Effect Site Concentration During Propofol TCI Sedation
A
Comparison Of Sedation Score With Two Pharmacokinetic Models
Barakat
A1,2, Sutcliffe N2, Schwab M1,2
1)
Glasgow University, UK, 2) Golden Jubilee National Hospital, Glasgow, UK
Background:
TCI
pumps incorporate a programme that is based on a pharmacokinetic/
pharmacodynamic (PK/PD) model to calculate the predicted plasma and effect
site concentration of the drug. The Diprifusor manufactured by Astra- Zenica
was the first available propofol TCI pump which was based on the Marsh PK/PD
model1. More recently a different PK/PD model known as the Schnider
model2 has been introduced. During induction of anaesthesia, the
Schnider model predicts faster propofol effect site equilibration than the
Marsh model. We aim to study which PK/PD model correlates better with the
clinically observed effect of propofol as assessed by the responsive component
of the Observer Assessment of Alertness/Sedation Score OAAS3,4
(table1).
Table
1. Responsive Component of Observer Assessment of Alertness/Sedation Score
OAAS
|
Score |
Responsiveness |
|
5 |
Responds
readily to name spoken in a normal tone. |
|
4 |
Lethargic
response to name spoken in a normal tone. |
|
3 |
Responds
only after name is spoken loudly and repeatedly or both. |
|
2 |
Responds
only after mild prodding or shaking. |
|
1 |
Does
not respond to mild prodding or shaking. |
|
0 |
Does
not respond to noxious stimulus. |
Patients
and Methods:
After
informed consent, we studied 20 unpremedicated patients undergoing surgical
procedures under spinal anaesthesia with propofol sedation. Patients were
observed and assessed for the responsive component of the OAAS score as they
were sedated by propofol TCI to a target concentration of 2mg/ml. Patients
were assessed every 30 seconds for their OAAS score for 15 minutes unless they
scored a sedation score of 0 before the end of the observation period. Half of
the patients were sedated using Schnider PK/PD model with effect site
concentration target and the other half were sedated with Marsh PK/PD model
with plasma concentration target. A PK/PD simulation program (TIVA trainer)
was used to calculate the effect site concentration predicted by both the
Marsh and Schnider models.
Results:
Demographic
Data: Table 2 shows patients data
Table
2: Demographic Data: Mean (Range)
|
|
Marsh |
Schneider |
Overall |
|
Age |
66.9
(52-88) |
59.1
(38-70) |
63.8
(38-88) |
|
Weight |
75.0
(56-99) |
77.3
(69-90) |
67.1
(56-99) |
|
Height |
160.1
(148-170) |
164
(153-178) |
161.7
(148-178) |
Sedation
Score:
Figures
1 & 2 show the propofol effect site prediction and the recorded sedation
score for patients sedated by the Marsh and Schneider models respectively. We
have plotted the OAAS sedation score as 5 minus OAAS score to generate a scale
that increases with increased depth of sedation.
Conclusions:
The
changes in sedation score are better mirrored by the effect site prediction
generated by the Marsh model even when propofol was administered by Schneider
model. The achievement of a certain level of sedation was actually slower in
patients sedated by Schneider model in effect control TCI compared to the same
target in Marsh plasma controlled TCI.
References:
1)
Marsh B,
White M, Morton N, Kenny G. Pharmacokinetic model driven infusion of propofol
in children. Br J Anaesth.1991;67(1):41-8.
2)
Schnider
TW, Minto CF, Shafer SL et al. The influence of age on propofol
pharmacodynamics. Anesthesiology. 1999; 90(6):1502-16.
3)
Glass
PS, Bloom M, Kearse L et al. Bispectral analysis measures sedation and memory
effects of propofol, midazolam,isoflurane and alfentanil in healthy
volunteers. Anesthesiology. 1997; 86(4):836-47.
4)
Doufas
AG, Bakhshandeh M, Bjorksten AR et al. Automated responsiveness test (ART)
predicts loss of conciousness and adverse physiologic responses during
propofol conscious sedation. Anesthesiology. 2001; 94:585-92.
