Effect of Intraoperative Sedation on PND in Elderly Patients

The aim of this study was to identify the effects of different depths of sedation and choices of sedative drugs on perioperative neurocognitive disorders in the elderly patients receiving hip surgery under spinal anesthesia.

PND is a complication of the central nervous system after anesthesia and surgery which is considered to be a common complication in elderly patients. Age is an independent risk factor for the occurrence of PND. Prolonged hospitalization, incapacity and long duration of PND aggravate the economic burden of individuals, families and society. The pathogenesis of PND is still unclear. Recent studies suggest that the blood-brain barrier (BBB) is damaged by surgery or anesthesia, which causes the activation of inflammatory factors such as TNF α and NF - κ B, and then leads to the decline of hippocampus cognitive function. In recent years, it has been found that dexmedetomidine can reduce the brain injury during ischemia-reperfusion and reduce the occurrence of PND. BDNF is a neurotrophin, which plays an important role in the growth, differentiation, synaptic plasticity, survival and repair of neurons. Studies have shown that the decrease of BDNF concentration is related to PND, which can be used as an index to evaluate brain injury and predict PND. S100 β protein is a specific low molecular calcium binding protein of nervous system which can be increased early after brain injury, so it can be used to reflect the severity and prognosis of brain injury and predict PND.In this randomized controlled trial, investigators will compare the incidence of PND in hip surgery with four intraoperative sedation regimens. After spinal anesthesia, the following sedation regimen will be used: (1) Intravenous infusion of propofol to make patients receive lighter sedation(modified observer's assessment of alertness/sedation score\[MOAA/S\],0-2) (2) Intravenous infusion of propofol to make patients receive heavier sedation(MOAA/S,3-5) (3)After a bolus of dexmedetomidine, intravenous infusion of dexmedetomidine to make patients receive lighter sedation(MOAA/S,0-2) (4) After a bolus of dexmedetomidine, intravenous infusion of dexmedetomidine to make patients receive heavier sedation(MOAA/S,3-5). 3ml venous blood samples were collected before anesthesia (T0), 1 h after operation (T1), 1 day after operation (T2) and 7 days after operation (T3). Plasma samples were collected after centrifugation and the concentrations of BDNF and S100 β were determined by ELISA. After 7days of surgery, PND is screened by CAM with a trained research assistant everyday, and CAM positive patients are judged by a qualified psychiatrist to meet DSM-V criteria until the patient is discharged. For patients with PND, the delirium rating scale (DRS) was used to assess the degree of delirium.

Eligibility Criteria:
Inclusion Criteria:

1. Acquisition of informed consent,
2. Patients with hip fracture surgery under spinal anesthesia,
3. Grade I to III based on American Society of Anesthesiologists ASA classification,
4. Age ≥65.

Exclusion Criteria:

1. There was a history of cardiovascular and cerebrovascular adverse events in the past six months, including myocardial infarction, angina pectoris, severe arrhythmia, stroke or transient ischemic attack (TIA)
2. Heart failure (NYHA III / IV and / or LVEF \< 30%)
3. Bradycardia
4. Respiratory failure (need oxygen)
5. Glasgow Coma Scale ≤ 14 points
6. Severe hepatic and renal insufficiency (child Pugh grade B or C)
7. Preoperative cognitive impairment or sedative drugs (benzodiazepines, etc.).
8. Adverse reactions such as allergy to dexmedetomidine or / or propofol
9. Preoperative bilateral hip fracture or other trauma need simultaneous operation
10. Contraindications of spinal anesthesia