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The objectives of this study were, firstly, to characterize the inter-patient variability in the dose of propofol required to achieve a bispectral index <70 and ‘time to eye opening’ following propofol infusion and, secondly, to determine if the pharmacodynamic parameter ‘time to achieve bispectral index <70’ was influenced by genotype of the sex-linked drug receptor gene GABRE or if pharmacokinetic parameters such as clearance and ‘time to eye opening’ were influenced by the genotype of the metabolizing enzyme CYP2B6.
One hundred and fifty patients received a standardized anaesthetic. Apparent systemic clearance values were estimated. Correlation was sought between carriers of different CYP2B6 and GABRE genotypes and apparent systemic clearance, ‘time to achieve bispectral index <70’ and ‘time to eye opening’.
Propofol induction/emergence characteristics varied, with slow recovery times in a subset of males. Time to loss of verbal contact and time to bispectral index <70 varied 6.6- and 4.3-fold, respectively. At emergence, there was a 15.5- to 111-fold variability in the measured time intervals. Clearance varied from 9.1 to 55.8 mL min−1 kg−1. The CYP2B6 C1459T (R487C) genotype frequencies were TT 1%, TC 22% and CC 67%. The three major haplotypes of CYP2B6 (R487C, K262R and Q172H variants) were not significantly associated with time to eye opening or clearance. Clearance was similar in 487C carriers and 487RR genotypes. There was no statistically significant correlation between the four major haplotypes of GABRE variants investigated ([mRNA358]G/T, 20118C/T, 20326C/T and 20502 A/T) and the observed anaesthesia induction time.
Great inter-patient variability exists in the dose of propofol required to achieve bispectral index <70, apparent systemic propofol clearance and time to eye opening. Common haplotypic differences at the CYP2B6 and GABRE genes do not appear to account for the majority of the observed inter-patient variability.
Delayed recovery of cognitive function is a well-recognized phenomenon in older patients. The potential for the volatile anaesthetic used to contribute to alterations in postoperative cognitive function in older patients following minor surgical procedures has not been determined. We compared emergence from isoflurane and sevoflurane anaesthesia in older surgical patients undergoing urological procedures of short duration.
Seventy-one patients, 60 yr of age or older, undergoing anaesthesia expected to last less than 60 min for ambulatory surgery, were randomly assigned to receive isoflurane or sevoflurane. A standardized anaesthetic protocol was used, with intravenous fentanyl 1 μg kg−1 and propofol 1.5–2.0 mg kg−1 administered to induce anaesthesia. Anaesthesia was maintained with either sevoflurane or isoflurane in 65% nitrous oxide and oxygen. Early and intermediate recovery times were recorded. The mini mental state examination and digit repetition forwards and backwards were administered at baseline, and at 1, 3 and 6 h postoperatively, to assess cognitive function.
There were no between-group differences in (sevoflurane vs. isoflurane, mean ± standard error of the mean) times to removal of the laryngeal mask airway (7.7 ± 0.6 vs. 7.1 ± 0.4 min), verbal response time (10.1 ± 0.7 vs. 9.9 ± 0.7 min) and orientation (12.1 ± 0.7 vs. 12.1 ± 0.7 min). Intermediate recovery, as measured by time to readiness for discharge from the post anaesthesia care unit (44.9 ± 1.5 vs. 44.3 ± 1.5 min), was similar in the two groups. Postoperative indices of cognitive function and attention were comparably reduced at 1 h, but returned to baseline in both groups at 6 h.
Isoflurane and sevoflurane anaesthesia resulted in similar clinical and neurocognitive recovery profiles in older patients undergoing ambulatory surgical procedures of short duration.
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