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Test of neural inertia in humans during general anaesthesia

(2018) BRITISH JOURNAL OF ANAESTHESIA. 120(3). p.525-536
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Abstract
Background: Neural inertia is defined as the tendency of the central nervous system to resist transitions between arousal states. This phenomenon has been observed in mice and Drosophila anaesthetized with volatile anaesthetics: the effect-site concentration required to induce anaesthesia in 50% of the population (C-50) was significantly higher than the effect-site concentration for 50% of the population to recover from anaesthesia. We evaluated this phenomenon in humans using propofol or sevoflurane (both with or without remifentanil) as anaesthetic agents. Methods: Thirty-six healthy volunteers received four sessions of anaesthesia with different drug combinations in a stepup/step-down design. Propofol or sevoflurane was administered with or without remifentanil. Serum concentrations of propofol and remifentanil were measured from arterial blood samples. Loss and return of responsiveness (LOR-ROR), response to pain (PAIN), Patient State Index (PSI) and spectral edge frequency (SEF) were modeled with NONMEM (R). Results: For propofol, the C-50 for induction and recovery of anaesthesia was not significantly different across the different endpoints. For sevoflurane, for all endpoints except SEF, significant differences were found. For some endpoints (LOR and PAIN) the difference was significant only when sevoflurane was combined with remifentanil. Conclusions: Our results nuance earlier findings with volatile anaesthetics in mice and Drosophila. Methodological aspects of the study, such as the measured endpoint, influence the detection of neural inertia. A more thorough definition of neural inertia, with a robust methodological framework for clinical studies is required to advance our knowledge of this phenomenon.
Keywords
PHARMACODYNAMIC INTERACTION, BISPECTRAL INDEX, IN-VITRO, REMIFENTANIL, PROPOFOL, AROUSAL, PHARMACOKINETICS, RESPONSIVENESS, VOLUNTEERS, SLEEP, anaesthesia, general, anaesthesia, inhalation, anaesthesia, intravenous, consciousness monitors, unconsciousness/drug effects

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Chicago
Kuizenga, MH, Pieter Colin, KMEM Reyntjens, DJ Touw, H Nalbat, FH Knotnerus, HEM Vereecke, and Michel Struys. 2018. “Test of Neural Inertia in Humans During General Anaesthesia.” British Journal of Anaesthesia 120 (3): 525–536.
APA
Kuizenga, M., Colin, P., Reyntjens, K., Touw, D., Nalbat, H., Knotnerus, F., Vereecke, H., et al. (2018). Test of neural inertia in humans during general anaesthesia. BRITISH JOURNAL OF ANAESTHESIA, 120(3), 525–536.
Vancouver
1.
Kuizenga M, Colin P, Reyntjens K, Touw D, Nalbat H, Knotnerus F, et al. Test of neural inertia in humans during general anaesthesia. BRITISH JOURNAL OF ANAESTHESIA. 2018;120(3):525–36.
MLA
Kuizenga, MH, Pieter Colin, KMEM Reyntjens, et al. “Test of Neural Inertia in Humans During General Anaesthesia.” BRITISH JOURNAL OF ANAESTHESIA 120.3 (2018): 525–536. Print.
@article{8574336,
  abstract     = {Background: Neural inertia is defined as the tendency of the central nervous system to resist transitions between arousal states. This phenomenon has been observed in mice and Drosophila anaesthetized with volatile anaesthetics: the effect-site concentration required to induce anaesthesia in 50% of the population (C-50) was significantly higher than the effect-site concentration for 50% of the population to recover from anaesthesia. We evaluated this phenomenon in humans using propofol or sevoflurane (both with or without remifentanil) as anaesthetic agents. 
Methods: Thirty-six healthy volunteers received four sessions of anaesthesia with different drug combinations in a stepup/step-down design. Propofol or sevoflurane was administered with or without remifentanil. Serum concentrations of propofol and remifentanil were measured from arterial blood samples. Loss and return of responsiveness (LOR-ROR), response to pain (PAIN), Patient State Index (PSI) and spectral edge frequency (SEF) were modeled with NONMEM (R). 
Results: For propofol, the C-50 for induction and recovery of anaesthesia was not significantly different across the different endpoints. For sevoflurane, for all endpoints except SEF, significant differences were found. For some endpoints (LOR and PAIN) the difference was significant only when sevoflurane was combined with remifentanil. 
Conclusions: Our results nuance earlier findings with volatile anaesthetics in mice and Drosophila. Methodological aspects of the study, such as the measured endpoint, influence the detection of neural inertia. A more thorough definition of neural inertia, with a robust methodological framework for clinical studies is required to advance our knowledge of this phenomenon.},
  author       = {Kuizenga, MH and Colin, Pieter and Reyntjens, KMEM and Touw, DJ and Nalbat, H and Knotnerus, FH and Vereecke, HEM and Struys, Michel},
  issn         = {0007-0912},
  journal      = {BRITISH JOURNAL OF ANAESTHESIA},
  keywords     = {PHARMACODYNAMIC INTERACTION,BISPECTRAL INDEX,IN-VITRO,REMIFENTANIL,PROPOFOL,AROUSAL,PHARMACOKINETICS,RESPONSIVENESS,VOLUNTEERS,SLEEP,anaesthesia,general,anaesthesia,inhalation,anaesthesia,intravenous,consciousness monitors,unconsciousness/drug effects},
  language     = {eng},
  number       = {3},
  pages        = {525--536},
  title        = {Test of neural inertia in humans during general anaesthesia},
  url          = {http://dx.doi.org/10.1016/j.bja.2017.11.072},
  volume       = {120},
  year         = {2018},
}

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