably play an important role in development of acute 
sarcopenia, we chose not to register the actual nutritional intake in hospital with food record 
charts, because such measurements are very much observer-dependent and hereby very 
prone to inaccuracy.  
The most important  advantage of our study is that muscle mass will be measured via 
ultrasound, which is a relatively new way of sarcopenia screening and assessment [18, 40]. It 
is much more available than bio-impedance analysis or DEXA, and with less side effects 
than CT. It can easily be performed on a daily basis in all patients at risk for sarcopenia. 

Other strengths of this study are the size of the study population (due to the multicenter 
setting), the comprehensiveness of assessment and the frequent, regular follow-up 
measurements. 
There are some limitations to the study. Food intake during hospitalization will not be 
measured. Although nutritional intake is an important factor in retaining muscle mass, it is 
very difficult to correctly assess caloric and protein intake in acute patients. Also, no good 
measure for physical activation prior to hospitalisation is included in this research, as making 
a correct assessment of total exercise time and level through post-hoc recollection is often 
biased.  
Once risk factors of acute sarcopenia are identified, we suggest to screen in those 
individuals in the first instance, and to pay attention to available prevention and treatment 
strategies. First of these strategies are physical activity interventions, with early mobilisation 
and intensive physical activity during hospitalisation [41]. Especially resistance exercise 
training and moderate aerobic exercises have been shown beneficial in improving muscle 
mass and function [42]. Furthermore, some nutritional interventions like protein 
supplementation are believed to help to prevent loss of muscle mass [43]. Especially leucine 
amino acid intake would be important [44]. Other interventions are still more controversial. 
Neuromuscular electrical stimulation (NMES) is described to prevent reductions in muscle 
fibre cross-sectional area [45]. This technique is however not very useful for prevention of 
total body skeletal muscle loss. Pharmacological interventions have been suggested for 
treatment of established sarcopenia, like Calorie Restriction Mimetics (CRM) and Exercise 
Mimetics (EM) under the form of phytochemicals [46]. Also recombinant growth hormone, 
testosterone supplementation, dihydroepiandosteron and myostatine have been trialled with 
variable results [47-49][50]. More studies are needed to establish better pharmacological 
therapies to prevent or treat (acute) sarcopenia. 
 
4. Conclusions 
This protocol has been designed to evaluate the effect of acute illnesses followed by 
hospitalisation on the development of acute sarcopenia. The study is set up as a prospective 
observational study in which muscle mass will be measured through ultrasound assessment 
of the 4 bellies of the quadriceps muscle. Through the concomitant screening of other 
parameters as described above, their contribution to the decline in muscle mass and function 
in acute sarcopenia will be evaluated. When we better understand the process of 
development of acute sarcopenia, it might be possible to make targeted interventions for 
prevention and treatment of the individuals at risk. 
 
Contributors 
??? 

Declaration of interest 
None of the authors have declared any conflict of interest relating to this research. 
Acknowledgements 
The contribution of all authors is acknowledged.  
Funding 
This research did not receive any specific grant from funding agencies in the public, 
commercial or not-for-profit sectors. 
 
 

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Appendix 
Table 1: Inclusion and exclusion criteria for patient participation 
Inclusion criteria 
Exclusion criteria 
Admitted from 01/11/2018 – 31/10/2019 
Dialysis 
65 years or older 
Previous/actual stroke 
 
Actual hypo-or hyperthyroidism. 
 
Oedema of the lower limbs 
 
Severely dehydration 
 
Systemic connective tissue disorders 
• 
Polyarteritis nodosa and related 
conditions 
• 
Other necrotizing vasculopathies 
• 
Systemic lupus erythematosus 
• 
Dermatopolymyositis 
• 
Systemic sclerosis – scleroderma 
• 
Other systemic involvement of 
connective tissue 
• 
Systemic disorders of connective tissue 
in diseases classified elsewhere 
 
Myositis 
 
Calcification and ossification of muscle 
 
Systemic atrophies primarily affecting the 
central nervous system  
• 
Huntington's disease 
• 
Hereditary ataxia 
• 
Spinal muscular atrophy and related 
syndromes 
• 
Systemic atrophies primarily affecting 
central nervous system in diseases 
classified elsewhere 
• 
Postpolio syndrome  
 
Demyelinating diseases of the central nervous 
system  
• 
 Multiple sclerosis 
• 
 Other acute disseminated demyelination  
• 
 Other demyelinating diseases of central 
nervous system 
 
The chronic use of oral corticosteroids