We expect to provide evidence for our hypothesis stating that patients who develop infectious complications after trauma are characterized by a specific subset of circulating neutrophils displaying a reduced capacity to eradicate bacteria.…
ID
Source
Brief title
Condition
- White blood cell disorders
- Immune disorders NEC
- Bacterial infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The difference in (anti-bacterial) characteristics of circulating neutrophils
between trauma patients who develop sepsis and non-septic patients.
Secondary outcome
- The difference in (anti-bacterial) characteristics of circulating neutrophils
between trauma patients who develop infectious complications other than sepsis
(e.g. pneumonia, meningitis, urinary tract infections, pericarditis, abdominal
abscesses, wound infections and fracture related infections) and non-infectious
patients.
- The difference in (anti-bacterial) characteristics of circulating neutrophils
between trauma patients who develop pro-inflammatory complications (e.g. SIRS)
and patients who don't develop these complications.
- The difference in (inducible) activation status of neutrophils between
patients with and without infectious or inflammatory complications
Background summary
Severely injured patients are prone to suffer from infectious complications and
even sepsis. Despite tremendous efforts, the etiology of this increased
susceptibility to infectious complications of trauma patients is not fully
understood. Clinical signs and symptoms aswell as current diagnostic clinical
tests (WBC, CRP, cytokines, interleukines) lack sensitivity or specifity 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 succesfull eradication of a pathogen,
neutrophils need to exert specific functions: e.g. chemotaxis, migration,
phagocytosis, degranulation and production of radical oxygen species. Previous
research on the altered bactericidal functions of neutrophils shows
inconclusive results. For adequate determination of the neutrophil's capicity
to eradicate bacteria we developed a novel in-vitro assay in which neutrohpils
are accurately tested for their capability to kill bacteria. This assay allows
us to identify dysfunctional neutrophils (or neutrophils subsets) adequately.
The main focus of this study is the determination of the (antibacterial)
functionality of specific neutrophils circulating in the peripheral blood of
severly injured patients following trauma.
Study objective
We expect to provide evidence for our hypothesis stating that patients who
develop infectious complications after trauma are characterized by a specific
subset of circulating neutrophils displaying a reduced capacity to eradicate
bacteria. Furthermore we hypothesize that this deterioration in function will
occur days before the actual development of clinical symptoms due to an
infection. For that matter we will make use of our novel in-vitro techniques.
Establishing the correlation between an acquired dysfunctional innate immune
system and the development of infectious complications would have great
implications for future trauma patients and their treatment. This might lead to
early identification of patients at risk for infectious complications. Thereby
providing physicians clinical guidelines for either agressive pharmaceutical
preventive therapy or postponement of surgical treatments to avoid these
infectious and/or inflammatory complications.
Study design
A prospective cohort trial. A maximum of 8 milliliters blood will be obtained
within 12 hours of arrival at the Emergency Department. Succeeding samples will
be drawn at day 3, 6, 10 and 15 days after admission (9 milliliters per
timepoint). These samples will enable us to study the (bactericidal)
characteristics of neutrophils throughout time, making use of isolated
neutrophils.
Study burden and risks
A total of max. 44 milliliter will be sampled from the patient over a period of
15 days. Sampling of this amount of blood will (insignificantly) diminish the
total volume of circulating blood in the vasculature of these patients
temporarily. The daily average volume of bloodsampling sampling of patients on
the ICU is 53.2 milliliters. Even if this sampling volume would increase with
18 milliliter every day during 15 days, the additional risk for clinical signs
and symptoms due to anemia is not significant (citation: Andrew W Lyon and
others, *Simulation of Repetitive Diagnostic Blood Loss and Onset of Iatrogenic
Anemia in Critical Care Patients with a Mathematical Model.*, Computers in
biology and medicine, 1 (2012), 1-7).
Blood sampling from the arterial line during the patient's stay on the IMCU/ICU
or venapunctures on the surgical ward will be combined with regular sampling
performed for clinical diagnostic tests. The placement of this arterial
catheter is standard care in this group of trauma patients and sampling from
this line will not result in any form of discomfort for the patient. If the
arterial line is removed, the blood will be drawn through vena puncture. This
will be combined with clinical blood withdraw as much as possible. We expect a
patient to require 1 additional venapuncture during the study period on
average.
Heidelberglaan 100
Utrecht 3508 GA
NL
Heidelberglaan 100
Utrecht 3508 GA
NL
Listed location countries
Age
Inclusion criteria
1. Severely injured trauma patients based on the following criteria:
- Severe injury (e.g. AIS > 3) in at least 2 body regions
- Physiological disturbances on hospital admission based on:
* Heart rate > 100 beats/min, and/or
* Systolic blood pressure < 100 mmHg, and/or
* Base excess < -6 mmol/L, and/or
* pH < 7,20, and/or
* Hb < 5,5
2. Admission to the IMCU or ICU of the UMCU with an expected stay of at least
48 hours.
3. Age: 18 - 80 years
4. Informed consent (when proxy consent is obtained and the patient leaves the
IMCU/ICU in good mental health, personal informed consent is additionally
necessary)
Exclusion criteria
- Immunosuppressive medication
- Known HIV positive status and related diseases
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | 43279 |
| CCMO | NL43279.041.13 |