CORRESPONDENCE |
Relationship between bispectral index and effect-site EC50 for propofol
* E-mail: talim{at}medic.upm.edu.myEditor—We read with interest the study by Iannuzzi and colleagues1 regarding the correlation between propofol effect-site concentration and the bispectral index (BIS). In their article, the authors noted that the higher effect-site concentrations they obtained were because of the achievement of steady state conditions and the pharmacokinetic model used.
We constructed a graph (Fig. 1) using the effect-site concentrations and the corresponding BIS reported by Iannuzzi and colleagues, together with the values from the two previous studies quoted in their paper.2 3 To this, we added data from an on-going study in our institution where unpremedicated patients were given a constant rate infusion of propofol at 25 mg min–1. In our study, the effect-site concentrations were predicted using the pharmacokinetic parameter set described in Marsh and colleagues,4 and an effect-site equilibrium rate constant (keo) of 0.8 min–1.5 After 15 patients, we found the effect-site concentration at which 50% of the patients (Ce50) had loss of eyelash reflex to be 1.82 µg ml–1. The corresponding BIS value was 84.1. The values for loss of response to verbal command were 2.35 µg ml–1 and 75.2.
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As shown in the graph, an increase in the predicted Ce50 appears to be related to a decrease in BIS. This occurred despite the fact that the data were obtained from four studies using different pharmacokinetic parameter sets and different dosing regimens. Furthermore, a concentration–effect relationship could be derived using a sigmoid Emax model. The concentration where the BIS was 50% of maximal (EC50) was 4.14 µg ml–1.
In the absence of real-time measurement of propofol concentrations, anaesthetists have to rely on predicted concentrations to guide their dosing regimens. The patient's general condition and the manner in which the drug is to be delivered are likely to influence the predictive ability of any one parameter set. Patients having a slowly increasing plasma propofol concentration (e.g. a constant rate infusion) may require values that are different from patients who achieve a high concentration rapidly (e.g. a target controlled infusion). However, as long as an appropriate pharmacokinetic set is used, the predicted effect-site concentration should correlate well with the BIS.
The different effect-site concentrations reported in the above-mentioned studies are most likely attributable to the different pharmacodynamic end-points used.
Kuala Lumpur, Malaysia
E-mail: micheleiannuzzi{at}libero.it
Editor—There are a quite a number of studies regarding the relationship between EEG derived indexes and anaesthetic drugs in the literature. All demonstrate that a decrease in BIS correlates with an increase in the Ce propofol. I agree with Lim and colleagues that a lack of consensus regarding the definition of clinical endpoints and pharmacokinetic-dynamic parameters to test the ability of an EEG derived index is a potential problem.
I believe that the difference noted in the data sets extrapolated from different papers are a result of the use of different clinical endpoints and different pharmacokinetic models. The unpublished data presented here add more heterogeneity to the scenario because they are comparing different clinical endpoints from previously cited papers and are using a constant infusion total i.v. anesthesia technique rather than a target controlled infusion.
I believe that clinical judgement should always accompany the increasing application of technology in clinical anaesthesia.
Naples, Italy
References
1 Iannuzzi M, Iannuzzi E, Rossi F, et al. Relationship between bispectral index, electroencephalographic state entropy and effect-site EC50 for propofol at different clinical endpoints. Br J Anaesth 2005; 94: 613–16[Abstract]
2 Milne SE, Troy A, Irwin MG, et al. Relationship between bispectral index, auditory evoked potential index and effect-site EC50 for propofol at two clinical end-points. Br J Anaesth 2003; 90: 127–31
3 Irwin MG, Hui TW, Milne SE, et al. Propofol effective concentration 50 and its relationship to bispectral index. Anaesthesia 2002; 57: 242–8[CrossRef][Web of Science][Medline]
4 Marsh B, White M, Morton N, et al. Pharmacokinetic model driven infusion of propofol in children. Br J Anaesth 1991; 67: 41–8
5 Lim TA. A novel method of deriving the effect compartment equilibrium rate constant for propofol. Br J Anaesth 2003; 91: 730–2
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