This study has been approved by the hospital Ethics Committee ((2019) No. 46) and registered in the Chinese Clinical Trial Registry (ChiCTR2000030569).
Case selection
Inclusion criteria: ① patients undergoing elective hip replacement, ② age ≥ 65 years, ③ American Society of Anesthesiologists (ASA) grade I∼III, ④ no obvious abnormalities in routine blood test findings, liver and kidney function, or coagulation function.
Exclusion criteria: ① preoperative psychiatric or neurological or psychiatric disease; ② difficult airway; ③ contraindications to neuraxial anesthesia; ④ severe intraoperative hemodynamic fluctuation that necessitated continuous treatment with vasoactive drugs.
Anesthesia
Patients were scheduled for a routine preoperative visit the day before surgery to collect general data such as their name, sex, and age and have them sign an informed consent form. Information was collected regarding each patient's past medical history of hypertension, heart disease, diabetes mellitus, cerebrovascular disease, mental or neurological disorders and previous treatment with medication. Additionally, electrocardiography (ECG), cardiac echocardiography, routine blood tests, liver function tests, renal function tests, and coagulation function tests were performed. Patients were assessed for airway condition to determine whether they had a difficult airway, and they were also assessed for previous history of trauma or lumbar surgery with or without contraindications to intravertebral anesthesia. ASA grading was performed on a patient-by-patient basis to screen for eligibility under the inclusion criteria.
The patients were randomly divided into a general anesthesia group (group G) and an intravertebral anesthesia group (group P). On the day of surgery, they signed an informed consent form explaining the study for their peace of mind and confirming that they had followed standard preoperative precautions regarding food and liquid intake.
Patients entered the operating room immediately for routine monitoring of noninvasive blood pressure, ECG signals, and pulse oxygen saturation. Open venous access was established, along with ultrasound-guided radial artery puncture catheterization with connection of a pressure transducer for invasive monitoring of arterial blood pressure. Ultrasound-guided internal jugular vein puncture catheterization was performed as needed, and patients in group G were connected to an anesthesia depth monitor.
In the general anesthesia group, induction of anesthesia was administered with midazolam 0.05 mg/kg, dezocine 5 mg, etomidate 0.3 mg/kg, rocuronium 0.9 mg/kg, and sufentanil 0.5∼1 µg/kg. To maintain a partial pressure of end-tidal carbon dioxide of 35 to 45 mmHg, a laryngeal mask was placed after the anesthetic drugs had fully taken effect, and an anesthetic machine was connected for mechanical ventilation, maintaining the tidal volume at 6ཞ10 ml/kg, the ventilation frequency at 10 to 15 breaths/min, and the partial pressure of end-tidal carbon dioxide at 35ཞ45 mmHg. Propofol 4ཞ12 mg/kg/h, remifentanil 0.25∼0.5 µg/kg/h, cisatracurium 0.06∼0.18 mg/kg/h, and inhalation of 1% sevoflurane were administered to maintain anesthesia; the pump rate of propofol was adjusted to maintain a patient state index (PSI) of 25∼50 according to electroencephalography (EEG).
Patients in group P were placed in a lateral decubitus position with the affected side up, and subarachnoid blocks were performed using a specific fluid configuration: 1% ropivacaine 2 ml + distilled water 1 ml, administered in the subarachnoid space in a volume of 2∼2.5 ml according to patient height, weight and physical status.
In the perioperative period, patients were maintained in a hemodynamically stable state, as measured by systolic and diastolic blood pressure, diastolic blood pressure, heart rate, and oxygen saturation; the use of vasoactive drugs (methoxyamine, norepinephrine, epinephrine) and atropine to achieve these goals was recorded from patients before anesthesia, 5 minutes after anesthesia, immediately at the end of surgery, and before transfer from the operating room.
Specimen collection and processing
Venous blood samples (5 ml) were drawn from all patients before the start of anesthesia; additionally, samples were drawn from group G when the patients fully regained consciousness after surgery, as well as from group P approximately 1 h after surgery. These samples were placed in tubes of ethylenediaminetetraacetic acid anticoagulant and refrigerated at 4 ℃.
After horizontal centrifugation at 800 G / min at 4°C for 10 min, 2 ml of the yellowish plasma supernatant was aspirated with a pipette gun and placed in a cryogenic storage tube, which was labeled with the specimen number and stored at -80°C.
All samples were taken in equal amounts and mixed together to create a quality control (QC) sample, which was used to assess the stability of the platform during MS monitoring, with QC samples being interspersed between other samples. To examine a sample, the same volume of the QC sample was removed during sample processing.
After the samples were pretreated, they underwent analysis using a Nexera UHPLC LC-30A Ultra Performance Liquid Chromatography system, developed by Waters Corporation in Hercules, California, USA.
Statistical analysis was conducted using SPSS 20.0 software, and the chi-squared test was utilized to compare count data, which were expressed as the mean ± standard deviation (‾ x ± s). Additionally, the paired-samples t test was employed to compare measurement data. A significance criterion of P < 0.05 was established as the threshold for statistical significance.