Comparing Four Pharmacokinetic/ Pharmacodynamic Models Target Controlled Infusion of Propofol in a Younger Population

 

Martin McCormick¹ , Jörg Prinzlin², and Nick Sutcliffe²

1. University Department of Anaesthesia, Glasgow Royal Infirmary

2. Department of Anaesthesia, Golden Jubilee National Hospital, Clydebank G81 4HX, Scotland

 

 

Background and Goal of Study:  We compared the predicted effect site concentration at loss and return of clinical endpoints in 4 different pharmakokinetic/pharmacodynamic (PK/PD) models suitable for use in target controlled infusion (TCI) of propofol. Our hypothesis was that the predicted values for effect site concentration (Ce) of propofol at loss of, and return of, consciousness should be similar in an ideal model. We used verbal response and eyelash reflex as markers of consciousness.

 

Materials and Methods: We studied 30 ASA I-II patients aged 22 to 60 years for elective surgery with no sedative premedication. Anaesthesia was induced with TCI propofol (Marsh model1) plasma target (Cpt) of 4 or 6 mcg/ml depending on the patient age. Time to loss of verbal response (LOVR1) and eyelash reflex (LOER1) was noted. TCI was stopped at LOER1 and times recorded to regaining eyelash and verbal responses (ROER and ROVR respectively). TCI was then restarted at the initial target and the time for loss of verbal response (LOVR2) and eyelash reflexes (LOER2) recorded. The TivaTrainer PK/PD simulation programme was used to reproduce the infusion regimen and predicted Ce at each clinical endpoint using the models of Marsh¹, Schnider², Schüttler³ and White-Kenny (WK)4. Data  were compared with linear regression to calculate coefficients of determination (CoD).

 

Results and Discussion: The CoDs are shown below:

 

Marsh

Schüttler

Schnider

WK

LOER1/ROER

0.78

0.41

0.20

0.72

LOER2 /ROER

0.85

0.66

0.24

0.82

LOVR1/ ROVR

0.64

0.33

0.37

0.57

LOVR2/ ROVR

0.87

0.66

0.29

0.81

LOVR1/LOVR2

0.50

0.17

0.40

0.39

LOER1/LOER2

0.63

0.35

0.69

0.55

 

The Marsh model consistently showed the best when assessed in this way, except when comparing LOER1/LOER2, where the Schnider model had the most accurate predictive value

 

Conclusion: In this age group, the Marsh model had the best predictive accuracy of effect site concentration in the majority of the awake-asleep comparisons.

 

References:

1) Marsh B. BJA 1991; 67:41-8

2) Schnider T.  Anesthesiology 1999; 90: 1502-16

3) Schüttler J. Anesthesiology 2000; 92:727-73

4) Kenny GN. BJA submitted, personal communication