Effects of dexmedetomidine on kidney and brain tissue microcirculation and histology in ovine cardiopulmonary bypass: a randomised controlled trial

Effects of dexmedetomidine on kidney and brain tissue microcirculation and histology in ovine cardiopulmonary bypass: a randomised controlled trial

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...

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Bibliographic Details
Published in:Anaesthesia Vol. 78; no. 12; pp. 1481 - 1492
Main 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, A, Bellomo, R, Miles, L F, Lankadeva, Y R
Format: Journal Article
Language:English
Published: England Blackwell Publishing Ltd 01-12-2023
Subjects:
Anesthesia
Animal models
Animals
Brain
Cardiopulmonary Bypass
Cerebrum
Circulatory system
Cognition
Creatinine
Delirium
Dexmedetomidine - therapeutic use
Heart surgery
Histology
Hypoxia
Inflammation
Injuries
Intravenous infusion
Kidney
Kidneys
Mental disorders
Microcirculation
Neuroinflammatory Diseases
Oxygenation
Perfusion
Placebos
Sheep
Sodium chloride
Tissues
cardiopulmonary bypass
dexmedetomidine
acute kidney injury
postoperative cognitive dysfunction
neuroinflammation
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Summary: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 α -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 .h ) 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.
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ISSN:0003-2409
1365-2044
DOI:10.1111/anae.16152