Evaluation of Intestinal Brush Border Enzyme Function in Critically Ill Patients

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

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

Study Overview

• Status: Completed
• Conditions: Critical Illness; Septic Shock; SIRS
• Intervention / Treatment: Procedure: Gastroscopy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University Vienna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Septic Shock; 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; 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
Other: SIRS; 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; 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
Other: healthy/controls; 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Ulrike Holzinger, MD, Medical University of Vienna

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: April 12, 2012
• First Submitted That Met QC Criteria: April 24, 2012
• First Posted (Estimate): April 26, 2012

Study Record Updates

• Last Update Posted (Actual): August 29, 2017
• Last Update Submitted That Met QC Criteria: August 28, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Shock; Sepsis; Shock, Septic; Critical Illness
• Other Study ID Numbers: BBM_septic_shock