Taxane modulation of anesthetic sensitivity in surgery for nonmetastatic breast cancer
Abstract
Study objective and design The mechanism of action of commonly used general anesthetics is largely unknown. One hypothesized mechanism is through modulation of microtubule stability. Taxanes, a subset of chemotherapeutic drugs known to alter microtubule stability and commonly used to treat breast cancer, offer a natural experiment to test our hypothesis that patients exposed to taxanes prior to surgery, as compared to after surgery, would have a partial resistance to general anesthetics.Setting, patients, and measurements The anesthetic record of adult women with nonmetastatic breast cancer was used to obtain changes in heart rate and blood pressure surrounding incision, and the amount of inhaled anesthetic agent, induction, and rescue drugs administered.Main results Change in blood pressure in response to incision was significantly higher in the neoadjuvant group (P = .03), whereas change in heart rate was not (P = .53). A greater amount of morphine was administered in the neoadjuvant group (26.3 vs 15.5 mg, P = .02), although not a higher concentration of inhaled anesthetics (P = .15).Conclusion These results suggest that the alteration of microtubule stability is one of a number of mechanisms of inhaled anesthetics.
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In vivo relevance of anesthetic action on the cytoskeleton is validated in tadpoles showing increased anesthetic resistance with microtubule-stabilizing drugs and suggested in humans.
“The in vivo relevance of anesthetic action on the cytoskeleton has been validated in tadpoles that demonstrate increased anesthetic resistance in the presence of microtubule-stabilizing drugs and also suggested in humans [85, 87].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [87]
Our findings are consistent with the report of partial anesthetic resistance in human surgical patients treated with taxane MT-stabilizing chemotherapy.
“Our findings are consistent with the report of partial anesthetic resistance in human surgical patients treated with taxane MT-stabilizing chemotherapy (Linganna et al., 2015) that was a primary motivation for our study in rats.”
From Microtubule-stabilizer epothilone B delays anesthetic-induced unconsciousness in rats (2024) · cites this paper as Linganna et al., 2015
There was no significant change in heart rate or anesthetic delivery during surgery in the taxane group compared with controls.
“there was no significant change in the heart rate or anesthetic delivery during surgery in the taxane group as compared with controls.”
From Microtubule-stabilizer epothilone B delays anesthetic-induced unconsciousness in rats (2024) · cites this paper as Linganna et al., 2015
Recipients of taxane chemotherapy had a significantly elevated blood pressure response to incision during breast cancer surgery and required significantly more opioid analgesic compared with patients who did not receive taxane chemotherapy.
“Recipients of taxane chemotherapy had a significantly elevated blood pressure response to incision during surgery for breast cancer and required significantly more opioid analgesic, as compared with patients who did not receive taxane chemotherapy (Linganna et al., 2015).”
From Microtubule-stabilizer epothilone B delays anesthetic-induced unconsciousness in rats (2024) · cites this paper as Linganna et al., 2015
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“There is evidence of specific tubulin binding for most of the general anesthetics, as well as evidence of modulation of tubulin polymerization by these drugs in vitro [3,4].”
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Magnetic field effects in biology from the perspective of the radical pair mechanism
Zadeh-Haghighi, H., & Simon, C. (2022) · Journal of The Royal Society Interface · doi:10.1098/rsif.2022.0325 · Cited by 197 · see citing works
The Biology of General Anesthesia from Paramecium to Primate
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“Similarly, a clinical study of anesthetic usage by human surgery patients given MT-stabilizing chemotherapy (which generally penetrates poorly into the brain) compared to control subjects found a slight anesthetic resistance in the patients given the MT-binding drug (Linganna et al. 2015).”
Microtubule-stabilizer epothilone B delays anesthetic-induced unconsciousness in rats
Khan, S., Huang, Y., Timuçin, D., Bailey, S., Lee, S., Lopes, J., Gaunce, E., Mosberger, J., Zhan, M., Abdelrahman, B., et al. (2024) · eneuro · doi:10.1523/eneuro.0291-24.2024 · Cited by 30 · see citing works
- Authors
- Linganna, R. E., Levy, W. J., Dmochowski, I. J., Eckenhoff, R. G., & Speck, R. M.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Speck, Rebecca M.
- Venue
- Journal of Clinical Anesthesia
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 27
- Issue
- 6
- Pages
- 481-485
- ISSN
- 0952-8180 (ISSN-L)
- OpenAlex
- W2126612411
- Cited by
- 18
- References
- 11
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 1 · 2022: 2 · 2019: 1 · 2016: 1
- FWCI
- 0.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Anesthesia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pennsylvania
- Topics
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Health Sciences › Medicine › Psychiatry and Mental health › Cancer, Stress, Anesthesia, and Immune Response
- Health Sciences › Medicine › Surgery › Anesthesia and Pain Management
- Keywords
- taxanes, anesthetic sensitivity, general anesthesia, microtubule stability, non-metastatic breast cancer, neoadjuvant chemotherapy, inhalational anesthetics, heart rate, morphine use, anesthesia induction
- MeSH terms
- Adult, Aged, Anesthesia, General, Antineoplastic Agents, Blood Pressure, Breast Neoplasms, Drug Interactions, Female, Heart Rate, Humans, Mastectomy, Microtubules, Middle Aged, Retrospective Studies, Cohort Studies, Mastectomy, Segmental, Chemotherapy, Adjuvant, Anesthetics, General, Taxoids
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