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A2090
October 12, 2014
8:00 AM - 10:00 AM
Room Hall B1-Area C
Digital Substitution Test Reveals Preservation of Cognitive Reserve After Phaxan™ But Not After Propofol Anaesthesia
Colin S. Goodchild, M.A.,M.B., B.Chir., Ph.D., FRCA, FANZCA, FFPMANZCA, John Monagle, M.B.B.S., FANZCA, Lyndon Siu, M.B.B.S., FANZCA, Jodie Worrell, R.N., Juliet M. Serrao, M.B.B.S., Ph.D., F.R.C.A.
Monash Institute of Medical Research, Malvern, Victoria, Australia
Introduction:

Phaxan is an aqueous solution of alphaxalone. A recent study used the Digital Symbol Substitution Test (DSST) to compare recovery after Phaxan and propofol. Recovery of pre anaesthetic performance in DSST occurred 35 minutes after injection of Phaxan and propofol. A literature search revealed that DSST performance increases with repeat testing paradigms like that used in the Phaxan study; this indicates "Cognitive Reserve" in the test subjects1. Data from repeat DSST were analysed to investigate cognitive reserve after anaesthesia with Phaxan and propofol.

Methods:

The study was randomised, double blind, comparing propofol and Phaxan using a Bayesian algorithm to determine dose equivalence for effects on the bispectral index (BIS). 24 male volunteers ASA grade 1 gave written informed consent (n=12 per group; propofol, Phaxan). DSST was measured every 15 minutes for one hour before and 35, 50, 65 and 80 minutes after anaesthesia with Phaxan or propofol. The numbers of correct answers at each of the 8 testing times were standardised for each subject as % of the fourth measurement for that individual (last of the pre anaesthetic readings). DSST measurements published for normal individuals of the same age (Zihl et al1) were similarly treated for comparison. Values so calculated for each group (Phaxan, propofol and Zihl) were subjected to linear regression for measurements 1-4 and 5-8. Thus improvement of DSST scores in normal subjects1 could be compared with data before (measurements 1-4) and after (measurements 5-8) equipotent doses of Phaxan and propofol.

Results:

Eleven subjects in each group were anaesthetised to BIS value ≤ 50: propofol 2.3 (3.0-1.8); Phaxan 0.5 (0.6-0.5); median, IQ mg/kg . Nine subjects in each group received doses of drug that were within the IQ range, the lowest average BIS reached being 28 for both propofol and Phaxan subjects. The DSST score profiles of these subjects were analysed further.

DSST scores 35 minutes after anaesthesia with equipotent doses of Phaxan and propofol were equal to those measured before anaesthesia. There were significant improvements in DSST scores for subjects in the Phaxan and propofol groups prior to anaesthesia equal with normal published data (table 1). Phaxan treated subjects continued to improve their DSST scores after anaesthesia (measurements 5-8) at the same rate as those published for normal subjects1 whereas propofol treated subjects did not change their performance significantly even until 80 minutes after drug injection (table 1).

Table : results of linear regression [Graphpad Prism ver 6]

Conclusions:

Phaxan causes fast onset short duration anaesthesia equivalent to propofol but with less cardiovascular and respiratory depression and no pain on injection. Using DSST as a measure of recovery from sedation, Phaxan and propofol treated subjects recovered their pre anaesthetic performance equally by 35 minutes after drug injection. However, under the repeat testing paradigm used for DSST, there is normally significant improvement in performance from test 5 through 8 1. This normal progression occurred with Phaxan but not after propofol anaesthesia. These results suggest that cognitive reserve as defined by Zihl et al1 is preserved after Phaxan anaesthesia but it is compromised for at least 80 minutes after propofol. The relevance and longer term implications of these findings warrant further study.

References:

1.

Zihl J, et al 2014; Cognitive Reserve in Young and Old Healthy Subjects: Differences and Similarities in a Testing-the-Limits Paradigm with DSST. PLoS ONE 9(1): e84590.
Figure 1

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