To the Editor:
We read with great interest the recent article by Itakura et al.1 The authors clearly demonstrated a decrease in plasma propofol concentration during rapid fluid infusion, especially hydroxyethyl starch. Several studies have evaluated cardiovascular effects on plasma propofol concentrations and proposed mechanisms for a decrease in drug concentration.2–4 Itakura et al.1 emphasized the effect of increased metabolic clearance of propofol. It was suggested that rapid fluid infusion would decrease the blood concentration of drugs during target-controlled infusion and recommended that anesthesiologists increase propofol infusion rates up to two times during rapid infusion. However, rapid fluid infusion may affect propofol pharmacodynamics as well as pharmacokinetics.5 Hemodilution secondary to rapid fluid infusion might enhance the hypnotic activity of propofol despite decreasing plasma concentration.4,6 Propofol pharmacodynamics may vary due to many factors, including cardiac output, metabolic rate, and hemodilution (which results in anemia and hypoalbuminemia).5,7 The free propofol percentage is modified by fluid infusion.8 Propofol and hydroxyethyl starch might form a complex and potentially result in a clinically important interaction.9 Thus, the conclusions of Itakura et al.1 may need some revision.
Although target-controlled infusion techniques are available for patients with various medical conditions,10 practitioners should focus more on maintaining the appropriate depth of anesthesia than on maintaining a constant plasma concentration of propofol. It is surprising therefore that Itakura et al.1 conducted the study without evaluating depth of anesthesia. Further investigations of the effects of rapid fluid infusion on the pharmacodynamics of propofol and depth of anesthesia may be informative.
The authors declare no competing interests.