Anestesi och perioperativa neurokognitiva störningar hos äldre patienter som genomgår plattformsprövning för höftfrakturkirurgi (ANDES Platform Trial) (ANDES platform)

Participants receive standard anesthesia care plus preoperative regional nerve block, as described in sub-trial protocol 1. Participants in this arm who are planned to undergo general anesthesia may also enter the second nested randomization and be assigned in a 1:1 ratio to total intravenous anesthesia or volatile anesthesia maintenance.

Participants receive a preoperative regional nerve block as soon as possible after randomization. Ultrasound guidance is recommended, and fascia iliaca block is the recommended block technique.

Standard anesthesia care consists of routine general or regional anesthesia according to usual practice at each study center. Participants randomized to the shared control group do not receive protocol-specified trial interventions unless otherwise required by the Trial Steering Committee. Changes to standard anesthesia care are made in accordance with the prespecified adaptive decision framework. The independent Data Monitoring Committee reviews accumulating data and makes recommendations to the Trial Steering Committee, which makes the final platform decisions.

For participants randomized to the nerve block group, 1.33% bupivacaine liposome is recommended as a long-acting local anesthetic, with a maximum dose not exceeding 133 mg, to maintain the continuity of the nerve block effect.

For participants randomized to the nerve block group, regular local anesthetic, such as bupivacaine or ropivacaine, may be used with continuous electronic analgesic pump infusion or multiple single injections to maintain the continuity of the nerve block effect.

Among participants who are eligible under the master protocol and for whom general anesthesia is planned, anesthetic maintenance may be assigned by the second nested randomization to total intravenous anesthesia maintenance in a 1:1 ratio. Total intravenous anesthesia maintenance is recommended to be mainly propofol-based, and analgesics such as remifentanil or fentanyl are recommended.

Among participants who are eligible under the master protocol and for whom general anesthesia is planned, anesthetic maintenance may be assigned by the second nested randomization to volatile anesthesia maintenance in a 1:1 ratio. Following intravenous induction, anesthesia maintenance mainly with sevoflurane or isoflurane is recommended.

Participants receive standard anesthesia care plus perioperative intravenous lidocaine infusion, as described in sub-trial protocol 2. Participants in this arm who are planned to undergo general anesthesia may also enter the second nested randomization and be assigned in a 1:1 ratio to total intravenous anesthesia or volatile anesthesia maintenance.

Standard anesthesia care consists of routine general or regional anesthesia according to usual practice at each study center. Participants randomized to the shared control group do not receive protocol-specified trial interventions unless otherwise required by the Trial Steering Committee. Changes to standard anesthesia care are made in accordance with the prespecified adaptive decision framework. The independent Data Monitoring Committee reviews accumulating data and makes recommendations to the Trial Steering Committee, which makes the final platform decisions.

Among participants who are eligible under the master protocol and for whom general anesthesia is planned, anesthetic maintenance may be assigned by the second nested randomization to total intravenous anesthesia maintenance in a 1:1 ratio. Total intravenous anesthesia maintenance is recommended to be mainly propofol-based, and analgesics such as remifentanil or fentanyl are recommended.

Among participants who are eligible under the master protocol and for whom general anesthesia is planned, anesthetic maintenance may be assigned by the second nested randomization to volatile anesthesia maintenance in a 1:1 ratio. Following intravenous induction, anesthesia maintenance mainly with sevoflurane or isoflurane is recommended.

Participants randomized to the lidocaine group receive ECG monitoring, oxygen saturation monitoring, blood pressure monitoring, and an open intravenous route on the morning of surgery. It is recommended to start the infusion of lidocaine as soon as possible in the ward. A portable electronic infusion pump is recommended for drug delivery. The loading dose is 1 mg/kg, and the maintenance dose range is 1 to 2 mg/kg/h. The specific dose is determined by the anesthesiologist according to the patient's condition. The infusion ends when the patient leaves the post-anesthesia care unit after surgery, and the infusion time and total amount are recorded. Intravenous infusion of lidocaine should be administered under ECG monitoring.

Participants receive standard anesthesia care. Participants for whom general anesthesia is planned may also enter the second nested randomization and be assigned in a fixed 1:1 ratio to total intravenous anesthesia maintenance or volatile anesthesia maintenance.

Standard anesthesia care consists of routine general or regional anesthesia according to usual practice at each study center. Participants randomized to the shared control group do not receive protocol-specified trial interventions unless otherwise required by the Trial Steering Committee. Changes to standard anesthesia care are made in accordance with the prespecified adaptive decision framework. The independent Data Monitoring Committee reviews accumulating data and makes recommendations to the Trial Steering Committee, which makes the final platform decisions.

Among participants who are eligible under the master protocol and for whom general anesthesia is planned, anesthetic maintenance may be assigned by the second nested randomization to total intravenous anesthesia maintenance in a 1:1 ratio. Total intravenous anesthesia maintenance is recommended to be mainly propofol-based, and analgesics such as remifentanil or fentanyl are recommended.

Among participants who are eligible under the master protocol and for whom general anesthesia is planned, anesthetic maintenance may be assigned by the second nested randomization to volatile anesthesia maintenance in a 1:1 ratio. Following intravenous induction, anesthesia maintenance mainly with sevoflurane or isoflurane is recommended.

Neurocognitive Disorders includes:

1. Postoperative delirium (POD) was mesaured by 3D-CAM;
2. Neurocognitive decline was mesaured within 7 postoperative days by: Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), and neuropsychological tests containing 5 cognitive domains (1. digit span test (DST); 2. trail making test (TMT); 3. Boston naming test (BNT); 4. auditory verbal learning test-Huashan version (AVLT-H)；5. clock drawing test (CDT).）, and active report of patients or family members).

Neurocognitive function is assessed at screening, postoperative day 3, and postoperative day 7. If discharge occurs on postoperative day 5 or 6, the final assessment is performed on the day of discharge; if discharge occurs on postoperative day 4, no repeat cognitive assessment is performed. A participant with postoperative delirium and/or postoperative neurocognitive decline is classified as positive for the primary outcome.

Using CAM-S, and in units of days from the onset of delirium symptoms to the disappearance of symptoms or when the patient is discharged.

Neurocognitive decline was mesaured by: Mini-Mental State Examination (MMSE) or Montreal Cognitive Assessment (MoCA), or neuropsychological tests containing 5 cognitive domains (1. digit span test (DST); 2. trail making test (TMT); 3. Boston naming test (BNT); 4. auditory verbal learning test-Huashan version (AVLT-H)；5. clock drawing test (CDT).）, or active report of patients or family members.

This was mesaured by: Mini-Mental State Examination (MMSE) or Montreal Cognitive Assessment (MoCA), or neuropsychological tests containing 5 cognitive domains(1. digit span test (DST); 2. trail making test (TMT); 3. Boston naming test (BNT); 4. auditory verbal learning test-Huashan version (AVLT-H)；5. clock drawing test (CDT).）, or active report of patients or family members.

Using Visual Analogue Scale (VAS)

Important intraoperative adverse events are defined as adverse events requiring treatment.

including pulmonary infection, myocardial infarction, renal failure, gastrointestinal obstruction, etc.

Quality of life will be assessed using the EuroQol Five Dimensions Questionnaire (EQ-5D). Prefracture quality of life will be assessed retrospectively for the week before fracture.

Postoperative neurocognitive disorder will be determined as a binary outcome according to the prespecified neurocognitive assessment framework. Cognitive assessments, including the Mini-Mental State Examination, Montreal Cognitive Assessment, multidomain neuropsychological tests, and patient- or caregiver-reported cognitive change, will be integrated according to the prespecified criteria to determine whether postoperative neurocognitive disorder is present. The reported outcome is the proportion of participants with postoperative neurocognitive disorder.

Using Hachinski Ischemic Scale (HIS) combined with clinical symptoms and auxiliary examination to mesaure the type of postoperative NCD. HIS ≥7 was considered as vascular cognitive impairment.

Health economic outcomes include direct medical costs, direct nonmedical costs, and indirect costs. Direct medical costs include anesthesia and related costs, surgical treatment costs, medication and biological product costs, diagnosis-related costs, supportive treatment costs, rehabilitation costs, blood and blood product costs, and consumable material costs. Direct nonmedical costs include paid caregiver costs, transportation costs, and accommodation costs related to medical care. Indirect costs mainly include productivity losses of family members or unpaid caregivers due to accompanying or caring for the participant.

We will collect the following known potential risks of general and local anesthesia from the start of the intervention to the subject's discharge and assess the overall incidence:

1. cardiopulmonary resuscitation;
2. Malignant hyperthermia or anaphylaxis;
3. Aspiration pneumonia ; 4. Epidural hematoma requiring surgical intervention within 24 hours after regional anesthesia; 5. Lower-limb paralysis lasting more than 24 hours after regional anesthesia or nerve block; 6. Unplanned postoperative mechanical ventilation lasting more than 6 hours in patients who did not require mechanical ventilation before surgery; 7. Other adverse events during postoperative hospitalization.