Gastroparesis

Intensive care units (ICUs) are areas where advanced technologies and multidisciplinary care are provided together to sustain and treat critically ill patients. Patients treated in the ICU due to reasons such as inadequate gas exchange, increased respiratory workload, and inability to maintain airway patency are intubated and placed on mechanical ventilation support. ICU patients dependent on mechanical ventilators become reliant on external nutrition during the treatment process as they cannot meet their nutritional needs. In ICU patients, damage to the digestive mucosa due to stress may occur, leading to various gastrointestinal (GI) problems such as increased residual volume, diarrhea, constipation, and malnutrition. Therefore, providing accurate and adequate nutritional support is critically important in the treatment processes of ICU patients. In recent years, nutritional support has been included among therapeutic methods in ICUs. Studies have shown that appropriately timed nutritional support positively affects the clinical outcomes of patients in intensive care units. Enteral or parenteral nutrition methods can be chosen based on the patient's health status and guidelines. For ICU patients on mechanical ventilator support, if the gastrointestinal tract is functional, enteral nutrition is frequently preferred. Enteral nutrition is the delivery of nutrients to the stomach or small intestine via a tube, catheter, or stoma. Enteral nutrition is a commonly used method for patients who cannot eat orally. It can reduce infection risk, shorten catabolic responses, the formation of gastric ulcers, and the length of hospital stay. Starting enteral nutrition within the first 48 hours for patients admitted to the ICU has been reported to shorten hospital stay and reduce mortality rates. Although enteral nutrition has high physiological response rates, there are also risks and potential side effects. The most common GI complications encountered in patients receiving enteral nutrition are gastrointestinal complications. GI complications in enteral nutrition are influenced by many factors, including the patient's general condition, mechanical ventilation, hemodynamic parameters, and administered medications. These complications include aspiration, diarrhea, constipation, abdominal distension, and nausea/vomiting. These side effects have been observed in 62% of patients receiving this type of nutrition. Constipation is a digestive system complication that is often overlooked in ICU patients. Immobility, hypotension, the use of vasopressors and narcotics, and lack of access to appropriate conditions and facilities are among the reasons for constipation development. Constipation prolongs the duration of mechanical ventilation and increases the length of stay in ICUs. In a study evaluating enteral nutrition complications, 48.5% of the patients experienced dislodgement of their nasogastric tube, 45.5% had electrolyte imbalances, 34.5% developed hyperglycemia, 32.8% had diarrhea, 29.7% experienced constipation, 20.4% had vomiting, and 3.1% developed pulmonary aspiration.Another study found that 32% of ICU patients receiving enteral nutrition experienced increased gastric residual volume, while 46% developed gastrointestinal intolerance. GI problems encountered in ICUs can be prevented, reduced, and patient comfort can be increased through pharmacological and non-pharmacological treatments (abdominal massage, aromatherapy, acupuncture, mobilization, etc.). A study investigating nutrition and motility issues in ICUs found that non-pharmacological methods, alongside pharmacological approaches, were also emphasized, with abdominal massage applied in 39% of cases to address motility problems. Non-pharmacological methods have various advantages over pharmacological approaches. The most important advantage of these methods is that they can be easily applied to individuals. Additionally, they offer a more cost-effective solution in terms of both patient and hospital costs. Abdominal massage, which aims to stimulate and increase intestinal peristalsis, is performed by applying effleurage, petrissage, and vibration techniques clockwise on the abdomen for 15-20 minutes. Abdominal massage, performed by nurses, caregivers, or family members, is a safe, non-invasive method with no known side effects. This massage has been shown to be effective for those experiencing defecation issues, abdominal pain caused by gas or cramps, individuals with altered abdominal muscle tone, and those suffering from fecal incontinence or chronic constipation. Studies evaluating the effectiveness of abdominal massage in preventing GI complications in ICUs are relatively limited. A study found that abdominal massage was effective in reducing constipation and improving quality of life.A study on patients receiving enteral nutrition in neurology and neurosurgery clinics stated that abdominal massage could be used to prevent abdominal distension and increased gastric residual volume (GRV). According to a study conducted in Germany, it was reported that abdominal massage began to be used to improve GI complications in 38.8% of ICU patients. There are studies in the literature examining the effects of abdominal massage on gastrointestinal system functions. Existing studies generally focus on the effects of abdominal massage on geriatric patient populations or evaluate it in intensive care patients with limited parameters. However, this research will specifically investigate the effects of abdominal massage on gastrointestinal system functions in patients who are mechanically ventilated and receiving enteral nutrition in the intensive care unit. The findings of this study will contribute to the adoption and standardization of abdominal massage practices by intensive care nurses in the care of this specific patient group, supported by scientific evidence. To contribute to this area in the literature, the study aims to evaluate the effects of abdominal massage on gastric residual volume, frequency of defecation, and abdominal distension in mechanically ventilated patients receiving enteral nutrition in the intensive care unit. Three different sets of hypotheses have been established in the study. These are: First Hypothesis Set H0: Abdominal massage applied to patients who are mechanically ventilated and receiving enteral nutrition in the intensive care unit has no effect on the frequency of defecation. H1: Abdominal massage applied to patients who are mechanically ventilated and receiving enteral nutrition in the intensive care unit has an effect on the frequency of defecation. Second Hypothesis Set H0: Abdominal massage applied to patients who are mechanically ventilated and receiving enteral nutrition in the intensive care unit has no effect on abdominal distension. H1: Abdominal massage applied to patients who are mechanically ventilated and receiving enteral nutrition in the intensive care unit has an effect on abdominal distension. Third Hypothesis Set H0: Abdominal massage applied to patients who are mechanically ventilated and receiving enteral nutrition in the intensive care unit has no effect on gastric residual volume. H1: Abdominal massage applied to patients who are mechanically ventilated and receiving enteral nutrition in the intensive care unit has an effect on gastric residual volume. Method\* Type of Research The study is designed as a prospective, single-blind randomized controlled trial to determine the effects of abdominal massage on gastrointestinal system functions (frequency of defecation, abdominal distension, gastric residual volume) in mechanically ventilated patients receiving enteral nutrition in the intensive care unit. The research is prepared based on the 25-item checklist and flowchart included in the "Consolidated Standards of Reporting Trials (CONSORT-2017)." The study's Clinical Trials protocol registration will be done via ClinicalTrials.gov. Location and Characteristics of the Research The research will be conducted at Mersin Toros State Hospital's general and surgical intensive care units between between January 2025 and August 2025. The internal intensive care unit at Mersin Toros State Hospital has 9 beds, while the surgical intensive care unit has 10 beds. The general intensive care unit consists of two separate rooms, with the first room containing 2 isolation rooms and a 3-bed ward system, and the second room having a 4-bed ward system separated by a wall. There are 22 nurses working in the general intensive care unit. The surgical intensive care unit is located in a single room with a 9-bed ward system, separated by walls and includes 1 isolation room. There are 24 nurses in the surgical intensive care unit, and health personnel from both units provide shared services, including a total of 8 clinical support staff, 6 cleaning staff, 1 attendant, 1 security personnel, and 1 medical secretary. The same physicians are on duty in both intensive care units, totaling 13 anesthesia specialists and 1 intensive care specialist. Both intensive care units are at level 3, and since enteral nutrition is administered cyclically, the patients are similar. The enteral nutrition planning for patients in the intensive care units will be done in cooperation with nutrition nurses and dietitians. The planned enteral nutrition will be administered and monitored by the nurses. Randomization The listing of individuals forming the study sample will be done by an independent researcher who is not participating in the study. After obtaining consent from the relatives of patients who are willing to participate in the study and meet the criteria, the allocation of patients to the intervention or control group will be determined randomly using the website randomizer.org. Individuals included in the sampling will be listed from 1 to 70. The program will input the information that there will be two different groups of 35 individuals and that participants are numbered between 1 and 70. The program will randomly assign the two groups. The individuals listed by an independent researcher will be randomly numbered by the system (randomizer.org). Blinding Due to the nature of the study, the researcher will not be blinded. Thus, the research will be conducted as a single-blind randomized controlled trial. Upon completion of the study, data will be entered into the computer by an independent researcher without specifying the intervention or control group, coded as groups A and B. Data analysis and the writing of the research report will be conducted by a statistician who does not know which group is which, using the codes A and B. Data Collection Preparation of Data Collection Tools A "Data Collection Form" has been used in the data collection phase of the research. The data will be collected using a data collection form consisting of three sections: "Patient Clinical Condition Information Form," "Enteral Nutrition Monitoring Form," and "Bristol Stool Consistency Scale." Patient Clinical Condition Information Form: This form containing patient clinical condition information has been prepared by the researcher to determine the socio-demographic characteristics of the participants after a review of the relevant literature. It includes an assessment of individual characteristics, the APACHE II (Acute Physiology and Chronic Health Evaluation) scoring system, and the Glasgow Coma Scale (GCS). Individual characteristics include age, gender, reason for admission to intensive care, chronic disease status, sedation status, intubation, and the start date of enteral nutrition. APACHE II Scale: This scale is used for the evaluation of a patient's acute physiological and chronic health condition; it was developed to provide an objective assessment of the mortality risk, severity, and criticality of diseases in patients in the intensive care unit. The scoring range is between 12-71. As the score increases, the patient's prognosis worsens. GCS: This will be used to assess the patient's level of consciousness. The scale assesses a patient as being in a coma if the score is between 0-3, stupor if between 3-8, confused if between 8-13, and oriented if between 13-14. Enteral Nutrition Monitoring Form: The enteral nutrition monitoring form was created by the researcher according to the literature. This form will record the frequency of defecation, abdominal distension, GRV measurement, and the rate of intake of the nutritional solution to evaluate the effectiveness of gastrointestinal functions. Frequency of Defecation: This is the assessment of patients' daily bowel movement status and is derived from routine patient monitoring forms in the intensive care unit. Abdominal Distension: This is evaluated by applying pressure to the abdominal wall using the palpation method, assessing the tension of the abdominal wall during the applied pressure. GRV Measurement: This refers to the volume of stomach contents measured by aspiration via a nasogastric tube using a syringe. Bristol Stool Consistency Scale: Developed by a team of gastroenterologists in 1997 at the University of Bristol in England, the Bristol Stool Consistency Scale is used to assess stool form and provide information about changes in bowel habits and possible pathological conditions in the bowel. This scale is designed to classify stool into seven separate categories, reflecting an individual's bowel movements. According to the Bristol Stool Consistency Scale, Types 1 and 2 indicate constipation, Types 3 and 4 indicate normal stool, and Types 5, 6, and 7 indicate diarrhea. Implementation of Data Collection Forms The study has two groups assigned through randomization: intervention and control. Relatives of patients meeting the research criteria will be informed about the study in the General Intensive Care and Surgical Intensive Care units at Mersin Toros State Hospital. Informed consent forms will be signed by the relatives of patients who agree to participate in the study, and the data collection forms will be implemented. Relatives in the intervention group will be informed about the procedure, and abdominal massage along with routine nursing care will be applied to the accepted patients. Implementation Environment: The study will be conducted at the bedside in the General Intensive Care and Surgical Intensive Care Units of Mersin Toros State Hospital. To ensure patient privacy, the curtains at the bedside will be drawn. The intervention will be carried out one-on-one at the patient's bedside. Implementation Position: In the intervention group, in addition to routine nursing care, abdominal massage will be applied while the patient's head will be elevated at an angle of 30-45° in a semi-fowler position before enteral nutrition is started. The patient should be stable during the abdominal massage, and monitoring should be conducted carefully. Routine nursing care will be applied to the control group. During enteral feeding, the head elevation will be maintained at an angle of 30-45°. Frequency/Duration of Implementation: Based on previous studies, abdominal massage will be performed twice a day, at 15:00 and 21:00, for each patient over a total of 3 days. Each abdominal massage session will last for 15 minutes. Massage measurements will be taken afterward. Stages of Abdominal Massage Application: Abdominal massage consists of four fundamental movements: superficial effleurage (stroking), deep effleurage, petrissage (kneading), and vibration. Effleurage (stroking) is a technique applied with the palm or fingers over the abdominal area in both deep and superficial movements. Abdominal massage begins and ends with effleurage. During superficial effleurage, a movement is made with the palm from over the iliac bones to both sides of the pelvis and down towards the groin. Deep effleurage is applied along the ascending colon, transverse colon, and descending colon to support the movement of fecal contents through the intestines. In the petrissage technique, circular movements of the hands and fingers lift the muscle mass and compress the tissue. It is applied upwards along the ascending colon and downwards along the descending colon. It should not be repeated continuously in the same area. The vibration technique consists of vibration movements performed with the hands and fingers over the same muscle in the abdominal area. This method helps expel gas from the intestines. Flow of the Research Process: First Stage (Preparation Stage): A suitable environmental arrangement will be made in the General Intensive Care and Surgical Intensive Care Units of Mersin Toros State Hospital for the patients included in the intervention and control groups. Second Stage (Application Stage): This stage will consist of four steps. First Step: In the first step of the application, brief information about the research will be provided to the relatives of eligible patients at Mersin Toros State Hospital General Intensive Care and Surgical Intensive Care Units, and written consents will be obtained from the relatives. Second Step: Sampling will be completed according to the inclusion, exclusion, and withdrawal criteria of the study, followed by randomization to form two randomized groups. The purpose and process of the research will be explained to the patient/relative individuals, who will then fill out the "Informed Consent Form" and the "Patient Clinical Status Information Form." Routine nursing care procedures will be applied to both groups. Third Step: The abdominal massage procedure will be performed on the first day at 15:00. After a 30-minute break from enteral feeding, GRV measurements will be recorded using a syringe, abdominal distension measurements will be taken by palpation, and defecation counts will be recorded using the nurse observation form in the "Enteral Feeding Monitoring Form." The appearance of the stool will be evaluated by the researcher according to the "Bristol Stool Form Scale." The intervention group will receive a 15-minute abdominal massage. No intervention will be made in the control group other than routine nursing care. Fourth Step: The abdominal massage procedure will be performed on the first day at 21:00. After a 30-minute break from enteral feeding at 20:30, GRV measurements will be recorded using a syringe, abdominal distension measurements will be taken by palpation, and defecation counts will be recorded using the nurse observation form in the "Enteral Feeding Monitoring Form." The appearance of the stool will be evaluated by the researcher according to the "Bristol Stool Form Scale." The intervention group will receive a 15-minute abdominal massage. No intervention will be made in the control group other than routine nursing care. In the intervention group, abdominal massage will be performed for a total of 6 sessions over 3 days, twice daily, using the "Enteral Feeding Monitoring Form" and "Bristol Stool Form Scale," with measurements recorded. In the control group, no interventions will be made other than routine nursing care throughout the 3-day process. Measurements will also be recorded using the "Enteral Feeding Monitoring Form" and "Bristol Stool Form Scale" twice a day for a total of 6 sessions. To eliminate ethical issues that may arise in the control group, abdominal massage will be performed on these patients after the data collection process of the research is completed. Third Stage (Reporting Stage): In this stage, the statistical analysis of the data obtained from the patients will be performed, and the research report will be written. Ethical Aspect of the Research: The research will be conducted in accordance with the Helsinki Declaration. Written ethical approval will be obtained from the Mersin University Clinical Research Ethics Committee and written permission from the Mersin Provincial Health Directorate before data collection begins. Written permissions will also be obtained from the developers of the scales planned to be used in the research. Patient selection in the research will be based on voluntary participation. Principles of confidentiality and privacy will be observed, and patients/relatives will be informed that they can withdraw from the study at any time, after which their written consents will be obtained. Furthermore, patients will be informed that all data collected will be kept confidential and stored securely by the researcher. Data Evaluation: The data obtained from the research will be evaluated using appropriate statistical methods. Parametric or non-parametric tests will be used based on the normal distribution of comparative data analysis. Descriptive statistics will include counts and percentages. For normally distributed data, mean and standard deviation values will be provided, while for non-normally distributed data, minimum and maximum values along with median and 25th-75th percentiles will be reported.

The GENESIS study is a multicenter, prospective, non-interventional, clinical study with a target of 12,000 subjects and an anticipated total duration of 36 months. The aim of study GENESIS is to provide a pilot map of HLA genetic variation in the Greek population in order to be used in medical research and for possible clinical applications (evaluation of possible correlations with selected underlying diseases). During the study, each subject will conduct one visit to the participating cite, in which they will provide: 1. Demographic information \[i.e. date of birth, gender, race, ancestry (including information about the subject's grandparents' birthplace), height, weight\], 2. Other information about smoking/vaping, alcohol consumption, arterial blood pressure, diagnosed diseases (if any), current treatments (if any), and 3. Recent (up to 12 months prior to sample collection) results if/when are available from clinical lab tests such as blood count (Hct, Hb, RBC, WBC, PLT count), including a metabolic panel, liver enzymes and biochemical parameters (Glu, HbA1c, TC, TG, LDL-C, HDL-C, ALT, AST, ALP, γGT, bilirubin, LDH, insulin, C-peptide). Upon completion of the data registry, two buccal swabs will be collected per subject and they will be stored at ALTP premises until their shipment to Galatea.Bio. All buccal swab samples will be subjected to genetic material (DNA) extraction. The DNA samples will be further proceeded for HLA genotyping analysis. A follow up analysis will be performed in selected DNA samples via full low-pass whole genome sequencing (LP-WGS), which aims to further investigate the association between the HLA region and autoimmune diseases. Upon completion of the analysis, an individualized ancestry report will be securely made available to all study subjects which they can access, as and if they elect to.

Frailty is a common clinical syndrome in older adults that may carry an increased risk for poor health outcomes including falls, hospitalisation, and mortality. Having a colonoscopy can be associated with potential adverse outcomes in frail patients. At present, however, frailty is not routinely assessed in gastroenterological clinical practice. In a prospective randomised controlled study consenting patients over 65 years at the Princess Alexandra Hospital will receive either a) personalised (tailored) approach that includes assessment of frailty and structured information provided to the consumer or b) current standard practice in regards to having a surveillance colonoscopy to determine the effects on patient satisfaction and percentage of colonoscopies avoided. It is expected that engagement with patients and clinicians in regards to frailty will address expectations and subsequently support the ability of patients/consumers and clinicians to make informed decisions that minimise risks and maximise benefits in regards to surveillance colonoscopies.

An Effectiveness-Implementation Hybrid Design with a two stage randomisation will be used to determine and compare efficacy and cost-effectiveness of different management approaches/interventions for patients with relevant, chronic, or relapsing gastrointestinal symptoms without concerning features and on the wait list for integrated care clinic at the Princess Alexandra Hospital. Approximately 200 patients will initially receive standardised assessment of symptoms and wheat intolerance. Those patients that continue to experience symptoms will then be randomised to a pre-consultation intervention (a) standardised dietician supervised intervention, b) exercise intervention, c) internet delivered cognitive behavior therapy or d) nothing) followed by randomisation to the consultation intervention (a) consultant-led outpatient clinic or b) an integrated care clinic conditional on their response to the initial intervention. Specific aims of the study include Aim 1: Determine efficacy (symptom improvement) and cost-effectiveness (quality adjusted life years) of a structured, digital technology enabled approach for the management of patients with severe functional gastrointestinal disorders as compared to established service models; Aim 2: Identify response-predictors for the pre-clinical dietary intervention, internet delivered cognitive behavior therapy, exercise physiology and the various clinical interventions; Aim 3: Define acceptance of consumers and staff for the new service model relative to established models of care and Aim 4. To determine the dietary patterns of people with functional gastrointestinal disorders who are presenting with symptoms necessary to access tertiary care and to further examine changes in diet after a range of interventions delivered by telehealth.

The purpose of this post-market clinical follow up study is to assess the efficacy on clinical symptoms of LARS of low volume Transanal Irrigation by MiniGo in conjunction with conservative treatment versus conservative treatment at 3 months.

Cyclic vomiting syndrome is a disorder of gut-brain interaction characterized by severe, stereotypical and disabling episodes of intense nausea and vomiting, lasting anywhere from 2 hours to 7 days. The disorder is more prevalent than commonly recognized and is estimated to occur in 1.9% of children. The medical costs for the diagnosis and treatment of CVS are immense and quality of life is markedly affected and worse in children with CVS compared to other gut-brain disorders. About 80% of patients with CVS suffer from concurrent migraine headaches or abdominal migraines during the episodes. Therapies are therefore targeted both towards both nausea and vomiting and aggressive pain control. Therapies are empiric, and response is often variable with numerous patients still requiring Emergency Room visits or hospital admissions. Tricyclic antidepressants are traditionally the most commonly used "off-label" drugs for children with CVS. These drugs may cause serious side effects, and are frequently discontinued due to intolerable adverse effects. Most recent CVS treatment guidelines in fact call for use of these antidepressants only in refractory cases and increased use of non-pharmacological interventions in all children with CVS. Safer and more effective treatments for children with CVS are much needed. Currently, there are no FDA-approved drugs for the treatment of CVS in children. The mechanisms underlying CVS remain unclear but there is emerging consensus of altered brain-gut neurocircuitry and autonomic nervous system imbalance. Autonomic abnormalities are previously documented in both children and adults with CVS. We have recently demonstrated significantly altered dynamic, cardiac vagal function in children with CVS compared to age and size matched healthy controls, supporting the use of interventions that target vagal signaling. Interventions targeting the underlying autonomic imbalance such as auricular vagal nerve stimulation are likely targeting the underlying autonomic imbalance via stimulation of the auricular branch of the vagus in the outer ear. The ear is innervated by several cranial nerves including the vagus (CN X) which projects directly brainstem nausea and vomiting centers. Stress and elevated sympathetic nervous system activity may contribute to initiation of vomiting in CVS patients and therapy via vagal modulation may alter these signals and prevent episodes. Non-invasive, auricular neurostimulation using the percutaneous electrical nerve field stimulation (PENFS) device has been demonstrated effective for gastrointestinal pain in a randomized, sham controlled clinical trial. More recently, we demonstrated efficacy of PENFS in an open-label, prospective pilot study of 30 children with drug-refractory CVS. There was a significant improvement in both frequency and duration of CVS episodes from baseline (p\<0.0001). Notably, a positive effect on quality of life was demonstrated at long-term follow-up after only 6 weeks of therapy. At 6 months follow-up, 80% demonstrated at least 50% improvement in either frequency or duration of episodes with a median response duration of 113 days. Importantly, 100% of these patients were satisfied with the treatment and no serious side effects were reported. Auricular neurostimulation thus modulates autonomic nervous system balance, thereby improving nausea and vomiting presumably by altering vagal signaling with secondary effects of improving quality of life. The aim of this study is to further investigate the efficacy of auricular neurostimulation using PENFS using a randomized, sham controlled study design in a large cohort of children with CVS. Children ages 5-18 years, evaluated at Children's Wisconsin hospital gastroenterology clinic and meeting formal criteria for CVS based on 2025 NASPGHAN guidelines may be eligible to participate. Subjects will be randomized 2:1 to receive 5 consecutive weeks of active or sham device in a blinded fashion. Subjects will be followed for 12 months after completion of therapy.

The purpose of this study is to check how well LY35327021 works and how safe it is for controlling nausea and vomiting caused by chemotherapy. Participants who join this study will be in it until all parts are finished, which could take about 2 months.

The purpose of this study is to learn more about a new medicine called PF-08634404, and how well it works in people with cancer of the colon or rectum (CRC)). The goal is to understand if the new study medicine, combined with chemotherapy that is approved for colorectal cancer, can help people whose cancer has spread or returned after treatments taken before. To join the study, participants must meet the following conditions: * Be 18 years or older. * Have colorectal cancer that has spread to other parts of your body. * Be in good enough health to receive study treatment. * Should not be pregnant before starting treatment. Participants will be randomized (like flipping a coin) to one of 2 different treatment arms. The first arm (Arm A) will include the new medicine PF-08634404 in combination with chemotherapy that is approved for colorectal cancer, and the second arm (Arm B) will include an approved medicine for colorectal cancer, called Bevacizumab, in combination with chemotherapy that is approved for this type of cancer. Participants and their doctors will not know which arm they are being assigned to. Participants will receive all the study medications through intravenous (IV) infusions, which means the medicine is given directly into a vein. The treatment will be given in cycles, and participants may continue receiving it if it is helping and they are not experiencing serious side effects. The medicine will be given at a clinical site, where trained medical staff will check participants during and after each treatment. * The study is expected to last approximately 33 months for each participant. * Participants will have regular visits to the study site for treatment, health checks, and tests. * After stopping treatment, participants will return for a final visit about 30 to37 days later to check their health and review any side effects. * Follow-up will continue every 12 weeks by phone or in person or by reviewing health records to check on health status and any new treatments.

The study aimed to determine the effect of a hot water bag applied to the abdominal region on pain caused by decreased or cessation of intestinal peristalsis in individuals diagnosed with ileus on reducing or relieving pain and restoring intestinal peristalsis. Data will be evaluated using a literature-based Patient Personal Information Form, Visual Analog Scale, burping, and auscultation of bowel sounds with a stethoscope. Sample calculations were performed using a priori power analysis (t-test) for the intervention and control groups. Accordingly, with an effect size of d=2.06, a 5% error rate (α=0.01), and 99% power (1-β=0.99), the minimum sample size for both groups was calculated as 54. Considering potential losses, the total sample size was increased by 10%, resulting in 30 patients in each group (Experimental Group: 30, Control Group: 30), and a total of 60 patients.

Rationale and clinical significance of the hypothesis It has already been stated that nutritional support represents a crucial component in the care of critically ill patients. High metabolic demand encountered for critically ill patients may cause significant energy deficits responsible for increased risk of infection, prolonged mechanical ventilation and ICU stay. Aditionally, providing nutritional support in ICU patients is often deeemd challenging, as enteral feeding intolerance devolps secondary to gastrointestinal dysfunction. Although some authors opinioned that reducing energy targets might be beneficial, several studies proved that permissive underfeeding has no positive impact on outcome. Morover, reduction of energy target recommendation was associated with a scondary decrease of protein supplementation. Apart from disscussing nutritional intake, great emphasis should be placed on nutritional uptake as an increased percentage of critically ill patients fail to reach nutritional targets often due to gastrointestinal dysfunction. Gastrointestinal dyfunction may be defined by a variety of functional impairements affecting motility, absorbtion, microbiome composition or perfusion, but still, at this momement there is a lack of recommendation regarding monitoring methods\[6\]. At the bedside, assesement of gastrointestinal dysfunction often relies on measuring GRV. However, gastric emptying rate proved to be poorly correlated with GRV. This monitoring technique may also result in a decresed amount of nutrients delivery. Since ultrasound has became a popular diagnostic tool also in the ICU, several studies indicated that ultrasonographic measurement of gastric antral cross-sectional area has a good correlation with both aspirated GRV and gastric volume measured by computerised tomography. Considering that paracetamol has little to no absorption in the stomach and is completely absorbed at the intestinal level, paracetamol absorption test (PAT) has been proposed as a simple, indirect method for evaluating gastric emptying. As the pharmacokinetic studies have established that gastric emptying is a rate-limiting step for paracetamol absorbtion, studies where PAT was used, validated a significant correlation with scintigraphy results. The combination of reduced tolerance to enteral feeding at the initiation of nutritional support, along with the initiation of nutritional support within 48 hours, has been proven to be responsible for a progressively significant and intractable energy deficit. It has been found that continuing enteral feeding under these circumstances is ineffective in resolving this energy debt which is proportional with an increased risk of nosocomial infections. Using SPN for patients who cannot tolerate EN proved to be safe and was associated with improved cumulative energy balance, decreased rate of infections and significant cost reduction. Although SPN is proposed both by ESPEN and ASPEN guideline as an efficient alternative when energy and protein target are not achieve by oral or enteral route, recent data revealed that SPN use is rather limited\[14\]. The primary concern regarding SPN use is the risk of overfeeding. However, utilizing the appropriate concept of SPN and measuring energy needs by indirect calorimetry may overcome administering feeds in an unphysiological manner. Besides intake and uptake, muscle capacity to respond to nutritional protein should also be taken into account. Several different tools have been proposed for body composition analysis of critically ill patients. Ultrasound with different protocols has also been used to assess muscle mass even in ICU patients with greater fluid shifts\[16\]. Studies have indicated that a significant reduction in muscle mass may be identified by both rectus femoris cross-sectional area and quadriceps muscle layer thickness measurements. Bioelectrical impedance analysis is another non-invasive, low-cost technique used for body composition assesment. Despite reported limitations related with frequent overhydration states in critically ill patients, this method can still provide reliable data if the appropriate timing for examination is chosen. Nevertheless, bioelectrical impedance analysis-derived phase angle proved to be a trustworthy parameter not only for evaluating fat-free mass, but also mortality. Functional parameters, such as handgrip strengts measurements should be also included when effectivness of nutritional support is evaluated. However, it is important to acknowledge barriers to collecting functional outcome data particularly when critically ill patients are studied. Study design 1. Study type This single-center controlled randomized pragmatic trial will be conducted in the 34-bed general intensive care of Clinical Emergency Hospital of Bucharest, a tertiary-care university affiliated hospital. Participating site data: Department of Anaesthesia and Intensive Care from the Clinical Emergency Hospital of Bucharest disposes in total of 86 intensive care beds Considering that there is no globally validated single definition that can be used to objectify this gastrointestinal dysfunction, real prevalence of this dysfunction is not quantified. It has been reported that one-third of all enterally fed, mechanically ventilated, critically ill patients are presenting enteral feed intolerance, but many more patients may have subclinical gastrointestinal dysmotility, the estimated percentage could reach as high as 80%. Taking into account the annual rate of admission in our unit it is feasible to complete the inclusion process by July 2025 (1 year and 8 months). Nevertheless, maintaining this study as monocentric will provide better control over potential confounding factors and reduce heterogeneity. Furthermore, it will enhance internal validity and streamline coordination efforts. Ethics: Study protocol together with a a model of informed consent were submitted to the Clinical Emergency Hospital of Bucharest Ethics Committee and the final approval has been obtained on 18.05.2023. 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. 2. Description of the study population (inclusion and exclusion criteria) All adults (\> 18 years old) are eligible for inclusion if it will be expected to require mechanical ventilation for more than four days, have a controlled shock state (hemodynamic and tissue perfusion goals are reached) and impaired intestinal absorbtion, defiend by both ultrasound measurement of gastric residual volume and paracetamol absorbtion test. Exclusion criteria are patients on non-invasive mechanichal ventilation, contraindication for EN for \> 48 h after admission, patients with gastrointestinal surgical intervention within 3 months, history of malabsorption, inflammatory bowel disease, short bowel syndrom, anorexia nervosa, gastrointestinal bleeding, cirrhosis, traumatic brain injury, subarahnoidal hemorrhage, neoplasia, post cardiac arrest patients, patients on chronic therapy with corticosteroids and pregnant women. e. Methods and techniques Randomisation: Selected patients for inclusion will be allocated in one of the two groups after stratified randomisation. The patient population can be stratified into three groups based on their admission type, which includes General Surgery, Multiple Trauma, and Internal Medicine. To perform stratified randomization, three separate randomization lists would be required - one for each stratum. These lists could be generated using techniques such as block randomization. Depending on the stratum a patient belongs to, the corresponding randomization list would be utilized to allocate the patient to one of the nutritional protocol being compared. Nutritional protocol: Nutritional targets are based on ESPEN guidelines recommendation (calories administration based on indirect calorimetry study, proteins 1.3 g/kg/day). From the first day of ICU admission indirect calorimetry will be performed daily in order to evaluate energy requirements. For both groups enteral nutritional support will be started after 48 hours since admission or after controlled shock state will be confirmed. Enteral nutrition will be incrementally escalated using a ramped fashioned approach, with the goal of reaching 25 to 50% of the energy target determined by indirect calorimetry by day 2. Subsequently, on days 3 and 4, the target will be gradually raised to 75%. Enteral nutrition will be administered continuously. On the fourth day, the patient will undergo a gastric residual volume measurement and a paracetamol absorption test. If gastrointestinal dysfunction is detected, the patient will be assigned to a study group based on the randomization protocol. In the EN group, enteral nutrition intake will progressively be increased according to the gastrointestinal tolerance (evaluated based on ultrasound guided gastric residual volume measurement) until the target of 100% is attained following admission to the ICU. The SPN group will gradually initiate supplemental parenteral nutrition in order to achieve the target of 80% by the fifth day. Trophic feed will be administered to cover the remaining 20% of the targeted nutrition intake. Figure 1 depicts a graphical illustration of the nutritional protocol. Products: EN formula for EN group and trophic feeds: polymeric, fibre-enriched formulas - Fresubin® Original Fibre (15% proteins, 30% lipids, 52% carbohydrates, Fibre 3 %) PN formula for SPN group: SMOFKABIVEN EXTRA NITROGEN 16 gN - 1518 ml - 10% amino acids, 20% lipid emulsion (SMOFlipid 20%), 42% glucose, and electrolytes Ultrasound guided gastric residual volume measurement: Gastric ultrasound assessment will be performed by two independent observers in supine position. Both sets of measurements will be performed after a minimum of six hours of fasting. Antral cross-sectional area (ACSA) area will be calculated by using antero-posterior and cranio-caudal antral diameters (measured from serosa to serosa) and the formula of the area of an elipse ( )/4). Furthermore, the gastric volume will be calculated according to the model proposed by Perlas et al. Gastric Volume (ml) = 27.63 + 0.16 x weight (kg) + 1.24 x BMI - 0.013 x (time since last meal in hours) x (antral cross-sectional area in cm²). A gastric residual volume above 200 ml will be considered positive for impaired gastric motility. Paracetamol absorbtion test: In order to evaluate paracetamol absorbtion, area under the plasma concentration curve was chosen to be calculated at 240 mins (AUC240) by using the trapezoidal method. In order to be able to obtain AUC240 five different measurements will be carried out at predetermined intervals, namely at the baseline (before paracetamol administration), at 30 minutes, 60 minutes, 120 minutes, and 240 minutes. Paracetamol 15 mg/kg disolved in 10 ml aqueous solution followed by 20 ml of water will be adminsitered. Afterwards Enzyme Multiplied Immunoassay Technique (EMIT) will be used to detect paracetamol level. Principle of technique: The technique involves conjugating an enzyme with a small target molecule specific to the analyte being tested, in this case acetaminophen. Binding of a specific target antibody inhibits the enzymatic activity. The enzyme glucose-6-phosphate dehydrogenase is bound to the antigen for acetaminophen, which oxidizes glucose-6-phosphate to gluconolactone-6-phosphate and reduces NAD to NADH. If a free target molecule such as acetaminophen is present in the plasma, inhibition is weakened by competition for the antibody, leading to restoration of enzymatic activity and intensity of the signal proportional to the concentration of the free target molecule. Enzymatic activity is measured by spectroscopic analysis of the amount of NADH produced, which correlates directly to the amount of acetaminophen in the specimen. Blood samples will be collected from patients in vacutainer tubes with sodium citrate or EDTA anticoagulant under vacuum to facilitate plasma separation and prevent hemolysis. Bioelectrical impedance analysis (BIA): We will use the InBody BWA 2.0 BIA machine to perform BIA measurements. The following measurements will be collected for analysis: impedance, phase angle, resistance, reactance, Waist/Hip Ratio, body cellular mass, lean body mass and fat-free mass index. Measurement of rectus femoris cross sectional area: B-mode ultrasonography utilizing an 8 MHz 5.6 cm linear transducer array will be employed to measure the Cross-sectional area of the rectus femoris (RFCSA), employing a previously described technique. The transducer will be positioned perpendicularly to the long axis of the thigh, on its superior aspect, specifically three-fifths of the way from the anterior superior iliac spine to the superior patellar border.