Lung and Systemic Inflammation in the Critically Ill Patient

Acute Pulmonary and Systemic Inflammation in Mechanically Ventilated Intensive Care Patients

Acute respiratory distress syndrome (ARDS) is a devastating form of acute lung inflammation, that may be caused by a variety of insults with pulmonary and systemic infectious disease being the most common predisposing factor. Sepsis, on the other hand, represents the systemic inflammatory response to an invading pathogen, which may inflict damage upon the host through organ dysfunction. ARDS and sepsis are heterogenous clinical conditions that have a high mortality, and both diseases involve a complex interplay of different inflammatory mediators and cell types. It has been suggested that locally released inflammatory mediators pass from the lungs into the bloodstream following ARDS, triggering systemic inflammation. Conversely, it is possible that severe systemic inflammation may lead to ARDS by an influx of inflammatory mediators from the bloodstream to the lungs. However, the time course and the possible pathways for this transmission of disease have yet to be established.

Investigators hypothesize that:

1. Primary systemic inflammation is followed by a secondary pulmonary inflammatory response
2. Primary pulmonary inflammation is followed by a secondary systemic inflammatory response
3. Both primary and secondary inflammatory responses are characterized by the appearance of pro-inflammatory cytokines, inflammatory cells and production of collagen-like proteins (termed 'lectins')
4. The inflammatory response is most pronounced in the primary afflicted compartment.

Study Overview

• Status: Terminated
• Conditions: Sepsis; Acute Respiratory Distress Syndrome (ARDS); Systemic Inflammatory Response Syndrome (SIRS)

• Study Type: Observational
• Enrollment (Actual): 8

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen Ø, Denmark, 2100
    • Intensive Care Unit, 4131, Rigshospitalet

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Intensive care unit

Description

Inclusion Criteria:

General:

• Age >18 years
• Mechanically ventilated
• < 48 hours after admission to the Intensive Care Unit

Specific:

-ARDS: acute (< 1 week) respiratory failure, characterized by hypoxemia (PaO2/FiO2 < 300 mmHg/40kPa), and bilateral infiltrates on x-ray or CT of thorax, that can not be explained by heart failure og overhydration.

OR

- SIRS (two of the following): Temperature > 38°C or < 36°C, heart rate > 90/min, respiratory frequency > 20 or PaCO2 < 4.2 kPa, leukocytosis (> 12x10^9/L) or leukopenia (< 4x10^9/L)

OR

ARDS + SIRS

Exclusion Criteria:

One lung ventilation; Tube size < 8.0 mm; INR > 1.5 or thrombocytes < 40x10^9/L; Intracranial hypertension; Malignant arrythmias

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Acute respiratory distress syndrome (ARDS)
Systemic inflammatory response syndrome (SIRS)
ARDS+SIRS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Tumor necrosis factor alpha (TNF-a) bioactivity	Day one
Tumor necrosis factor alpha (TNF-a) bioactivity	Day three
Tumor necrosis factor alpha (TNF-a) bioactivity	Day seven
Tumor necrosis factor alpha (TNF-a) bioactivity	Day fourteen

Secondary Outcome Measures

Outcome Measure	Time Frame
Interleukin (IL)-6	Day one
Mannose binding lectin (MBL)	Day one
Ficolin-1,2,3	Day one

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: July 16, 2013
• First Submitted That Met QC Criteria: July 19, 2013
• First Posted (Estimate): July 24, 2013

Study Record Updates

• Last Update Posted (Actual): December 11, 2018
• Last Update Submitted That Met QC Criteria: December 9, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Shock; Lung Injury; Infant, Premature, Diseases; Syndrome; Inflammation; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Systemic Inflammatory Response Syndrome
• Other Study ID Numbers: 959521891