Elevated circulating BMP9 aggravates pulmonary angiogenesis in hepatopulmonary syndrome rats through ALK1-Endoglin-Smad1/5/9 signalling.

BACKGROUND: Bone morphogenetic protein 9 (BMP9) is a hepatokine that plays a pivotal role in the progression of liver diseases. Moreover, an increasing number of studies have shown that BMP9 is associated with hepatopulmonary syndrome (HPS), but its role in HPS is unclear. Here, we evaluated the influence of CBDL on BMP9 expression and investigated potential mechanisms of BMP9 signalling in HPS. METHODS: We profiled the circulating BMP9 levels in common bile duct ligation-induced HPS rat model, and then investigated the effects and mechanisms of HPS rat serum on pulmonary vascular endothelial dysfunction in rat model, as well as in primarily cultured rat pulmonary microvascular endothelial cells. RESULTS: Our data revealed that circulating BMP9 levels were significantly increased in the HPS rats compared to control group. Besides, the elevated BMP9 in HPS rat serum was not only crucial for promoting endothelial cell proliferation and tube formation through the activin receptor-like kinase1 (ALK1)-Endoglin-Smad1/5/9 pathway, but also important for accumulation of monocytes. Treatments with ALK1-Fc or silencing ALK1 expression to inhibit the BMP9 signalling pathway effectively eliminated these effects. In agreement with these observations, increased circulating BMP9 was associated with an increase in lung vessel density and accumulation of pro-angiogenic monocytes in the microvasculature in HPS rats. CONCLUSIONS: This study provided evidence that elevated circulating BMP9, secreted from the liver, promote pulmonary angiogenesis in HPS rats via ALK1-Endoglin-Smad1/5/9 pathway. In addition, BMP9-regulated pathways are also involved in accumulation of pro-angiogenic monocytes in the pulmonary microvasculature in HPS rats.

MiR181-5p promotes pathogenic angiogenesis of hepatopulmonary syndrome by negatively regulating Wnt inhibitor Wif1.

Objectives: Hepatopulmonary syndrome is a serious respiratory injury caused by chronic liver disease. Excessive pulmonary capillary angiogenesis is the key pathological event. However, the mechanism of microRNA regulatory pulmonary capillary angiogenesis is still unclear. Materials and Methods: The hepatopulmonary syndrome rat model was constructed by Common bile duct ligation (CBDL) surgery. The expression tread of miR181-5p and Wif1 was detected by qRT-PCR and western blot in various tissues and disease processes. Wif1 was predicted as one of the potential target genes of miR181-5p by bioinformatic assay. miR181-5p mimics and inhibitors were used to increase/decrease miR181-5p levels in pulmonary microvascular cells. And Wif-1 specific recombinant lentiviruses were used to up-regulate and down-regulate Wif1 in pulmonary microvascular cells. Then, CCK8, Transwell, and tube formation assay were used for pulmonary microvascular cell proliferation, migration, and tube formation. And Dual-luciferase reporter assay was used to assess that miR181-5p may direct regulate Wif-1 in HPS rats. Results: The result showed miR181-5p specifically activates the Wnt signaling pathway by inhibiting Wif1 and then promotes pulmonary microvascular cell proliferation, migration, and tube formation, thereby accelerating the process of HPS. We finally verified Wif1 as a novel and direct target of miR181-5p in HPS. Conclusion: Taken together, we revealed an important miR-181-5p/Wif1/Wnt pathway in regulating pathological angiogenesis. It will prove beneficial as a therapeutic strategy for hepatopulmonary syndrome.

Dynamic Nomogram for Predicting the Risk of Perioperative Neurocognitive Disorders in Adults.

BACKGROUND: Simple and rapid tools for screening high-risk patients for perioperative neurocognitive disorders (PNDs) are urgently needed to improve patient outcomes. We developed an online tool with machine-learning algorithms using routine variables based on multicenter data. METHODS: The entire dataset was composed of 49,768 surgical patients from 3 representative academic hospitals in China. Surgical patients older than 45 years, those undergoing general anesthesia, and those without a history of PND were enrolled. When the patient's discharge diagnosis was PND, the patient was in the PND group. Patients in the non-PND group were randomly extracted from the big data platform according to the surgical type, age, and source of data in the PND group with a ratio of 3:1. After data preprocessing and feature selection, general linear model (GLM), artificial neural network (ANN), and naive Bayes (NB) were used for model development and evaluation. Model performance was evaluated by the area under the receiver operating characteristic curve (ROCAUC), the area under the precision-recall curve (PRAUC), the Brier score, the index of prediction accuracy (IPA), sensitivity, specificity, etc. The model was also externally validated on the multiparameter intelligent monitoring in intensive care (MIMIC) Ⅳ database. Afterward, we developed an online visualization tool to preoperatively predict patients' risk of developing PND based on the models with the best performance. RESULTS: A total of 1051 patients (242 PND and 809 non-PND) and 2884 patients (6.2% patients with PND) were analyzed on multicenter data (model development, test [internal validation], external validation-1) and MIMIC Ⅳ dataset (external validation-2). The model performance based on GLM was much better than that based on ANN and NB. The best-performing GLM model on validation-1 dataset achieved ROCAUC (0.874; 95% confidence interval [CI], 0.833-0.915), PRAUC (0.685; 95% CI, 0.584-0.786), sensitivity (72.6%; 95% CI, 61.4%-81.5%), specificity (84.4%; 95% CI, 79.3%-88.4%), Brier score (0.131), and IPA (44.7%), and of which the ROCAUC (0.761, 95% CI, 0.712-0.809), the PRAUC (0.475, 95% CI, 0.370-0.581), Brier score (0.053), and IPA (76.8%) on validation-2 dataset. Afterward, we developed an online tool (https://pnd-predictive-model-dynnom.shinyapps.io/ DynNomapp/) with 10 routine variables for preoperatively screening high-risk patients. CONCLUSIONS: We developed a simple and rapid online tool to preoperatively screen patients' risk of PND using GLM based on multicenter data, which may help medical staff's decision-making regarding perioperative management strategies to improve patient outcomes.

Prophylactic Administration with Methylene Blue Improves Hemodynamic Stabilization During Obstructive Jaundice-Related Diseases' Operation: a Blinded Randomized Controlled Trial.

OBJECTIVES: Patients with obstruction jaundice are at a high risk of hypotension and need high volume of fluids and a high dose of catecholamine to maintain organ perfusion during operation procedure. All these likely contribute to high perioperative morbidity and mortality. The aim of the study is to evaluate the effects of methylene blue on the hemodynamics in patients undergoing surgeries associated with obstructive jaundice. DESIGN: A prospective, randomized, and controlled clinical study. SETTING: The enrolled patients randomly received 2 mg/kg of methylene blue in saline or saline (50 ml) before anesthesia induction. The primary outcome was the frequency and dose of noradrenaline administration to maintain mean arterial blood pressure over 65 mmHg or > 80% of baseline, and systemic vascular resistance (SVR) over 800 dyne/s/cm5 during operation. The secondary outcomes were liver and kidney functions, and ICU stay. PATIENTS: Seventy patients were enrolled in the study and randomly assigned to receive either methylene blue or control (n = 35/group). RESULTS: Fewer patients received noradrenaline in the methylene blue group when compared with the control group (13/35 vs 23/35, P = 0.017), and the noradrenaline dose administrated during operation was reduced in the methylene blue group when compared with the control group (0.32 ± 0.57 mg vs 1.787 ± 3.51 mg, P = 0.018). The blood level of creatinine, glutamic oxalacetic transaminase, and glutamic-pyruvic transaminase after the operation was reduced in the methylene blue group when compared with the control group. CONCLUSIONS: Prophylactic administration of methylene blue before operation associated with obstructive jaundice improves hemodynamic stability and short-term prognosis. QUESTION: Methylene blue use prevented refractory hypotension during cardiac surgery, sepsis, or anaphylactic shock. It is still unknown that methylene blue on the vascular hypo-tone associated with obstructive jaundice. FINDINGS: Prophylactic administration with methylene blue improved peri-operative hemodynamic stability, and hepatic and kidney function on the patients with obstructive jaundice. MEANINGS: Methylene blue is a promising and recommended drug for the patients undergoing the surgeries of relief obstructive jaundice during peri-operation management.

Inhalational Versus Propofol-based Intravenous Maintenance of Anesthesia for Emergence Delirium in Adults: A Meta-analysis and Trial Sequential Analysis.

Emergence delirium (ED) is a severe postoperative complication that increases the risk for injury, self-extubation, and hemorrhage. Inhalational maintenance of anesthesia is a risk factor for ED in pediatric patients, but its impact in adults is undefined. This meta-analysis compares the incidence of ED between inhalational and propofol-based intravenous maintenance of anesthesia. Following a search of the PubMed, Medline, Embase, and Cochrane Library databases, 12 high-quality randomized controlled trials including 1440 patients, were identified for inclusion in the meta-analysis. Compared with propofol-based intravenous maintenance of anesthesia, inhalational maintenance increased the incidence of ED in adults (risk ratio [RR], 2.02; 95% confidence interval [CI]: 1.30-3.14; P =0.002). This was confirmed by sensitivity analysis, trial sequential analysis, and subgroup analyses of studies that assessed ED via Aono's four-point scale (RR, 3.72; 95% CI: 1.48-9.31; P =0.005) and the Ricker Sedation Agitation Scale (RR, 3.48; 95% CI: 1.66-7.32; P =0.001), studies that included sevoflurane for maintenance of anesthesia (RR, 1.87; 95% CI: 1.13-3.09; P =0.02), studies that reported ED as the primary outcome (RR, 2.73; 95% CI: 1.53-4.86; P =0.0007), and studies that investigated ocular (RR, 2.98; 95% CI: 1.10-8.10; P =0.03), nasal (RR; 95% CI: 1.27-6.50; P =0.01), and abdominal (RR, 3.25; 95% CI: 1.12-9.40; P =0.03) surgeries, but not intracranial surgery (RR, 0.72; 95% CI: 0.34-1.54; P =0.40). In summary, inhalational maintenance of sevoflurane was a risk factor for ED compared with propofol-based intravenous maintenance in adults who underwent ocular, nasal, and abdominal surgeries but not intracranial surgery.

Cognitive function and delirium following sevoflurane or propofol anesthesia for valve replacement surgery: A multicenter randomized controlled trial.

Cognitive dysfunction is a common postoperative neurological complication in patients undergoing valve replacement surgery. This study aimed to compare the effects of sevoflurane versus propofol-based total intravenous anesthesia on the incidence of cognitive dysfunction following valve replacement surgery. This multicenter, randomized, controlled double-blinded study was conducted in three teaching hospitals in China. Patients receiving on-pump valve replacement surgery were enrolled. Stratified block randomization was used to randomly assign patients 1:1 to receive sevoflurane (1.0-1.5 MAC) or propofol (2.0-3.0 mg/kg/h) for anesthesia maintenance. The primary outcome was the incidence of cognitive dysfunction assessed by four cognitive tests before, as well as 7-14 days after surgery. Patients were randomly assigned to receive sevoflurane anesthesia (n = 144) or propofol-based total intravenous anesthesia (n = 145). The incidence of postoperative cognitive dysfunction in the sevoflurane anesthesia group (31.9%) was significantly lower than that in the total intravenous anesthesia group (43.4%; relative risk 0.61, 95% confidence interval [CI]: 0.38-0.97, p = 0.044). There was no difference in the incidence of delirium between patients receiving sevoflurane and total intravenous anesthesia (27.8% [35/144] vs. 25.9% [35/145], 1.10, 95% CI: 0.64 to 1.90, p = 0.736). There was a significant difference in the Katz Index on day 3 after surgery (3 [0.9) vs. 3 (1.0], 0.095, 95% CI: 0.05 to 0.43, p = 0.012). No difference was observed in other outcomes between the two groups. For patients undergoing on-pump valve replacement surgery, sevoflurane anesthesia had a smaller effect on cognitive function and independence in daily life activities compared with propofol anesthesia.

Effects of General Anesthesia on Changes of Serum Hepatitis B Virus-DNA Levels in Infected Patients Underwent Non-Hepatobiliary Minimally Invasive Surgery: A Pilot Observational Study.

Objective: To investigate the effects of different general anesthesia methods on the changes of serum hepatitis B virus deoxyribonucleic acid (HBV-DNA) levels in the hepatitis B virus (HBV) infected patients. Methods: This pilot prospective observational study was carried out from March 2021 to January 2022. Forty patients infected by HBV, who underwent non-hepatobiliary minimally invasive surgery, were allocated into an intravenous anesthesia group maintained with propofol (Group P, n = 20) and an inhalation anesthesia group maintained with sevoflurane (Group S, n = 20) by a random envelope method. Patient's blood was drawn before operation (Tbaseline), at 24 hours (Tpost 24hrs) and 48 hours (Tpost 48hrs) after operation to detect the serum HBV-DNA levels and analyze the subset levels of T, B lymphocytes and NK cells (TBNK) in two groups. The serum HBV-DNA level was used as the major outcome, and it was analyzed by repeated-measures analysis of variance after natural logarithm transformation. Results: In Group P and Group S, compared with the baseline, the serum HBV-DNA levels decreased significantly at Tpost 24hrs and Tpost 48hrs, P<0.05. The total ratio of CD4+T cells and the ratio of CD4+T to CD8+T cells (CD4+/CD8+) were lower at Tpost 24hrs, P<0.05, and the total ratio of B cells was significantly increased at Tpost 24hrs, P<0.05. Compared with the values at Tpost 24hrs, the total ratio of CD4+ T cells, CD4+/CD8+ T cells, and the total ratio of B cells were significantly increased at Tpost 48hrs in both groups, P<0.05. However, there were no statistical differences between Group P and Group S. Conclusion: The levels of serum HBV-DNA decreased within 48 hours after general anesthesia. There were no significant differences between the effects of intravenous and inhalation anesthesia on the serum HBV-DNA levels. Trial Registration: This study has been prospectively registered in the Clinical Trials Registry (NCT02038088, 1/28/2015).

Advantages of Transmuscular Quadratus Lumborum Block via Subfascial Approach Versus Extrafascial Approach for Postoperative Analgesia After Laparoscopic Cholecystectomy: A Randomized Controlled Study.

OBJECTIVE: We aimed to compare the analgesic effect and incidence of lower limb weakness of transmuscular quadratus lumborum (TQL) block via subfascial approach with that via extrafascial after laparoscopic cholecystectomy (LC). METHODS: Eighty patients undergoing LC were randomized to receive ultrasound-guided bilateral TQL block via subfascial (subfascial group) or extrafascial (extrafascial group) using 30 mL of 0.33% ropivacaine unilaterally. Pain scores of port sites while rest and coughing at 1, 6, 12, 24, 36, and 48 hours postoperatively as primary outcome were compared. Modified Lovett Rating Scale, ambulatory dependency, and rescue analgesia requirement was also compared. RESULTS: The pain score of the subxiphoid and of the right subcostal port site for up to the postoperative 36 hours (2 [1 to 2]) and 24 hours (2 [2 to 3]) in the subfascial group was significantly lower than that in extrafascial group (2 [2 to 2] and 3 [2.25 to 4]). Up to postoperative 24 hours, the rescue analgesia requirement in subfascial group was significantly lower than that in extrafascial group, namely less fentanyl consumption and parecoxib (1.3 [±5.5] µg vs. 5.6 [±10.6] µg; 17.5% vs. 37.5%). The ratio of patients with LRS score of 6 at postoperative 1 hour (65.0%), and with dependent ambulation at postoperative 1 and 6 hours in subfascial group (15.0% and 0.0%) was significantly lower than that in extrafascial group (10.0%, 80.0%, and 17.5%). CONCLUSION: TQL block via subfascial had the advantages of better analgesic effect and less lower limbs weakness after LC over that via extrafascial.

Optimization of anesthetic decision-making in ERAS using Bayesian network.

Enhanced recovery after surgery (ERAS) can accelerate patient recovery. However, little research has been done on optimizing the ERAS-related measures and how the measures interact with each other. The Bayesian network (BN) is a graphical model that describes the dependencies between variables and is also a model for uncertainty reasoning. In this study, we aimed to develop a method for optimizing anesthetic decisions in ERAS and then investigate the relationship between anesthetic decisions and outcomes. First, assuming that the indicators used were independent, the effects of combinations of single indicators were analyzed based on BN. Additionally, the impact indicators for outcomes were selected with statistical tests. Then, based on the previously selected indicators, the Bayesian network was constructed using the proposed structure learning method based on Strongly Connected Components (SCC) Local Structure determination by Hill Climbing Twice (LSHCT) and adjusted according to the expert's knowledge. Finally, the relationship is analyzed. The proposed method is validated by the real clinical data of patients with benign gynecological tumors from 3 hospitals in China. Postoperative length of stay (LOS) and total cost (TC) were chosen as the outcomes. Experimental results show that the ERAS protocol has some pivotal indicators influencing LOS and TC. Identifying the relationship between these indicators can help anesthesiologists optimize the ERAS protocol and make individualized decisions.

Learning to predict in-hospital mortality risk in the intensive care unit with attention-based temporal convolution network.

BACKGROUND: Dynamic prediction of patient mortality risk in the ICU with time series data is limited due to high dimensionality, uncertainty in sampling intervals, and other issues. A new deep learning method, temporal convolution network (TCN), makes it possible to deal with complex clinical time series data in ICU. We aimed to develop and validate it to predict mortality risk using time series data from MIMIC III dataset. METHODS: A total of 21,139 records of ICU stays were analysed and 17 physiological variables from the MIMIC III dataset were used to predict mortality risk. Then we compared the model performance of the attention-based TCN with that of traditional artificial intelligence (AI) methods. RESULTS: The area under receiver operating characteristic (AUCROC) and area under precision-recall curve (AUC-PR) of attention-based TCN for predicting the mortality risk 48 h after ICU admission were 0.837 (0.824 -0.850) and 0.454, respectively. The sensitivity and specificity of attention-based TCN were 67.1% and 82.6%, respectively, compared to the traditional AI method, which had a low sensitivity (< 50%). CONCLUSIONS: The attention-based TCN model achieved better performance in the prediction of mortality risk with time series data than traditional AI methods and conventional score-based models. The attention-based TCN mortality risk model has the potential for helping decision-making for critical patients. TRIAL REGISTRATION: Data used for the prediction of mortality risk were extracted from the freely accessible MIMIC III dataset. The project was approved by the Institutional Review Boards of Beth Israel Deaconess Medical Center (Boston, MA) and the Massachusetts Institute of Technology (Cambridge, MA). Requirement for individual patient consent was waived because the project did not impact clinical care and all protected health information was deidentified. The data were accessed via a data use agreement between PhysioNet, a National Institutes of Health-supported data repository (https://www.physionet.org/), and one of us (Yu-wen Chen, Certification Number: 28341490). All methods were carried out in accordance with the institutional guidelines and regulations.

Methionine Restriction Prevents Lipopolysaccharide-Induced Acute Lung Injury via Modulating CSE/H2S Pathway.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) result in high mortality, whereas effective treatments are limited. Methionine restriction (MR) has been reported to offer various benefits against multiple pathological processes of organ injuries. However, it remains unknown whether MR has any potential therapeutic value for ALI/ARDS. The current study was set to investigate the therapeutic potential of MR on lipopolysaccharide (LPS)-induced ALI and its underlying mechanisms. We found that MR attenuated LPS-induced pulmonary edema, hemorrhage, atelectasis, and alveolar epithelial cell injuries in mice. MR upregulated cystathionine-gamma-lyase (CSE) expression and enhanced the production of hydrogen sulfide (H2S). MR also inhibited the activation of Toll-like receptors 4 (TLR4)/NF-κB/NOD-like receptor protein 3 (NLRP3), then reduced IL-1ß, IL-6, and TNF-α release and immune cell infiltration. Moreover, the protective effects of MR on LPS-induced ALI were abrogated by inhibiting CSE, whereas exogenous H2S treatment alone mimicked the protective effects of MR in Cse-/- mice after LPS administration. In conclusion, our findings showed that MR attenuated LPS-induced lung injury through CSE and H2S modulation. This work suggests that developing MR towards clinical use for ALI/ARDS patients may be a valuable strategy.

Fiberoptic-guided tracheal intubation under precise anesthesia and topicalization with spontaneous respiration preservation for an uncooperative patient with severe postburn mentosternal contracture.

Airway management of patients with difficult airways is a challenge to the anesthesiologists and awake tracheal intubation is the recommended strategy. Successful fiberoptic-guided tracheal intubation under precise anesthesia and topicalization with spontaneous respiration preservation was achieved in an uncooperative patient with severe postburn mentosternal contracture scheduled for release of contracture.

A Simple and Quick Screening Method for Intrapulmonary Vascular Dilation in Cirrhotic Patients Based on Machine Learning.

BACKGROUND AND AIMS: Screening for hepatopulmonary syndrome in cirrhotic patients is limited due to the need to perform contrast enhanced echocardiography (CEE) and arterial blood gas (ABG) analysis. We aimed to develop a simple and quick method to screen for the presence of intrapulmonary vascular dilation (IPVD) using noninvasive and easily available variables with machine learning (ML) algorithms. METHODS: Cirrhotic patients were enrolled from our hospital. All eligible patients underwent CEE, ABG analysis and physical examination. We developed a two-step model based on three ML algorithms, namely, adaptive boosting (termed AdaBoost), gradient boosting decision tree (termed GBDT) and eXtreme gradient boosting (termed Xgboost). Noninvasive variables were input in the first step (the NI model), and for the second step (the NIBG model), a combination of noninvasive variables and ABG results were used. Model performance was determined by the area under the curve of receiver operating characteristics (AUCROCs), precision, recall, F1-score and accuracy. RESULTS: A total of 193 cirrhotic patients were ultimately analyzed. The AUCROCs of the NI and NIBG models were 0.850 (0.738-0.962) and 0.867 (0.760-0.973), respectively, and both had an accuracy of 87.2%. For both negative and positive cases, the recall values of the NI and NIBG models were both 0.867 (0.760-0.973) and 0.875 (0.771-0.979), respectively, and the precisions were 0.813 (0.690-0.935) and 0.913 (0.825-1.000), respectively. CONCLUSIONS: We developed a two-step model based on ML using noninvasive variables and ABG results to screen for the presence of IPVD in cirrhotic patients. This model may partly solve the problem of limited access to CEE and ABG by a large numbers of cirrhotic patients.

Intraoperative Hypotension and Related Risk Factors for Postoperative Mortality After Noncardiac Surgery in Elderly Patients: A Retrospective Analysis Report.

BACKGROUND: Blood pressure fluctuation is very common during non-cardiac surgery in elderly. This retrospective study was to analyse whether intraoperative hypotension in elderly and other risk factors relate to the postoperative mortality. METHODS: A total of 118 cases (Observational group), who underwent noncardiac surgery in three medical centers between September 2014 and March 2017, and died in the hospital after the noncardiac surgery. With 1:2 ratio of propensity matching, 236 survival cases (Control group) were selected for comparison analyses with the death cases. Intraoperative blood pressure and perioperative parameters from both groups were collected from electronic anaesthesia charts. Data were analysed with univariate logistic regression analysis where variables with p values less than 0.05 were analysed with multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was constructed. RESULTS: There are five risk factors related to postoperative death in elderly patients: ASA grade, COPD, emergency surgery, general anesthesia, 60 < MAP ≤ 65mmHg (OR > 1), and one factor may reduce the risk of postoperative mortality, which is PACU therapy (OR < 1). Compared with the Control group, the Observational group had a higher proportion of cerebral hernia, kidney injury and trauma (p < 0.001). The intraoperative blood transfusion volume and intraoperative blood loss volume were higher in the Observational group than the Control group (p < 0.001). The proportion of using vasoactive drugs was higher in the Observational group (p < 0.001), and there was more urine output during the operation in the Observational group (p = 0.005). CONCLUSION: The intraoperative MAP of geriatric patients lower than 65mmHg is highly related to the postoperative mortality. Elderly patients with emergency surgery, high ASA grade and a history of COPD have an increased risk of postoperative mortality. General anesthesia is a risk factor for postoperative death in elderly patients, and the PACU therapy is a protective factor to avoid postoperative death. TRIAL REGISTRATION: This study has been retrospectively registered in the Chinese Clinical Trials Registry (ChiCTR2000038912, 10/10/2020).

Effects of circadian rhythm on Narcotrend index and target-controlled infusion concentration of propofol anesthesia.

BACKGROUND: The effects of circadian rhythms on drug metabolism and efficacy are being increasingly recognized. However, the extent to which they affect general anesthesia remains unclear. This study aims to investigate the effects of circadian rhythms on anesthetic depth and the concentrations of propofol target-controlled infusion (TCI). METHODS: Sixty patients undergoing laparoscopic surgeries were sequentially assigned to four groups. Group ND (n = 15): Propofol TCI with Narcotrend monitor during the day (8:00-18:00), Group NN (n = 15): Propofol TCI with Narcotrend monitor during the night (22:00-5:00), Group CLTD (n = 15): Propofol closed-loop TCI guided by bispectral index (BIS) during the day (8:00-18:00), Group CLTN (n = 15): Propofol closed-loop TCI guided by BIS during the night (22:00-5:00). The Narcotrend index, mean arterial pressure (MAP) and heart rate (HR) were compared between group ND and NN at 7 time points, from 5 min before induction to the end of operation. The propofol TCI concentrations, MAP and HR were compared between group CLTD and CLTN at 7 time points, from 5 min after induction to the end of operation. RESULTS: The Narcotrend index, MAP, and HR in group NN were lower than those in group ND from the beginning of mechanical ventilation to the end of operation (p < 0.05). The propofol TCI concentrations in group CLTN were lower than those in group CLTD from the beginning of operation to the end of operation (p < 0.05). CONCLUSION: Circadian rhythms have a significant effect on the depth of anesthesia and drug infusion concentrations during propofol TCI. When using general anesthesia during night surgery, the propofol infusion concentration should be appropriately reduced compared to surgery during the day. TRIAL REGISTRATION: The present study was registered on the ClinicalTrials.gov website ( NCT02440269 ) and approved by the Medical Ethics Committee of Southwest Hospital of Third Military Medical University (ethics lot number: 2016 Research No. 93). All patients provided informed written consent to participate in the study.

M2 macrophage accumulation contributes to pulmonary fibrosis, vascular dilatation, and hypoxemia in rat hepatopulmonary syndrome.

Hepatopulmonary syndrome (HPS) markedly increases the mortality of patients. However, its pathogenesis remains incompletely understood. Rat HPS develops in common bile duct ligation (CBDL)-induced, but not thioacetamide (TAA)-induced cirrhosis. We investigated the mechanisms of HPS by comparing these two models. Pulmonary histology, blood gas exchange, and the related signals regulating macrophage accumulation were assessed in CBDL and TAA rats. Anti-polymorphonuclear leukocyte (antiPMN) and anti-granulocyte-macrophage colony stimulating factor (antiGM-CSF) antibodies, clodronate liposomes (CL), and monocyte chemoattractant protein 1 (MCP1) inhibitor (bindarit) were administrated in CBDL rats, GM-CSF, and MCP1 were administrated in bone marrow-derived macrophages (BMDMs). Pulmonary inflammatory cell recruitment, vascular dilatation, and hypoxemia were progressively developed by 1 week after CBDL, but only occurred at 4 week after TAA. Neutrophils were the primary inflammatory cells within 3 weeks after CBDL and at 4 week after TAA. M2 macrophages were the primary inflammatory cells, meantime, pulmonary fibrosis, GM-CSFR, and CCR2 were specifically increased from 4 week after CBDL. AntiPMN antibody treatment decreased neutrophil and macrophage accumulation, CL or the combination of antiGM-CSF antibody and bindarit treatment decreased macrophage recruitment, resulting in pulmonary fibrosis, vascular dilatation, and hypoxemia in CBDL rats alleviated. The combination treatment of GM-CSF and MCP1 promoted cell migration, M2 macrophage differentiation, and transforming growth factor-ß1 (TGF-ß1) production in BMDMs. Conclusively, our results highlight neutrophil recruitment mediates pulmonary vascular dilatation and hypoxemia in the early stage of rat HPS. Further, M2 macrophage accumulation induced by GM-CSF/GM-CSFR and MCP1/CCR2 leads to pulmonary fibrosis and promotes vascular dilatation and hypoxemia, as a result, HPS develops.

Hepatopulmonary syndrome delays postoperative recovery and increases pulmonary complications after hepatectomy.

BACKGROUND: This study attempted to investigate the impact of hepatopulmonary syndrome (HPS) on postoperative outcomes in hepatitis B virus-induced hepatocellular carcinoma (HBV-HCC) patients. METHODS: HBV-HCC patients undergoing primary curative hepatectomy for HCC in our hospital were diagnosed with HPS by contrast-enhanced echocardiography (CEE) and arterial blood gas analysis. Patients were divided into HPS, intrapulmonary vascular dilation (IPVD) (patients with positive CEE results and normal oxygenation) and control (patients with negative CEE results) groups. Baseline information, perioperative clinical data and postoperative pulmonary complications (PPCs) were compared among all groups. Cytokines in patient serums from each group (n = 8) were also assessed. RESULTS: Eighty-seven patients undergoing hepatectomy from October 2019 to January 2020 were analyzed. The average time in the postanaesthesia care unit (112.10 ± 38.57 min) and oxygen absorption after extubation [34.0 (14.5-54.5) min] in the HPS group was longer than in IPVD [81.81 ± 26.18 min and 16.0 (12.3-24.0) min] and control [93.70 ± 34.06 min and 20.5 (13.8-37.0) min] groups. There were no significant differences in oxygen absorption time after extubation between HPS and control groups. The incidence of PPCs, especially bi-lateral pleural effusions in the HPS group (61.9%), was higher than in IPVD (12.5%) and control (30.0%) groups. Increased serum levels of the growth-regulated oncogene, monocyte chemoattractant protein, soluble CD40 ligand and interleukin 8 might be related to delayed recovery in HPS patients. CONCLUSIONS: HPS patients with HBV-HCC suffer delayed postoperative recovery and are at higher risk for PPCs, especially bi-lateral pleural effusions, which might be associated with changes in certain cytokines.

Effects of dexmedetomidine on the function of distal organs and oxidative stress after lower limb ischaemia-reperfusion in elderly patients undergoing unilateral knee arthroplasty.

AIMS: This study aims to evaluate the effects of dexmedetomidine on organ function, inflammation response, and oxidative stress in elderly patients following iatrogenic lower limb ischaemia-reperfusion (IR) during unilateral total knee arthroplasty. METHODS: Following unilateral total knee arthroplasty, 54 elderly patients were randomized to receive either intraoperative intravenous injection of dexmedetomidine (n = 27) or equivalent volume of 0.9% saline (n = 27). Blood samples were harvested at 5 minutes before lower limb tourniquet release (baseline); and 1, 6 and 24 hours after tourniquet release. Surrogate markers of cardiac, pulmonary, hepatic and renal function, oxidative stress, inflammatory response, along with parasympathetic and sympathetic activity were recorded and analysed. RESULTS: The levels of blood xanthine oxidase, creatine kinase, lactic acid and respiratory index increased in patients following tourniquet-induced lower limb IR injury. Dexmedetomidine administration decreased the respiratory index (P = .014, P = .01, and P = .043) and the norepinephrine level (P < .001) at 1, 6 and 24 hours; and decreased the xanthine oxidase level (P = .049, P < .001) at 6 and 24 hours after tourniquet release compared with the Control group. Other measurements, including creatine kinase isoenzyme, lactate dehydrogenase, creatinine, urea nitrogen, glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase, malondialdehyde, interleukin-1, interleukin-6 and tumour necrosis factor-α, were not statistically significantly different between the 2 groups. CONCLUSIONS: Intraoperative dexmedetomidine administration in elderly patients dampens the deterioration in respiratory function and suppresses the oxidative stress response in elderly patients following iatrogenic lower limb IR injury.

Liposomal Bupivacaine Single-Injection Compared With Continuous Local Anesthetic Nerve Blocks for Painful Surgeries: A Meta-Analysis of Randomized Controlled Trials and Trial Sequential Analysis.

OBJECTIVE: This meta-analysis aimed to determine whether liposomal bupivacaine (LB) single-injection could achieve an analgesic effect similar to that of continuous local anesthetic nerve blocks (CNBs) after painful surgeries. METHODS: Embase, PubMed, and the Cochrane Library databases were comprehensively searched. Randomized controlled trials (RCTs) with a modified Jadad score ≥ 4 compared LB single-injection with CNBs in patients after painful surgeries were included. The primary outcomes were VAS pain score and opioid consumption. The secondary outcomes were complications and length of hospital stay. Review Manager 5.3 and trial sequential analysis (TSA) 0.9.5.10 were used to analyze the extracted data. RESULTS: Six RCTs of 625 patients were included for meta-analysis. Both groups in 5 RCTs described standard concomitant treatment with multimodal analgesia. There were no significant differences in mean VAS scores for postoperative day 0 (P = 0.12), day 1 (P = 0.18), and day 2 (P = 0.41); highest VAS scores for day 0 (P = 0.18), day 1 (P = 0.46), and day 2 (P = 0.18); total opioid consumption for day 0 (P = 0.05), day 1 (P = 0.28), and day 2 (P = 0.57); complications (P = 0.30); and length of hospital stay (P = 0.64) between the 2 groups. TSA of primary outcomes showed that all cumulative Z curves failed to cross the TSA boundary and did not reach the required information size. CONCLUSIONS: This meta-analysis showed that LB single-injection and CNBs have similar efficacy of pain relief and safety in patients after painful surgeries when concomitant with multimodal analgesia. However, the results of TSA indicate that further trials are still needed to confirm these findings.

The Effect of Mechanical Ventilation With Low Tidal Volume on Blood Loss During Laparoscopic Liver Resection: A Randomized Controlled Trial.

BACKGROUND: Control of bleeding during laparoscopic liver resection (LLR) is important for patient safety. It remains unknown what the effects of mechanical ventilation with varying tidal volumes on bleeding during LLR. Thus, this study aims to investigate whether mechanical ventilation with low tidal volume (LTV) reduces surgical bleeding during LLR. METHODS: In this prospective, randomized, and controlled clinical study, 82 patients who underwent scheduled LLR were enrolled and randomly received either mechanical ventilation with LTV group (6-8 mL/kg) along with recruitment maneuver (once/30 min) without positive end-expiratory pressure (PEEP) or conventional tidal volume (CTV; 10-12 mL/kg) during parenchymal resection. The estimated volume of blood loss during parenchymal resection and the incidence of postoperative respiratory complications were compared between 2 groups. RESULT: The estimated volume of blood loss (median [interquartile range {IQR}]) was decreased in the LTV group compared to the CTV group (301 [148, 402] vs 394 [244, 672] mL, P = .009); blood loss per cm2 of transected surface of liver (5.5 [4.1, 7.7] vs 12.2 [9.8, 14.4] mL/cm2, P < .001) and the risk of clinically significant estimated blood loss (>800 mL) were reduced in the LTV group compared to the CTV group (0/40 vs 8/40, P = .003). Blood transfusion was decreased in the LTV group compared to the CTV group (5% vs 20% of patients, P = .043). No patient in the LTV group but 2 patients in the CTV group were switched from LLR to open hepatectomy. Airway plateau pressure was lower in the LTV group compared to the CTV group (mean ± standard deviation [SD]) (12.7 ± 2.4 vs 17.5 ± 3.5 cm H2O, P = .002). CONCLUSIONS: Mechanical ventilation with LTV may reduce bleeding during laparoscopic liver surgery.