None listed
Conditions
Brief summary
The systemic inflammatory response syndrome (SIRS) characterises up to 80% of critical illness in children. The fundamental pathophysiological features underpinning SIRS are changes to the vascular endothelium, which include: 1) increased permeability to fluid and protein ("leaky") and, 2) increased activation ("sticky"). We recently published data which confirms a direct role for Eph/ephrin signalling in endothelial leakage both in a mouse gut ischaemia/reperfusion injury model of systemic inflammation and in vitro in TNF-induced vascular leakage in human umbilical venous endothelial cells. Based on this data we hypothesise that vascular endothelial function can be monitored in the intensive care unit by: (a) quantifying interstitial protein levels by microdialysis; measuring urinary albumin; and (c) measuring plasma levels of Eph/ephrins a s endothelial activation markers. Positive fluid balance is a poor prognostic sign, but without clear science, opinion on fluid management in the critically-ill patient remains divided. The aim of this project is to determine whether it is feasible to monitor the integrity of the vascular endothelium in critically-ill children by: a) using microdialysis to quantify interstitial protein levels; (b) measuring plasma levels of Eph/ephrin proteins as endothelial activation biomarkers and (c) monitoring urinary albumin (microalbuminuria). This preliminary feasibility study will be undertaken in post-operative paediatric cardiac surgical patients who are routinely admitted to a paediatric intensive care unit for cardiorespiratory support and monitoring. (The control patients undergo an elective cardiac catheterisation without the inflammatory stimulus of cardiopulmonary bypass.) Monitoring the permeability of the vascular endothelium may inform clinicians about the stage and severity of SIRS and assist in clinical decision-making regards fluid resuscitation and fluid balance management. This may improve supportive care in the ICU and result in reduced ventilator days, hospital length of stay and mortality in critically-ill children.
Interventions
Experimental patients will undergo the insertion of a microdialysis catheter to monitor interstitial protein levels and serial blood tests for biomarkers of inflammation (cytokines) and endothelial activation.
A 66 Linear Microdialysis Catheter (AshMed Medical Pty Ltd) will be inserted under the skin of the forearm in anaesthetised children by the research personnel under the supervision of the anaesthetist. The microdialysis catheter will be perfused with sterile saline (0.9% NaCl) solution.
Experimental patients will undergo the insertion of a microdialysis catheter to monitor interstitial protein levels and serial blood tests for biomarkers of inflammation (cytokines) and endothelial activation. A 66 Linear Microdialysis Catheter (AshMed Medical Pty Ltd) will be inserted under the skin of the forearm in anaesthetised children by the research personnel under the supervision of the anaesthetist. The microdialysis catheter will be perfused with sterile saline (0.9% NaCl) solution. The microdialysis pump will run at 1 microliter per minute. Dialysate samples will be collected every 2 ± 2 hours in 0.5 mL Eppendorf tubes. The tubes will be placed on ice and transferred to the laboratory. The microdialysate will be analysed for protein and inflammatory markers. Second hourly urine samples from the indwelling urinary catheter will be collected throughout the procedure and for the first 48 post-operative hours. As per the paediatric intensive care unit (PICU) protocol, all patients will have routine post-operative blood taken for blood gas analysis (including lactate and central venous oxygen saturations), full blood count, plasma electrolytes, renal and liver functions tests and coagulation profiles. At this time researchers will organise the collection of an additional 1.0-2.0mL of blood. In this sample 200 µL of plasma will be used to measure levels of EphA2 (Human Magnetic Luminex® Screening Assay kit, R&D Systems, Inc.), EphA4, EphB4, ephrin-A1 and ephrin-B2 (ELISA, R&D Systems Inc.). We will also measure inflammatory markers (CRP, procalcitonin), complement (C5a), endothelial markers (endocans, VEGF, Ang-1, Ang-2) and cytokines (TNF-a, IL-1ß, IL-6, IL-8, IL-10 and IFN-gamma) using standard Bio-RAD ELISA kits as per the manufacturers’ instructions. The catheter will remain in situ for the duration of the study - experimental patients 72 hours, control patients until discharge from the recovery ward. If the catheter is accidentally dislodged the researchers will decide if the catheter should be replaced.
Sponsors
The University of Queensland
Study design
Allocation
Non-randomised trial
Intervention model
Parallel
Primary purpose
Diagnosis
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
No minimum to 16 Years
Healthy volunteers
No
Inclusion criteria
1. control - children undergoing cardiac catheterisation under general anaesthesia for diagnosis of congenital cardiac disease prior to elective surgical correction. 2. experimental - undergoing surgical correction of congenital cardiac disease either cardiopulmonary bypass and non bypass cases.
Exclusion criteria
No exclusion criteria
Outcome results
None listed