2004 Annual Scientific Meeting - CLICK FOR PROGRAMME

Title: Predictive performance of the Domino model for target controlled infusion of ketamine.

Authors: M. Lee, A. Absalom.

Institution: University Department of Anaesthesia, Addenbrookes Hospital, Cambridge, UK

Introduction: Several cognitive and behavioural studies have used target controlled infusions (TCI) of ketamine based on the pharmacokinetic parameters derived by Domino: V₁ = 0.063 L kg ^-1 constants (min^-1): k₁₀=0.438, k₁₂ = 0.592, k₁₃ = 0.59, k₂₁ = 0.247, k₃₁= 0.0146. ¹ The aim of our study was to determine the accuracy of these parameters in normal volunteers.

Method: Sixteen healthy .adult volunteers undergoing functional neuroimaging and behavioural testing received TCI ketamine at target concentrations of 100ng/ml from time zero to 105 minutes, and then 200ng/ml until time 195 minutes. Venous samples were obtained at 20, 55, 105, 130, 195 and 210 minutes. The samples were stored and later assayed by gas chromatography for plasma concentrations (C_m). For each sample point, performance error (PE) was calculated from the equation: PE (%)=((C_m – C_pred)/C_pred) x 100. Bias, precision, wobble and divergence were calculated as recommended by Varvel. ²

Figure1: Mean (standard deviation) PE calculated at each sampling point, over time.

Results: Mean MDPE (bias) was -8.2%, mean MDAPE (precision or inaccuracy) was 31.0%, mean wobble 21.7%, and divergence 0.066 %.min^-1.

Discussion: Overall bias was small, but the divergence in performance errors over time (see figure 1) compromised the overall precision. Although the performance of the TCI system is clinically acceptable, further modifications of the model could provide better predictive accuracy.

Acknowledgement:  The authors wish to thank collaborators from the Cambridge University Department of Psychiatry.

References:

1. Domino EF, Zsigmond EK, Domino LE, Domino KE, Kothary SP, Domino SE. Plasma levels of ketamine and two of its metabolites in surgical patients using a gas chromatographic mass fragmentographic assay. Anesth Analg 1982;61(2):87-92.

2. Varvel JR, Donoho DL, Shafer SL. Measuring the predictive performance of computer-controlled infusion pumps. J Pharmacokinet Biopharm 1992;20(1):63-94.