Primary objective is to show the presence of endogenous ligands of TLR4 in the lung of patients being mechanically ventilated in a standardised way with clinical parameters. Secondary objective is to investigate the amount of endogenous ligands of…
ID
Source
Brief title
Condition
- Immune disorders NEC
- Lower respiratory tract disorders (excl obstruction and infection)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The studied variable is the IL-8 concentration of the HEK293-TLR4 reporter
assay after exposure to bronchotracheal aspirate.
Secondary outcome
Not applicable.
Background summary
Mechanical ventilation (MV) is commonly used in general anesthesia during
surgery or in the critically ill patient at the Intensive Care. Besides the
obvious beneficial effects of MV there is increasing evidence that MV worsens
lung injury, but can also induce lung injury in healthy lungs. This has been
termed Ventilator Induced Lung Injury (VILI). Animal and human research
revealed that MV can induce an inflammatory reaction with cytokine release and
activation of the innate immune system. Results from our own experimental
studies support these findings. Recently it has been demonstrated that the
intrapulmonary cytokine release is triggered by the activation of Toll-like
receptor 4 (TLR4). This receptor can be triggered by certain endogenous
ligands. In animal studies we have found that endogenous ligands of TLR4 are
released in response to MV. However, the release of endogenous ligands after MV
has never been demonstrated in humans. Finding endogenous ligands of TLR4 after
MV gives support to the hypothesis that MV in humans leads to the release of
endogenous ligands which triggers the cytokine release.
Study objective
Primary objective is to show the presence of endogenous ligands of TLR4 in the
lung of patients being mechanically ventilated in a standardised way with
clinical parameters. Secondary objective is to investigate the amount of
endogenous ligands of TLR4 in relation to the duration of mechanical
ventilation.
Study design
At defined time points perioperatively (t=0, t=60, t=90, t=120 minutes) the
lung is flushed with 10 mL of saline via a suction catheter inserted in the
endotracheal tube via a special conduit. Bronchotracheal aspirate is obtained
and analysed for the presence of endogenous ligands for TLR4 using a
HEK293-TLR4 reporter assay.
Study burden and risks
This study can be completely integrated in regular healthcare. There is no
extra time burden for the participating patient. Extra risks for the patient
are minimal. A lung lavage with a similar small amount of saline will not
impair lung function, especially considering the ASA class (1 or 2) of the
participating patients. Furthermore, this procedure is part of regular care at
the Intensive Care Unit and is performed by nurses regularly. A standard
bronchoalveolar lavage as performed by pulmonologist is done with a volume of
up to 400 mL in a specific lobe. Therefore, we deem the risk for patients
participating in this study to be minimal.
Postbus 9101
6500 HB Nijmegen
Nederland
Postbus 9101
6500 HB Nijmegen
Nederland
Listed location countries
Age
Inclusion criteria
Between 18-65 years old, American Society of Anesthesiologists (ASA) status 1 or 2, ability to speak Dutch, no (N)SAID intake within 36 hours prior to surgery, no history of drug dependency or abus, body weight between 60-100 kg with a BMI <30 kg/m2.
Exclusion criteria
Patients with pulmonary, cardiac, hepatic or renal disease or significant or instable disease of the central nervous system, patients that smoke, use of (N)SAIDs within 36 hours prior to surgery, history of drug dependence or drug abuse, BMI > 30 kg/m2 or <20 kg/m2.
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 |
|---|---|
| CCMO | NL21222.091.07 |