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Published, Version of Record (VoR)CC BY V4.0, Open
Journal article
Analysis of stochastic fluctuations in responsiveness is a critical step toward personalized anesthesia
ELife, v 8, e50143
03 Dec 2019
PMCID: PMC6890463
PMID: 31793434
Abstract
Traditionally, drug dosing is based on a concentration-response relationship estimated in a population. Yet, in specific individuals, decisions based on the population-level effects frequently result in over or under-dosing. Here, we interrogate the relationship between population-based and individual-based responses to anesthetics in mice and zebrafish. The anesthetic state was assessed by quantifying responses to simple stimuli. Individual responses dynamically fluctuated at a fixed drug concentration. These fluctuations exhibited resistance to state transitions. Drug sensitivity varied dramatically across individuals in both species. The amount of noise driving transitions between states, in contrast, was highly conserved in vertebrates separated by 400 million years of evolution. Individual differences in anesthetic sensitivity and stochastic fluctuations in responsiveness complicate the ability to appropriately dose anesthetics to each individual. Identifying the biological substrate of noise, however, may spur novel therapies, assure consistent drug responses, and encourage the shift from population-based to personalized medicine.
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Details
- Title
- Analysis of stochastic fluctuations in responsiveness is a critical step toward personalized anesthesia
- Creators
- Andrew R. McKinstry-Wu - University of PennsylvaniaAndrzej Z. Wasilczuk - University of PennsylvaniaBenjamin A. Harrison - University of PennsylvaniaVictoria M. Bedell - University of PennsylvaniaMathangi J. Sridharan - The Ohio State UniversityJayce J. Breig - Drexel UniversityMichael Pack - University of PennsylvaniaMax B. Kelz - University of PennsylvaniaAlexander Proekt - University of Pennsylvania
- Publication Details
- ELife, v 8, e50143
- Publisher
- ELIFE SCIENCES PUBLICATIONS LTD; CAMBRIDGE
- Number of pages
- 25
- Grant note
- National Institutes of Health K08 GM123317 Andrew R McKinstry-Wu; National Institutes of Health R01 GM124023 Alexander Proekt; National Institutes of Health R01 GM088156 Max B Kelz; National Institutes of Health R01 GM107117 Max B Kelz; National Institutes of Health T32 GM112596 Max B Kelz
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Drexel University
- Web of Science ID
- WOS:000500957300001
- Scopus ID
- 2-s2.0-85076324519
- Other Identifier
- 991021860714804721
InCites Highlights
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biology