Neuroplasticity Induced by General Anaesthesia
Condition: Healthy Volunteers; General Anaesthesia; Neuroplasticity
Study type: Interventional

Summary: 
      The aim of this study is to use magnetic resonance imaging to explore and compare possible de
      novo neuroplastic changes induced by the isolated effects of the hypnotic agents sevoflurane
      and propofol, respectively. In addition, to explore possible associations between
      neuroplastic changes and clinical and/or biochemical outcomes. It is a randomised,
      cross-over, single blinded clinical study. N = 30. Female:male ratio 1:1.
    

Detailed description: 
      Background

      In the perioperative period, severe changes can be observed in the endocrine, immune, and
      nervous system. These changes are called the surgical stress response. Clinically, this can
      be observed as increased pain response and disturbances in the circadian rhythm, memory,
      cognitive and executive functions, and may lead to post-operative delirium. The
      post-operative cognitive dysfunction is associated with increased mortality and risk of
      prematurely leaving occupation. Post-operative delirium with fluctuating levels of attention
      and consciousness is a serious condition associated with poor outcome, including longer
      hospitalisation and increased early mortality.

      General anaesthesia may contribute to the surgical stress response. Some data indicate that
      general anaesthesia per se can cause alterations and disturbances in the brain such as sleep
      and circadian disturbances. Recent evidence suggests that anaesthetic agents may impair
      neurogenesis and cause memory impairment. In addition, inhalation anaesthesia may result in
      more cerebral disturbances compared to total intravenous anaesthesia (TIVA). In this study,
      we will isolate the effects of the two primary hypnotic agents used in general anaesthesia,
      sevoflurane and propofol, without the interactions and confounders of polypharmacy and
      varying levels of disease among a surgical population.

      Materials

      The study consists of two study sessions. In each study session magnetic resonance imaging
      (MRI) scans will be obtained before and after general anaesthesia, and in addition after one
      and eight days.

      The following imaging modalities will be employed: (i) T1-weighted 3D anatomy (T1w3D), (ii)
      Diffusion Tensor Imaging (DTI), (iii) resting state functional MRI (rsfMRI). The MRI scans
      will be supplemented with cognitive testing, sleep evaluation and blood sampling. Thus, the
      set-up for each volunteer will be:

      Session one:

      Day 0: MRI 1, cognitive testing, questionnaires, and blood sampling. General anaesthesia
      (maintenance phase with sevoflurane OR propofol according to randomisation), and
      post-anaesthesia care. MRI 2 and repeated cognitive testing, questionnaires, and blood
      sampling.

      Day +1: MRI 3, cognitive testing, questionnaires, and blood sampling.

      Day +8: MRI 4, cognitive testing, and questionnaires.

      Session two: Identical to session one, except the volunteer will receive the remaining type
      of general anaesthesia (sevoflurane or propofol, opposite to session one).

      Data evaluation will be conducted with assessor blinded to anaesthesia type.
    

Intervention name(s): Sevoflurane-propofol
Intervention type(s): Drug
Intervention description(s): General anaesthesia with a maintenance phase of two hours duration with either sevoflurane or propofol.
Other intervention name(s): Propofol-sevoflurane
Intervention MeSH terms: Propofol; Sevoflurane
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Randomisation to one of two options in session 1: sevoflurane or propofol. In session 2, the remaining option is administered.
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Neuroplasticity; Neuroplastic changes; General anaesthesia; Magnetic resonance imaging; Sevoflurane; Propofol; Healthy volunteers; Consciousness; Cognitive; Fatigue