Evaluation of Intestinal Brush Border Enzyme Function in Critically Ill Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the role of several enzymes of the gut mucosa in preventing invasion of gastrointestinal bacteria.

Detailed Description
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Systemic Inflammatory Response Syndrome (SIRS), sepsis, septic shock and concomitant multiorgan failure are major causes of morbidity and mortality in intensive care units. During SIRS and septic shock the role of the gut seems to be uncertain. As it serves as an intestinal barrier which allows the symbiotic relationship between man and enteric bacteria, increased gut permeability during critical illness is accused to promote sepsis. Brush border enzymes have the ability to detoxify lipopolysaccharides and prevent bacterial invasion across the gut mucosal barrier. A reduced brush border enzyme function could contribute to the gastrointestinal intolerance in critically ill patients, which is frequently observed. The aim of this study is to assess the influence of SIRS and septic shock on brush border enzyme morphology and function in men.

Official Title
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Evaluation of Intestinal Brush Border Enzyme Function in Patients With SIRS and Septic Shock Compared to Control Patients

Conditions
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Critical Illness, Septic Shock, SIRS

Intervention / Treatment
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* Procedure: Gastroscopy


Participation Criteria
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Eligibility Criteria
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Septic Shock: Recruitment and inclusion criteria 15 mechanically ventilated critically ill patients fulfilling criteria of SIRS (2 symptoms: RR > 20/min, HR > 90/min, Temp. > 38°/< 36°, 12G/l< WBC < 4G/l; assumed or proven infection, persistent hypotension refractory to fluid therapy and need for vasopressors. Time window for inclusion: up to 72h after onset of symptoms Exclusion criteria PLT < 50G/l, PT < 50%, Continuous therapeutic anticoagulation, DIC, st. p. MCI within 14 days, Gastrointestinal perforation, Age < 18 years, Age > 80 Years SIRS: Recruitment and inclusion criteria 15 mechanically ventilated critically ill patients fulfilling criteria of SIRS (2 symptoms: RR > 20/min, HR > 90/min, Temp. > 38°/< 36°, 12G/l < WBC < 4G/l; assumed or proven infection Time window for inclusion: up to 72h after onset of symptoms Exclusion criteria: PLT < 50G/l, PT < 50%, continuous therapeutic anticoagulation, DIC, st. p. MCI within 14 days, Gastrointestinal perforation, Age < 18 years, Age > 80 Years Healthy/controls: 15 control subjects will be recruited from the outpatient ward referred to the endoscopy of the Department of Medicine III - Division of Gastroenterology and Hepatology for upper GI-endoscopy because of epigastric pain or reflux symptoms. Inclusion criteria: Signed informed consent Exclusion criteria: Patients with diarrhea of unknown origin, IBD or known celiac disease Age < 18 years Age > 80 Years PLT < 50G/l, PT < 50% Therapeutic oral anticoagulation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Septic Shock<br>Activity of the brush border membrane enzymes intestinal alkaline phosphatase, maltase and lactase, as well as brush border morphology determined from duodenal biopsies in patients with septic shock | Procedure: Gastroscopy<br>* When gastroscopy is indicated for clinical reasons, duodenal biopsies to determine the activity of the brush border membrane enzymes intestinal alkaline phosphatase, maltase and lactase, as well as assessing brush border morphology are taken<br>|
| Other: SIRS<br>Activity of the brush border membrane enzymes intestinal alkaline phosphatase, maltase and lactase, as well as brush border morphology determined from duodenal biopsies in patients with SIRS | Procedure: Gastroscopy<br>* When gastroscopy is indicated for clinical reasons, duodenal biopsies to determine the activity of the brush border membrane enzymes intestinal alkaline phosphatase, maltase and lactase, as well as assessing brush border morphology are taken<br>|
| Other: healthy/controls<br>Activity of the brush border membrane enzymes intestinal alkaline phosphatase, maltase and lactase, as well as brush border morphology determined from duodenal biopsies in patients without SIRS/septic shock | Procedure: Gastroscopy<br>* When gastroscopy is indicated for clinical reasons, duodenal biopsies to determine the activity of the brush border membrane enzymes intestinal alkaline phosphatase, maltase and lactase, as well as assessing brush border morphology are taken<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| activity of the brush border membrane enzyme intestinal alkaline phosphatase | Duodenal biopsies will be taken on day 0 (at inclusion) and will be subsequently frozen. Determination of enzyme activity will be done within 28 days. | at inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| activity of the brush border membrane enzyme maltase | Duodenal biopsies will be taken on day 0 (at inclusion) and will be subsequently frozen. Determination of enzyme activity will be done within 28 days. | at inclusion | 
| activity of the brush border membrane enzyme lactase | Duodenal biopsies will be taken on day 0 (at inclusion) and will be subsequently frozen. Determination of enzyme activity will be done within 28 days. | at inclusion | 
| Brush border morphology | Duodenal biopsies will be taken on day 0 (at inclusion) and will be subsequently frozen. Determination of enzyme activity will be done within 28 days. | at inclusion | 
| ICU mortality | only for groups septic shock and SIRS | at ICU discharge | 
| hospital mortality | only for groups septic shock and SIRS | at hospital discharge | 
| mortality (6 months) |  | 6 months after inclusion |