Disorder of Neutrophils, Innate Immune Response, Multiple Organ Dysfunction Syndrome, Multiple Trauma, Sepsis
Conditions
Keywords
Inflammation, Multiple Organ Failure, Sepsis, Wounds and Injuries, Pathologic Processes, Shock, Infection, Systemic Inflammatory Response Syndrome, Neutrophils, PMN, Granulocytes, Innate immunity, ICU, Intensive Care, polytrauma, host-pathogen
Brief summary
Patients admitted to the Intensive Care Unit after severe injury are prone to suffer from infectious complications and even sepsis. Despite tremendous efforts the etiology of this increased susceptibility to infectious pathogens is incompletely understood. Clinical signs and symptoms as well as current diagnostic clinical tests (WBC, CRP, cytokines, interleukines) lack sensitivity or specificity for adequate prediction of the development of infectious complications or sepsis. Neutrophil granulocytes, cells of the innate immune system, play an important role in the defence against invading bacterial pathogens and are crucial in preventing fulminant infections. For successful eradication of a bacterium neutrophils need to exert specific functions: chemotaxis, migration, phagocytosis, degranulation and production of radical oxygen species. Much research has focused on the effect of trauma on neutrophil's individual capacities to kill bacteria with conflicting interpretations as a result. For adequate determination of the neutrophil's capacity to eradicate bacteria from tissue of trauma patients we developed novel in-vitro assays in which neutrophils are tested for all of these functions combined. This assay allows us to identify dysfunctional neutrophils adequately. The main focus of this study is the determination of the functionality of aberrant neutrophils circulating in the peripheral blood of severly injured following trauma.
Interventions
None listed
Sponsors
UMC Utrecht
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Admitted to the ICU * Expected stay of at least 2 days * Age: 18 - 80 years * Informed consent (when proxy consent is obtained and the patient leaves the ICU in good mental health, personal informed consent is additionally necessary)
Exclusion criteria
* Immunosuppressive medication * HIV and related diseases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bactericidal capacity of neutrophils and sepsis | 15 days following admission on ICU | The correlation between reduced bactericidal capacity of neutrophils acquired from severely injured patients and the late occurrence of sepsis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bactericidal capacity of neutrophils and infectious complications | 15 days following admission to the ICU | The correlation between reduced bacterial killing by neutrophils acquired from trauma patients and the occurrence of infectious complications (e.g pneumonia, meningitis, pericarditis, urinary tract infections, abdominal abscesses) |
| Bactericidal capacity of neutrophils and pro-inflammatory complications | 15 days following admission to the ICU | The correlation between bactericidal function of neutrophils and the occurrence of pro-inflammatory complications (SIRS). |
| Priming capacity of neutrophils and infectious complications | 15 days following admission on the ICU | The relationship between the responsiveness of neutrophils to a priming stimulus (fMLP) and the occurrence of infectious complications |
| Complement system and infectious complications | 15 days following admission to the ICU | The correlation between functionality of the complement system and the occurence of infectious complications. |
| T-cell proliferation and infectious complications | 15 days following admission on ICU | The difference in suppression of T-cell proliferation in patients suffering infectious complications versus non-infectious patients. |
Countries
Netherlands
Outcome results
None listed