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.

Competing Interests

The authors declare no competing interests.

References

References
1.
Itakura
S
,
Masui
K
,
Kazama
T
:
Rapid infusion of hydroxyethyl starch 70/0.5 but not acetate Ringer’s solution decreases the plasma concentration of propofol during target-controlled infusion.
Anesthesiology
2016
;
125
:
304
12
2.
Adachi
YU
,
Watanabe
K
,
Higuchi
H
,
Satoh
T
:
The determinants of propofol induction of anesthesia dose.
Anesth Analg
2001
;
92
:
656
61
3.
Kazama
T
,
Ikeda
K
,
Morita
K
,
Ikeda
T
,
Kikura
M
,
Sato
S
:
Relation between initial blood distribution volume and propofol induction dose requirement.
Anesthesiology
2001
;
94
:
205
10
4.
Adachi
YU
,
Satomoto
M
,
Higuchi
H
,
Watanabe
K
:
Rapid fluid infusion therapy decreases the plasma concentration of continuously infused propofol.
Acta Anaesthesiol Scand
2005
;
49
:
331
6
5.
Kurita
T
,
Takata
K
,
Morita
K
,
Morishima
Y
,
Uraoka
M
,
Katoh
T
,
Sato
S
:
The influence of hemorrhagic shock on the electroencephalographic and immobilizing effects of propofol in a swine model.
Anesth Analg
2009
;
109
:
398
404
6.
Dahaba
AA
,
Rinnhofer
S
,
Wang
G
,
Xu
X
,
Liu
XY
,
Wu
XM
,
Rehak
PH
,
Metzler
H
:
Influence of acute normovolaemic haemodilution on bispectral index monitoring and propofol dose requirements.
Acta Anaesthesiol Scand
2008
;
52
:
815
20
7.
Bienert
A
,
Wiczling
P
,
Grześkowiak
E
,
Cywiński
JB
,
Kusza
K
:
Potential pitfalls of propofol target controlled infusion delivery related to its pharmacokinetics and pharmacodynamics.
Pharmacol Rep
2012
;
64
:
782
95
8.
Dawidowicz
AL
,
Kalitynski
R
:
Effects of intraoperative fluid infusions, sample storage time, and sample handling on unbound propofol assay in human blood plasma.
J Pharm Biomed Anal
2005
;
37
:
1167
71
9.
Silva
A
,
Sousa
E
,
Palmeira
A
,
Amorim
P
,
Guedes de Pinho
P
,
Ferreira
DA
:
Interaction between hydroxyethyl starch and propofol: Computational and laboratorial study.
J Biomol Struct Dyn
2014
;
32
:
1864
75
10.
Cavaliere
F
,
Conti
G
,
Moscato
U
,
Meo
F
,
Pennisi
MA
,
Costa
R
,
Proietti
R
:
Hypoalbuminaemia does not impair Diprifusor performance during sedation with propofol.
Br J Anaesth
2005
;
94
:
453
8