Effects of total intravenous anesthesia with etomidate and propofol on postoperative cognitive dysfunction.

Increased incidence of postoperative cognitive dysfunction (POCD) is observed in elderly patients underwent intravenous anesthesia (TIVA) with endotracheal intubation. Modulation of anesthetics compatibility may reduce the severity of POCD. Elderly patients scheduled for TIVA with endotracheal intubation were randomly divided into the control group (1.00?2.00 mg/kg propofol) and the etomidate and propofol combination group (1.00?2.00 mg/kg propofol and 0.30 mg/kg etomidate). Serum cortisol, S100?, and neuron-specific enolase (NSE), interleukin (IL)-6, and IL-10 were monitored during or after the operation. Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were utilized to assess the severity of POCD. 63 elderly patients in the etomidate and propofol combination group and 60 patients in the control group were enrolled, and there was no significant difference in gender, American Society of Anesthesiologists (ASA) physical status, surgical specialty, intraoperative blood loss, and operation time between the two groups. Significantly increased serum cortisol, S100?, NSE, IL-6, and reduced MMSE and MoCA scores were detected in the control group at different time points after the operation (0-72 h post operation) when compared to those before the operation. Similar trends for these observed factors were found in the etomidate and propofol combination group. In addition, the etomidate and propofol combination group showed better effects in reducing the serum levels of cortisol, S100?, NSE, IL-6, and increasing the MMSE and MoCA scores when compared to the control group. The present study demonstrates that the combination of propofol with etomidate could alleviate POCD in elderly patients underwent TIVA with endotracheal intubation anesthesia.

Comparison of the recovery profile of remimazolam with flumazenil and propofol anesthesia for open thyroidectomy.

BACKGROUND: Previous studies have consistently reported a slower recovery of consciousness following remimazolam-based total intravenous anesthesia without flumazenil than with propofol. This study aimed to compare the reversal effect of flumazenil on the recovery of consciousness after remimazolam-based total intravenous anesthesia with the propofol recovery profile. METHODS: This prospective, single-blinded, randomized trial included 57 patients undergoing elective open thyroidectomy at a tertiary university hospital. Patients were randomly allocated to receive either remimazolam- or propofol-based total intravenous anesthesia (remimazolam group: 28 patients, propofol group: 29 patients). The primary outcome was the time from the end of general anesthesia to first eye opening (min). The secondary outcomes were the time from the end of the general anesthesia to extubation (min), initial modified Aldrete score measured at the post-anesthesia care unit, length of stay at the post-anesthesia care unit (min), occurrence of postoperative nausea and vomiting during the first 24 h postoperatively, and Korean version of Quality of Recovery-15 score at 24 h postoperatively. RESULTS: The remimazolam group showed significantly faster first eye opening time (2.3 [interquartile range, IQR: 1.8-3.3] min vs. 5.0 [IQR: 3.5-7.8] min, median difference:-2.7 [95% confidence interval, CI: -3.7 to -1.5] min, P < 0.001) and extubation time (3.2 [IQR: 2.4-4.2] min vs. 5.7 [IQR: 4.7-8.3] min, median difference: -2.7 [97.5% CI: -5.0 to -1.6] min, P < 0.001). There were no significant differences in other postoperative outcomes. CONCLUSIONS: The planned incorporation of flumazenil with remimazolam-based total intravenous anesthesia provided rapid and reliable recovery of consciousness.

Effects of spinal anaesthesia and intravenous general anaesthesia on the absorption of normal salinein patients undergoing hysteroscopic endometrial resection: an observational study.

INTRODUCTION: The absorption of uterine distention fluid during hysteroscopic endometrial resection can cause volumeoverload, which can lead to coagulation dysfunction, acute left heart failure and pulmonary oedema in patients. The effects of spinal anaesthesia and intravenous general anaesthesia on the absorption of normal saline as uterine distention fluid during hysteroscopic surgery remain unclear. The aim of this clinical trial was toobserve the effects of spinal anaesthesia and intravenous general anaesthesia on the absorption of normal saline in patients undergoing hysteroscopic endometrial resection. METHODS: A total of 126 patients undergoing elective hysteroscopic endometrial resection were divided into a spinal anaesthesia group (s group) and a propofol-fentanyl intravenous anaesthesia group (PF group), with 63 cases in each group, and both groups were divided into a short-term group (S1 group and PF1 group) and a long-term group (S2 group and PF2 group) according to the operation time. The primary outcome was the absorption of normal saline, and the secondary outcomes included the perioperative SBP, DBP, HR and SpO2 and postoperative haematocrit values, and the incidence of postoperative complications. RESULTS: The volume of saline absorbed was significantly increased in the S2 and PF2 groups compared with the S1 and PF1 groups (P < 0.001). There was a significant positive correlation between the amount of normal saline absorbed and the operation time (r = 0.895, P < 0.001). The postoperative haematocrit value was slightly lower than that before the operation in all four groups (P < 0.05), and there were no differences in the incidences of urinary retention, sinus bradycardia or hypotension between groups (P > 0.05). CONCLUSIONS: There was no difference in the effects of spinal anaesthesia and intravenous general anaesthesia on the absorption of normal saline during hysteroscopic endometrial resection, and the absorption of normal saline increased accordingly with the extension of operation time.

Feasibility pilot trial for the Trajectories of Recovery after Intravenous propofol versus inhaled VolatilE anesthesia (THRIVE) pragmatic randomised controlled trial.

INTRODUCTION: Millions of patients receive general anaesthesia for surgery annually. Crucial gaps in evidence exist regarding which technique, propofol total intravenous anaesthesia (TIVA) or inhaled volatile anaesthesia (INVA), yields superior patient experience, safety and outcomes. The aim of this pilot study is to assess the feasibility of conducting a large comparative effectiveness trial assessing patient experiences and outcomes after receiving propofol TIVA or INVA. METHODS AND ANALYSIS: This protocol was cocreated by a diverse team, including patient partners with personal experience of TIVA or INVA. The design is a 300-patient, two-centre, randomised, feasibility pilot trial. Patients 18 years of age or older, undergoing elective non-cardiac surgery requiring general anaesthesia with a tracheal tube or laryngeal mask airway will be eligible. Patients will be randomised 1:1 to propofol TIVA or INVA, stratified by centre and procedural complexity. The feasibility endpoints include: (1) proportion of patients approached who agree to participate; (2) proportion of patients who receive their assigned randomised treatment; (3) completeness of outcomes data collection and (4) feasibility of data management procedures. Proportions and 95% CIs will be calculated to assess whether prespecified thresholds are met for the feasibility parameters. If the lower bounds of the 95% CI are above the thresholds of 10% for the proportion of patients agreeing to participate among those approached and 80% for compliance with treatment allocation for each randomised treatment group, this will suggest that our planned pragmatic 12 500-patient comparative effectiveness trial can likely be conducted successfully. Other feasibility outcomes and adverse events will be described. ETHICS AND DISSEMINATION: This study is approved by the ethics board at Washington University (IRB# 202205053), serving as the single Institutional Review Board for both participating sites. Recruitment began in September 2022. Dissemination plans include presentations at scientific conferences, scientific publications, internet-based educational materials and mass media. TRIAL REGISTRATION NUMBER: NCT05346588.

The analgesic effect of total intravenous anaesthesia with propofol versus inhalational anaesthesia for acute postoperative pain after hepatectomy: a randomized controlled trial.

BACKGROUND: Postoperative pain control can be challenging in patients undergoing hepatectomy. A previous retrospective study on hepatobiliary/ pancreatic surgeries showed better postoperative pain control in patients who received propofol TIVA. The aim of this study was to determine the analgesic effect of propofol TIVA for hepatectomy. This clinical study has been registered at ClinicalTrials.gov (NCT03597997). METHODS: A prospective randomized controlled trial was performed to compare the analgesic effect of propofol TIVA versus inhalational anaesthesia. Patients aged between 18 and 80 years old with an American Society of Anesthesiologist (ASA) physical status of I-III scheduled for elective hepatectomy were recruited. Ninety patients were randomly allocated to receive either propofol TIVA (TIVA group) or inhalational anaesthesia with sevoflurane (SEVO group). Perioperative anaesthetic/analgesic management was the same for both groups. Numerical rating scale (NRS) pain scores, postoperative morphine consumption, quality of recovery, patient satisfaction and adverse effects were evaluated during the acute postoperative period and at 3 and 6 months after surgery. RESULTS: No significant differences were found for acute postoperative pain scores (both at rest and during coughing) and postoperative morphine consumption between TIVA and SEVO groups. Patients given TIVA had lower pain scores with coughing at 3 months after surgery (p = 0.014, and FDR < 0.1). TIVA group was associated with better quality of recovery on postoperative day (POD) 3 (p = 0.038, and FDR < 0.1), less nausea (p = 0.011, and FDR < 0.1 on POD 2; p = 0.013, and FDR < 0.1 on POD 3) and constipation (p = 0.013, and FDR < 0.1 on POD 3). CONCLUSION: Propofol TIVA did not improve acute postoperative pain control compared to inhalational anaesthesia in patients who underwent hepatectomy. Our results do not support the use of propofol TIVA for reducing acute postoperative pain after hepatectomy.

Relationship between decrement time and recovery time in pediatric total intravenous anesthesia with propofol and remifentanil.

BACKGROUND: Propofol target-controlled infusion is now used in many countries for the administration of total intravenous anesthesia (TIVA) and uses population pharmacokinetic data incorporated into the target-controlled infusion pump to administer a dose which will achieve a target concentration selected by the practitioner. Modern target-controlled infusion pumps can include an estimate of how long it will take for the plasma propofol concentration to fall to a value programmed into the pump, once the propofol infusion is stopped. This is known as decrement time. Many users consider decrement time to be equivalent to recovery time for the patient, despite the several assumptions that makes. AIM: To determine if the decrement time estimated by the target-controlled infusion pumps at the end of anesthesia could be reliably used to predict recovery time for individual patients. METHODS: Target-controlled infusion pumps at Birmingham Children's Hospital are programmed with a propofol decrement concentration of 1.5 µg.mL-1 . Patients for a variety of surgical procedures were anesthetised with propofol-remifentanil TIVA. Eye opening was used as a surrogate of recovery time. Data were analyzed using median absolute deviation, Mann-Whitney U test, and linear regression to see if there was any correlation with decrement time and recovery time, total dose of propofol administered, duration of anesthesia and patient age. RESULTS: A total of 55 patients were audited. Median age was 7.2 years (range 0.9-15.9), and median weight was 26 kg (range 8.5-77). Median decrement time was 11.8 min (IQR 8.3-21), while median recovery time was 15 min (IQR 9-20). Recovery time was the same as decrement time in 2% of patients, less than in 40% of patients and more in 58% of patients. Two thirds of patients opened eyes at an estimated plasma propofol concentration between 1.2 and 1.8 µg.mL-1 . The median absolute deviation for the difference between decrement time and recovery time was 5.7 min, from a median of 1 min. Analysis demonstrated there was no statistical correlation between decrement time to 1.5 µg.mL-1 and recovery time, age, total propofol dose administered, or duration of anesthesia, for individual patients. CONCLUSION: There was variation between decrement time to 1.5 µg.mL-1 and recovery time of over 5 min in nearly half of patients. Decrement time to 1.5 µg.mL-1 must be used with caution when trying to predict recovery time for individual patients following TIVA.

Ketamine-propofol for total intravenous anaesthesia in rabbits: a comparison of premedication with acepromazine-medetomidine, acepromazine-midazolam or acepromazine-morphine.

OBJECTIVE: To describe ketamine-propofol total intravenous anaesthesia (TIVA) following premedication with acepromazine and either medetomidine, midazolam or morphine in rabbits. STUDY DESIGN: Randomized, crossover experimental study. ANIMALS: A total of six healthy female New Zealand White rabbits (2.2 ± 0.3 kg). METHODS: Rabbits were anaesthetized on four occasions, each separated by 7 days: an intramuscular injection of saline alone (treatment Saline) or acepromazine (0.5 mg kg-1) in combination with medetomidine (0.1 mg kg-1), midazolam (1 mg kg-1) or morphine (1 mg kg-1), treatments AME, AMI or AMO, respectively, in random order. Anaesthesia was induced and maintained with a mixture containing ketamine (5 mg mL-1) and propofol (5 mg mL-1) (ketofol). Each trachea was intubated and the rabbit administered oxygen during spontaneous ventilation. Ketofol infusion rate was initially 0.4 mg kg-1 minute-1 (0.2 mg kg-1 minute-1 of each drug) and was adjusted to maintain adequate anaesthetic depth based on clinical assessment. Ketofol dose and physiological variables were recorded every 5 minutes. Quality of sedation, intubation and recovery times were recorded. RESULTS: Ketofol induction doses decreased significantly in treatments AME (7.9 ± 2.3) and AMI (8.9 ± 4.0) compared with treatment Saline (16.8 ± 3.2 mg kg-1) (p < 0.05). The total ketofol dose to maintain anaesthesia was significantly lower in treatments AME, AMI and AMO (0.6 ± 0.1, 0.6 ± 0.2 and 0.6 ± 0.1 mg kg-1 minute-1, respectively) than in treatment Saline (1.2 ± 0.2 mg kg-1 minute-1) (p < 0.05). Cardiovascular variables remained at clinically acceptable values, but all treatments caused some degree of hypoventilation. CONCLUSIONS AND CLINICAL RELEVANCE: Premedication with AME, AMI and AMO, at the doses studied, significantly decreased the maintenance dose of ketofol infusion in rabbits. Ketofol was determined to be a clinically acceptable combination for TIVA in premedicated rabbits.

Deep reinforcement learning-based propofol infusion control for anesthesia: A feasibility study with a 3000-subject dataset.

In this work, we present a deep reinforcement learning-based approach as a baseline system for autonomous propofol infusion control. Specifically, design an environment for simulating the possible conditions of a target patient based on input demographic data and design our reinforcement learning model-based system so that it effectively makes predictions on the proper level of propofol infusion to maintain stable anesthesia even under dynamic conditions that can affect the decision-making process, such as the manual control of remifentanil by anesthesiologists and the varying patient conditions under anesthesia. Through an extensive set of evaluations using patient data from 3000 subjects, we show that the proposed method results in stabilization in the anesthesia state, by managing the bispectral index (BIS) and effect-site concentration for a patient showing varying conditions.

Inhalational Anesthesia is Noninferior to Total Intravenous Anesthesia in Terms of Surgical Field Visibility in Endoscopic Sinus Surgery: A Randomized, Double-Blind Study.

Purpose: Regarding the quality of surgical field visibility, previous studies and meta-analyses comparing total intravenous anesthesia (TIVA) and inhalational anesthesia (IA) in endoscopic sinus surgery (ESS) have presented inconsistent findings. Considering that IA has some advantages over TIVA, we aimed to test the hypothesis that IA with sevoflurane-remifentanil is noninferior to TIVA with propofol-remifentanil in terms of surgical field visibility quality during ESS. Patients and Methods: In this randomized, double-blind, noninferiority clinical trial, 110 adult patients were recruited and randomly assigned to the IA (n = 55) or TIVA (n = 55) group. The primary outcome was the quality of surgical field visibility, as measured by the intraoperative mean Boezaart score (BS). Additionally, post hoc analysis was performed for patients with Lund-Mackay scores of ≤ 12 or > 12. Other secondary outcomes included total blood loss, bleeding rate, total fluid, mean arterial pressure, heart rate, dose of remifentanil for anesthesia maintenance, end-tidal CO2, length of stay in the post anesthesia care unit, postoperative hypoxemia, sore throat, and nausea. Results: The intraoperative mean BS of the IA group was noninferior to that of the TIVA group [medians with interquartile ranges (IQRs), 2.0 (1.7-2.2) vs 2.0 (1.8-2.1), P = 0.923]. Moreover, post hoc analysis confirmed no difference between IA and TIVA for patients with Lund-Mackay scores ≤ 12 (P = 0.403) or > 12 (P = 0.226). No differences in total blood loss, bleeding rate, or other intraoperative indicators or complications were observed between groups. Conclusion: Regarding surgical field visibility during ESS, IA with sevoflurane-remifentanil is noninferior to TIVA with propofol-remifentanil anesthesia maintenance.

Postoperative acute kidney injury after volatile or intravenous anesthesia: a meta-analysis.

Postoperative acute kidney injury (AKI) is a common complication after surgery. The pathophysiology of postoperative AKI is complex. One potentially important factor is anesthetic modality. We, therefore, conducted a meta-analysis of the available literature regarding anesthetic modality and incidence of postoperative AKI. Records were retrieved until January 17, 2023, with the search terms ("propofol" OR "intravenous") AND ("sevoflurane" OR "desflurane" OR "isoflurane" OR "volatile" OR "inhalational") AND ("acute kidney injury" OR "AKI"). A meta-analysis for common effects and random effects was performed after exclusion assessment. Eight records were included in the meta-analysis with a total of 15,140 patients (n = 7,542 propofol and n = 7,598 volatile). The common and random effects model revealed that propofol was associated with a lower incidence of postoperative AKI compared with volatile anesthesia [odds ratio: 0.63 (95% confidence interval: 0.56-0.72) and 0.49 (95% confidence interval: 0.33-0.73), respectively]. In conclusion, the meta-analysis revealed that propofol anesthesia is associated with a lower incidence of postoperative AKI compared with volatile anesthesia. This may motivate choosing propofol-based anesthesia in patients with increased risk of postoperative AKI due to preexisting renal impairment or surgery with a high risk of renal ischemia.NEW & NOTEWORTHY This study analyzed the available literature on anesthetic modality and incidence of postoperative AKI. The meta-analysis revealed that propofol is associated with lower incidence of AKI compared with volatile anesthesia. It might therefore be considerable to use propofol anesthesia in surgeries with increased susceptibility for developing renal injuries such as cardiopulmonary bypass and major abdominal surgery.

Perioperative management and surgical field optimization in functional endoscopic sinus surgery.

A sound anesthesiologist-surgeon collaboration is crucial for the success of functional endoscopic sinus surgery (FESS). The aim of this narrative review was to describe if and how anesthetic choice can decrease bleeding and improve visibility in the surgical field (VSF) and thus contribute to successful FESS. A literature search was conducted on evidence-based practices published from 2011 to 2021 describing perioperative care, intravenous/inhalation anesthetics, and operative approaches for FESS and their effects on blood loss and VSF. With regards to preoperative care and operative approaches, best clinical practices include topical vasoconstrictors at the time of surgery, medical management (steroids) preoperatively, and patient positioning, as well as anesthetic techniques including controlled hypotension, ventilation settings, and anesthetics choices. Four out of five meta-analyses and six out of 11 randomized controlled trials favored total intravenous anesthesia (TIVA) over inhalation anesthesia (IA) for improved VSF. The effects on VSF were more dependent on adjunct medications used (remifentanil, alpha-2 agonists, etc.), rather than the choice of anesthetic technique (i.e., TIVA vs. IA). The current literature is inconclusive regarding the impact of anesthetic choice on VSF during FESS. We recommend that anesthesiologists use the anesthetic technique with which they are most comfortable to facilitate efficiency, recovery, cost, and collaboration with the perioperative team. Future studies should be designed to consider disease severity, the method for measuring blood loss, and a standardized VSF score. Studies should also investigate the long-term effects of TIVA- and IA- induced hypotension.

Comparison of Postoperative Recovery between Balanced and Total Intravenous Anesthesia in Patients Undergoing Off-Pump Coronary Artery Bypass (OPCAB) Surgery: A Prospective, Single-Blind Randomized Study.

Recovery after anesthesia has a significant impact on a patient's return to daily life. This study was performed to compare the postoperative quality of recovery according to the method of anesthesia administered among patients undergoing OPCAB using the Korean version of the Quality of Recovery-40 (QoR-40K) questionnaire. This single-blind, prospective study (trial number: KCT0004726) was performed using a population of 102 patients undergoing OPCAB under general anesthesia. The patients were randomly assigned to one of two groups using a computer-generated list: a total intravenous anesthesia group (Group T) and a balanced anesthesia group (Group B). The QoR-40K score was measured preoperatively and at 24 and 48 h after extubation. There was no significant difference in the QoR-40K scores between the groups at 24 and 48 h after extubation. In addition, there were no significant differences between groups with respect to any of the five dimensions of QoR-40K at 24 and 48 h after extubation. Finally, there were no differences in the postoperative opioid consumption, time to extubation, or length of hospital stay. In this study, there was no difference in the QoR-40K score at 24 h after extubation between Groups T and B. Therefore, both methods of anesthesia are suitable for use when performing OPCAB.

Comparison of alfaxalone and propofol on haematological and serum biochemical variables in cats undergoing radiotherapy with sevoflurane maintenance.

OBJECTIVE: To evaluate effects of repeated alfaxalone or propofol administration on haematological and serum biochemical variables in cats undergoing radiotherapy. STUDY DESIGN: Prospective, block-randomized, clinical trial. ANIMALS: A group of 39 client-owned cats. METHODS: After butorphanol (0.2 mg kg-1) and midazolam (0.1 mg kg-1) sedation, cats were randomly assigned to receive either alfaxalone or propofol for induction of anaesthesia and sevoflurane maintenance. Cats were anaesthetized daily with the same induction agent for 10-12 days. Complete blood counts, reticulocytes, Heinz body score and serum biochemistry were performed before the first treatment (T1), at T6, T10 and 3 weeks after the final treatment (T21). Cumulative induction agent dose for each cat at each time point was evaluated for an effect on Heinz body score. Data are shown as mean ± standard deviation; p < 0.05. RESULTS: At baseline there were no significant differences in signalment or blood variables between groups. A significant decrease in haematocrit of 2.3% ± 0.77 (p = 0.02) between T1-T6 and T1-T10 [mean 4.1% (± 0.78, p < 0.0001)] was detected, with a significant increase in haematocrit of 2.1% ± 0.80 (p = 0.046) between T6-T21 and 4.0% ± 0.8 (p < 0.001) between T10-T21. Heinz body score significantly increased by 1.86 ± 0.616 (p = 0.013) between T1-T10. In the propofol group, reticulocytes increased significantly between T1-T6 [mean 23,090 µL-1 ± 7670 (p = 0.02)] and T1-T10 [mean 27,440 µL-1 ± 7990 (p = 0.007)]. Mean cumulative dose at T10 was 19.65 mg kg-1 ± 5.3 and 43.4 mg kg-1 ± 14.4 for alfaxalone and propofol, respectively, with no significant effect on Heinz body formation at any time point. CONCLUSIONS AND CLINICAL RELEVANCE: Haematocrit decreased in both groups with recovery after 3 weeks. Repeated alfaxalone and propofol administration was not associated with marked haematological or serum biochemistry changes.

Effects of dexmedetomidine on evoked potentials in spinal surgery under combined intravenous inhalation anesthesia: a randomized controlled trial.

OBJECTIVE: We aimed to investigate the effects of different doses of dexmedetomidine (Dex) on evoked potentials in adult patients undergoing spinal surgery under intravenous anesthesia with low-concentration desflurane. METHODS: Ninety patients were divided into three groups at random. To maintain anesthesia in the control group (group C), desflurane 0.3 MAC (minimal alveolar concentration), propofol, and remifentanil were administered. Dex (0.5 µg·kg-1) was injected for 10 min as a loading dose in the low-dose Dex group (group DL), then adjusted to 0.2 µg·kg-1·h-1 until the operation was completed. Dex (1 µg·kg-1) was injected for 10 min as a loading dose in the high-dose Dex group (group DH), then adjusted to 0.7 µg·kg-1·h-1 until the operation was completed. The additional medications were similar to those given to group C. The perioperative hemodynamics, body temperature, intraoperative drug dosages, fluid volume, urine volume, blood loss, the latency and amplitude of somatosensory evoked potentials (SEPs) at four different time points, the incidence of positive cases of SEPs and transcranial motor evoked potentials (tcMEPs), and perioperative adverse reactions were all recorded. RESULTS: Data from 79 patients were analyzed. The MAP measured at points T2-T4 in group DH was higher than at corresponding points in group C (P < 0.05). The MAP at point T4 in group DL was higher than at corresponding points in group C (P < 0.05). The remifentanil dosage in group DH was significantly lower than in group C (P = 0.015). The fluid volume in group DL was significantly lower than in group C (P = 0.009). There were no significant differences among the three groups in the amplitude and latency of SEP at different time points, nor in the incidence of warning SEP signals. The incidence of positive tcMEP signals did not differ significantly between groups C and DL (P > 0.05), but was significantly higher in group DH than in groups DL (P < 0.05) or C (P < 0.05). The incidence of intraoperative hypertension was significantly higher in group DH than in group C (P = 0.017). CONCLUSIONS: Low-dose Dex has no effect on the SEPs and tcMEPs monitoring during spinal surgery. High-dose Dex has no effect on SEPs monitoring, but it may increase the rate of false positive tcMEPs signals and the incidence of intraoperative hypertension. TRIAL REGISTRATION: This study has completed the registration of the Chinese Clinical Trial Center at 11/09/2020 with the registration number ChiCTR2000038154.