Genetic and cognitive aspects on recovery after propofol anaesthesia
Author: Lindqvist, Marja
Date: 2015-02-13
Location: Nanna Svartz Auditorium, Karolinska Universitetssjukhuset, Solna
Time: 09.00
Department: Inst för fysiologi och farmakologi / Dept of Physiology and Pharmacology
Abstract
Propofol is one of the most used intravenous anaesthetics in the western world. It is often
used for ambulatory surgery due to favourable pharmacokinetic properties allowing quick
onset and short emergence time. However, there is considerable interindividual variation in
pharmacokinetics and dynamics as well as gender differences. Differences in metabolism due
to polymorphic enzymes may be a contributing factor to this variation. To enable early and
smooth discharge from hospital after ambulatory surgery, a quick postoperative cognitive
recovery is essential. It is not known whether the great variation in propofol
pharmacokinetics and pharmacodynamics affect the cognitive recovery of the ambulatory
patient receiving propofol.
By studying correlation between genotype and propofol metabolite production both in liver microsomes and in humans after propofol anaesthesia, we aimed to further describe the variations in propofol pharmacokinetics. Postoperative cognitive recovery in women undergoing ambulatory breast cancer surgery with propofol or desflurane anaesthesia was studied, using the PQRS and CFQ as assessment tools. Further the cognitive performance according to PQRS in a test re-test situation in pre-surgery cancer patients compared to controls was evaluated.
Our results demonstrate a great variation in production of propofol metabolites in vitro and in vivo, but no correlation between metabolite level and genotype. Females showed a higher propofol metabolite level compared to men after both bolus dose and infusion of propofol. Cognitive recovery was similar after propofol and desflurane anaesthesia, and subjectively not complete one week after surgery. We found that pre-surgery cancer patients expressed a higher level of anxiety and had lower cognitive baseline test performance compared to controls, resulting in a high exclusion rate in the patient group. The groups had a similar retest performance in the PQRS cognitive domain.
In conclusion, we found a considerable variability in production of propofol metabolites but no correlation to genotype. There was an increased production of propofol metabolites in women compared to men. The protracted postoperative cognitive recovery assessed by PQRS and CFQ after ambulatory surgery was similar after propofol and desflurane anaesthesia, suggesting that possible remains of propofol or its metabolites do not affect cognitive performance more than residual effects of desflurane. When assessing postoperative cognitive recovery it should be acknowledged that the anxiety and stress caused by a severe disease and wait for surgery may have an impact on cognitive PQRS test performance. The use of the revised PQRS cognitive scoring system may lead to the exclusion of a considerable part of the patients due to too low baseline performance.
By studying correlation between genotype and propofol metabolite production both in liver microsomes and in humans after propofol anaesthesia, we aimed to further describe the variations in propofol pharmacokinetics. Postoperative cognitive recovery in women undergoing ambulatory breast cancer surgery with propofol or desflurane anaesthesia was studied, using the PQRS and CFQ as assessment tools. Further the cognitive performance according to PQRS in a test re-test situation in pre-surgery cancer patients compared to controls was evaluated.
Our results demonstrate a great variation in production of propofol metabolites in vitro and in vivo, but no correlation between metabolite level and genotype. Females showed a higher propofol metabolite level compared to men after both bolus dose and infusion of propofol. Cognitive recovery was similar after propofol and desflurane anaesthesia, and subjectively not complete one week after surgery. We found that pre-surgery cancer patients expressed a higher level of anxiety and had lower cognitive baseline test performance compared to controls, resulting in a high exclusion rate in the patient group. The groups had a similar retest performance in the PQRS cognitive domain.
In conclusion, we found a considerable variability in production of propofol metabolites but no correlation to genotype. There was an increased production of propofol metabolites in women compared to men. The protracted postoperative cognitive recovery assessed by PQRS and CFQ after ambulatory surgery was similar after propofol and desflurane anaesthesia, suggesting that possible remains of propofol or its metabolites do not affect cognitive performance more than residual effects of desflurane. When assessing postoperative cognitive recovery it should be acknowledged that the anxiety and stress caused by a severe disease and wait for surgery may have an impact on cognitive PQRS test performance. The use of the revised PQRS cognitive scoring system may lead to the exclusion of a considerable part of the patients due to too low baseline performance.
List of papers:
I. Influence of sex on propofol metabolism, a pilot study: implications for propofol anesthesia. Loryan I, Lindqvist M, Johansson I, Hiratsuka M, van der Heiden I, van Schaik RH, Jakobsson J, Ingelman-Sundberg M. Eur J Clin Pharmacol (2012) 68:397–406
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Sex difference in formation of propofol metabolites: a replication study. Choong E, Loryan I, Lindqvist M, Nordling A, El Bouazzaoui S, van Schaik RH, Johansson I, Jakobsson J, Ingelman-Sundberg M. Basic & Clinical Pharmacology & Toxicology, 2013, 113, 126–131
Fulltext (DOI)
Pubmed
View record in Web of Science®
III. Cognitive recovery after ambulatory anaesthesia based on desflurane or propofol: a prospective randomised study. Lindqvist M, Schening A, Granstrom A, Bjorne H, Jakobsson JG. Acta Anaesthesiol Scand 2014 Oct; (9): 1111-20
Fulltext (DOI)
Pubmed
View record in Web of Science®
IV. Cognitive baseline test and re-test performance according to the revised Postoperative Quality of Recovery Scale in pre-surgery cancer patients -a controlled study. Lindqvist M, Granstrom A, Schening A, Bjorne H, Jakobsson JG. [Submitted]
I. Influence of sex on propofol metabolism, a pilot study: implications for propofol anesthesia. Loryan I, Lindqvist M, Johansson I, Hiratsuka M, van der Heiden I, van Schaik RH, Jakobsson J, Ingelman-Sundberg M. Eur J Clin Pharmacol (2012) 68:397–406
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Sex difference in formation of propofol metabolites: a replication study. Choong E, Loryan I, Lindqvist M, Nordling A, El Bouazzaoui S, van Schaik RH, Johansson I, Jakobsson J, Ingelman-Sundberg M. Basic & Clinical Pharmacology & Toxicology, 2013, 113, 126–131
Fulltext (DOI)
Pubmed
View record in Web of Science®
III. Cognitive recovery after ambulatory anaesthesia based on desflurane or propofol: a prospective randomised study. Lindqvist M, Schening A, Granstrom A, Bjorne H, Jakobsson JG. Acta Anaesthesiol Scand 2014 Oct; (9): 1111-20
Fulltext (DOI)
Pubmed
View record in Web of Science®
IV. Cognitive baseline test and re-test performance according to the revised Postoperative Quality of Recovery Scale in pre-surgery cancer patients -a controlled study. Lindqvist M, Granstrom A, Schening A, Bjorne H, Jakobsson JG. [Submitted]
Institution: Karolinska Institutet
Supervisor: Jakobsson, Jan
Issue date: 2015-01-14
Rights:
Publication year: 2015
ISBN: 978-91-7549-663-4
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