The acute and residual effects of escalating, analgesic-range doses of ketamine on driving performance: A simulator study

Ketamine hydrochloride elicits potent psychotomimetic and neurobehavioural effects which make it incompatible with driving; however, the direct effect on driving performance is yet to be assessed. Using an open label, within-subjects protocol, 15 males and 5 females (mean age = 30.8 years) were administered three fixed, stepwise increasing sub-anaesthetic doses of intravenous (IV) ketamine solution [(i) 8 mg/h IV infusion plus 30 mg bolus, (ii) 12 mg/h IV infusion and (iii) 20 mg/h infusion]. Whole blood ketamine and norketamine concentrations were determined at each treatment step and at 2 h post-infusion. Driving performance was assessed at baseline, at each treatment step and at 2 h post-treatment using a validated computerised driving simulator. Standard Deviation of Lateral Position (SDLP) and Steering Variability (SV) were assessed. Linear Fixed Effect Modelling indicated a main effect for time (dose) for SDLP (F-[4,F-72] = 33.22, p < 0.0001) and SV (F-[4,F-72] = 4.65, p < 0.002). Post-hoc analyses revealed significant differences from baseline at each treatment step for SDLP (all p < 0.001), and for 12 mg/h treatment step for SV (p = 0.049). Post-treatment driving performance returned to baseline levels. Weak positive linear associations were observed between SDLP and whole blood ketamine concentrations (R-2 = 0.11, beta = 29.96, p = 0.001) and norketamine (R-2 = 0.09, beta = 28.87, p = 0.003). These findings suggest that even under highly controlled conditions, ketamine intoxication significantly alters simulated driving performance. At the highest dose, ketamine produced changes to SDLP considered incompatible with safe driving, highlighting how ketamine consumption may translate to an increased risk of road trauma.