Driving Simulator Performance After Administration of Analgesic Doses of Ketamine With Dexmedetomidine or Fentanyl.


Journal

Journal of clinical psychopharmacology
ISSN: 1533-712X
Titre abrégé: J Clin Psychopharmacol
Pays: United States
ID NLM: 8109496

Informations de publication

Date de publication:
Historique:
pubmed: 23 8 2019
medline: 30 1 2020
entrez: 22 8 2019
Statut: ppublish

Résumé

As a sole agent, ketamine acutely compromises driving ability; however, performance after coadministration with the adjuvant sedating agents dexmedetomidine or fentanyl is unclear. Using a randomized within-subject design, 39 participants (mean ± SD age, 28.4 ± 5.8 years) received 0.3 mg/kg bolus followed by 0.15 mg kg h infusion of ketamine (3-hour duration), in addition to either (i) 0.7 μg kg h infusion of dexmedetomidine for 1.5 hours (n = 19; KET/DEX) or (ii) three 25 μg fentanyl injections for 1.5 hours (n = 20; KET/FENT). Whole blood drug concentrations were determined during ketamine only, at coadministration (KET/DEX or KET/FENT) and at 2 hours after treatment. Subjective effects were determined using a standardized visual analog scale. Driving performance was assessed at baseline and at posttreatment using a validated computerized driving simulator. Primary outcomes included SD of lateral position (SDLP) and steering variability (SV). Administration of ketamine with dexmedetomidine but not fentanyl significantly increased SDLP (F1,18 = 22.60, P < 0.001) and reduced SV (F1,18 = 164.42, P < 0.001) 2 hours after treatment. These deficits were comparatively greater for the KET/DEX group than for the KET/FENT group (t37 = -5.21 [P < 0.001] and t37 = 5.22 [P < 0.001], (respectively). For the KET/DEX group, vehicle control (SV) and self-rated performance (visual analog scale), but not SDLP, was inversely associated with ketamine and norketamine blood concentrations (in nanograms per milliliter). Greater subjective effects were moderately associated with driving deficits. Driving simulator performance is significantly compromised after coadministration of analgesic range doses of ketamine with dexmedetomidine but not fentanyl. An extended period of supervised driver abstinence is recommended after treatment, with completion of additional assessments to evaluate home readiness.

Sections du résumé

PURPOSE/BACKGROUND OBJECTIVE
As a sole agent, ketamine acutely compromises driving ability; however, performance after coadministration with the adjuvant sedating agents dexmedetomidine or fentanyl is unclear.
METHODS/PROCEDURES METHODS
Using a randomized within-subject design, 39 participants (mean ± SD age, 28.4 ± 5.8 years) received 0.3 mg/kg bolus followed by 0.15 mg kg h infusion of ketamine (3-hour duration), in addition to either (i) 0.7 μg kg h infusion of dexmedetomidine for 1.5 hours (n = 19; KET/DEX) or (ii) three 25 μg fentanyl injections for 1.5 hours (n = 20; KET/FENT). Whole blood drug concentrations were determined during ketamine only, at coadministration (KET/DEX or KET/FENT) and at 2 hours after treatment. Subjective effects were determined using a standardized visual analog scale. Driving performance was assessed at baseline and at posttreatment using a validated computerized driving simulator. Primary outcomes included SD of lateral position (SDLP) and steering variability (SV).
FINDINGS/RESULTS RESULTS
Administration of ketamine with dexmedetomidine but not fentanyl significantly increased SDLP (F1,18 = 22.60, P < 0.001) and reduced SV (F1,18 = 164.42, P < 0.001) 2 hours after treatment. These deficits were comparatively greater for the KET/DEX group than for the KET/FENT group (t37 = -5.21 [P < 0.001] and t37 = 5.22 [P < 0.001], (respectively). For the KET/DEX group, vehicle control (SV) and self-rated performance (visual analog scale), but not SDLP, was inversely associated with ketamine and norketamine blood concentrations (in nanograms per milliliter). Greater subjective effects were moderately associated with driving deficits.
IMPLICATIONS/CONCLUSIONS CONCLUSIONS
Driving simulator performance is significantly compromised after coadministration of analgesic range doses of ketamine with dexmedetomidine but not fentanyl. An extended period of supervised driver abstinence is recommended after treatment, with completion of additional assessments to evaluate home readiness.

Identifiants

pubmed: 31433347
doi: 10.1097/JCP.0000000000001101
doi:

Substances chimiques

Analgesics 0
Analgesics, Opioid 0
Hypnotics and Sedatives 0
Dexmedetomidine 67VB76HONO
Ketamine 690G0D6V8H
Fentanyl UF599785JZ
norketamine XQY6JVF94X

Types de publication

Comparative Study Journal Article Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

446-454

Auteurs

Amie C Hayley (AC)

From the Centre for Human Psychopharmacology, Swinburne University of Technology, Hawthorn.

Luke A Downey (LA)

From the Centre for Human Psychopharmacology, Swinburne University of Technology, Hawthorn.
Institute for Breathing and Sleep, Austin Hospital, Melbourne.

Maja Green (M)

Department of Oncology, Monash Health Translation Precinct, Monash University, Clayton.
Program of Critical Care and Perioperative Medicine, School of Clinical Sciences, Monash University, Melbourne.

Brook Shiferaw (B)

From the Centre for Human Psychopharmacology, Swinburne University of Technology, Hawthorn.

Michaela Kenneally (M)

Forensic Science South Australia, Adelaide, South Australia, Australia.

Michael Keane (M)

From the Centre for Human Psychopharmacology, Swinburne University of Technology, Hawthorn.
Program of Critical Care and Perioperative Medicine, School of Clinical Sciences, Monash University, Melbourne.

Mark Adams (M)

Program of Critical Care and Perioperative Medicine, School of Clinical Sciences, Monash University, Melbourne.

Yahya Shehabi (Y)

Program of Critical Care and Perioperative Medicine, School of Clinical Sciences, Monash University, Melbourne.

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Classifications MeSH