[Pharmacodynamics of propofol in children and adults: comparison based on the auditory evoked potentials index].

INTRODUCTION

The clinically useful concentrations of propofol to provide loss of consciousness in children have not been determined. Therefore, target-controlled infusion systems are used with parameters taken from results for adults. As a result, hypnosis can be inadequate in the pediatric population. We studied the dose-response relationship by comparing the predicted effect-site concentration (Ce) and the level of hypnosis measured by a monitor of depth of anesthesia based on auditory evoked potentials.

MATERIAL AND METHODS

After injection of a submaximal bolus dose of propofol, the auditory evoked potential index was measured in 25 children (3-11 years old) and 25 adults (35-48 years old). We calculated the predicted Ce of propofol using the plasma effect-site equilibration rate constant (ke0) for each patient and the pharmacodynamic parameters of propofol for adults from the model of Schnider and for children from the models of Kataria and of the Paedfusor system. The relation of Ce to evoked potentials was analyzed with a sigmoid Emax model in the NONMEM program.

RESULTS

The mean (SD) propofol doses in adults and children were 1.6 (0.1) mg x kg(-1) and 2.7 (0.3) mg x kg(-1), respectively. The Ce associated with auditory evoked potentials at 50% of the maximum effect (Ce50) for adults was 6.45 (0.59) microg/mL(-1), which was significantly higher than that estimated by either model for children (Kataria, 2.06 [0.24] microg/mL(-1); Paedfusor, 3.56 [0.22] microg/mL; P<0.001 between adults and children for both models).

CONCLUSION

Children seem to be more sensitive to propofol than adults, suggesting that the higher dose requirements described for children would be attributable to pharmacokinetic differences between the 2 populations.