Luis I. Cortínez MD*, Pablo Sepulveda MD†, Gastón Núñez MD†, Alejandro Recart MD†

†Clinica Alemana-Universidad del Desarrollo, *Pontificia Universidad Católica de Chile

Running Head: Propofol k_e0 estimation using electroencephalographic derived indices is affected by its rate of infusion.

Abstract

Background:

 Electroencephalographic indices are frequently used to measure the hypnotic effect of anesthetic drugs. All available indices have different time lags to react to a change in the level of anesthesia.(1) In addition these delays also vary depending on the speed of change of the level of anesthesia.(1) This is a limitation of these monitors for pharmacodynamic studies. The aim of this study is to estimate the K_e0 of propofol at two different induction rates using the Cerebral State Index (CSI) (Danmeter, Odense, Denmark) as the measure of its hypnotic effect.

Methods:

After routine non-invasive monitoring of arterial pressure, electrocardiogram, pulse oximetry, and consciousness (CSI). Ten healthy adult volunteers, aged 21-44 yr, received a short infusion of propofol 1.8 mg kg^-1 at a rate of 1200 ml hr^-1. After spontaneous recovery of the CSI to basal values an infusion of propofol was started at a rate of 70 ml hr^-1 until CSI ≤ 50. The study finished after CSI spontaneously returned to basal values. The CSI response was automatically recorded every 1 second using the Danmeter A/S CSM capture V2.02 software throughout the study period. The complete response curves (induction-recovery) of CSI were then used to calculate the propofol k_e0s during the fast and slow induction periods. A non-parametric method implemented in Excel with the “K_e0Objfx” of PKPD tools software (www.pkpdtools.com) was used to calculate the k_e0s in each individual subject. The pharmacokinetic model published by Marsh was used to predict the plasma concentrations of propofol during the study period. The ke0s obtained in both periods were compared with Mann-Whitney´s test. A p value < 0.05 was considered significant. Values are median (range).

Results:

 All patients completed the study. The propofol k_e0s estimated were 1.39 (0.61 - 1.95) min^-1 during the fast induction period and 0.57 (0.17 – 1.41) min^-1 during the slow induction period (P=0.01)).

Conclusions:

 The Speed of induction affects the k_e0 estimation of propofol when the CSI is used as the measured response. This is consistent with the longer time delays of these electroencephalographic-derived indices reported during small steps changes in the level of anesthesia.

1) Pilge S., Zanner R., eta al. Time Delay of Index Calculation. Anesthesiology 2006;104:488-94.