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Introduction Dexmedetomidine (DEX) as a nerve block adjuvant can significantly prolong analgesia. However, whether perineural or systemic administration of DEX is more beneficial in patients undergoing total knee arthroplasty (TKA) has not been thoroughly investigated. To this end, we evaluated the effects of perineural and systemic DEX administration on postoperative analgesia in patients undergoing TKA surgery. Methods We randomly assigned patients undergoing TKA under general anesthesia combined with femoral nerve block and sciatic nerve block to one of three groups: (1) ropivacaine plus perineural dexmedetomidine (DP): 0.25% ropivacaine 40 mL plus 0.5 μg/kg dexmedetomidine; (2) ropivacaine plus systemic dexmedetomidine (DS): 0.25% ropivacaine 40 mL plus systemic 0.5 μg/kg dexmedetomidine; (3) control group (C): 0.25% ropivacaine 40 mL. Results The average length of time until patients first experienced postoperative pain was significantly longer in the DP group (26.0 h [22.0–30.0 h]) than in the DS group (22.4 h [18–26.8 h]) and the control group (22.9 h [19.5–26.3 h], P = 0.001). For this result there was no significant difference between the DS and the control group. Compared with the DS and control groups, patients in the DP group had lower resting visual analogue scale (VAS) scores at 24, 48, and 72 h after surgery (P

Autophagy allows cancer cells to respond changes in nutrient status by degrading and recycling non-essential intracellular contents. Inhibition of autophagy combined with nutrient deprivation is an effective strategy to treat cancer. Pain is a primary determinant of poor quality of life in advanced cancer patients, but there is currently no satisfactory treatment. In addition, effective treatment of cancer does not efficiently relieve cancer pain, but may increase pain in many cases. Hence, few studies focus on simultaneous cancer therapy and pain relief, and made this situation even worse. Method: Ropivacaine was loaded into tumor-active targeted liposomes. The cytotoxicity of ropivacaine-based combination therapy in B16 and HeLa cells were tested. Moreover, a mice model of cancer pain which was induced by inoculation of melanoma near the sciatic nerve was constructed to assess the cancer suppression and pain relief effects of ropivacaine-based combination therapy. Results: Ropivacaine and ropivacaine-loaded liposomes (Rop-DPRL) were novelly found to damage autophagic degradation. Replicated administration of Rop-DPRL and calorie restriction (CR) could efficiently repress the development of tumor. In addition, administration of Rop-DPRL could relieve cancer pain with its own analgestic ability in a short duration, while repeated administration of Rop-DPRL and CR resulted in continuous alleviation of cancer pain through reduction of VEGF-A levels in advanced cancer mice. Further, dual inhibition of phosphorylation of STAT3 at Tyr705 and Ser727 by Rop-DPRL and CR contribute to the reduction of VEGF-A. Conclusion: Combination therapy with Rop-DPRL and nutrient deprivation simultaneously suppresses cancer growth and relieves cancer pain.

BackgroundSufentanil has sedative and inhibitory effects on the intubation response, but high doses of sufentanil can cause coughing and respiratory depression. Dezocine has been documented effectively suppressing sufentanil-induced cough. Whether dezocine can inhibit the respiratory depression caused by sufentanil is unknown. This study aims to observe the efficacy of dezocine combined with sufentanil in awake intubation.MethodsFour hundred and three patients of American Society of Anesthesiologists physical status Classes I and II, aged 18–65 years, were randomly allocated into four groups: Group saline (saline + 0.4 ug/kg sufentanil), Group D0.05 (dezocine 0.05 mg/kg + 0.4 ug/kg sufentanil), Group D0.10 (dezocine 0.10 mg/kg + 0.4 ug/kg sufentanil), and Group D0.15 (dezocine 0.15 mg/kg + 0.4 ug/kg sufentanil). The primary outcome of our study was to observe the incidence of respiratory depression. Secondary outcomes included the success rate of intubation, ease of intubation, intubation comfort score, sore throat, hoarseness, lethargy, limb movement, glottis exposing and the satisfaction of patients during intubation. Hemodynamic changes were recorded after sufentanil injection and awake intubation.ResultsThere was no difference in the effect of normal saline and 0.05 mg/kg dezocine on respiratory depression (P = 0.603). The incidence of respiratory depression in Group D0.10 and Group D0.15 was lower than that of Group saline. Cough was statistically different between the four groups (P P P > 0.05).ConclusionsOur study indicated that 0.10 mg/kg and 0.15 mg/kg dezocine might prevent the occurrence of cough and respiratory depression induced by sufentanil during awake intubation and improve patient satisfaction.Trial registrationClinicaltrials.gov (NCT02673723), 2- 4- 2016.

Background Peripheral local anaesthetic blockade has an important role in multimodal postoperative analgesia after video-assisted thoracic surgery. Intercostal nerve block has an opioid-sparing effect after thoracoscopic surgery, but there is little information about an intra-operative opioid-sparing effect. Objective This prospective randomised trial was designed to evaluate the feasibility of a modified intercostal nerve block and its potential opioid-sparing effect during single-port thoracoscopic lobectomy. Design This was a randomised controlled study. Setting The First Affiliated Hospital of Anhui Medical University, Hefei, China, from January 2020 to April 2020. Patients Fifty patients scheduled for single-port thoracoscopic lobectomy were enrolled. Intervention Patients were randomised to receive the intercostal nerve block using 10 ml 0.35% ropivacaine (group MINB) or conventional general anaesthesia (group CGA). Following a bolus of 0.5 to 1.0 μg kg remifentanil, it was then infused at 0.2 to 0.5 μg kg min during surgery to keep mean arterial pressure or heart rate values around 20% below baseline values. Main outcome measures The primary outcome was intra-operative remifentanil consumption. Results Median [IQR] remifentanil consumption was reduced in the MINB group [0 μg (0 to 0 μg)] compared with the CGA group [1650.0 μg (870.0 to 1892.5 μg)]. The median difference was 1650.0 μg (95%CI 1200.0 to 1770.0 μg; P = 0.00). The total number of analgesic demands during the first 24 and 48 h in the MINB group was significantly less than in the CGA group (difference = 1; 95% CI 1 to 3; P = 0.00 and difference = 4; 95% CI 3 to 5; P = 0.00; respectively). The difference in time to first demand for analgesia was significant [difference = 728 min (95% CI 344 to 1381 min), P = 0.00] and also in the number of patients requiring additional tramadol (P = 0.03). Conclusion We have shown intra-operative opioid-sparing with a modified intercostal nerve block during single-port thoracoscopic lobectomy, with opioid-sparing extending 48 h after surgery. However, the opioid-sparing effect was not associated with a reduction in opioid side effects. Trial registration http://www.chictr.org.cn, ChiCTR2000029337.

Background: The widespread use of total knee arthroplasty(TKA) to treat patients who suffer knee osteoarthritis(KOA) has led to a number of postoperative problems, including the recovery of postoperative quality of life and postoperative delirium(POD). Both problems could cause profound damages to patients and their families. This study assessed and compared the effects of total intravenous anesthesia with propofol versus inhalational anesthesia (sevoflurane) on postoperative quality of life and POD in patients who underwent TKA.Methods: One hundred and fifty patients American Society of Anesthesiologists(ASA) I-III were assessed for inclusion in this study, and randomly divided into inhalational anesthesia with sevoflurane group(group S), and total intravenous anesthesia with propofol group(group P). The primary outcome was postoperative quality of life and secondary outcome was POD.Results: The quality of life at the first month after surgery in group S was better than that in group P(P=0.02). However, there was no significant difference in quality of life between the two groups at 1 day before surgery, 1 day after surgery, 3 days after surgery, 7 days after surgery and 3 months after surgery. In group P, 19 patients (31.1%) had no anxiety/depression problems, 40 patients (65.6%) had moderate problems, and 2 patients (3.3%) had severe problems.In group S, 37 patients (60.6%) had no problems in anxiety/depression, 23 patients (37.7%) had moderate problems, and 1 patient had severe problems (1.7%). These two outcomes had significant differences (P=0.005) .The incidence of POD within 3 days after surgery was 24.6% (15/61) in group P and 36.1% (22/61) in group S. There was no significant difference in the incidence of POD between the two groups (P=0.17).Conclusions: Group S patients have a better quality of life at the first month after surgery in comparison with those in group P regarding anxiety/depression. However, there were no significant differences in the quality of lives between the two groups at 1 day before surgery, 1 day after surgery, 3 days after surgery, 7 days after surgery, and 3 months after surgery. There was also no significant difference in POD. Thus, we concluded that both anesthetic technologies could be extensively used for TKA.Trial registration: This trial was registered at the Chinese Clinical Trial Registry (ChiCRT-IOR-17012428). Date of Registration: 21 Aug. 2017.

We aimed to evaluate the effect of Dexmedetomidine (Dex) on immunology function of macrophages and inflammatory reactions in non-ventilated lung tissues from both humans and rats.Patients scheduled for lung lobectomy were randomly assigned to traditional anesthesia group or Dex anesthesia group, 15 subjects in each group. CD68, CD86 and CD206 were used to mark activate and polarized macrophages using immunofluorescence staining in human lung tissues. Sprague-Dawley rats were used to set lung injury model and randomly divided into Control group, one-lung ventilation group (CLI group) and CLI + Dex group. Lung tissues and bronchoalveolar lavage fluid (BALF) from non-ventilated lungs were collected. The acquired lung tissues were subjected to hematoxylin-eosin (HE) staining and the inflammatory cells in BALF were calculated. Levels of cytokines and chemokines were detected by enzyme-linked immunosorbent assays (ELISA).Results from humans showed that anesthesia with Dex decreased the number of both CD68 positive cells and CD86 positive cells and down-regulated level of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and monocyte chemotactic protein 1 (MCP-1) in human lung. Results from rats demonstrated that treatment with Dex reversed the increased inflammatory cells in lung and the increased levels of TNF-α, interleukin-1β (IL-β), MCP-1 and chemokine (C-X-C motif) ligand 1 (CXCL1) resulted from non-ventilation; Dex increased the anti-inflammatory cytokine interleukin-10 (IL-10) in BALF from non-ventilated lung.This study showed that Dex modulated the activation and immunological function of macrophages in non-ventilated lung and revealed a protective role in collapsed lung injury.

Background Dexmedetomidine potentially confers an advantage to reduce the incidence of postoperative delirium (POD) in surgical patients. Anti-inflammation is important effect of this sedative drug. In this study, we aimed to investigate whether the effect of dexmedetomidine on the postoperative cognitive function is via inhibiting peripheral inflammation. Methods A prospective, randomized, controlled study was conducted with patients 65 years of age or above who received total knee arthroplasty from January 2019 to May 2019. The patients were randomly assigned to receive spinal anesthesia supplemented with propofol or dexmedetomidine for sedation. The incidence of POD was the primary endpoint and was evaluated with the Confusion Assessment Method, and incidence of postoperative cognitive dysfunction was assessed with the Mini-Mental State Examination. Blood samples were collected postoperatively to test the plasma concentrations of interleukin-6, tumor necrosis factor-α, and S100β. Results A total of 366 patients were randomly assigned to 2 groups. Patients who received dexmedetomidine sedation had lower incidences of POD and better postoperative cognitive function than patients sedated with propofol. There was no difference in postoperative plasma concentrations of tumor necrosis factor-α and interleukin-6 between the 2 groups. The concentration of S100β 48 hours after surgery was higher in patients sedated with propofol than in patients who received dexmedetomidine sedation. Conclusion Intraoperative sedation with dexmedetomidine conferred better postoperative neurocognitive function for elderly patients who received total knee arthroplasty. This effect was unrelated to the modulation of dexmedetomidine on peripheral inflammation.

Background Peripheral nerve block is a preferable method for elderly patients receiving hip arthroplasty. Sedation with dexmedetomidine may reduce postoperative delirium (POD). The aim of this study was to investigate whether intraoperative sedation with dexmedetomidine, as a supplementary to peripheral nerve block for elderly patients receiving total hip arthroplasty, can decrease the prevalence of POD. Methods A prospective, randomized controlled study was conducted with patients 65 years of age or older who underwent total hip arthroplasty between June 2016 and June 2017. The patients were randomly assigned to receive a lumbosacral plexus plus T12 paravertebral block supplemented with propofol or dexmedetomidine for sedation. Incidence of POD was the primary endpoint and was determined with the confusion assessment method, and incidence of postoperative cognitive dysfunction (POCD) was assessed with the mini-mental state examination. The time of ambulation, discharge time, and complications over a 30-day postsurgery period were also recorded. Results A total of 296 patients were randomly assigned to 2 groups. The patients sedated with dexmedetomidine had lower incidences of POD and POCD and were out of bed and discharged sooner than the patients sedated with propofol. There was no difference in complications between the 2 groups. Conclusions As a supplementary to peripheral nerve block, intraoperative sedation with dexmedetomidine could be associated with a lower incidence of POD, which may have benefits on reducing the incidence of early POCD and offering a better short-term recovery for elderly patients receiving hip arthroplasty.

Background Children with multiple exposures to anesthesia and surgery may have an increased risk of developing cognitive impairment. Sevoflurane, a commonly used anesthetic in children, has been reported to decrease levels of postsynaptic density 95 protein. However, the upstream mechanisms and downstream consequences of the sevoflurane-induced reduction in postsynaptic density 95 protein levels remains largely unknown. We therefore set out to assess whether sevoflurane acts on ubiquitination–proteasome pathway to facilitate postsynaptic density 95 protein degradation. Methods Six-day-old wild-type mice received anesthesia with 3% sevoflurane 2 h daily for 3 days starting on postnatal day 6. We determined the effects of the sevoflurane anesthesia on mRNA, protein and ubiquitinated levels of postsynaptic density 95 protein in neurons, and synaptosomes and hippocampus of young mice. Cognitive function in the mice was determined at postnatal day 31 by using a Morris water maze. Proteasome inhibitor MG132 and E3 ligase mouse double mutant 2 homolog inhibitor Nutlin-3 were used for the interaction studies. Results The sevoflurane anesthesia decreased protein, but not mRNA, levels of postsynaptic density 95, and reduced ubiquitinated postsynaptic density 95 protein levels in neurons, synaptosomes, and hippocampus of young mice. Both MG132 and Nutlin-3 blocked these sevoflurane-induced effects. Sevoflurane promoted the interaction of mouse double mutant 2 homolog and postsynaptic density 95 protein in neurons. Finally, MG132 and Nutlin-3 ameliorated the sevoflurane-induced cognitive impairment in the mice. Conclusions These data suggest that sevoflurane acts on the ubiquitination–proteasome pathway to facilitate postsynaptic density 95 protein degradation, which then decreases postsynaptic density 95 protein levels, leading to cognitive impairment in young mice. These studies would further promote the mechanistic investigation of anesthesia neurotoxicity in the developing brain.

The cellular mechanisms underlying amnesia produced by the analgesic ketamine are not clear. The current study examined the effects of ketamine on memory consolidation in rats trained in a Morris water maze task, and further tested whether the glycogen synthase kinase (GSK)3β/β-catenin signaling pathway was involved in mediating the effects of posttraining ketamine on retention. Adult male Sprague-Dawley rats were injected with ketamine (0, 25, 50, or 100mg/kg) immediately after an eight-trial water maze training session. A probe trial was carried out 24 h later to examine the effects of ketamine on memory. Rats hippocampi were subjected to western blot assays to measure levels of native versus phosphorylated (p) GSK3β and β-catenin protein. Memory performance was significantly impaired in rats injected with ketamine (100 mg/kg) after training. Western blots showed that p-GSK-3β(Ser9) levels were reduced and p-β-catenin(Ser33/37/Thr41) levels were elevated in ketamine treated rats during consolidation. These posttraining changes in hippocampal p-GSK-3β and p-β-catenin were blocked by injection of 100mg/kg ketamine immediately after training, indicating that the 100mg/kg dose of ketamine altered activation of GSK3β/β-catenin signaling pathway in the hippocampus. Acute injection of the GSK3β specific inhibitor SB216763 (1 ng/0.5 μl/side) into area CA1 of the hippocampus after water maze training prevented ketamine-induced impairment of memory and blocked ketamine-induced effects on the GSK3β/β-catenin signaling pathway in the hippocampus. Our results suggest that an anesthetic dose of ketamine injected immediately after Morris water maze training impaired memory consolidation and support the hypothesis that GSK3β/β-catenin signaling may play a role in ketamine-induced retrograde amnesia.

Postoperative cognitive dysfunction is a common complication of anesthesia and surgery. Attention networks are essential components of cognitive function and are subject to impairment after anesthesia and surgery. It is not known whether such impairment represents a global attention deficit or relates to a specific attention network. We used an Attention Network Task (ANT) to examine the efficiency of the alerting, orienting, and executive control attention networks in middle-aged women (40-60 years) undergoing gynecologic surgery. A matched group of medical inpatients were recruited as a control.Fifty female patients undergoing gynecologic surgery (observation group) and 50 female medical inpatients (control group) participated in this study. Preoperatively patients were administered a mini-mental state examination as a screening method. The preoperative efficiencies of three attention networks in an attention network test were compared to the 1st and 5th post-operative days.The control group did not have any significant attention network impairments. On the 1st postoperative day, significant impairment was shown in the alerting (p=0.003 vs. control group, p=0.015 vs. baseline), orienting (p0.001 vs. both baseline level and control group), and executive control networks (p=0.007 vs. control group, p=0.002 vs. baseline) of the observation group. By the 5th postoperative day, the alerting network efficiency had recovered to preoperative levels (p=0.464 vs. baseline) and the orienting network efficiency had recovered partially (p=0.031 vs. 1st post-operative day), but not to preoperative levels (p=0.01 vs. baseline). The executive control network did not recover by the 5th postoperative day (p=0.001 vs. baseline, p=0.680 vs. 1st post-operative day).Attention networks of middle-aged women show a varying degree of significant impairment and differing levels of recovery after surgery and propofol anesthetic.

Previous reports have suggested that polymorphism of the opioid receptor A118G affects the efficacy of opioid analgesia. The aim of this study was to investigate whether such polymorphism contributed to variability in epidural mixture (sufentanil plus ropivacaine) requirements through patient-controlled epidural analgesia (PCEA) after cesarean section.One hundred eighty consenting women undergoing elective cesarean delivery were enrolled in the study. Patients received sufentanil and ropivacaine for pain control after surgery. Sufentanil (50 mcg) diluted with 0.2% ropivacaine in a total volume of 100 mL was administered by PCEA with a background infusion rate of 2 mL/h and a pump program set to deliver 0.5-mL boluses with a lockout time of 15 minutes. The analgesic effect and adverse effects were measured with rating scales. The total consumption of the epidural mixture in the first 24 hours postoperatively was recorded. Blood samples were genotyped to classify patients into 3 groups according to A118G polymorphism.Of 161 patients included in the analysis, 63 were homozygous (AA), 81 were heterozygous (AG), and 17 were homozygous (GG) for the A118G polymorphism. No difference was observed among groups in the consumption of the epidural mixture within the first 24 hours postoperatively (P = 0.3). Satisfaction with analgesia, pain scores, and adverse effects were similar among the groups.The analgesic requirements of patients receiving sufentanil and ropivacaine through PCEA after caesarean section were not associated with A118G polymorphism.