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Title: | Effects of dexmedetomidine on kidney and brain tissue microcirculation and histology in ovine cardiopulmonary bypass: a randomised controlled trial. | Austin Authors: | Jufar, A H;May, C N;Booth, L C;Evans, R G;Cochrane, A D;Marino, B;Birchall, I;Hood, S G;McCall, P R;Sanders, R D;Yao, S T ;Ortega-Bernal, V;Skene, Alison ;Bellomo, R;Miles, L F;Lankadeva, Y R | Affiliation: | Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Physiology, Monash University, Melbourne, Australia. Pre-Clinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, Melbourne, Australia. Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Physiology, Monash University, Melbourne, Australia. Department of Paediatrics, University of Melbourne, Melbourne, Australia. Cell Saving and Perfusion Resources, Melbourne, Australia. Neurohistology Laboratory, Florey Institute of Neuroscience and Mental Health, Melbourne, Australia. Department of Critical Care, University of Melbourne, Melbourne, Australia. Central Clinical School and NHMRC Clinical Trials Centre, Faculty of Medicine and Health, University of Sydney, Sydney, Australia. Cardiovascular Neuroscience Laboratory, Department of Anatomy and Physiology, University of Melbourne, Melbourne, Australia. Anatomical Pathology Department of Critical Care, University of Melbourne, Melbourne, Australia. Pre-Clinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, Melbourne, Australia. |
Issue Date: | Dec-2023 | Date: | 2023 | Publication information: | Anaesthesia 2023-12; 78(12) | Abstract: | Cardiac surgery requiring cardiopulmonary bypass is associated with postoperative acute kidney injury and neurocognitive disorders, including delirium. Intra-operative inflammation and/or impaired tissue perfusion/oxygenation are thought to be contributors to these outcomes. It has been hypothesised that these problems may be ameliorated by the highly selective α2 -agonist, dexmedetomidine. We tested the effects of dexmedetomidine on renal and cerebral microcirculatory tissue perfusion, oxygenation and histology in a clinically relevant ovine model. Sixteen sheep were studied while conscious, after induction of anaesthesia and during 2 h of cardiopulmonary bypass. Eight sheep were allocated randomly to receive an intravenous infusion of dexmedetomidine (0.4-0.8 μg.kg-1 .h-1 ) from induction of anaesthesia to the end of cardiopulmonary bypass, and eight to receive an equivalent volume of matched placebo (0.9% sodium chloride). Commencement of cardiopulmonary bypass decreased renal medullary tissue oxygenation in the placebo group (mean (95%CI) 5.96 (4.24-7.23) to 1.56 (0.84-2.09) kPa, p = 0.001), with similar hypoxic levels observed in the dexmedetomidine group (6.33 (5.33-7.07) to 1.51 (0.33-2.39) kPa, p = 0.002). While no differences in kidney function (i.e. reduced creatinine clearance) were evident, a greater incidence of histological renal tubular injury was observed in sheep receiving dexmedetomidine (7/8 sheep) compared with placebo (2/8 sheep), p = 0.041. Graded on a semi-quantitative scale (0-3), median (IQR [range]) severity of histological renal tubular injury was higher in the dexmedetomidine group compared with placebo (1.5 (1-2 [0-3]) vs. 0 (0-0.3 [0-1]) respectively, p = 0.013). There was no difference in cerebral tissue microglial activation (neuroinflammation) between the groups. Dexmedetomidine did not reduce renal medullary hypoxia or cerebral neuroinflammation in sheep undergoing cardiopulmonary bypass. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/34099 | DOI: | 10.1111/anae.16152 | ORCID: | 0000-0002-3589-9111 | Journal: | Anaesthesia | PubMed URL: | 37880924 | ISSN: | 1365-2044 | Type: | Journal Article | Subjects: | acute kidney injury cardiopulmonary bypass dexmedetomidine neuroinflammation postoperative cognitive dysfunction |
Appears in Collections: | Journal articles |
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