About this trial
Perioperative neurocognitive disorder (PND) is one of the most common postoperative complications among elderly patients. However, the mechanism and targeted intervention of PND remains unclear. Our previous clinical studies demonstrated the association between olfactory impairment and PND. Moreover, our translational studies showed that anesthesia/surgery induced olfactory impairment and caused cognitive impairment in mice and olfactory enrichment could prevent the anesthesia/surgery-induced cognitive impairment. However, there was no clinical investigation to determine whether olfactory enrichment can mitigate PND in elderly patients. Therefore, we propose determining whether olfactory enrichment can prevent and/or treat PND in elderly patients.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥65 years old.
Having a scheduled surgery (≥2 hours, general anesthesia) (e.g., total hip replacement, toal knee replacement, open reduction and internal fixation of hip and lumbar spine).
Being able to complete neuropsychological tests, 3D-CAM and CAM-S.
Chinese Mandarin as their native language.
Disqualifiers
Having delirium, assessed by 3D-CAM, before surgery.
Having a brain tumour, stroke or mental disorders (eg, major depressive disorder or dementia).
Participating in other clinical studies at the time of screening.
Unwillingness to comply with the protocol or procedures.
Trial design
Parallel
Treatments tested in this trial
Olfactory Enrichment
Other interventionEach participant will be equipped with an electrical odor dispenser which allowed to distribute 8 odors (grapefruit, lavender, lemon, peppermint, menthol, tangerine, green tea, and bergamot). The choice of odors was guided by (1) pleasantness of the odors, (2) presence of slight trigeminal activation in some of the odors, e.g., peppermint, (3) evaporation characteristics, so that the odors would last for the duration of the experiment, (4) technical issues mostly in terms of compatibility with the odor cartridge, (5) availability, and (6) inspiration from the previous studies.
Sham
Other interventionThe containers provided to the sham group will be odorless. The odor containers and labels will appear identical to those used in the olfactory enrichment group.
Treatment groups
Trial outcomes
Primary outcomes
Incidence of postoperative delirium
The presence of postoperative delirium will be defined according to 3D-CAM, which includes four entries: acute onset and fluctuating course, inattention, disorganized thinking and altered level of consciousness. To diagnose delirium, both the first and second criteria have to be present plus the third and/or fourth criteria. Every participant will be assessed twice daily after anesthesia/surgery from postoperative day 1 to postoperative day 3, with the first assessment between 8:00 and 10:00. The second assessment will be between 15:00 and 17:00.
Secondary outcomes
Incidence of delayed neurocognitive recovery and postoperative neurocognitive disorder
Participants' cognitive function will be assessed at baseline, on postoperative day 21, and at postoperative month 6 using a battery of neuropsychological tests, including the Montreal Cognitive Assessment (MoCA), Hopkins Verbal Learning Test Retention (HVLTRet), Hopkins Verbal Learning Test Total Recall (HVLTTR), Brief Visuospatial Memory Test Total Recall (BVMTTR), Brief Visuospatial Memory Test Delayed Recall (BVMTDR), Benton Judgment of Line Orientation (JLO), Digit Span Test (DST), Verbal Fluency Test (VFT) and Trail Making Test (TMT). Cognitive Change Index will be calculated by subtracting baseline scores from postoperative scores in each of the neuropsychological tests. Delayed neurocognitive recovery or postoperative neurocognitive disorder will be defined as by a decrease by one or more standard deviations in at least two of the neuropsychological tests from the baseline to 21 days or 6 months after anesthesia/surgery.
Other outcomes
Severity of delirium
Severity of delirium will be assessed by the CAM-S. CAM-S includes 10 items: acute onset or symptom fluctuation, inattention, disorganized thinking, altered level of consciousness, disorientation, memory impairment, perceptual disturbances, psychomotor agitation, psychomotor retardation and sleep-wake cycle disturbance. Each item is scored as absent (0), mild (1) or marked (2), except acute onset or fluctuation, which is scored as absent (0) or present (1). The sum of CAM-S ranges from 0 (none) to 19 (most severe). The Delirium Symptom Interview (DSI) Daily will be used to determine CAM-S grades. The incidence of postoperative delirium will also be referred to the records by nurses on duty.
Severity of delayed neurocognitive recovery and postoperative neurocognitive disorder
Severity of delayed neurocognitive recovery and postoperative neurocognitive disorder will be assessed by battery of neuropsychological tests at baseline, on postoperative day 21, and at postoperative month 6. The scores of neuropsychological tests indicate cognitive functions which can reflect the severity of delayed neurocognitive recovery and postoperative neurocognitive disorder.
Activities of Daily Living
Activities of daily living will be assessed using the Chinese version of the ADL scale at baseline, and on postoperative day 21 days and 6 months after anesthesia/surgery, including a Physical Self-Maintenance Scale and an Instrumental Activities of daily living at baseline (before the surgery) and follow-ups. There are a total of 14 items in the Activities of daily living. For each item, scoring is determined by a 4-point coding system: 1 = 'can do it myself,' 2 = 'have some difficulty but can still do it by myself,' 3 = 'need help to do it,' and 4 = 'cannot do it at all.' A higher score therefore indicates greater impairment in activities of daily living. Specifically, a total activities of daily living score of 14 signifies no impairment, scores of 15-21 indicate mild impairment, and scores of ≥22 reflect severe impairment. Participants with Activities of daily living scores of more than 22 points will be considered to have substantive impairment in Activities of daily living.
Plasma Tau-PT217 Concentrations
Five milliliters of blood will be collected from participants immediately before and after anesthesia/surgery, 3 days, 21 days and 6 months postoperatively. Blood samples will be centrifuged at 500 g for 10 minutes, and the plasma supernatant will be collected. The plasma will be collected in EDTA tubes, immediately placed on ice, and then stored in a -80°C freezer until analysis. The samples will be thawed at the time of measurement. Tau-PT217 concentrations in plasma will be measured using Nanoneedle technology.
Sponsors and contacts
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Shanghai 10th People's Hospital
Lead sponsor
National Natural Science Foundation of China
Collaborator