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Quantification of lipid and leucocyte filtration and the effects on cerebral and renal injury markers and pulmonary function during cardiopulmonary bypass

Quantification of lipid and leucocyte filtration and the effects on cerebral and renal injury markers and pulmonary function during cardiopulmonary bypass
Quantification of lipid and leucocyte filtration and the effects on cerebral and renal injury markers and pulmonary function during cardiopulmonary bypass
Background: Despite the extremely low mortality and morbidity rates of coronary artery bypass graft (CABG) surgery involving cardiopulmonary bypass (CPB), there are a number of pathological injuries believed to be due to the CPB circuit. Lipid Microemboli (LME) are produced when fats are released from bone marrow during a sternotomy, which then mix with blood in the pericardium during surgery. This blood is passed into the CPB circuit and reintroduced into the systemic circulation and is thought to promote an increased inflammatory response and ischaemia-inducing blockages. There are at present no adequate methods of dealing with this problem.

Methods: A randomised controlled trial was undertaken to determine if a new Oxygenator, the RemoweLL, which contains a lipid and leucocyte filter, can effectively remove LME from the patient’s circulation compared with current gold standard CPB technologies and examine the effects on markers of cerebral, renal injury; neuron specific enolase, Cystatin C and pulmonary function. The Null hypothesis was that there would be no difference in peak neuron specific enolase concentrations.

Results: The data presented in this Thesis provide the first biochemical evidence for a direct effect of LME upon neuron specific enolase release, which correlates in a linear fashion with increasing numbers of LME. The filtration of LME does not appear to significantly reduce systemic levels of activated leucocytes, which is reflected in similar pulmonary functions of those patients with and without LME filtration. However, there is evidence of a weak association towards renal protection with LME, with peak Cystatin C clearance lower than non-filtered patients. This met statistical trial stopping criteria.

Conclusions: The RemoweLL CPB system removes significant numbers of LME compared to current CPB technology. Significant differences in the release of neuron specific enolase in the immediate postoperative period have been demonstrated. Furthermore, there is weak evidence towards improved clearance of Cystatin C. Further work is now planned to determine if LME filtration translates into longer-term neurocognitive and renal protection. The statistical differences between groups were so great from neuron specific enolase that the Ethics Committee advised early termination of the trial.
University of Southampton
Issitt, Richard William
e5d2a06c-e3c3-439c-ba9a-c94777f1a12b
Issitt, Richard William
e5d2a06c-e3c3-439c-ba9a-c94777f1a12b
Voegeli, David
e6f5d112-55b0-40c1-a6ad-8929a2d84a10
Walsh, Bronagh
5818243e-048d-4b4b-88c5-231b0e419427

Issitt, Richard William (2017) Quantification of lipid and leucocyte filtration and the effects on cerebral and renal injury markers and pulmonary function during cardiopulmonary bypass. University of Southampton, Doctoral Thesis, 137pp.

Record type: Thesis (Doctoral)

Abstract

Background: Despite the extremely low mortality and morbidity rates of coronary artery bypass graft (CABG) surgery involving cardiopulmonary bypass (CPB), there are a number of pathological injuries believed to be due to the CPB circuit. Lipid Microemboli (LME) are produced when fats are released from bone marrow during a sternotomy, which then mix with blood in the pericardium during surgery. This blood is passed into the CPB circuit and reintroduced into the systemic circulation and is thought to promote an increased inflammatory response and ischaemia-inducing blockages. There are at present no adequate methods of dealing with this problem.

Methods: A randomised controlled trial was undertaken to determine if a new Oxygenator, the RemoweLL, which contains a lipid and leucocyte filter, can effectively remove LME from the patient’s circulation compared with current gold standard CPB technologies and examine the effects on markers of cerebral, renal injury; neuron specific enolase, Cystatin C and pulmonary function. The Null hypothesis was that there would be no difference in peak neuron specific enolase concentrations.

Results: The data presented in this Thesis provide the first biochemical evidence for a direct effect of LME upon neuron specific enolase release, which correlates in a linear fashion with increasing numbers of LME. The filtration of LME does not appear to significantly reduce systemic levels of activated leucocytes, which is reflected in similar pulmonary functions of those patients with and without LME filtration. However, there is evidence of a weak association towards renal protection with LME, with peak Cystatin C clearance lower than non-filtered patients. This met statistical trial stopping criteria.

Conclusions: The RemoweLL CPB system removes significant numbers of LME compared to current CPB technology. Significant differences in the release of neuron specific enolase in the immediate postoperative period have been demonstrated. Furthermore, there is weak evidence towards improved clearance of Cystatin C. Further work is now planned to determine if LME filtration translates into longer-term neurocognitive and renal protection. The statistical differences between groups were so great from neuron specific enolase that the Ethics Committee advised early termination of the trial.

Text
Final DClinP eThesis 2018-05-09 - Version of Record
Available under License University of Southampton Thesis Licence.
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Published date: March 2017

Identifiers

Local EPrints ID: 422268
URI: http://eprints.soton.ac.uk/id/eprint/422268
PURE UUID: 744705f9-fb98-4d5e-8807-89f7b6e95f71
ORCID for David Voegeli: ORCID iD orcid.org/0000-0003-3457-7177
ORCID for Bronagh Walsh: ORCID iD orcid.org/0000-0003-1008-0545

Catalogue record

Date deposited: 20 Jul 2018 16:30
Last modified: 16 Mar 2024 03:00

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Contributors

Author: Richard William Issitt
Thesis advisor: David Voegeli ORCID iD
Thesis advisor: Bronagh Walsh ORCID iD

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