In Reply

We thank Adachi et al. for their interest in our article¹  showing that a rapid infusion of hydroxyethyl starch (HES) but not acetate Ringer’s solution decreased plasma propofol concentration during target-controlled infusion. They have focused on the influence of rapid fluid infusion on propofol pharmacodynamics. As it is unlikely that a rapid fluid infusion of HES itself changes the anesthetic potency of propofol in the brain, we discuss the influence of HES on the pharmacokinetics of propofol.

There is a good study by Takizawa et al.²  for this issue. Briefly, this study clarified that a 30 ml/kg but not a 10 ml/kg isovolemic hemorrhage followed by crystalloid resuscitation significantly increased the unbound fraction of propofol in blood and also showed that a 10 ml/kg isovolemic hemorrhage did not decrease the bispectral index (BIS) value. Their results suggest that an 8 ml/kg rapid fluid administration without hemorrhage in our study¹  is unlikely to have increased the ratio of unbound propofol in blood. As a rapid infusion of 8 ml/kg HES decreased total plasma concentration of propofol in our study,¹  there is a possibility of anesthetic awareness under propofol anesthesia during a rapid infusion of HES.

A previous study suggested that a chemical interaction between propofol and HES might influence the pharmacokinetic behavior of propofol in vivo although this interaction was confirmed in vitro.³  This interaction might decrease unbound propofol in blood, which might increase anesthetic awareness during rapid infusion of HES under propofol anesthesia.

A single bolus of rocuronium without an additional dose was administered to all patients so that the levels of neuromuscular block were different among the patients. As neuromuscular block can influence the BIS value,⁴  we did not evaluate the BIS values in our study although we monitored BIS values to avoid anesthetic awareness. Therefore, we would like to note that we recommend to consider increasing the targeted concentration of propofol during a rapid infusion of HES and that the influence of a rapid HES infusion should be examined in a further study as described in the conclusion of our article.¹