Neuroplasticity Induced by General Anaesthesia
Overview
- Phase
- Not Applicable
- Intervention
- Sevoflurane-propofol
- Conditions
- Healthy Volunteers
- Sponsor
- Signe Sloth Madsen
- Enrollment
- 20
- Locations
- 2
- Primary Endpoint
- Changes in T1w3D
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief 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.
Investigators
Signe Sloth Madsen
Principal Investigator
Rigshospitalet, Denmark
Eligibility Criteria
Inclusion Criteria
- •Age ≥18 and ≤
- •Healthy individual.
- •BMI ≥18 kg/m2 and ≤30kg/m
- •Normal electrocardiogram (ECG).
- •Normal physical examination, including neurological examination, auscultation of the heart and lungs, and measurement of blood pressure and pulse.
- •American Society of Anaesthesiologists (ASA) class
- •Mallampati I-II and simplified airway risk index (SARI) 0-2 (i.e. no indication of difficult intubation). See appendix for details.
- •Right-handed.
- •Female participants must use safe contraceptives (hormonal or mechanical, including intrauterine devices).
- •Speaks and understand Danish.
Exclusion Criteria
- •Contraindications to MRI.
- •Left-handedness or ambidexterity.
- •History of complications to general anaesthesia, including malignant hyperthermia.
- •Family history of malignant hyperthermia.
- •Known incident of malignant hyperthermia or any unexplained complication to general anaesthesia among close relatives.
- •Allergy to any kind of medication or material to which the volunteer could be exposed during this study.
- •History of serious illness.
- •History of cancer, immune disease, autoimmune disease, chronic pain or neurological / psychiatric illness.
- •Major trauma or head trauma with any symptoms present at the time of inclusion.
- •Surgery less than six weeks prior to the study period.
Arms & Interventions
Sevoflurane-Propofol
Session one: Sevoflurane as maintenance anaesthetic during general anaesthesia. Session two: Propofol as maintenance anaesthetic during general anaesthesia.
Intervention: Sevoflurane-propofol
Propofol-Sevoflurane
Session one: Propofol as maintenance anaesthetic during general anaesthesia. Session two: Sevoflurane as maintenance anaesthetic during general anaesthesia.
Intervention: Sevoflurane-propofol
Outcomes
Primary Outcomes
Changes in T1w3D
Time Frame: 8 days
Volume and morphology of selected brain regions and anatomical structures as recorded by T1w3D anatomy MRI.
Changes in DTI
Time Frame: 8 days
White matter microstructure as measured using Diffusion Tensor Imaging (DTI)
Secondary Outcomes
- Changes in rsfMRI(8 days)
- Changes in fatigue(8 days)
- Cognitive performance(8 days)