ImpACt of Very High Protein Content Enteral nUtrition Formulas on Protein Metabolism and Residual Gastric Volume in Critically Ill MUltipLe trAuma paTiEnts
Conditions: Metabolism, Trauma, Nutritional Deficiency, Protein Malnutrition, Gastroparesis, Muscle Loss, Calorie Malnutrition Protein
Sponsor: Romanian Society for Enteral and Parenteral Nutrition

 
 
 
 
ImpACt of very high protein Content enteral nUtrition 
formulas on protein metabolism and residual gastric 
volume in critically ill MUltipLe trAuma paTiEnts – 
ACCUMULATE trial - 
Study Protocol 
02.12.2022 
 

ImpACt of very high protein Content enteral nUtrition 
formulas on protein metabolism and residual gastric volume 
in critically ill MUltipLe trAuma paTiEnts  
 
– ACCUMULATE trial -  
 
 
Background and rationale: 
 
 
Despite an increased survival among critically ill patients,  many of the ICU “survivors” 
may develop prolonged functional disabilities(1). It has already been proven that nutritional 
therapy is essential, considering that an adequate provision of calories and proteins may 
influence patients prognostic(1).  
 
Multiple trauma patients are on a particular nutritional risk, since their high nitrogen 
demands and associated nutritional therapy challenges, caused by repeated surgical 
intervention or  multiple imagistic procedures(2). Although nutritional therapy impact on 
mortality is still in debate, clear, positive results were obtained in decreasing ICU and hospital 
stay after adequate nutritional support(3).  
 
According to ESPEN guideline on clinical nutrition in the ICU early enteral nutrition 
(within 48 h) should be initiated in order to assure an adequate calorie and protein intake(4). 
Beside optimal timing, the management of nutrition therapy in critically ill patients should 
also integrate the optimal route and caloric/protein targets(4). 
 
Energy requirements monitoring through indirect calorimetry has been proposed as a 
standard-of-care method for critically ill patients, considering its proven superiority towards 
predictive equation(5).  
 
Beyond calorie intake, proteins proved to play a central role in maintain lean body 
mass, healing wounds and supporting immune function(5).For multiple trauma patients it was 
reported that protein losses may reach 14 % of the total body stores, thus this type of patients 
are exposed to a particular increased risk of protein deficits(6). If calorie administration 
benefits from a proper monitoring tool, protein requirements are still based on predictive 
equation(6). The impact of protein administration is also lacking of direct measurements 
techniques(7). Lean body mass evaluation by ultrasound and computerized tomography has 
been reported to have a good correlation with hospital stay and pots-ICU functional 
capacity(7). Moreover muscle function evaluation through a hand-grip dynamometer was 
also tested with good results in patients with ARDS(7). 
 
Source of administered protein may also influence nitrogen balance, considering that 
whey proteins (rich in leucine) promote a slower hydrolysis and allow a longer period for 
absorption(8). 
 
Reaching the recommended goals is often impeded by gastric intolerance manifested 
through increased gastric volume residues(4). It has been already demonstrated that large 
gastric volume residues are associated with impaired absorption and an increased incidence 
of aspiration pneumonia(9).  
 
Gastrointestinal dysfunction in multiple trauma patients admitted to the intensive 
care unit (ICU) is an important yet underrecognized consequence(10). There are various 

causes of gastrointestinal tract dysfunction mostly related to patients general health 
condition and to their diagnostics(11). Gastrointestinal failure may be induced by several 
factors like immunological, biological and mechanical barrier disruption and it may be 
manifested through stress ulceration, bacterial translocation, ileus, intra-abdominal 
hypertension, diarrhoea and constipation(2). 
 
Whether residual gastric volume monitoring should be regularly performed has been 
extensively discussed. Although the results from some randomised trials which focused on 
monitoring gastric residual volume, did not find any difference in outcomes, this 
measurement was far for being abandoned(12). Moreover, gastric residual volume 
monitoring is still an essential component of enteral nutrition patient care(13). 
 
Although several monitoring methods for gastric volume residue measurements were 
described, there is no generally accepted technique for daily use(12,13). 
 
Body composition monitoring 
 
Objective: 
 
 
This prospective observational randomized study aims to determine energy, protein 
intake and gastrointestinal tolerance while using enteral nutrition formulas with very high 
protein content and enteral nutrition formulas with normal protein content. 
 
Outcomes will be assessed as:  
§ Primary outcome parameter: 
- Differences regarding achieving protein and calorie daily targets in grams per 
kilogram of body weight (g/kg BW) at day 5 of the intervention period and at day 10 
when using enteral nutrition formulas with different protein content 
- Differences regarding residual gastric volume when using enteral nutrition formulas 
with different protein content 
Secondary outcome parameter: 
Differences regarding body composition when using enteral nutrition formulas with 
different protein content: 
 
a) Quadriceps rectus femoris thickness measured by B-mode ultrasonography on 
admission, on day 5,  on day 10 and 15. 
 
b) Body composition assessment (Fat-Free mass, Total Body water, Phase angle) using 
bioimpedance analysis after patient has been stabilized (24 hours after extubation 
and on day 5 after extubation) 
 
c) Plasmatic levels of prealbumin and inflammatory markers (C reactive protein) on 
day 5 and on day 10; 
 
d) Muscle function evaluation using handgrip dynamometer after extubation and 
sedation cessation. (24 hours after extubation and on day 5 after extubation) 

 
§ Safety points: 
- 
Clinical parameters – vomiting, diarrhoea 
- 
Biochemical parameters – base excess, urea levels 
- 
Daily gastric residual volume evaluation using ultrasound gastric antrum 
measurements after 24 hours of continuous enteral nutrition administration 
using both types of formulas; 
 
Study population  
 
Consecutive patients with multiple trauma intubated and mechanical ventilated, 
admitted to the intensive care unit (ICU).  
Inclusion criteria:  
§ Adult patients (>18 yrs) admitted to the ICU  
§ Multiple trauma (Injury severity score > 18) 
§ Intubation and mechanical ventilation upon admission in ICU or during the first 24 
hours of admission, for at least 48 h 
Exclusion criteria  
o Age < 18 years  
o Pregnant women 
o Patients not intubated or not mechanically ventilated or receiving only non–
invasive ventilation  
o Patients with enteral feeding contraindication 48 h after admission 
o Patients with recent gastrointestinal surgical intervention 
o Patients on chronic therapy with corticosteroids 
Sample size calculation  
 
Since the hypotheses of the study are exploratory, no formal sample size 
calculation has been performed. This prospective observational study aims to recruit 
>60 multiple trauma patients. 
Randomization:  
Simple randomization method will be used to assign subjects into two groups A and 
B. 
 
Group A – Nutrison Protein Plus with 6.3 g/100 ml protein 
 
Group B - Nutrison Protein Intense with 10 g/100 ml protein 
Ethical considerations: 

 
This study will be conducted in full conformity with the Declaration of Helsinki and Good 
Clinical Practices.   
 
Local ethical committee approval will be asked before any patient will be included.  
 
Considering that nutritional support has become a standard-of-care in every intensive care 
unit in the world, it is considered that this research is based on collecting data routinely available for 
every critically ill patient. Although no intervention is performed an informed consent will be provided.  
 
Taking into account that the included patients are not able to provide informed consent at the 
time of recruitment (on ICU admission), a Power of Attorney or a Legal tutor will act as Consultee and 
will be asked to consent/decline participation to the study on legal behalf of the patient. If patients 
have Advance Decision Plan including participation in research studies the Plan will be respected and 
recruitment pursued/abandoned accordingly.  
 
After regaining capacity, all patients will be asked to provide Informed Consent for using their 
personal data and will be given the possibility to:  
§ 
Provide Informed Consent for the acute data and follow-up. 
§ 
Deny research participation and request destruction of acute data collected.  
 
Study participant research data, which is for purposes of statistical analysis and scientific 
reporting, will be transmitted to the Data Manager and the Statistician of the study. 
 
Expected impact of the study  
KNOWLEDGE  
 
Investigators aim to provide a detailed description of protein administration using two 
different types of enteral formulas. The main objectives of the study are to evaluate energy, protein 
intake and gastrointestinal tolerance while using enteral nutrition formulas with different protein 
content. Nevertheless, investigators want to provide data about the impact of these different 
enteral nutrition formulas on body composition as well as on functionality.  
 
Regarding of the obtained data a change on local and national recommendation considering 
enteral nutrition in multiple trauma patients is to be expected. 
Funding 
All the enteral nutrition products are donated by the Nutricia Global.  
No funding will be received for this study. 
Reference: 
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