Impact of Desflurane Versus Isoflurane on Early Cognitive Function of the Elderly Undergoing Lumbar Surgery: A Randomized Clinical Trial

Trial design This single-center, randomized, controlled trial will enroll patients undergoing elective lumbar decompression and fusion at Zhongshan Hospital Fudan University, Shanghai, China. Written informed consent is obtained from all the participants. By Feb 21, 2024, the trial was approved for Zhongshan Hospital, Fudan University (China) with the approval number B2024-063R.

Anesthesia After the patients entered the operating room, the vital signs are monitored, the patients are given oxygen inhalation (> 8L/min). General anesthesia is induced with sufentanil (0.2ug/kg), propofol [target controlled infusion (TCI) at plasma concentration of 3ug/ml) , remifentanil(TCI at plasma concentration of 3 ng/ml) and rocuronium (0.6mg/kg). The narcotic and vasoactive drugs are used during the operation according to anesthesia depth, the blood pressure, and respiratory parameters. A patient-controlled intravenous analgesia (PCIA) pump (sufentanil 250ug, and ramosetron 0.6mg) is connected after the surgery.

Detection and preparation of LINC01844 Total RNA is extracted from peripheral blood samples using TRIzol LS (Invitrogen, USA) according to the instructions from the manufacturer. Briefly, after homogenizing the blood sample (250 μL) with TRIzol LS regent (750 μL), chloroform (200 μL) is added for further analysis. The sample is centrifuged at 12,000 × g, 4˚C for 15 min, then the aqueous phase containing the RNA is transferred to a new tube and isopropanol (0.5 mL) is added for RNA precipitation. The RNA pellet is washed by 75% ethanol (1 mL), and finally resuspended in RNase free water (10-20 μL), the RNA quality is determined with NanoDrop2000. An optical density ratio of 260/280 >1.80 is an indication that the sample could be used in subsequent experiments. Next, we use M-MLV reverse transcriptase (Promega, USA) for the synthesis of cDNA. A real-time quantitative polymerase chain reaction (qRT-PCR) was utilized for the final analysis according to the instructions from the SYBR Green PCR Master Mix Kit (Qiagen). The PCR parameters: 95˚C for 10 min; 45 cycles at 95˚C for 15 s, 60˚C for 30s, and 72˚C 30s. GAPDH is chosen as a reference gene, fold change (2 -44Ct ) is utilized to analyze LINC01844 relative levels.

Neuropsychological test evaluation and POCD assessment One day before surgery, patients will be assessed for depression using the patient health Questionnaire-9 (PHQ-9), while patients with previous severe cognitive impairment are excluded using the mini mental state examination (MMSE) (MMSE score < 24). A battery of neuropsychological tests will be performed 1 day before operation and 1st, 3rd and 5th day after operation to evaluate the cognitive function of patients, including Hopkins auditory learning test-revised (HALT-R), brief visuospatial memory test-revised (BVMT-R), trail making test (TMT), digit span test (DST), digital symbol substitution test (DSST) and verb and graph recall test. All these tests are performed in a quiet environment by a trained doctor who is blinded to the surgical procedure and blood sample. At the same time, 20 healthy volunteers without surgery will be recruited as the control group, with age, sex and education years matched. The neuropsychological test will be performed in control group to determine the normal reference value of cognitive function, with the same interval. Baseline scores and learning outcomes were subtracted from each neuropsychological test score according to the international guidelines for the study of postoperative cognitive impairment, and divided by the standard deviation of baseline scores in the control group. The result was designated a Z score. When at least two Z scales are greater than 1.961, POCD was considered.

Study visits and data collection Patients will be visited preoperatively and postoperative day (POD) 1 and 3 and 5. The patients will be screened according to the inclusion criteria. All patients meeting the inclusion criteria will be registered in a screening log file. The investigators will explain the course and purpose of the study and provide written information on the study. Patients willing to participate in the study will be required to provide written informed consent.