N. Khalili-Mahani, C.H. Martini, E. Olofsen, A. Dahan, M. Niesters

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Effect of subanaesthetic ketamine on plasma and saliva cortisol secretion N. Khalili-Mahani, C.H. Martini, E. Olofsen, A. Dahan, M. Niesters British Journal of Anaesthesia Volume 115, Issue 1, Pages 68-75 (July 2015) DOI: 10.1093/bja/aev135 Copyright © 2015 The Author(s) Terms and Conditions

Fig 1 (a) Mean ketamine concentrations during and following i.v. infusion of 0.29 mg kg−1 h−1 for 1 h and 0.57 mg kg−1 h−1 for 1 h (green lines). (b) Mean plasma cortisol concentrations in the ketamine (closed symbols) and placebo (open symbols) sessions and the difference in cortisol concentration between the ketamine and placebo sessions (half open symbols). (c) Mean salivary cortisol concentrations in the ketamine (closed symbols) and placebo (open symbols) sessions and the difference in cortisol concentration between the ketamine and placebo sessions (half open symbols). British Journal of Anaesthesia 2015 115, 68-75DOI: (10.1093/bja/aev135) Copyright © 2015 The Author(s) Terms and Conditions

Fig 2 Pharmacokinetic–pharmacodynamic model describing the production of plasma and salivary cortisol by ketamine. V1 is the volume of the single ketamine compartment, CL is the ketamine clearance, kIN is the endogenous production of cortisol, which is under the influence of the circadian rhythm (clock) and ketamine, CCp and CCs are the plasma and salivary cortisol concentrations, and kOUT is the cortisol elimination rate. British Journal of Anaesthesia 2015 115, 68-75DOI: (10.1093/bja/aev135) Copyright © 2015 The Author(s) Terms and Conditions

Fig 3 Individual plasma and salivary cortisol levels, individual (blue) and population data fits (pink) for (a) plasma cortisol/ketamine treatment, (b) plasma cortisol/placebo treatment, (c) salivary cortisol/ketamine treatment, and (d) salivary cortisol/placebo treatment. British Journal of Anaesthesia 2015 115, 68-75DOI: (10.1093/bja/aev135) Copyright © 2015 The Author(s) Terms and Conditions

Fig 4 (a–c) Goodness of fit plots, measured vs individual predicted concentrations for (a) ketamine, (b) plasma cortisol, and (c) salivary cortisol. (d and e) Standardized visual predictive checks for ketamine and cortisol (plasma and saliva) concentrations. The broken lines represent the 2.5 and 97.5% confidence limits. For ketamine and cortisol, 95% of the data lies within the 95% CIs. P is probability. British Journal of Anaesthesia 2015 115, 68-75DOI: (10.1093/bja/aev135) Copyright © 2015 The Author(s) Terms and Conditions