The effect of intravenous granisetron on prophylactic ephedrine for preventing hypotension after general anaesthesia induction in elderly patients: a randomized controlled trial.

Serotonin 3 receptor antagonists, a commonly used drug for preventing postoperative nausea and vomiting, have recently been reported to decrease the incidence of hypotension and the need for vasoactive drugs after spinal anaesthesia in obstetric surgery. However, it remains unknown whether they could also prevent hypotension after induction of general anaesthesia. In the current study, we aimed to investigate the effect of intravenous granisetron on prophylactic ephedrine for preventing hypotension after general anaesthesia induction in elderly patients. Sixty elderly patients were randomly assigned to receive granisetron or saline control 30 min before induction of general anaesthesia. The first patient in each group received a prophylactic dose of ephedrine (0.15 mg kg-1) to prevent hypotension. The prophylactic dose for each patient was increased or decreased by 0.05 mg/kg based on the efficacy results of the previous patient. The up-down sequential allocation analysis and probit regression was used to calculate the effective dose for 50% of patients (ED50) with prophylactic ephedrine. In the up-down sequential allocation analysis, the ED50 of ephedrine was significantly lower in group granisetron (0.08 mg kg-1 [95% CI, 0.06-0.11 mg kg-1]) when compared with group control (0.14 mg kg-1 [95% CI, 0.13-0.16 mg kg-1]) (P < 0.001). The conclusion was further supported by probit regression analysis (0.09 mg kg-1 [95% CI, 0.05-0.12 mg kg-1] in group granisetron and 0.14 mg kg-1 [95% CI, 0.12-0.16 mg kg-1] in group control). Intravenous granisetron reduced the requirement of prophylactic ephedrine in preventing hypotension after general anaesthesia induction in elderly patients.

Lipocalin 2 in the Paraventricular Thalamic Nucleus Contributes to DSS-Induced Depressive-Like Behaviors.

The incidence rate of anxiety and depression is significantly higher in patients with inflammatory bowel diseases (IBD) than in the general population. The mechanisms underlying dextran sulfate sodium (DSS)-induced depressive-like behaviors are still unclear. We clarified that IBD mice induced by repeated administration of DSS presented depressive-like behaviors. The paraventricular thalamic nucleus (PVT) was regarded as the activated brain region by the number of c-fos-labeled neurons. RNA-sequencing analysis showed that lipocalin 2 (Lcn2) was upregulated in the PVT of mice with DSS-induced depressive behaviors. Upregulating Lcn2 from neuronal activity induced dendritic spine loss and the secreted protein induced chemokine expression and subsequently contributed to microglial activation leading to blood-brain barrier permeability. Moreover, Lcn2 silencing in the PVT alleviated the DSS-induced depressive-like behaviors. The present study demonstrated that elevated Lcn2 in the PVT is a critical factor for DSS-induced depressive behaviors.

Unexpected difficult airway due to severe upper tracheal distortion: A case report.

BACKGROUND: Difficult airway is a significant cause of anesthesia-associated death and disability. Currently, physical examinations of thyromental distance, mouth opening, Mafampaii classification, etc. combined with X-ray, computed tomography (CT), and other imaging technologies are mainly used to evaluate difficult airways. However, in many special cases, i.e., emergency surgery, imaging examinations cannot be completed preoperatively. Such patients' airway can only be evaluated through general physical examination, which inevitably increases the likelihood of an unexpected difficult airway during anesthesia. CASE SUMMARY: We report a rare case of difficult intubation because of severe upper trachea distortion after induction. Emergency holmium laser lithotripsy was performed under transurethral ureteroscopy because the patient had anuria for 4 d and a creatinine level of 890 µmol/L. Due to the urgency of the condition, chest radiography or chest CT was not examined before surgery and the anesthesiologist did not evaluate the airway adequately, resulting in an unexpected difficult airway. CONCLUSION: The incidence of tracheal malformation and tracheal stenosis is extremely low, but the risk of hypoxia and even death due to difficult airways is extremely high for such patients. It is recommended to complete preoperative imaging examinations of the airway. For life-threatening emergency patients, a pre-anesthesia reassessment should be performed and surgeons should be prepared to prevent and manage the difficult airway.

Egr2 contributes to age-dependent vulnerability to sevoflurane-induced cognitive deficits in mice.

Sevoflurane inhalation is prone to initiate cognitive deficits in infants. The early growth response-2 (Egr-2) gene is DNA-binding transcription factor, involving in cognitive function. In this study we explored the molecular mechanisms underlying the vulnerability to cognitive deficits after sevoflurane administration. Six-day-old (young) and 6-week-old (early adult) mice received anesthesia with 3% sevoflurane for 2 h daily for 3 days. We showed that multiple exposures of sevoflurane induced significant learning ability impairment in young but not early adult mice, assessed in Morris water maze test on postnatal days 65. The integrated differential expression analysis revealed distinct transcription responses of Egr family members in the hippocampus of the young and early adult mice after sevoflurane administration. Particularly, Egr2 was significantly upregulated after sevoflurane exposure only in young mice. Microinjection of Egr2 shRNA recombinant adeno-associated virus into the dentate gyrus alleviated sevoflurane-induced cognitive deficits, and abolished sevoflurane-induced dendritic spins loss and BDNF downregulation in young mice. On the contrary, microinjection of the Egr2 overexpression virus in the dentate gyrus aggravated learning ability impairment induced by sevoflurane in young mice but not early adult mice. Furthermore, we revealed that sevoflurane markedly upregulated the nuclear factors of activated T-cells NFATC1 and NFATC2 in young mice, which were involved in Egr2 regulation. In conclusion, Egr2 serves as a critical factor for age-dependent vulnerability to sevoflurane-induced cognitive deficits.

Analgesic efficacy and safety of erector spinae plane block in breast cancer surgery: a systematic review and meta-analysis.

BACKGROUND: Surgical resection is considered to be the primary and most effective therapy for breast cancer, postoperative pain is an issue gaining significant attention. In recent years, erector spinae plane block (ESPB) has attracted much attention in postoperative analgesia, but its effectiveness is still controversial. This meta-analysis was implemented to verify the clinical analgesic efficacy and safety of erector spinae plane block in patients undergoing breast cancer surgery. METHODS: We searched PubMed, EMBASE, Web of Science, the Cochrane Library and ClinicalTrials.gov for randomized controlled trials (RCTs) comparing ESPB with general anesthesia (GA) in breast cancer surgery that were published before December 25, 2020. The primary outcome was opioid consumption at the first 24 h after surgery, while secondary outcomes included pain scores at 1, 6,12 and 24 h after surgery, opioid consumption at 1, 6 and 12 h after surgery, intraoperative opioid consumption, number of patients who need for rescue analgesia, and the incidence of postoperative nausea and vomiting (PONV). RESULTS: Eleven randomized controlled trials involving 679 patients met the study inclusion criteria and were included in this study. In comparison to GA group, the ESPB group showed a significant reduction in morphine consumption at the first 24 h after surgery by a mean difference (MD) of - 7.67 mg [95% confidence interval (CI) - 10.35 to - 5.00] (P <  0.01). In addition, the ESPB group showed lower pain scores than the GA group in the four time periods (1, 6, 12 and 24 h after surgery). ESPB group significantly reduce the intraoperative consumption of fentanyl, the need for postoperative rescue analgesia, and the incidence of PONV. CONCLUSIONS: Ultrasound-guided ESPB is an effective approach for reducing morphine consumption and pain intensity within the first 24 h after breast cancer surgery, compared with GA alone.

The potential mechanism of postoperative cognitive dysfunction in older people.

Postoperative cognitive dysfunction (POCD) is a common disorder following surgery, which seriously threatens the quality of patients' life, especially the older people. Accumulating attention has been paid to POCD worldwide in pace with the popularization of anesthesia/surgery. The development of medical humanities and rehabilitation medicine sets higher demands on accurate diagnosis and safe treatment system of POCD. Although the research on POCD is in full swing, underlying pathogenesis is still inconclusive due to these conflicting results and controversial evidence. Generally, POCD is closely related to neuropsychiatric diseases such as dementia, depression and Alzheimer's disease in molecular pathways. Researchers have come up with various hypotheses to reveal the mechanisms of POCD, including neuroinflammation, oxidative stress, autophagy disorder, impaired synaptic function, lacking neurotrophic support, etc. Recent work focused on molecular mechanism of POCD in older people has been thoroughly reviewed and summed up here, concerning the changes of peripheral circulation, pathological pathways of central nervous system (CNS), the microbiota-gut-brain axis and the related brain regions. Accordingly, this article provides a better perspective to understand the development situation of POCD in older people, which is conductive to uncover the pathological mechanism and exploit reasonable treatment strategy of POCD.

Insights Into Translatomics in the Nervous System.

Most neurological disorders are caused by abnormal gene translation. Generally, dysregulation of elements involved in the translational process disrupts homeostasis in neurons and neuroglia. Better understanding of how the gene translation process occurs requires detailed analysis of transcriptomic and proteomic profile data. However, a lack of strictly direct correlations between mRNA and protein levels limits translational investigation by combining transcriptomic and proteomic profiling. The much better correlation between proteins and translated mRNAs than total mRNAs in abundance and insufficiently sensitive proteomics approach promote the requirement of advances in translatomics technology. Translatomics which capture and sequence the mRNAs associated with ribosomes has been effective in identifying translational changes by genetics or projections, ribosome stalling, local translation, and transcript isoforms in the nervous system. Here, we place emphasis on the main three translatomics methods currently used to profile mRNAs attached to ribosome-nascent chain complex (RNC-mRNA). Their prominent applications in neurological diseases including glioma, neuropathic pain, depression, fragile X syndrome (FXS), neurodegenerative disorders are outlined. The content reviewed here expands our understanding on the contributions of aberrant translation to neurological disease development.

Ilioinguinal/iliohypogastric nerve block versus transversus abdominis plane block for pain management following inguinal hernia repair surgery: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Controversy still exists regarding the efficiency and safety of ilioinguinal/iliohypogastric nerve (II/IH) block versus transversus abdominis plane (TAP) block for pain management after inguinal hernia repair. The purpose of the current meta-analysis was to perform a relatively credible and comprehensive assessment to compare the efficiency and safety of II/IH versus TAP for pain management after inguinal hernia repair. METHODS: The PUBMED, CENTRAL, and EMBASE were systematically searched. Studies comparing II/IH versus TAP for pain management in adult patients undergoing inguinal herniorrhaphy were included. The results of this study are synthesized and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: Six studies with 632 patients were included in this study. No statistically significant difference was observed between the II/IH and TAP groups in postoperative opioid use, the time to first request for rescue analgesia, the incidence of postoperative nausea and vomiting (PONV), incidence of complication related with nerve blocks and patient satisfaction. The TAP group had a significantly higher pain score at 6 and 8 hours postoperatively (6 hours: mean difference [MD] = 0.94, 95% confidence interval [CI] 0.67-1.22, I = 0%, P < .01; 8 hours: MD = 1.02, 95% CI 0.3-1.74, I = 59%, P < .01). However, no statistically significant difference was observed at 1, 2, 4, 12, 24, 48 hours, and 6 months postoperatively. CONCLUSIONS: In general, this meta-analysis revealed that both approaches have similar postoperative opioid consumption and no significant difference in postoperative complication and patient satisfaction. The II/IH block provides excellent analgesic effects at 6 and 8 hours after inguinal herniorrhaphy in compared with the TAP block. However, more high-quality randomized controlled trials with long-term follow-up are still required to make the conclusion.

The safety and efficiency of intravenous administration of tranexamic acid in coronary artery bypass grafting (CABG): a meta-analysis of 28 randomized controlled trials.

BACKGROUND: The safety and efficiency of intravenous administration of tranexamic acid (TXA) in coronary artery bypass grafting (CABG) remains unconfirmed. Therefore, we conducted a meta-analysis on this topic. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PUBMED and EMBASE for randomized controlled trials on the topic. The results of this work are synthetized and reported in accordance with the PRISMA statement. RESULTS: Twenty-eight studies met our inclusion criteria. TXA reduced the incidence of postoperative reoperation of bleeding (relative risk [RR], 0.46; 95% confidence interval [CI]; 0.31-0.68), the frequency of any allogeneic transfusion (RR, 0.64; 95% CI, 0.52-0.78) and the postoperative chest tube drainage in the first 24 h by 206 ml (95% CI - 248.23 to - 164.15). TXA did not significantly affect the incidence of postoperative cerebrovascular accident (RR, 0.93; 95%CI, 0.62-1.39), mortality (RR, 0.82; 95%CI, 0.53-1.28), myocardial infarction (RR, 0.90; 95%CI, 0.78-1.05), acute renal insufficiency (RR, 1.01; 95%CI, 0.77-1.32). However, it may increase the incidence of postoperative seizures (RR, 6.67; 95%CI, 1.77-25.20). Moreover, the subgroup analyses in on-pump and off-pump CABG, the sensitivity analyses in trials randomized more than 99 participants and sensitivity analyses that excluded the study with the largest number of participants further strengthened the above results. CONCLUSIONS: TXA is effective to reduce reoperation for bleeding, blood loss and the need for allogeneic blood products in patients undergoing CABG without increasing prothrombotic complication. However, it may increase the risk of postoperative seizures.

Autophagy activation prevents sevoflurane-induced neurotoxicity in H4 human neuroglioma cells.

AIM: The inhaled anesthetic sevoflurane may induce cognitive impairment in both animals and humans. Previous study has shown that sevoflurane triggers ER stress and may lead to apoptosis in rat hippocampal neurons. In this study, we examined whether sevoflurane caused autophagy and its contributions to sevoflurane induced neuronal cell injury. METHODS: H4 human neuroglioma cells were exposed to 4.1% sevoflurane for 6 h. Cell viability and apoptosis ratio were assessed using a CCK8 kit and flow cytometry, respectively. Autophagosomes in the cells were detected using GFP-LC3 plasmid transfection or transmission electronic microscopy. The expression of LC3B, p62/SQSTM, C/EBP homologous protein (CHOP) and glucose-related protein 78 (GRP78) was assessed with Western blotting. RESULTS: Sevoflurane treatment induced apoptosis and markedly increased the LC3-II level and GFP-LC3 puncta number, decreased p62 expression in H4 cells. Activation of autophagy by rapamycin (1 µmol/L) significantly reduced sevoflurane-induced apoptosis and increased cell viability, whereas inhibition of autophagy with 3-MA (5 mmol/L) caused the opposite effects. Furthermore, sevoflurane treatment markedly increased the expression of CHOP and GRP78, two hallmark proteins of ER stress. Inhibition of ER stress by 4-phenylbutyrate (500 µmol/L) abrogated sevoflurane-induced autophagy and apoptosis, and improved the viability. Moreover, sevoflurane-stimulated expression of CHOP and GRP78 was inhibited by rapamycin, but further enhanced by 3-MA. CONCLUSION: Sevoflurane treatment induces ER stress and activates autophagy, which antagonizes sevoflurane-induced apoptosis in H4 human neuroglioma cells. The results suggest that autophagy may be a potential therapeutic target in preventing sevoflurane-induced neurotoxicity.