Critical Illness, Gastro Intestinal Surgery, Enteral Feeding Intolerance, Gastro-Intestinal Disorder, Quality of Lifte
Conditions
Keywords
Zonulin, Intestinal fatty-acid binding protein (I-FABP), Ketones, enteral feeding, GNAK
Brief summary
Adult patients after elective major abdominal surgeries who are planned to be admitted to the Intensive Care Unit (ICU) can be included in the trial. Each patient will be fed via the gastrointestinal tract. Half of the patients will receive enteral nutrition (EN) with additional fluids, and the rest will receive undiluted EN. The primary aim of this study is to assess feeding intolerance in both patient groups.
Detailed description
Approximately 50 % of the intensive care unit (ICU) population has feeding intolerance (FI), which includes nausea, vomiting, diarrhea, and others. Some studies suggest that FI can be alleviated in patients fed with supplemental parenteral nutrition (PN). Adult patients after elective major abdominal surgeries who are planned to be admitted to the ICU can be included in the trial. After the ICU admission, the patient will be stabilized, including warming, correction of water, electrolyte, and acid-base disorders, and blood transfusion if required. The fluid therapy will be monitored using the transpulmonary dilution technique. Then, an attending physician will contact an investigator. The investigator will decide about the randomization (no contraindication). The investigators plan to maintain fluid therapy with continuous Glucose-Na-K Baxter 50 mg/ml solution for infusion (GNAK). GNAK will be administered in the same flow as EN, enterally or intravenously (i.v.). Patients will be randomized to one of two studied groups: Continuous EN will be administered solely to the GI tract in the first group. The same dose of GNAK will be given i.v. (IVF group). In the second group, GNAK will be administered enterally with EN, a routine practice in our department (ENF group). The attending physician will correct all fluid disturbances with balanced fluids or blood products according to laboratory tests and hemodynamic monitoring. GNAK will only be given as maintenance fluid with EN. The primary outcome of our study will be feeding intolerance (FI). FI is a composite outcome consisting of at least one of the following: * Incidents of vomiting * Administration of prokinetic agents. Starting with both erythromycin (125mg twice daily enterally) and metoclopramide (10mg three times per day i.v.) due to significant EN intolerance, i.e. ≥ 2 incidents of vomiting/24h; \> 500 mL of gastric volume/6h; presence of gastric contents/nutrition in the endotracheal tube due to regurgitation Secondary outcomes (routinely performed procedures): * Incidents of nausea (nausea measured with a 4-point verbal descriptive scale (0=no nausea, 1=mild, 2=moderate, 3=severe) * Incidents of diarrhea (≥ three loose stools per day) * Increased gastric residual volume (\> 500 ml of gastric aspirate/ 6 hours). Only in patients after lower GI tract surgeries (with intact stomach and gastric feeding) * Achieving target EN on day three and later: 80% of protein requirements according to ESPEN (1.3/kg of ideal body weight (patients BMI \< 30) or adjusted body weight, BMI ≥ 30) * PN requirements (days of support, grams of proteins, extra protein calories per day, contribution of PN in total nutrition) * Insulin consumption (units per day and total per stay) * Electrolyte supplementation (potassium, phosphorus, calcium, and magnesium in mmol/ stay) * Enteral access obstruction (rinsing with fluid, need for replacement) per stay * Intraabdominal pressure (twice daily) * Sequential Organ Failure Assessment Score (daily) * Acute Physiology and Chronic Health Evaluation II (daily) * Fluid balance: additional fluids given intravenously during ICU stay * Blood products transfusion * Acute kidney injury, according to KDIGO definition * Usage of vasoactive drugs: cumulative dose per stay * Hemodynamic parameters, measured at least twice per day, such as stroke volume variation, pulse pressure variation, cardiac output, global end-diastolic volume, systemic vascular resistance, and extravascular lung water * Laboratory tests, including lactate, electrolytes, arterial blood gas analysis, coagulation, total blood count * Infections during the stay (site, antibiotics requirements) * Mechanical ventilation time (hours) * ICU stay (days) * Hospital stay (days) * Hospital mortality Additional procedures: * Intestinal fatty-acid binding protein (I-FABP) collection from blood and urine once daily during ICU stay * Serum zonulin on the 1st day, 4th day, and at ICU discharge * Serum ketones collection at ICU admission, 4th day, and discharge * Gut microbiome collection at ICU admission and discharge (for 60 patients, 30 participants in each group) Follow-up: • Quality of recovery - phone interview 30 days after randomization
Interventions
OTHEREnteral fluid
GNAK will be administered to the gastrointestinal tract with EN in the same volume.
OTHERIntravenous fluid
Undiluted EN will be given to the gastrointestinal tract. GNAK, in the same volume, will be administered intravenously.
Sponsors
John Paul II Catholic University of Lublin
Center of Oncology of the Lublin Region
Provincial Specialist Hospital in Lublin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
Two groups will be randomly allocated to ENF or IVF group
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Adults, ≥18, Scheduled for major abdominal surgery requiring ICU admission Having access to the GI tract (gastric or jejunal) Planned to be fed enterally
Exclusion criteria
Patients unable to give informed consent After emergency surgeries Without access to the GI tract Individuals with contraindications to EN, such as short bowel syndrome, uncompensated shock, acidosis (pH \< 7.1; lactate \> 5 mmol/l), bleeding from the upper GI tract, obstruction, intestinal ischemia, abdominal compartment syndrome Patients with symptomatic gastro-esophageal reflux Expected ICU stay \< 3 days Pregnancy and lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants who received prokinetic agents. | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | Administration of prokinetic agents starting with both erythromycin (125mg twice daily enterally) and metoclopramide (10mg three times per day i.v.) due to significant EN intolerance, i.e. ≥ 2 incidents of vomiting/24h; \> 500 mL of gastric volume/6h; presence of gastric contents/nutrition in the endotracheal tube due to regurgitation |
| Number of patients having vomiting. | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | Any incidents of vomiting. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants having diarrhea | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | ≥ three loose stools per day |
| Number of participants having increased gastric residual volume | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | \> 500 ml of gastric aspirate/ 6 hours. Only in patients after lower GI tract surgeries (with intact stomach and gastric feeding) |
| Number of participants in whom target EN will be achieved | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | Achieving target EN on day three and later: 80% of protein requirements according to ESPEN (1.3/kg of ideal body weight (patients BMI \< 30) or adjusted body weight, BMI ≥ 30) |
| Insulin consumption | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | Insulin consumption (units per day and total per stay) |
| Electrolyte supplementation | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | Electrolyte supplementation (potassium, phosphorus, calcium, and magnesium in mmol/ stay) |
| Intraabdominal pressure | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | Intraabdominal pressure via urinary catheter twice daily |
| Sequential Organ Failure Assessment Score | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | Calculating SOFA daily - from 0 to 24 - 0 means the lack of organ failure; 24 multiorgan failure |
| APACHE II | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | APACHE II (Acute Physiology and Chronic Health Evaluation II) measured daily. Ranging from 0 to 71. 0 - meaning no organ failure. 71 - meaning multiorgan failure. |
| Fluid balance | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | Additional crystalloids or colloids given intravenously during ICU stay measured in milliliters |
| Blood products transfusion | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | Transfusion of any blood products, including red-packed cells, fresh-frozen plasma, platelets, and cryoprecipitate, measured in units per stay. |
| Acute kidney injury (AKI) | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | Recognition of AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) definition |
| Vasoactive drugs | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | Usage of vasoactive drugs including noradrenaline, dobutamine, dopamine, adrenaline, and others measured in milligrams as cumulative dose per stay |
| Stroke volume variation | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | Measurement of stroke volume variation presented in percent twice daily during the patient stay |
| Cardiac output | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | Measurement of cardiac output (L/min) twice daily during the patient's stay |
| Systemic vascular resistance | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | Measurement of systemic vascular resistance (dynes/sec/cm-5) twice daily during the patient's stay |
| Lactates | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | At least once daily, arterial blood lactates (mmol/L) will be measured |
| Complete blood count (CBC) | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | Once daily CBC will be tested |
| Blood proteins | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | Plasma protein concentrations (g/dL) will measured at least once a week. |
| Infection site | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | Site of infection during the ICU stay. |
| Antibiotics | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | Antibiotics wchich will be used in ICU. |
| Blood albumins | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | Plasma albumin concentrations (g/dL) will measured at least once a week. |
| C-reactive protein (CRP) | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | CRP (mg/L) will be measured once daily. |
| Procalcitonin (PCT) | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | PCT (ng/mL) will be measured once daily. |
| Mechanical ventilation | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | Mechanical ventilation time in hours per stay |
| Intensive care unit (ICU) stay | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | ICU stay in days |
| Hospital stay | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | Hospital stay in days |
| Hospital mortality | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | In-hospital mortality |
| . Intestinal fatty-acid binding protein (I-FABP) | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | I-FABP concentrations (nmol/mL) will be measured in the blood and urine once daily. |
| Zonulin | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | Zonulin concetration (ng/mL) will measured in the patient's blood on the 1st day, 4th day, and at the ICU discharge. |
| Ketones | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | Serum ketone concentrations (mmol/L) will be collected and measured at ICU admission, 4th day, and discharge |
| Microbiome | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | Intestinal microbiome collection upon admission and discharge from the ICU. Sequencing of the V3 V4 region of the 16SrRNA gene using NGS using Illumina technology, 2x250 bp, min. 100,000 readings, including DNA isolation. Preparation of the OTU table and basic alpha biodiversity measures |
| Days of support with PN | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | PN requirements (days of support, grams of proteins, extra protein calories per day, contribution of PN in total nutrition) |
| Quality of recovery | 30 days after randomization | Phone interview using a modified version of Quality of recovery-40 scale (37-185 points,more points better) 30 days after randomization |
| Number of participants having nausea | From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first | nausea measured with a 4-point verbal descriptive scale (0=no nausea, 1=mild, 2=moderate, 3=severe) |
Countries
Poland
Contacts
CONTACTMichal Borys
CONTACTKatarzyna Kosz
PRINCIPAL_INVESTIGATORMichał Borys
Medical Faculty, John Paul II Catholic University of Lublin
Outcome results
None listed