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Neurocognitive performance under combined regimens of ketamine-dexmedetomidine and ketamine-fentanyl in healthy adults: A randomised trial.

Publication ,  Journal Article
Hayley, AC; Green, M; Downey, LA; Keane, M; Kenneally, M; Adams, M; Shehabi, Y
Published in: Prog Neuropsychopharmacol Biol Psychiatry
August 30, 2019

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.

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Published In

Prog Neuropsychopharmacol Biol Psychiatry

DOI

EISSN

1878-4216

Publication Date

August 30, 2019

Volume

94

Start / End Page

109647

Location

England

Related Subject Headings

  • Young Adult
  • Recognition, Psychology
  • Reaction Time
  • Psychiatry
  • Memory, Short-Term
  • Male
  • Ketamine
  • Humans
  • Fentanyl
  • Female
 

Citation

APA
Chicago
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MLA
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Hayley, A. C., Green, M., Downey, L. A., Keane, M., Kenneally, M., Adams, M., & Shehabi, Y. (2019). Neurocognitive performance under combined regimens of ketamine-dexmedetomidine and ketamine-fentanyl in healthy adults: A randomised trial. Prog Neuropsychopharmacol Biol Psychiatry, 94, 109647. https://doi.org/10.1016/j.pnpbp.2019.109647
Hayley, Amie C., Maja Green, Luke A. Downey, Michael Keane, Michaela Kenneally, Mark Adams, and Yahya Shehabi. “Neurocognitive performance under combined regimens of ketamine-dexmedetomidine and ketamine-fentanyl in healthy adults: A randomised trial.Prog Neuropsychopharmacol Biol Psychiatry 94 (August 30, 2019): 109647. https://doi.org/10.1016/j.pnpbp.2019.109647.
Hayley AC, Green M, Downey LA, Keane M, Kenneally M, Adams M, et al. Neurocognitive performance under combined regimens of ketamine-dexmedetomidine and ketamine-fentanyl in healthy adults: A randomised trial. Prog Neuropsychopharmacol Biol Psychiatry. 2019 Aug 30;94:109647.
Hayley, Amie C., et al. “Neurocognitive performance under combined regimens of ketamine-dexmedetomidine and ketamine-fentanyl in healthy adults: A randomised trial.Prog Neuropsychopharmacol Biol Psychiatry, vol. 94, Aug. 2019, p. 109647. Pubmed, doi:10.1016/j.pnpbp.2019.109647.
Hayley AC, Green M, Downey LA, Keane M, Kenneally M, Adams M, Shehabi Y. Neurocognitive performance under combined regimens of ketamine-dexmedetomidine and ketamine-fentanyl in healthy adults: A randomised trial. Prog Neuropsychopharmacol Biol Psychiatry. 2019 Aug 30;94:109647.
Journal cover image

Published In

Prog Neuropsychopharmacol Biol Psychiatry

DOI

EISSN

1878-4216

Publication Date

August 30, 2019

Volume

94

Start / End Page

109647

Location

England

Related Subject Headings

  • Young Adult
  • Recognition, Psychology
  • Reaction Time
  • Psychiatry
  • Memory, Short-Term
  • Male
  • Ketamine
  • Humans
  • Fentanyl
  • Female