Diluted and Undiluted Enteral Nutrition

The Influence of Diluted and Undiluted Enteral Nutrition on Nutritional Tolerance in Critically Ill Patients After Gastrointestinal Surgery - a Randomized Controlled Trial

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 feeding intolerance assessment in both groups of patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Quality of Life; Critical Illness; Surgery; Enteral Feeding Intolerance; Gastro-Intestinal Disorder
• Intervention / Treatment: Other: Enteral fluid; Other: Intravenous fluid

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 nausea and vomiting (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)
• Administration of prokinetic agents. Starting with both erythromycin (125mg twice daily enterally) and metoclopramide (10mg three times per day i.v.)

Secondary outcomes (routinely performed procedures):

• 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 (twice daily)
• Fluid balance: additional fluids given intravenously during ICU stay
• Blood product 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
• 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

Follow-up:

• Quality of recovery - phone interview 30 days after randomization

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michal Borys, MD, PhD; Phone Number: +48 506350569; Email: michalborys1@gmail.com
• Study Contact Backup: Name: Pawel Piwowarczyk, MD, PhD; Phone Number: +48 511285352; Email: piwowarczyk.pawel@gmail.com

Study Locations

• Poland
  • Gorzów Wielkopolski, Poland, 66-400
    • Provincial Hospital in Gorzow Wielkopolski
    • Contact: Miroslaw Czuczwar, MD, PhD
  • Kraków, Poland, 30-901
    • Fifth Military Hospital
    • Contact: Wojciech Szczeklik, MD, PhD
  • Lublin, Poland, 20-081
    • II Department of Anesthesia and Intensive Care, Medical University of Lublin
  • Lublin, Poland, 20-049
    • First Military Hospital
    • Contact: Elzbieta Rypulak, MD, PhD; Phone Number: +48791127036; Email: elzbieta.rypulak@gmail.com
  • Opole, Poland, 45-372
    • Provincial Hospital in Opole
    • Contact: Tomasz Czarnik, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Enteral nutrition fluid - ENF; Enteral nutrition will be given continuously with glucose-Na-K Baxter 50 mg/ml solution for infusion (GNAK)-both products to the gastrointestinal tract in the same volume.	Other: Enteral fluid; GNAK will be administered to the gastrointestinal tract with EN in the same volume.; Other Names: ENF
Experimental: Intravenous fluid - IVF; Enteral nutrition will be given continuously to the gastrointestinal tract. GNAK will be given continuously intravenously in the same volume.	Other: Intravenous fluid; Undiluted EN will be given to the gastrointestinal tract. GNAK, in the same volume, will be administered intravenously.; Other Names: IVF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants having nausea and vomiting	Incidents of nausea and vomiting (nausea measured with a 4-point verbal descriptive scale (0=no nausea, 1=mild, 2=moderate, 3=severe))	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Number of participants having diarrhea	Incidents of diarrhea (≥ three loose stools per day)	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Number of participants having increased gastric residual volume	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)	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Number of participants in whom target EN will not be achieved	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)	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Number of participants in whom prokinetic agents will be used	Administration of prokinetic agents according to the intensivist discretion. Starting with both erythromycin (125 mg twice daily enterally) and metoclopramide (10mg three times per day i.v.)	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days of support with PN	Days of support with parenteral nutrition during the 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
Contribution of PN in total nutrition	Percentage contribution of parenteral nutrition in total patient feeding understand as protein demands	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	Insulin consumption - units per day and total per stay	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	Electrolyte supplementation - potassium, phosphorus, calcium, and magnesium in mmol/ stay	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Enteral access obstruction	Need for replacement outside the ICU or under endoscopy assistance. Number of such procedures per stay.	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	Intraabdominal pressure via urinary catheter twice daily	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Sequential Organ Failure Assessment Score (SOFA)	Calculating SOFA twice daily - from 0 to 24 - 0 means the lack of organ failure; 24 multiorgan failure	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Fluid balance	Additional crystalloids or colloids given intravenously during ICU stay measured in milliliters	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Blood products transfusion	Transfusion of any blood products, including red-packed cells, fresh-frozen plasma, platelets, and cryoprecipitate, measured in units per stay.	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Acute kidney injury (AKI)	Recognition of AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) definition	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Vasoactive drugs	Usage of vasoactive drugs including noradrenaline, dobutamine, dopamine, adrenaline, and others measured in milligrams as cumulative dose per stay	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Stroke volume variation	Measurement of stroke volume variation presented in percent twice daily during the patient stay	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Cardiac output	Measurement of cardiac output (L/min) with pulmonary thermodilution technique twice daily during the patient's stay	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Systemic vascular resistance	Measurement of systemic vascular resistance (dynes/sec/cm-5) with pulmonary thermodilution technique twice daily during the patient's stay	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Extravascular lung water	Measurement of extravascular lung water index (ml/kg) with pulmonary thermodilution technique twice daily during the patient's stay	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Lactates	At least once daily, arterial blood lactates (mmol/L) will be measured	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Complete blood count (CBC)	Once daily CBC will be tested	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Blood proteins	Plasma protein concentrations (g/dL) will measured at least once a week.	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Infection site	Site of infection during the 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
Antibiotics	Antibiotics wchich will be used in ICU.	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Blood albumins	Plasma albumin concentrations (g/dL) will measured at least once a week.	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
C-reactive protein (CRP)	CRP (mg/L) will be measured once daily.	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Procalcitonin (PCT)	PCT (ng/mL) will be measured once daily.	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	Mechanical ventilation time in hours per stay	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Intensive care unit (ICU) stay	ICU stay in days	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	Hospital stay in days	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Hospital mortality	In-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
Intestinal fatty-acid binding protein (I-FABP)	I-FABP concentrations (nmol/mL) will be measured in the blood and urine once daily.	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Zonulin	Zonulin concetration (ng/mL) will measured in the patient's blood on the 1st day, 4th day, and at the ICU discharge.	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Ketones	Serum ketone concentrations (mmol/L) will be collected and measured at ICU admission, 4th day, and discharge	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Microbiome	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	From the date of randomization until the date of the ICU discharge or death but no longer than 8 weeks, whichever came first
Quality of recovery	Phone interview using a modified version of Quality of recovery-40 scale (37-185 points,more points better) 30 days after randomization	30 days after randomization

Collaborators and Investigators

• Sponsor: Medical University of Lublin
• Collaborators: Nutricia Fundation; Catholic University of Lublin
• Investigators: Principal Investigator: Michal Borys, MD, PhD, Medical University of Lublin

Study record dates

Study Major Dates

• Study Start (Estimated): January 2, 2025
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: July 7, 2024
• First Submitted That Met QC Criteria: July 17, 2024
• First Posted (Actual): July 24, 2024

Study Record Updates

• Last Update Posted (Actual): July 26, 2024
• Last Update Submitted That Met QC Criteria: July 24, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Microbiome; Ketones; Zonulin; Intestinal fatty-acid binding protein (I-FABP)
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Gastrointestinal Diseases; Digestive System Diseases; Critical Illness; Intestinal Diseases
• Other Study ID Numbers: KE-0254/92/05/2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No