Oestrous cycle affects emergence from anaesthesia with dexmedetomidine, but not propofol, isoflurane, or sevoflurane, in female rats

Kathleen F Vincent; Olivia G Mallari; Emmaline J Dillon; Victoria G Stewart; Angel J Cho; Yuanlin Dong; Andrea G Edlow; Fumito Ichinose; Zhongcong Xie; Ken Solt

doi:10.1016/j.bja.2023.03.025

Oestrous cycle affects emergence from anaesthesia with dexmedetomidine, but not propofol, isoflurane, or sevoflurane, in female rats

Br J Anaesth. 2023 Jul;131(1):67-78. doi: 10.1016/j.bja.2023.03.025. Epub 2023 May 2.

Authors

Affiliations

¹ Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Anaesthesia, Harvard Medical School, Boston, MA, USA.
² Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Anesthesiology, Columbia University, New York, NY, USA.
³ Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Brigham Young University, Provo, UT, USA.
⁴ Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Touro College of Osteopathic Medicine, New York, NY, USA.
⁵ Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, USA; Department of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, MA, USA.
⁶ Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Anaesthesia, Harvard Medical School, Boston, MA, USA. Electronic address: ksolt@mgh.harvard.edu.

PMID: 37142466
PMCID: PMC10308440 (available on 2024-07-01)
DOI: 10.1016/j.bja.2023.03.025

Abstract

Background: Although sex differences in anaesthetic sensitivity have been reported, what underlies these differences is unknown. In rodents, one source of variability in females is the oestrous cycle. Here we test the hypothesis that the oestrous cycle impacts emergence from general anaesthesia.

Methods: Time to emergence was measured after isoflurane (2 vol% for 1 h), sevoflurane (3 vol% for 20 min), dexmedetomidine (50 μg kg^-1 i.v., infused over 10 min), or propofol (10 mg kg^-1 i.v. bolus) during proestrus, oestrus, early dioestrus, and late dioestrus in female Sprague-Dawley rats (n=24). EEG recordings were taken during each test for power spectral analysis. Serum was analysed for 17β-oestradiol and progesterone concentrations. The effect of oestrous cycle stage on return of righting latency was assessed using a mixed model. The association between righting latency and serum hormone concentration was tested by linear regression. Mean arterial blood pressure and arterial blood gases were assessed in a subset of rats after dexmedetomidine and compared in a mixed model.

Results: Oestrous cycle did not affect righting latency after isoflurane, sevoflurane, or propofol. When in the early dioestrus stage, rats emerged more rapidly from dexmedetomidine than in the proestrus (P=0.0042) or late dioestrus (P=0.0230) stage and showed reduced overall power in frontal EEG spectra 30 min after dexmedetomidine (P=0.0049). 17β-Oestradiol and progesterone serum concentrations did not correlate with righting latency. Oestrous cycle did not affect mean arterial blood pressure or blood gases during dexmedetomidine.

Conclusions: In female rats, the oestrous cycle significantly impacts emergence from dexmedetomidine-induced unconsciousness. However, 17β-oestradiol and progesterone serum concentrations do not correlate with the observed changes.

Keywords: dexmedetomidine; emergence; isoflurane; oestrus; propofol; return of righting reflex; sevoflurane.

MeSH terms

Anesthesia, General
Animals
Dexmedetomidine* / pharmacology
Estradiol / pharmacology
Female
Gases
Isoflurane* / pharmacology
Male
Progesterone / pharmacology
Propofol* / pharmacology
Rats
Rats, Sprague-Dawley
Sevoflurane / pharmacology

Substances

Propofol
Sevoflurane
Isoflurane
Dexmedetomidine
Progesterone
Estradiol
Gases