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Title: Neurocognitive performance under combined regimens of ketamine-dexmedetomidine and ketamine-fentanyl in healthy adults: A randomised trial.
Austin Authors: Hayley, Amie C ;Green, Maja;Downey, Luke A;Keane, Michael;Kenneally, Michaela;Adams, Mark;Shehabi, Yahya
Affiliation: Department of Oncology, Monash Health Translation Precinct, Monash University, Clayton, Australia
Critical Care and Perioperative Medicine, School of Clinical Sciences, Monash University, Melbourne, South Australia, Australia
Institute for Breathing and Sleep, Austin Health, Heidelberg, Victoria, Australia
Forensic Science SA (FSSA), Adelaide, Australia
Centre for Human Psychopharmacology, Swinburne University of Technology, Hawthorn, Australia
Issue Date: 13-May-2019 2019-05-13
Publication information: Progress in neuro-psychopharmacology & biological psychiatry 2019; 94: 109647
Abstract: Analgesic doses of ketamine affects neurocognition; however, deficits under co-administration regimens are unknown. This study evaluated the effects of ketamine, alone and in combination with dexmedetomidine or fentanyl on neurocognition. Using a randomised, within-subjects gender stratified design, 39 participants (mean age = 28.4, SD ± 5.8) received a ketamine bolus of 0.3 mg/kg followed by 0.15 mg/kg/h infusion of ketamine (3 h duration). At 1.5 h post-ketamine infusion commencement, participants received either: i) 0.7 μg/kg/h infusion of dexmedetomidine (n = 19) (KET/DEX) or (ii) three 25 μg fentanyl injections over 1.5 h (n = 20) (KET/FENT). Reaction and Movement time (RTI, Simple and 5Choice), Visuospatial Working Memory (SWM) and Verbal Recognition Memory (VRM) were assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Whole blood drug concentrations were determined during ketamine-only infusion, at co-administration (KET/DEX or KET/FENT) and at 2-h post-treatment. Ketamine-only administration impaired psychomotor response speed (Simple and 5Choice) and impaired memory (all p < .001), however did not alter executive function abilities. Independent of sedation, co-administration of dexmedetomidine produced synergistic performance and memory deficits which persisted at post-treatment (KET/DEX) (all p < .001), and were comparatively greater than for KET/FENT (all p < .05). Ketamine, norketamine and dexmedetomidine concentrations were modestly associated with reduced psychomotor speed and accuracy (all p < .05), and an inverse relationship was found between blood concentrations of ketamine, norketamine and dexmedetomidine and performance on memory tasks. Co-administration of ketamine with dexmedetomidine but not with fentanyl exerts synergistic effects on psychomotor performance and memory without executive dysfunction. Assessment of these effects in clinical groups is warranted.
DOI: 10.1016/j.pnpbp.2019.109647
PubMed URL: 31095995
Type: Journal Article
Subjects: Analgesic
Appears in Collections:Journal articles

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