Prospective Study Evaluating the Prevalence of Intestinal Dysfunction

Prospective Study Evaluating the Prevalence of Intestinal Dysfunction in Hematology Patients Hospitalized in Intensive Care for Sepsis or Septic Shock

The intestinal tract has multiple functions within the body beyond its primary function of nutrient absorption. It acts as a true barrier protecting the body from living microorganisms and antigens in the intestinal lumen. Impairment of any component of the intestinal barrier results in nutrient malabsorption, an altered local digestive immune response, and increased intestinal permeability.

The primary function of this barrier is to limit the access of the contents of the intestinal lumen, which particularly includes the bacterial components of the microbiota, to the internal environment and the circulation. This physical barrier function is provided by a monolayer of epithelial cells, closely connected to each other by intercellular junctions (tight junctions, adherens and desmosomes, as well as by the mucus which covers the apical surface of the cells, the constituents of which, mucins, are secreted by the goblet cells. The term intestinal barrier is also used in a broader sense including a protective role against the invasion of environmental pathogens, while allowing toleranSepsis-associated intestinal failure is often underestimated, yet it is found in 20 to 60% of ICU (Intensive Care Unit)vpatients. However, its prognosis is poorly documented. For example, there is no consensus definition of this dysfunction or validated biomarkers for rapid assessment. Consequently, it does not appear in most prognostic scores (SOFA, IGS2, etc.).

Intestinal permeability, a risk factor for bacterial translocation when elevated, is increased in ICU (Intensive Care Unit) patients and associated with multiorgan failure system (MODS), particularly in cases of intestinal fasting. However, there is currently no validated marker of acute intestinal failure in intensive care or intensive care.ce towards commensal flora and foods.

Several markers of intestinal response have been studied and are still in the research field due to a lack of conclusive work on their impact.

Clinically, both in post-weaning children and in adults, citrullinemia (citrulline deficiency) is well established as a sensitive and specific indicator of functional absorptive enterocyte mass.

Fecal calprotectin is already used as a marker of neutrophil-mediated inflammation in inflammatory bowel disease.

A recent controlled observational study of 165 patients investigated serum calprotectin as a prognostic marker in sepsis patients hospitalized in critical care. The authors found a significant increase in serum calprotectin concentration in sepsis patients compared to control patients. Furthermore, it would appear that a high level of calprotectin upon admission to intensive care is a significant risk factor for long-term mortality.

Finally, in patients with sepsis, serum zonulin levels are elevated, which promotes bacterial translocation via the epithelium and thus bacteremia.

The risk of infection in immunocompromised patients is a therapeutic challenge due to its adverse prognostic impact. Sepsis-related mortality is higher (relative risk = 1.62) in immunocompromised patients. One of the mechanisms of sepsis in these patients is gastrointestinal bacterial translocation due to the gastrointestinal cytotoxicity of chemotherapy, microbiota alterations via antibiotic therapy, and low perfusion rates.

This study aims to assess the prevalence of intestinal inflammation in a population of patients with malignant hematological diseases undergoing treatment and admitted to intensive care for sepsis-septic shock. These patients are exposed to cytotoxic chemotherapies that attack the intestinal mucosa, making it more permeable and thus being the source of digestive translocations of bacteria from the intestinal microbiota into the bloodstream. In the absence of validated threshold values in the literature to define intestinal inflammation based on fecal calprotectin levels, it is necessary to have a control population also affected by sepsis but not carrying malignant hematological disease.

Inclusion Criteria:

Population with hematologic malignancy

• Patients over 18 years of age

• Suffering from hematologic malignancy

• Admitted to intensive care for sepsis or septic shock according to sepsis definition 3:

  • Sepsis: organ dysfunction (SOFA > or = 2) related to a host response to infection
  • Septic shock: sepsis with acute circulatory failure and metabolic abnormalities (serum lactate > 2 mmol/L) and vasopressors

• Patients who have read and understood the information letter and do not object to participating in the study

• Affiliated with or beneficiary of a social security scheme.

Control population

- Patient aged over 18

Admitted to intensive care for sepsis or septic shock according to the sepsis definition 3:

• Sepsis: organ dysfunction (SOFA > or = 2) related to a host response to infection

• Septic shock: sepsis with acute circulatory failure and metabolic abnormalities (serum lactate > 2 mmol/L) and vasopressors

  • Patient who has read and understood the information letter and does not object to participating in the study
  • Member of or beneficiary of a social security scheme

Exclusion Criteria:

For the control group and those with hematologic malignancies:

• Patient refusal
• Pregnant, parturient, or breastfeeding woman
• Person deprived of liberty by an administrative or judicial decision or person placed under judicial protection/guardianship or curatorship
• Person who does not understand or speak French
• Moribund
• Limitations of active therapies (LATA) established upon admission
• Hospitalization in intensive care > 72 hours