Effects of continuous infusion of phenylephrine vs. norepinephrine on parturients and fetuses under LiDCOrapid monitoring: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Hypotension following spinal anesthesia (SA) during cesarean delivery (CD) occurs commonly and is related with maternal and fetal complications. Norepinephrine infusion is increasingly used for prevention of post-SA hypotension; however, its effects as compared to the traditional phenylephrine infusion remain unclear. This study aimed to compare the effects of phenylephrine and norepinephrine administered as continuous infusion during elective CD on maternal hemodynamic parameters and maternal and fetal outcomes. METHODS: This prospective, single-center, randomized, controlled study included 238 consecutive term parturients who underwent CD from February 2019 to October 2019. They were randomized to receive continuous infusion of 0.25 µg/kg/min phenylephrine, 0.05 µg/kg/min norepinephrine, or placebo. Hemodynamic monitoring was performed at 10 time points using LiDCOrapid. We analyzed umbilical vein (UV), umbilical artery (UA), and peripheral vein (PV) blood gas indexes and recorded intraoperative complications. RESULTS: In phenylephrine group, the systolic blood pressure (SBP) remain during the whole operation. Compared to the control group, phenylephrine, but not norepinephrine, significantly increased the systemic vascular resistance (SVR) to counteract the SA-induced vasodilatation, 3 min following norepinephrine/phenylephrine/LR administration (T4): 957.4 ± 590.3 vs 590.1 ± 273.7 (P < 0.000001); 5 min following norepinephrine/phenylephrine/LR administration (T5): 1104 ± 468.0 vs 789.4 ± 376.2 (P = 0.000002). at the time of incision (T6): 1084 ± 524.8 vs 825.2 ± 428.6 (P = 0.000188). Parturients in the phenylephrine group had significantly lower UV (1.91 ± 0.43) (P = 0.0003) and UA (2.05 ± 0.61) (P = 0.0038) lactate level compared to controls. Moreover, the UV pH value was higher in the phenylephrine than in the control group7.37 ± 0.03(P = 0.0013). Parturients had lower incidence of nausea, tachycardia, hypotension in phenylephrine group. CONCLUSIONS: In this dataset, continuous phenylephrine infusion reduced the incidence of SA-induced hypotension, ameliorated SVR, while decreasing overall maternal complications. Phenylephrine infusions are considered the better choice during CD because of the significant benefit to the fetus. TRIAL REGISTRATION: Clinicaltrial.gov Registry, NCT03833895 , Registered on 1 February 2019.

Effect of optimizing cerebral oxygen saturation on postoperative delirium in older patients undergoing one-lung ventilation for thoracoscopic surgery.

OBJECTIVES: This randomized controlled trial investigated whether the regional cerebral oxygenation saturation (rScO2)-guided lung-protective ventilation strategy could improve brain oxygen and reduce the incidence of postoperative delirium (POD) in patients older than 65 years. METHODS: This randomized controlled trial enrolled 120 patients undergoing thoracic surgery who received one-lung ventilation (OLV). Patients were randomly assigned to the lung-protective ventilation group (PV group) or rScO2-oriented lung-protective ventilation group (TPV group). rScO2 was recorded during the surgery, and the occurrence of POD was assessed. RESULTS: The incidence of POD 3 days after surgery-the primary outcome-was significantly lower in the TPV group (23.3% versus 8.5%). Meanwhile, the levels of POD-related biological indicators (S100ß, neuron-specific enolase, tumor necrosis factor-α) were lower in the TPV group. Considering the secondary outcomes, both groups exhibited a lower oxygenation index after OLV, whereas partial pressure of carbon dioxide and mean arterial pressure were significantly increased in the TPV group. In addition, minimum rScO2 during surgery and mean rScO2 were higher in the TPV group than in the PV group. CONCLUSION: Continuous intraoperative monitoring of brain tissue oxygenation and active intervention measures guided by cerebral oxygen saturation are critical for improving brain metabolism and reducing the risk of POD.

Risk Factors for Postoperative Cognitive Decline After Orthopedic Surgery in Elderly Chinese Patients: A Retrospective Cohort Study.

Purpose: We aimed to identify the risk factors for postoperative cognitive decline (POCD) by evaluating the outcomes from preoperative comprehensive geriatric assessment (CGA) and intraoperative anesthetic interventions. Patients and Methods: Data used in the study were obtained from the Aged Patient Perioperative Longitudinal Evaluation-Multidisciplinary Trial (APPLE-MDT) cohort recruited from the Department of Orthopedics in Xuanwu Hospital, Capital Medical University between March, 2019 and June, 2022. All patients accepted preoperative CGA by the multidisciplinary team using 13 common scales across 15 domains reflecting the multi-organ functions. The variables included demographic data, scales in CGA, comorbidities, laboratory tests and intraoperative anesthetic data. Cognitive function was assessed by Montreal Cognitive Assessment scale within 48 hours after admission and after surgery. Dropping of ≥1 point between the preoperative and postoperative scale was defined as POCD. Results: We enrolled 119 patients. The median age was 80.00 years [IQR, 77.00, 82.00] and 68 patients (57.1%) were female. Forty-two patients (35.3%) developed POCD. Three cognitive domains including calculation (P = 0.046), recall (P = 0.047) and attention (P = 0.007) were significantly worsened after surgery. Univariate analysis showed that disability of instrumental activity of daily living, incidence rate of postoperative respiratory failure (PRF) ≥4.2%, STOP-Bang scale score, Caprini risk scale score and Sufentanil for maintenance of anesthesia were different between the POCD and non-POCD patients. In the multivariable logistic regression analysis, PRF ≥ 4.2% (odds ratio [OR] = 2.343; 95% confidence interval [CI]: 1.028-5.551; P = 0.046) and Sufentanil for maintenance of anesthesia (OR = 0.260; 95% CI: 0.057-0.859; P = 0.044) was independently associated with POCD as risk and protective factors, respectively. Conclusion: Our study suggests that POCD is frequent among older patients undergoing elective orthopedic surgery, in which decline of calculation, recall and attention was predominant. Preoperative comprehensive geriatric assessments are important to identify the high-risk individuals of POCD.

A retrospective study of risk factors for cardiopulmonary events during propofol-mediated gastrointestinal endoscopy in patients aged over 70 years.

BACKGROUND: Because of its rapid onset and recovery profile, propofol-mediated sedation is predominantly used during endoscopy. OBJECTIVE: To examine procedure-specific occurrence and risk factors for cardiopulmonary events during propofol-mediated gastrointestinal endoscopy in patients aged over 70 years. METHODS: Retrospective study with the anesthesia recorder system was performed to determine the occurrence and frequency of cardiopulmonary events. We enrolled 660 elderly outpatients who had undergone gastrointestinal endoscopies in our hospital between May 2006 and May 2007. Multivariate logistic regression analysis was performed using variables, including age, body mass, American Society of Anesthesiologists (ASA) classification, anddifferent anesthetic method either by monitored anesthesia care or intravenously administered propofol, to determine the risks of cardiopulmonary events. RESULTS: Slight adverse effects occurred in 88 patients during gastro-intestinal endoscopy, and no severe cardiopulmonary events occurred. There was no significant correlation between the adverse effects and sex or anesthetic methods (p = 0.95 and p = 0.053, respectively). There was a significant correlation between the occurrence of cardiopulmonary events and both age and body mass (p = 0.022 and p = 0.009, respectively). CONCLUSION: The procedure-specific risk factors for cardiopulmonary events during propofol-mediated gastrointestinal endoscopy in patients aged over 70 years include age and body mass. These factors should be taken into account during future comparative trials.

The Median Effective Dose and Bispectral Index of Remimazolam Tosilate for Anesthesia Induction in Elderly Patients: An Up-and-Down Sequential Allocation Trial.

Purpose: Remimazolam is a new type of ultrashort benzodiazepine drug with an unclear optimal dose for general anesthesia induction in elderly patients aged >60 years. Therefore, this study aimed to determine the effective dose of remimazolam tosilate induction and explore its correlation with the bispectral index (BIS). Patients and Methods: A total of 42 elderly patients were divided into two age groups: 60-69 (group A) and 70-85 (group B) years. An initial dose of 0.1mg/kg(Group A) and 0.05 mg/kg(Group B) remimazolam tosilate was administered, and the Modified Observer's Assessment of Alertness/Sedation scale was used to assess adequate responses. The dose was calculated using the up-and-down allocation technique based on the previous response. The sequential formula and probit regression model were used to calculate ED50 and BIS50. ED95 was determined using the probit regression model. Results: The ED50 of remimazolam tosilate for anesthesia induction were 0.088 mg/kg (95% confidence interval [CI] 0.071-0.108) and 0.061 mg/kg (95% CI 0.053-0.069) in groups A and B, respectively. ED95 was 0.118 mg/kg (95% CI 0.103-0.649) and 0.090 mg/kg (95% CI 0.075-0.199) in groups A and B, respectively. The remimazolam tosilate administration could decrease BIS. BIS50 was 86.0 (95% CI 83.7-88.6) and 85.4 (95% CI 84.1-86.8) in groups A and B, respectively. Conclusion: During the induction process, patients' consciousness should be observed. The dose of remimazolam tosilate could be chosen after careful consideration of individual variations.

Discovery of a selective and covalent small-molecule inhibitor of BFL-1 protein that induces robust apoptosis in cancer cells.

Induction of apoptosis by the FDA-approved drug Venetoclax in cancer cells mainly derives from blocking the interactions between BCL-2 and BH3-only proteins. Anti-apoptotic BFL-1, a homolog of BCL-2, also competitively binds to the BH3-only proteins and is responsible for Venetoclax-induced drug resistance. Compared to BCL-2, small-molecule inhibitors of BFL-1 are relatively underexplored. In order to tackle this issue, in-house compound library was screened and a hit compound was identified and optimized to obtain 12 (ZH97) functioning as a covalent and selective inhibitor of BFL-1. 12 modifies BFL-1 at the C55 residue, blocks BFL-1/BID interaction in vitro, promotes cellular cytochrome c release from mitochondria, and induced apoptosis in BFL-1 overexpressing cancer cells. Mechanistic studies show that 12 inhibited BFL-1/PUMA interaction in cell lysate and is effective in cancer cells that harboring high expression level of BFL-1. In summary, blockade of BFL-1/BH3-only proteins interactions with a covalent small-molecule inhibitor induced apoptosis and elicited antitumor activity. Thus, our study demonstrates an appealing strategy for selective modulation of cellular BFL-1 for cancer therapy.

Prophylactic administration of tranexamic acid combined with thromboelastography-guided hemostatic algorithm reduces allogeneic transfusion requirements during pediatric resective epilepsy surgery: A randomized controlled trial.

Background: Intraoperative bleeding and allogeneic transfusion remain common problems in pediatric resective epilepsy surgery. Tranexamic acid (TXA) is a widely recommended antifibrinolytic drug that reduces blood loss and transfusion requirements for bleeding patients. Thromboelastography (TEG)-guided hemostatic algorithm is commonly used in bleeding management. This trial was designed to validate the efficacy of a multimodal coagulation therapy involving continuous TXA infusion with TEG-guided hemostatic algorithm in reducing allogeneic exposure risk in pediatric resective epilepsy surgery. Methods: Eighty-three children undergoing resective epilepsy surgery were randomized into a treatment group (Group T; n = 42) and a control group (Group C; n = 41). Group T received prophylactic TXA (10 mg/kg followed by 5 mg/kg/h) with TEG-guided hemostatic algorithm, whereas Group C received conventional coagulation management. The primary outcome was allogeneic transfusion rate during surgery, and the secondary outcomes were intraoperative blood loss, incidence of postoperative seizures, and thromboembolic events during hospitalization. Results: The incidence of intraoperative allogeneic transfusion reduced by 34.7% with the use of a multimodal coagulation therapy (19.0% in Group T vs. 53.7% in Group C; RR 0.355, 95% CI 0.179-0.704; p = 0.001). This was mainly triggered by a significant reduction (44.1%) in intraoperative plasma transfusion (7.1% in Group T vs. 51.2% in Group C; RR 0.139, 95% CI 0.045-0.432; p = 0.000). The risk of intraoperative RBC transfusion was lower in Group T than in Group C, but the difference was not statistically significant (14.3% in Group T vs. 29.3% in Group C; RR 0.488, 95% CI 0.202-1.177; p = 0.098). No platelets were transfused in both groups. Further, 19 (45.2%) patients in Group T received fibrinogen concentrates guided by TEG data, whereas 1 (2.4%) patient in Group C received fibrinogen concentrates empirically. There were no significant differences in estimated blood loss and postoperative seizures between the two groups, and no thromboembolic events were observed after surgery. Conclusion: Prophylactic administration of TXA combined with TEG-guided hemostatic algorithm can be an effective multimodal coagulation strategy for reducing allogeneic transfusion requirements during pediatric resective epilepsy surgery. Clinical Trial Registration: www.chictr.org.cn/index.aspx, identifier ChiCTR1800016188.

[Application of ultrasonic surface location for internal jugular vein catheterization via central approach].

OBJECTIVE: To explore the clinical value of ultrasonic surface localization in internal jugular vein catheterization. METHODS: Totally 150 patients with American Society of Anesthesiologists physical status I -III who were planning to receive elective surgeries were randomized into anatomical landmark group, ultrasonic surface positioning group, and ultrasound-guided group using computed random table, with 50 cases in each group. The right internal jugular vein catheterization was performed after tracheal intubation. In the anatomic landmark group, patients were punctured using surface marks through central approach. In ultrasonic surface positioning group and ultrasound-guided group, patients were punctured with ultrasonic localization and guidance through central approach. The relationship between internal jugular vein and carotid artery, the position of the needle into the vein, the success rate of puncture, the change times of puncture point, and the complications were recorded. RESULTS: Ultrasound scan revealed that the relationship between the right internal jugular vein and the right common carotid artery could be divided into three types: parallel (12.7%), partial overlapping (69.3%), and complete overlapping (18.0%). The average "safety distance" of jugular vein puncture was (1.15 +/- 0.47) cm. The success rate of the first puncture attempt in ultrasonic surface positioning group and ultrasound-guided group were 78.0% and 82.0%, respectively, which was significantly higher than that in anatomic landmark group (22.0%) (P < 0.05), whereas the complication incidence in anatomic landmark group (12.0%) were significantly higher than those in ultrasonic surface positioning group (0) and ultrasound-guided group (0) (P < 0.05). CONCLUSIONS: Ultrasonic surface positioning applied during internal jugular vein catheterization is helpful to reveal the inner diameters as well as the origin and course of arteries and veins in the puncture and identify the abnormalities as early as possible. As a simple support technique for internal jugular vein puncture, it is suitable for clinical application.

Pharmacological inhibition of NF-κB-inducing kinase (NIK) with small molecules for the treatment of human diseases.

NIK is a key kinase required for the activation of alternative NF-κB signaling pathways. Overactivation of NIK in patients has been observed and is implicated in the pathogenesis of inflammatory diseases, B-cell malignances, and solid tumors. Over the past decade, inhibition of NIK overactivation with small molecules has been pursued as an attractive strategy for drug discovery, where numerous potent and selective NIK inhibitors with novel pharmacophores have been identified. This review summarizes the structural features and key efficacy studies of the NIK inhibitors reported, which justify the mechanism of action of such inhibitors in animal models driven by NIK overactivation. Given the strong pathological associations between overactivation of NIK and human diseases, human clinical trials of NIK inhibitors as drug candidates are eagerly awaited. Information showcased in this review article might be helpful for the discovery and clinical development of the next generation of NIK inhibitors in the near future.

The Analgesic Effect of Different Concentrations of Epidural Ropivacaine Alone or Combined With Sufentanil in Patients After Cesarean Section.

Background: Patients experience moderate-high intensity postoperative pain after cesarean section (CS). The aim of this study was to investigate the optimal concentrations of ropivacaine and sufentanil for use in controlling pain after CS. Methods: One hundred and seventy-four women undergoing elective CS were randomly allocated to four groups. Epidural analgesia was administered with 0.1% ropivacaine in the R1 group, 0.15% ropivacaine in the R2 group, a combination of 0.1% ropivacaine and 0.5 µg/ml of sufentanil in the R1S group, and a combination of 0.15% ropivacaine and 0.5 µg/ml of sufentanil in the R2S group (at a basal rate of 4 ml/h, bolus dose of 4 ml/20 min as needed). Pain scores (numerical rating scale [NRS]: 0-10 cm) at rest (NRS-R), during movement (NRS-M), and when massaging the uterus (NRS-U) were documented at 6 and 24 h. We also recorded patient satisfaction scores, time to first flatus, motor deficits, and adverse drug reactions. Results: NRS (NRS-R, NRS-M, NRS-U) scores in the R2S group (2 [1-3], 4 [3-5], 6 [5-6], respectively) were lower than in the R1 group (3 [3-4], 5 [4-6], 7 [6-8], respectively) (p < 0.001, p < 0.05, p < 0.01, respectively) at 6 h; and patient satisfaction (9 [8-10]) was improved compared to the R1 group (8 [6-8]) (p < 0.01). The time to first flatus (18.7 ± 11.8 h) was reduced relative to the R1 group (25.9 ± 12.0 h) (p < 0.05). The time to first ambulation was not delayed (p > 0.05). However, the incidence of pruritus (4 [9.3%]) was increased compared to the R2 group (0 [0]) (p < 0.05) at 6 h, and the incidence of numbness (23 [53.5%], 23 [53.5%]) was increased compared to the R1 group (10 [23.3%], 10 [23.3%]) (all p < 0.01) at both 6 and 24 h. Conclusions: Although we observed a higher incidence of pruritus and numbness, co-administration of 0.15% ropivacaine and 0.5 µg/ml of sufentanil administered epidurally optimized pain relief after CS, with treated subjects exhibiting lower NRS scores, shorter time to first flatus, and higher patient-satisfaction scores.

The Efficacy of Near-Infrared Spectroscopy Monitoring in Carotid Endarterectomy: A Prospective, Single-Center, Observational Study.

There has been no gold standard for intraoperative monitoring in carotid endarterectomy (CEA) till now. The purpose of the current study was to investigate the value of near-infrared spectroscopy (NIRS) monitoring in CEA and explore the thresholds for intraoperative cerebral hypoperfusion. Eighty-four consecutive patients who underwent CEA surgery in Xuan Wu Hospital of Capital Medical University from August 2015 to June 2016 were enrolled in this study. All patients were intraoperatively monitored by transcranial Doppler ultrasonography (TCD) and NIRS. Regional oxygen saturation (rSO2) monitored by NIRS and blood flow velocity of the middle cerebral artery (V-MCA) monitored by TCD were continuously recorded. Correlation analysis was conducted for NIRS and TCD monitoring values. Intraoperative shunting was performed in five patients according to the TCD monitoring results and surgeon preference. During clamping of the carotid artery, the Pearson correlation index between rSO2 and V-MCA was 0.581 (P<0.001). A cut-off of 12.3% decrease of rSO2 was identified as the optimal threshold for intraoperative hypoperfusion indicated by TCD monitoring, when the sensitivity and specificity were 74.6% and 91.7%, respectively, with a 0.609 Kappa value. Physical examination immediately after operation showed no ischemic injury occurred, and no death and stroke occurred during the postoperative hospitalization. Our study demonstrated that NIRS could serve as a favorable monitoring tool during CEA. A 12.3% decrease of rSO2 could be adopted as a reliable threshold for intraoperative cerebral hypoperfusion.