Critically Ill Intensive Care Unit Patients, Feeding Intolerance, Gastrointestinal Dysfunction
Conditions
Brief summary
Critically ill patients admitted to the intensive care unit (ICU) frequently present with gastrointestinal dysfunction and are at elevated risk of malnutrition. Gastrointestinal dysfunction is correlated with adverse clinical outcomes, including prolonged mechanical ventilation duration, extended ICU length of stay, and increased 90-day mortality. In critically ill ICU patients, severe gut microbiota dysbiosis and intestinal barrier impairment may occur due to the burden of primary critical illnesses, as well as the administration of proton pump inhibitors and antibiotics. This cascade contributes to a high prevalence of gastrointestinal dysfunction, alongside profound gut-derived systemic inflammatory responses and organ damage. Given the pivotal role of gut microbiota in maintaining intestinal homeostasis, fecal microbiota transplantation (FMT) holds promise as a novel therapeutic strategy for enteral feeding intolerance secondary to gastrointestinal dysfunction in critically ill ICU patients. This study intends to deliver FMT via a nasojejunal tube to critically ill patients with gastrointestinal dysfunction admitted to the ICU. Its objectives are to evaluate the intervention's effects on gastrointestinal function recovery and the alleviation of enteral feeding intolerance, while also assessing its impacts on intestinal barrier function, gut microbiota composition and metabolic profiles, serum metabolite signatures, immune-inflammatory responses (including lymphocyte subsets, cytokines, C-reactive protein, and procalcitonin), ICU delirium, ICU sleep quality, and clinical outcomes (encompassing ICU mortality, in-hospital mortality, 28-day all-cause mortality, 90-day all-cause mortality, 90-day readmission rate, and 90-day incidence of secondary infections).
Interventions
OTHERFecal microbiota transplantation (FMT)
Patients received FMT via a nasojejunal tube in addition to standard ICU care. Specifically, 50-100 mL of intestinal microbiota suspension was administered daily via the nasojejunal tube between 11:00 and 13:00 for three consecutive days.
Sponsors
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Aged 18 to 70 years inclusive, regardless of ethnicity or gender; 2. Female participants are either non-fertile (i.e., physiologically incapable of pregnancy, including women with ≥2 years of menopause) or have no pregnancy plans; 3. Have been admitted to the ICU for ≥24 hours; 4. Expected ICU stay ≥7 days after study enrollment; 5. Screened positive for ≥1 manifestation of gastrointestinal dysfunction (intra-abdominal hypertension \[IAH\], massive gastric retention, diarrhea, lower gastrointestinal paralysis, bowel dilatation); enteral nutrition is then implemented under the guidance of the enteral feeding intolerance (FI) score, and participants with persistent FI after a 3-day trial are formally enrolled; 6. Participants can actively cooperate or passively complete relevant examinations and follow-up procedures; 7. Have signed a written informed consent form.
Exclusion criteria
1. Severe systemic infection in the early resuscitation phase, with hemodynamic instability, insufficient tissue perfusion, or severe fluid-electrolyte and acid-base imbalances; 2. Patients assessed by clinicians as having a high risk of death within 5 days, or those with restricted treatment decisions; 3. Active gastrointestinal bleeding, perforation, or other conditions with severe intestinal barrier impairment; 4. Patients unable to tolerate enteral nutrition meeting 50% of caloric requirements due to severe diarrhea, significant fibrotic intestinal stenosis, massive gastrointestinal bleeding, or high-output enterocutaneous fistula; 5. Planned or recent abdominal surgery (within 14 days prior to enrollment); 6. Current diagnosis of fulminant colitis or toxic megacolon; 7. Neutropenia (neutrophil count \< 1500 cells/µL); 8. Patients with congenital or acquired immunodeficiency disorders; 9. Recent receipt of high-risk immunosuppressive or cytotoxic agents, e.g., rituximab, doxorubicin, or medium-to-high-dose corticosteroids (≥ 20 mg/day prednisone equivalent) for a duration of \> 4 weeks; 10. Pregnant or lactating women; 11. Participation in another clinical trial as a subject at the time of enrollment or within 3 months prior to enrollment; 12. Doubtful validity of informed consent: subjects with mental illness, intellectual disability, poor motivation, or other factors that restrict the validity of informed consent for participation in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Enteral nutrition FI improvement rate | 24, 48, 72, 96, and 120 hours after study enrollment |
Secondary
| Measure | Time frame |
|---|---|
| Gut microbiota composition as well as α and β diversity measured from rectal swabs by 16S rRNA gene sequencing | 24-0 hours and 120 hours after study enrollment |
| Fecal metabolite profile (by untargeted LC-MS) from rectal swabs | 24-0 hours and 120 hours after study enrollment |
| Serum metabolite profile (by untargeted LC-MS) | 24-0 hours and 120 hours after study enrollment |
| Serum level of citrulline | 0, 24, 48, 72, 96, and 120 hours after study enrollment |
| APACHE II score | 0, 24, 48, 72, 96, and 120 hours after study enrollment |
| SOFA score | 0, 24, 48, 72, 96, and 120 hours after study enrollment |
| Cumulative intravenous dose of vasopressor agents (including norepinephrine, epinephrine, dobutamine, etc.) | 0, 24, 48, 72, 96, and 120 hours after study enrollment |
| Serum level of C-reactive protein | 0, 24, 48, 72, 96, and 120 hours after study enrollment |
| Serum level of procalcitonin | 0, 24, 48, 72, 96, and 120 hours after study enrollment |
| Peripheral blood level of cytokines (including IL-6, IL-17, TNF-α, IL-10, IL-1β, etc.) | 0 and 120 hours after study enrollment |
| Peripheral blood lymphocyte subsets (including CD4+ T, CD8+ T, B lymphocytes, NK cells, etc.) | 0, 24, 48, 72, 96, and 120 hours after study enrollment |
| ICU mortality | Within 28 days after study enrollment |
| In-hospital mortality | Within 60 days after study enrollment |
| 28-day all-cause mortality | Within 28 days after study enrollment |
| 90-day all-cause mortality | Within 90 days after study enrollment |
| 90-day readmission rate | Within 90 days after study enrollment |
| 90-day secondary infection rate | Within 90 days after study enrollment |
Countries
China
Contacts
CONTACTJiancheng Zhang
Outcome results
None listed