Whole-exome sequencing reveals genetic variations in humans with differential sensitivity to sevoflurane：A prospective observational study

Wei, Yiyong; Zhang, Donghang; Zuo, Yunxia

doi:10.1016/j.biopha.2022.112724

Cited by 2 publications

(2 citation statements)

References 43 publications

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“…We found considerable variation within treatment in the times to reach all measures of insensibility, such as an exceptionally fast onset of recumbency (40 s) in one mouse in the 1.7% isoflurane treatment. Variation in sensitivity to volatile anesthetics is known in humans to be related to genetic differences, 19 a result that is consistent with known strain differences in the anesthetic potency of isoflurane. 20 The use of outbred (ICR) mice in the current study may have increased the variability in reactions to isoflurane.…”

Section: Discussionsupporting

confidence: 62%

Mouse isoflurane anesthesia using the drop method

2023

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Anesthesia with isoflurane prior to carbon dioxide euthanasia is recommended as a refinement, but vaporizer access can be limited. An alternative to vaporizers is the ‘drop’ method, introducing a fixed volume of isoflurane into the induction chamber. Previous work suggests that isoflurane administered at a concentration of 5% via the drop method is effective but aversive to mice; lower concentrations have not been tested. We assessed mouse behavior and insensibility with induction using the drop method for isoflurane concentrations below 5%. Male Crl:CD-1 (ICR) mice ( n = 27) were randomly allocated to one of three isoflurane concentrations: 1.7%, 2.7%, and 3.7%. During induction, measures of insensibility and stress-related behaviors were recorded. All mice reached a surgical plane of anesthesia, and mice exposed to higher concentrations did so more quickly; as concentrations increased from 1.7 to 2.7 and 3.7%, the time to recumbency (Least squares means ± SE: 120.5 s ± 8.1, 97.9 s ± 8.1, and 82.8 s ± 8.1, respectively), loss of righting reflex (149.1 s ± 8.5, 127.7 s ± 8.5, and 100.7 s ± 8.5, respectively), and loss of pedal withdrawal reflex (214.5 s ± 8.3, 172.2 s ± 8.3, and 146.4 s ± 8.3, respectively) all declined. Rearing was the most frequently performed stress-related behavior, and was most pronounced immediately following isoflurane administration for all treatments. Our results indicate that the drop method can be used to effectively anesthetize mice with isoflurane concentrations as low as 1.7%; future work should assess mouse aversion.

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Section: Discussionsupporting

confidence: 62%

Mouse isoflurane anesthesia using the drop method

2023

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“…Whilst these certainly have potential as tools to unravel mechanisms and aid drug discovery, the application of genetically informed personalized medicine to anaesthesia remains remote. Prior knowledge of small variations in sevoflurane sensitivity [51 ▪ ] hardly justifies the cost of sequencing and preliminary implementation research has so far offered equivocal results [52]. Plus ça change, plus c’est la même chose….…”

Section: What Constrains the Hunt For New IV Hypnotics?mentioning

confidence: 99%

Why sedative hypnotics often fail in development

Sneyd

2024

Current Opinion in Anaesthesiology

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Purpose of review Drug development to support anaesthesia and sedation has been slow with few candidates emerging from preclinical discovery and limited innovation beyond attempted reformulation of existing compounds. Recent findings The market is well supported by low-cost generic products and development compounds have not been shown to improve patient outcomes or possess other distinctive characteristics to justify the cost of development. Summary To make progress in a large-volume, low margin and highly competitive environment requires meaningful advances in relevant basic science. Opportunities exist, but probably require bolder initiatives than further attempts at reformulation or fiddling with the structure of propofol. Extending development ambitions to include nonanaesthesiologist providers challenges professional boundaries but may facilitate cost-effective changes in patterns of care.

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Whole-exome sequencing reveals genetic variations in humans with differential sensitivity to sevoflurane：A prospective observational study

Cited by 2 publications

References 43 publications

Mouse isoflurane anesthesia using the drop method

Mouse isoflurane anesthesia using the drop method

Why sedative hypnotics often fail in development

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