Risk factors for methotrexate resistance in low-risk gestational trophoblastic neoplasia patients (FIGO score 0-4).

The challenge of methotrexate (MTX) resistance among low-risk gestational trophoblastic neoplasia (GTN) patients has always been prominent. Despite the International Federation of Gynaecology and Obstetrics (FIGO) score of 0-4 patients comprising the majority of low-risk GTN patients, a comprehensive exploration of the prevalence and risk factors associated with MTX resistance has been limited. Therefore, we aimed to identify associated risk factors in GTN patients with a FIGO score of 0-4. Between January 2005 and December 2020, 310 low-risk GTN patients received primary MTX chemotherapy in two hospitals, with 265 having a FIGO score of 0-4. In the FIGO 0-4 subgroup, 94 (35.5%) were resistant to MTX chemotherapy, and 34 (12.8%) needed multi-agent chemotherapy. Clinicopathologic diagnosis of postmolar choriocarcinoma (OR = 17.18, 95% CI: 4.64-63.70, P < 0.001) and higher pretreatment human chorionic gonadotropin concentration on a logarithmic scale (log-hCG concentration) (OR = 18.11, 95% CI: 3.72-88.15, P < 0.001) were identified as independent risk factors associated with MTX resistance according to multivariable logistic regression. The decision tree model and regression model were developed to predict the risk of MTX resistance in GTN patients with a FIGO score of 0-4. Evaluation of model discrimination, calibration and net benefit revealed the superiority of the decision tree model, which comprised clinicopathologic diagnosis and pretreatment hCG concentration. The patients in the high- and medium-risk groups of the decision tree model had a higher probability of MTX resistance. This study represents the investigation into MTX resistance in GTN patients with a FIGO score of 0-4 and disclosed a remission rate of approximately 65% with MTX chemotherapy. Higher pretreatment hCG concentration and clinicopathologic diagnosis of postmolar choriocarcinoma were independent risk factors associated with resistance to MTX chemotherapy. The decision tree model demonstrated enhanced predictive capabilities regarding the risk of MTX resistance and can serve as a valuable tool to guide the clinical treatment decisions for GTN patients with a FIGO score of 0-4.

Postoperative pain after different doses of remifentanil infusion during anaesthesia: a meta-analysis.

BACKGROUND: This meta-analysis aimed to explore the correlation between the different doses of remifentanil-based anaesthesia and postoperative pain in randomised trials. METHODS: The electronic databases including PubMed, Cochrane, clinical trial registries, and Google Scholar were searched up to November 2022 for randomised controlled trials (RCTs) that assessed the dose dependent efficacy of remifentanil for postoperative pain intensity and hyperalgesia. RESULTS: 31 studies involving 2019 patients were included for analysis. Compared with the high remifentanil dose administration, patients in low doses showed less postoperative pain intensity at 1-2 h (weighted mean differences (WMD): 0.60, 95% CI, 0.05 to 1.15), 3-8 h (WMD: 0.38, 95% CI, 0.00 to 0.75), 24 h (WMD: 0.26, 95% CI, 0.04 to 0.48) and 48 h (WMD: 0.32, 95% CI, 0.09 to 0.55). Remifentanil-free regimen failed to decrease the pain score at 24 h (WMD: 0.10, 95% CI, -0.10 to 0.30) and 48 h (WMD: 0.15, 95% CI, -0.22 to 0.52) in comparison with remifentanil-based anaesthesia. After excluding trials with high heterogeneity, the dose of the remifentanil regimen was closely correlated with the postoperative pain score (P=0.03). In addition, the dose of the remifentanil regimen was not associated with the incidence of postoperative nausea and vomiting (PONV) (P=0.37). CONCLUSIONS: Our meta-analysis reveals that the low dose of remifentanil infusion is recommendable for general anaesthesia maintenance. No evidence suggests that remifentanil-free regimen has superiority in reducing postoperative pain. Moreover, remifentanil doesn't have a dose dependent effect in initiating PONV. TRIAL REGISTRATION: The protocol of present study was registered with PROSPERO (CRD42022378360).

Effect of superior laryngeal nerve block in alleviating sore throat after application of i-gel supraglottic airway: a randomized controlled trial.

BACKGROUND: Postoperative sore throat (POST) is a common complaint after supraglottic airway device (SAD) application. Internal branch of the superior laryngeal nerve (iSLN) block has the potential to alleviate POST. The aim of this trial was to explore the effect of iSLN block in alleviating sore throat, as well as to identify the potential risk factors for POST after SAD insertion. METHODS: One hundred thirty-four patients scheduled for elective gynecological surgery were randomized to either group T: tetracaine syrup (1%) for local lubrication on i-gel supraglottic device (n = 67) or group B: i-gel insertion with water based lubricant on it and followed by bilateral iSLN block (ropivacaine, 0.375%, 2 ml for each side) (n = 67). Under ultrasound guidance, iSLN was exposed below thyrohyoid membrane. The primary outcome was the intensity of sore throat at 6 h after surgery. In addition, POST score at 0.5 h and 24 h, the severity of postoperative swallowing discomfort, acoustic analysis and complications were measured. RESULTS: Compared with tetracaine syrup for local lubrication, iSLN block resulted in a reduced intensity of POST at 0.5 h (P = 0.044, OR = 1.99, 95%CI 1.02 to 3.88) and 6 h (P < 0.001, OR = 5.07, 95%CI 2.53 to 10.14) after surgery, as well as less severity of swallowing discomfort (P < 0.001, OR = 2.21, 95%CI 1.63 to 2.99) and cough (P = 0.039, OR = 1.97, 95%CI 1.04 to 3.73). The patients after iSLN block presented lower jitter and shimmer value in acoustic analysis at 6 h after surgery (P < 0.001). CONCLUSIONS: iSLN block was effective in alleviating POST, improving voice function, as well as reducing postoperative swallowing discomfort and coughing. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2000037974) on 8th Sept 2020.

Application Areas of Intermittent Pneumatic Compression in the Prevention of Deep Vein Thrombosis During Dixon Surgery: A Randomized, Controlled Trial.

PURPOSE: Deep vein thrombosis (DVT) is common in the lithotomy position after laparoscopic surgery. Intermittent pneumatic compression (IPC) plays an important role in DVT prevention. However, few studies have compared the different compression areas of IPC application. It was hypothesized that the location of the compression sleeves could have an impact on the effects of thromboprophylaxis. METHODS: In this randomized, controlled trial performed from August 2020 to March 2021, 164 patients scheduled to undergo laparoscopic Dixon surgery were randomly assigned to one of four groups, based on the bilateral placement of compression sleeves during surgery: feet, calves, thighs, or control (no IPC). Both lower extremities were monitored for DVT on days 1 and 7 after surgery, using ultrasonographic assessment of mean blood velocity, blood flow volume, and diameter of the common femoral veins. Thrombosis-related hematologic analysis was performed. FINDINGS: On day 1 after surgery, IPC of the feet or calves was associated with a reduced prevalence of DVT compared with controls (both: P = 0.024; OR = 0.09; 95% CI, 0.01-0.72), while IPC of the thighs had no significant benefit (P = 0.781; OR = 0.86; 95% CI, 0.29-2.55). The prevalence of DVT in the left extremity was lower with IPC of the feet and calves compared with controls (both, P = 0.048). The mean blood velocity in the common femoral vein was significantly increased after surgery with IPC of the left and right feet (P = 0.006 and 0.007, respectively) and calves (P = 0.011 and P = 0.026, respectively) compared with controls. Similarly, the volume of blood flow in the left common femoral vein was greater with IPC of the feet and calves (P = 0.03 and 0.027, respectively). However, on day 7 after surgery, the between-group differences in the prevalences of DVT and hematologic indicators of thrombosis were not significant. IMPLICATIONS: On day 1 after surgery, IPC application at the feet or calves facilitated venous return and, hence, reduced the prevalence of DVT, especially in the left extremities. However, there were no significant differences in the prevalences of DVT or thrombosis-related hematologic indicators among the four groups on the day 7 after surgery. Chinese Clinical Trial Registration identifier: ChiCTR2000035325.

Effect of transnasal humidified rapid-insufflation ventilatory exchange on gastric insufflation during anaesthesia induction: A randomised controlled trial and multivariate analysis.

BACKGROUND: Mask ventilation during anaesthesia induction is generally used to provide adequate oxygenation but improper mask ventilation can result in gastric insufflation. It has been reported that oxygen administered by transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) during anaesthesia induction can maintain oxygenation but its effect on gastric insufflation is unknown. OBJECTIVES: The primary aim of this study was to evaluate whether THRIVE provided adequate oxygenation without gastric insufflation. The secondary aim was to explore the change in cross-sectional area of the antrum (CSAa) during anaesthesia induction. Other potential risk factors of gastric insufflation were also explored. DESIGN: A prospective, randomised, double-blind study. SETTING: Single centre, Department of Anaesthesiology, 1 st Affiliated Hospital, Wenzhou Medical University, China, from May 2022 to September 2022. PATIENTS: A total of 210 patients (age >18 years, ASA classification I to III) scheduled to undergo general anaesthesia were enrolled. INTERVENTIONS: For induction of general anaesthesia, patients were randomised into two groups: THRIVE and pressure-controlled facemask ventilation (PCFV). The THRIVE group received high-flow nasal oxygen with no additional ventilation. The PCFV group had pressure-controlled positive pressure ventilation from the anaesthesia machine via a tight fitting facemask. Gastric insufflation was detected using real-time ultrasonography. The CSAa was measured from ultrasonography images obtained before anaesthesia induction and at 0, 1, 2 and 3 min after loss of consciousness. MAIN OUTCOME MEASURES: The incidence of gastric insufflation during the period from loss of consciousness until intubation. RESULTS: The THRIVE group had a lower incidence of gastric insufflation during anaesthesia induction than the PCFV group (13.0 vs. 35.3%, odds ratio (OR) = 0.27, 95% confidence interval (CI), 0.14 to 0.56, P  < 0.001). Increase in the CSA after anaesthesia induction was significantly correlated with gastric insufflation (OR = 5.35, 95% CI, 2.90 to 9.89, P  < 0.001). Multivariate logistic regression analysis showed that advancing age (OR = 1.04, 95% CI, 1.01 to 1.07), obstructive sleep apnoea syndrome (OR = 2.43, 95% CI, 1.24 to 4.76), higher Mallampati score (OR = 2.66, 95% CI, 1.21 to 5.85) and PCFV (OR = 4.78, 95% CI, 2.06 to 11.06) were important independent risk factors for gastric insufflation. CONCLUSION: During anaesthesia induction, the THRIVE technique provided adequate oxygenation with a reduced incidence of gastric insufflation. PCFV, advancing age, obstructive sleep apnoea syndrome and the Mallampati score were found to be independent risk factors for gastric insufflation during anaesthesia induction. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR200059555.

Antisense oligodeoxynucleotides against dynamin-related protein 1 reduce remifentanil-induced hyperalgesia by modulating spinal N-methyl-D-aspartate receptor expression in rats.

Background: Spinal N-methyl-D-aspartate (NMDA) receptor activation is attributed to remifentanil-induced hyperalgesia (RIH). However, the specific mechanism and subsequent treatment is still unknown. Previous studies have shown that the dynamin-related protein 1 (DRP1)-mitochondria-reactive oxygen species (ROS) pathway plays an important role in neuropathic pain. This study examined whether antisense oligodeoxynucleotides against DRP1 (AS-DRP1) could reverse RIH. Methods: The authors first measured changes in paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) at 24 hours before remifentanil infusion and 4, 8, 24, and 48 hours after infusion. The expression levels of DRP1 and NR2B were measured after behavioral testing using Western blotting. In addition, DRP1 expression was knocked down by intrathecal administration of AS-DRP1 to investigate the effects of DRP1 on RIH. The behavioral testing, the expression levels of spinal DRP1 and NR2B, and dorsal mitochondrial superoxide were measured. Changes in mitochondrial morphology were assessed using electron microscopy. Results: After remifentanil exposure, upregulation of spinal DRP1 and NR2B was observed along with a reduction in PWMT and PWTL. In addition, AS-DRP1 improved RIH-induced PWTL and PWMT (P < 0.001 and P < 0.001) and reduced remifentanil-mediated enhancement of spinal DRP1 and NR2B expression (P = 0.020 and P = 0.022). More importantly, AS-DRP1 reversed RIH-induced mitochondrial fission (P = 0.020) and mitochondrial superoxide upregulation (P = 0.031). Conclusions: These results indicate that AS-DRP1 could modulate NMDA receptor expression to prevent RIH through the DRP1-mitochondria-ROS pathway.

Predictors of Postoperative Nausea and Vomiting After Same-day Surgery: A Retrospective Study.

PURPOSE: Postoperative nausea and vomiting (PONV) are main issues after same-day surgery. This study aimed to retrospectively evaluate the electronic medical records of patients who underwent same-day operations under general anesthesia to identify the potential risk factors for PONV. METHODS: Records of 7759 adult patients who received general anesthesia with remifentanil were reviewed. The patients were assessed for the incidence and severity of PONV. Multiple logistic regression was used to identify risk factors for PONV. A nomogram was established to predict PONV after same-day operations. FINDINGS: Of 7759 patients, 2317 (29.9%) experienced PONV. In multiple logistic regression analysis, female sex, nonsmoker status, history of motion sickness or nausea, high body mass index (BMI), long surgical duration, laparoscopic procedure, and preoperative analgesic intake within 30 days were independent risk factors for PONV. No correlation was found between the severity of PONV and remifentanil exposure (odds ratio = 1.018; 95% CI, 0.861-1.204; P = 0.834) or remifentanil dose (odds ratio = 1.294; 95% CI, 0.760-2.205; P = 0.343). For the nomogram, which involved sex, laparoscopic procedure, BMI, history of nausea or motion sickness, and analgesic intake within 30 days, the receiver operating characteristic analysis revealed that the AUC values in the training and validation cohorts were 0.81 and 0.83, respectively. IMPLICATIONS: Predictors for PONV in same-day surgery include female sex, nonsmoker, history of motion sickness or nausea, high BMI, surgical duration >1 hour, laparoscopic procedure, and preoperative analgesic intake within 30 days. A new predictive model is feasible for predicting the incidence of PONV based on the preoperative and intraoperative predictors.

Internal branch of superior laryngeal nerve block by dexamethasone alleviates sore throat after thyroidectomy: a randomized controlled trial.

PURPOSE: Postoperative sore throat (POST) is a common complaint following thyroidectomy. Dexamethasone was reported to alleviate POST when administered via different routes. This study aimed to compare the effects of local spray and perineural injection surrounding the internal branch of superior laryngeal nerve (iSLN) in preventing POST and alleviating postoperative impaired voice function. METHODS: A randomized, double-blinded, controlled trial was performed to test the efficacy of the iSLN block in inhibiting of POST. A total of 161 patients who underwent elective thyroidectomy were randomly allocated to two groups. Group Spray: 4 mg dexamethasone was sprayed on to the vocal cord; Group iSLN: bilateral perineural injection with 4 mg dexamethasone around the iSLN. The incidence and severity of POST, swallowing pain, and its side effects were evaluated. Postoperative acoustic analysis, including jitter and shimmer, was also performed. RESULTS: Group iSLN exhibited a significantly less incidence and intensity of POST at 6 h and 24 h (P < 0.001). The patients experienced less swallowing pain at 6 h (P < 0.001) after the surgery, compared with Group Spray. When compared with Group Spray, Group iSLN improved postoperative voice function, which was characterized by lower jitter and lower shimmer value at 6 h and 24 h (P < 0.001) after the surgery. The severity of postoperative cough is higher in Group Spray (P < 0.001). CONCLUSIONS: Among patients undergoing elective thyroidectomy, those who received perineural injection surrounding iSLN with dexamethasone had improved voice function and presented with more excellence in the inhibition of POST and cough, in comparison with the local spray. REGISTER INFORMATION: This trial was registered in the Chinese Clinical Trial Registry on 4th Jan, 2021 (ChiCTR2100042145). The trial is registered at http://www.chictr.org.cn/showproj.aspx?proj=120142 .

Doxycycline can reduce glycocalyx shedding by inhibiting matrix metalloproteinases in patients undergoing cardiopulmonary bypass: A randomized controlled trial.

BACKGROUND: Cardiopulmonary bypass (CPB) leads to shedding of the glycocalyx of endothelial cells, resulting in a series of complications such as tissue edema and coagulatory and microcirculatory dysfunctions. Matrix metalloproteinases (MMPs) can cause glycocalyx shedding in a variety of pathological processes, but their role in the process of CPB is still unclear. We hypothesized that the MMPs inhibitor doxycycline would reduce glycocalyx shedding by inhibiting MMPs during CPB. METHODS: Thirty-six patients were randomized to receive either 100 mg oral doxycycline (an MMPs inhibitor) or a matching placebo pill twice a day for three days before CPB. The primary outcome was the concentration of plasma syndecan-1. Secondary outcomes included heparan sulphate, MMP-2, MMP-9, ratio of urinary albumin to creatinine, and short-term clinical outcomes. In order to further prove that MMPs in plasma caused the glycocalyx shedding, human umbilical vein endothelial cells were cultured with plasma obtained from cardiac surgery patients before or after CPB (with or without MMPs inhibitor GM6001). The change in glycocalyx content was detected by immunofluorescence. RESULTS: CPB resulted in an increase of MMPs and shedding of the glycocalyx. Plasma syndecan-1 was higher in the control group than in the doxycycline group (median difference:15.04 µg/L; 95% CI: 9.14-20.94 µg/L; P < 0.001). Similar to syndecan-1, plasma heparan sulphate, MMP-2, and MMP-9 concentrations in the doxycycline group were significantly lower than those in the control group during CPB. Doxycycline was also correlated with a reduction in the ratio of urinary albumin to creatinine and improved the short-term clinical outcomes of patients. Endothelial cells cultured with plasma from patients after CPB showed significant shedding of syndecan-1 and heparan sulphate (post-CPB group vs pre-CPB group, P < 0.001). GM6001 was shown to reduce shedding of syndecan-1 and heparan sulphate by inhibiting MMPs (post-CPB + GM6001 group vs post-CPB group, P < 0.001). CONCLUSION: Doxycycline can reduce glycocalyx shedding by inhibiting MMPs during CPB.

KCC2 receptor upregulation potentiates antinociceptive effect of GABAAR agonist on remifentanil-induced hyperalgesia.

GABAergic system disinhibition played an important role in the pathogenesis of remifentanil-induced hyperalgesia (RIH). K+-Cl--cotransporter-2 (KCC2) has the potential to enhance the strength of GABAergic signaling function. However, few reports have focused on the additive analgesic effect of KCC2 enhancer and GABAA receptor agonist on the spinal dorsal horn. Therefore, we evaluated the role of GABA type A receptor (GABAAR) agonist (muscimol), KCC2 enhancer (CLP257) in remifentanil-induced hyperalgesia, as well as GABA and KCC2 receptors responses in the dorsal spinal horn. Remifentanil started to reduce paw withdrawal mechanical thresholds at postoperative 4 h and lasted to 72 h. The RIH associated decreases in spinal GABA release was transient. The amount of spinal GABA transmitter by microdialysis was observed to be decreased at the beginning and reached bottom at 150 min, then returned to the baseline level at 330 min. The synthesis and transportation of GABA transmitter were inhibited, characterized as spinal GAD67 and GAT1 downregulation after the establishment of RIH model. The effect of RIH on GABA receptor downregulation was linked to the reduced expression of spinal KCC2 receptor. This decrease in KCC2 expression has coincided with an early loss of GABA inhibition. KCC2 enhancer, which is reported to lead to a reduction in intracellular Cl-, can enhance GABA-mediated inhibitory function. Both muscimol and CLP257 could dose-dependently inhibit mechanical hypersensitivity caused by remifentanil-induced downregulation of GABAAα2R and KCC2, respectively. Compared with muscimol acting alone, the joint action of CLP257 and muscimol showed a higher pain threshold and less c-fos expression via upregulation of KCC2 and GABAAα2R. Taken together, these findings suggested that the RIH was initiated by decreased GABA release. Downregulation of GABAAα2R and KCC2 receptor contributed to spinally mediated hyperalgesia in RIH. KCC2 enhancer was proved to potentiate antinociceptive effect of GABAAR agonist in RIH.

Ultrasound-Guided Superior Laryngeal Nerve Block Facilitates Anesthesia Management in Bariatric Surgery.

BACKGROUND: Patients with obesity usually have a narrow pharyngeal cavity. They are prone to exposure difficulties and intubation failure during endotracheal intubation, and even face mask oxygen supply difficulties and hypoxemia in severe cases. We described the successful completion of conscious endotracheal intubation with superior laryngeal nerve internal branch block (SLNi) in a patient with pathologic obesity. CASE REPORT: A 29-year-old, nondiabetic man with severe obesity (weight 211 kg, height 186 cm, and body mass index [BMI] 60.99 kg/m2) was scheduled for a laparoscopic sleeve gastrectomy. The superior laryngeal nerve internal branch was blocked under ultrasound guidance to eliminate the cough induced by fiberscope during awake endotracheal intubation. Why Should an Emergency Physician Be Aware of This? The cough caused by fiberscope was completely suppressed and the awake endotracheal intubation was completed successfully.

Protective effect of sevoflurane on vascular endothelial glycocalyx in patients undergoing heart valve surgery: A randomised controlled trial.

BACKGROUND: The glycocalyx plays an important physiological role and may be damaged during cardiopulmonary bypass. Sevoflurane can protect the glycocalyx; however, its relevance in a clinical setting is unknown. OBJECTIVE: Glycocalyx degradation during cardiopulmonary bypass in patients was investigated. On the basis of the available experimental data, we hypothesised that sevoflurane-based anaesthesia would confer additional protection against cardiopulmonary bypass-induced glycocalyx damage. DESIGN: Randomised controlled study. SETTING: Clinical study at The First Affiliated Hospital of Wenzhou Medical University between June 2018 and March 2019. PATIENTS: Fifty-one patients. INTERVENTIONS: After intubation and mechanical ventilation, patients undergoing elective heart valve surgery were maintained under general anaesthesia with either propofol or sevoflurane during surgery. MAIN OUTCOME MEASURES: Glycocalyx markers (such as syndecan-1, heparan sulphate and hyaluronan), sheddases responsible for the degradation of the endothelial glycocalyx (such as matrix metalloproteinase-9 and cathepsin-B), urine albumin-to-creatinine ratio and levels of lactic acid and myocardial enzymes were all measured. Postoperative mechanical ventilation time and length of stay in the cardiac care unit and hospital were also measured. Morbidity and mortality after 30 days and 1 year were evaluated. RESULTS: The vascular endothelial glycocalyx was damaged during cardiopulmonary bypass. The glycocalyx damage in the sevoflurane group was less extensive than that in the propofol group. The urine albumin-to-creatinine ratio increased in both groups but was lower in the sevoflurane group. Enzymes including matrix metalloproteinase-9 and cathepsin-B were positively correlated with glycocalyx marker concentrations. After operation, the sevoflurane group showed lower levels of lactic acid and myocardial enzyme, as well as shorter duration of postoperative mechanical ventilation than the propofol group. CONCLUSION: Sevoflurane can decrease glycocalyx degradation in patients undergoing heart valve surgery under cardiopulmonary bypass. TRIAL REGISTRATION: Chinese Clinical Trial Registry, chictr.org.cn, identifier: ChiCTR1800016367.

Wnt3a Inhibitor Attenuates Remifentanil-Induced Hyperalgesia via Downregulating Spinal NMDA Receptor in Rats.

PURPOSE: The upregulation of spinal NMDA receptor is a crucial mechanism in remifentanil-induced hyperalgesia (RIH). Wnt3a/ß-catenin pathway plays an important role in neuropathic pain. We hypothesized that wnt3a inhibitor (iwp-2) could downregulate the expression of NR2B subunit in NMDA receptor, in order to relieve RIH. MATERIALS AND METHODS: The study has 2 phases. The phase 1 study is designed by different doses of iwp-2 groups to create an appropriate iwp-2 dose used in RIH alleviation. The phase 2 study is designed to prove that the wnt3a inhibitor could downregulate the activation of the NR2B to inhibit RIH in rats. Thermal hyperalgesia (PWTL) and mechanical allodynia (PWMT) were evaluated after RIH. The area under the PWTL and PWMT curves (AUC) were calculated. The amount of activated NR2B subunit, c-fos, NF-κB, ß-catenin, wnt3a and p-GSK-3ß (Ser9) were detected in the lumbar spinal cord. RESULTS: Remifentanil infusion could induce overexpression of ß-catenin and wnt3a in rats. Iwp-2 (60µM, 120µM, 180µM) could dose-dependently inhibit thermal hyperalgesia and mechanical allodynia in rats. In phase 2 study, both NR2B subunit antagonist Ro25-6981 and iwp-2 decreased the amount of activated NR2B, enhanced p-GSK-3ß (Ser9), reduced ß-catenin, c-fos and NF-κB in the lumbar spinal cord (p < 0.001). In comparison with the group iwp-2, the group of Ro25-6981 had more benefit in reversing hyperalgesia, including higher AUC value of PWTL (p = 0.022) and PWMT (p = 0.035). CONCLUSION: Remifentanil exposure could induce overexpression of wnt3a and enhance the production of ß-catenin in the spinal dorsal horn. Inhibition of wnt3a response was capable of attenuating RIH in alleviating hyperalgesia-related behavioral parameters, as well as reducing overexpression of c-fos, NF-κB, NR2B in spinal dorsal horn.

Effect of Ketamine Added to Ropivacaine in Nerve Block for Postoperative Pain Management in Patients Undergoing Anterior Cruciate Ligament Reconstruction: A Randomized Trial.

PURPOSE: Nerve blocks are commonly used as a part of multimodal pain relief. It was previously shown that ketamine could enhance the analgesic effect of local anesthetics in nerve blocks. A literature review on adding ketamine to local anesthetics for ameliorating analgesia revealed inconsistencies in analgesic efficiency and safety. This prospective, randomized, double-blind trial was performed to evaluate the antinociceptive effect of mixing ketamine with local anesthetics in a combined femoral and sciatic nerve block (CFSNB) during anterior cruciate ligament (ACL) reconstruction. METHODS: Seventy-six patients undergoing preoperative ultrasound-guided CFSNB in ACL reconstruction were enrolled. Patients were randomly assigned to 3 groups: Group RNK received perineural administration of 40-mg ketamine plus 0.375% ropivacaine in 40-mL volume; Group RIK received 40 mL of 0.375% ropivacaine, as well as IV ketamine 40 mg; and Group R received 40 mL of 0.375% ropivacaine. Pain scores were recorded. AUC was calculated based on the pain scores at different times. Duration of CFSNB, postoperative analgesic demand, time to first analgesic demand, and adverse events were also examined. FINDINGS: Perineural ketamine decreased pain scores 20 and 24 h' postoperatively, as well as lowered AUC values (all, P = 0.001). Group RNK had a prolonged time to first analgesic request (P = 0.014), inhibited rebound pain (P = 0.001), and increased satisfactory score at 48 h' postsurgery (P = 0.001). Perineural ketamine prolonged the duration of sensory block (P = 0.001) with no effect on early mobilization. There were no significant differences between Group R and Group RIK in terms of postoperative pain scores, AUC of different time intervals (P = 0.832 or more), and time to first rescue analgesics (P = 0.585). Compared with the 2 other groups, IV ketamine had a higher incidence of hallucination after operations. IMPLICATIONS: Perineural ketamine added to the ropivacaine-enhanced analgesic efficacy of CFSNB with less rebound pain compared with the IV ketamine and control groups. IV ketamine had no effect in potentiating analgesia when a conventional multimodal approach was used in the study. Chinese Clinical Trial Registry: ChiCTR1900023867.

A small dose of remifentanil pretreatment suppresses sufentanil-induced cough during general anesthesia induction: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Intravenous use of sufentanil can elicit cough. This study aimed to evaluate the inhibitory effect of pre-injection of a mall dose of remifentanil on sufentanil-induced cough during the induction of general anesthesia. METHODS: This prospective, randomized, controlled trial was conducted from January 10, 2019 to March 01, 2019. A total of 100 patients undergoing elective surgery under general anesthesia were enrolled, and at last 84 patients were included and randomly allocated into two equal size groups (n = 42): Patients in the Remifentanil group (R group) received an intravenous infusion of remifentanil 0.3 µg/kg (diluted to 2 ml) 1 min before sufentanil injection; patients in the Control group (C group) received 2 ml of normal saline (NS) at the same time point. Injections of patients in both groups were completed within 5 s. Then, sufentanil 0.5 µg/kg was injected within 5 s and the number of coughs that occurred within 1 min after sufentanil injection were recorded. One minute after sufentanil injection, etomidate 0.3 mg/kg and cisatracurium 0.15 mg/kg were given for general anesthesia induction irrespective of the presence or absence of cough. The mean arterial pressure (MAP) and heart rate (HR) at time points just before remifentanil pretreatment administration (T0), 3 min after administration (T1), 1 min after intubation (T2), and 3 min after intubation (T3) were recorded. RESULTS: The incidence of cough in patients in the R group and C group was 4.8 and 31%, respectively. Compared with group C, the incidence and severity of cough in group R was significantly lower (P < 0.01). No significant differences were observed in MAP and HR at the time of general anesthesia induction between the two groups (P > 0.05). CONCLUSION: Pretreatment with a small dose of remifentanil effectively and safely reduced the incidence and severity of cough induced by sufentanil during anesthesia induction and can be used as an alternative treatment to inhibit coughing caused by sufentanil. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1900020587, registered date: January 9, 2019), http://www.chictr.org.cn.

Dexmedetomidine inhibits apoptosis and expression of COX-2 induced by lipopolysaccharide in primary human alveolar epithelial type 2 cells.

Alveolar epithelial type II cells (ATII cells) are the main target cells being damaged and releasing the inflammatory mediators during acute respiratory distress syndrome (ARDS). Extensive apoptosis of epithelial cells leads to the breakdown of the alveolar-epithelial barrier in ARDS. Cyclooxygenase-2 (COX-2) plays an important role in pulmonary inflammatory response. Dexmedetomidine (DEX), a potent selective α2 adrenergic receptor (α2-AR) agonist, presents sedative, anxiolytic, and analgesic effects for anesthetic procedures. DEX has anti-apoptotic and anti-inflammatory properties. Our study demonstrated that DEX exerted anti-apoptotic effect on primary human epithelial cells with the inhibition of caspase activation, which was partly via the α2AR/PI3K/AKT pathway. Moreover, DEX significantly reduced the expression of COX-2 as well as prostaglandinE2 (PGE2) and tumor necrosis factor-α (TNF-α) production induced by lipopolysaccharide (LPS). Our next step is to determine whether DEX can regulate apoptosis in animal models. These results suggest DEX may be a promising therapy for preventing and treating ARDS as well as chronic diseases by directly targeting epithelial cell actions.

Prognostic role of C-reactive protein in patients with nasopharyngeal carcinoma: A meta-analysis and literature review.

BACKGROUND: C-reactive protein (CRP) has been shown to be associated with several tumors. However, its association with nasopharyngeal carcinoma (NPC) is not well characterized. We performed a literature review and meta-analysis to assess the prognostic relevance of elevated CRP levels in patients with NPC. METHODS: A literature search for relevant studies was performed on PubMed (Medline), the Cochrane Library, and Web of Science databases. Hazard ratios (95% confidence intervals) were calculated to assess the association between elevated CRP levels and survival outcomes. RESULTS: Five studies with a combined study population of 5215 patients with NPC were included. Pooled hazard ratios for overall survival and distant metastasis-free survival were 1.84 (95% CI = 1.57-2.17) and 1.81 (95% CI = 1.53-2.14), respectively. Subgroup analyses showed that types of indicators and treatment before inclusion had no significant impact on the observed association. CONCLUSION: Elevated serum CRP levels in patients with NPC were associated with worse prognosis.

Randomized comparison of sevoflurane versus propofol-remifentanil on the cardioprotective effects in elderly patients with coronary heart disease.

BACKGROUND: It is skeptical about cardioprotective property of sevoflurane in patients undergoing noncardiac surgery, especially in the elderly patients with coronary heart disease. We hypothesized that long duration of sevoflurane inhalation in noncardiac surgery could ameliorate myocardial damage in such patients. METHODS: This was a randomized, prospective study. One hundred twenty-one elderly patients with coronary heart disease were randomly allocated into two groups. Maintenance of anesthesia was achieved by sevoflurane inhalation (Group S) or propofol-remifentanil respectively (Group PR). Serum cardiac troponin I (cTnI) and brain natriuretic peptide (BNP) were measured before anesthesia induction (T0), 8 h (T1) and 24 h (T2) after anesthesia respectively. The perioperative cardiac output, complications and postoperative 3-month follow-up from end of surgery were recorded. RESULTS: Between the two groups, there were no statistical differences in the values of cTnI and BNP during the study. However, The area under the curve of cTnI values over 24 h after operation was less in Group S. Group PR had lower cardiac output and consumed more amount of phenylephrine during the study (P < 0.05). CONCLUSIONS: Compared with the group PR, sevoflurane had no benefit in the myocardial protection for the elderly patients with CHD. However, Sevoflurane showed advantage in maintaining hemodynamic stability during the operative period. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IPR-16008871 , 21 July 2016.

Analgesic effect of perineural magnesium sulphate for sciatic nerve block for diabetic toe amputation: A randomized trial.

BACKGROUND AND OBJECTIVES: High concentrations of local anesthetics may be neurotoxic for diabetic patients. Additive perineural administration of magnesium was reported to decrease the consumption of local anesthetics for nerve block. It was hypothesized that MgSO4 added to dilute ropivacaine was equianalgesic to more concentrated ropivacaine for toe amputations in diabetic patients. METHODS: Seventy diabetic patients were allocated into 3 groups: 1) perineural 200 mg MgSO4 added to 0.25% ropivacaine, 2) 0.25% ropivacaine alone, and 3) 0.375% ropivacaine alone. All patients underwent popliteal sciatic nerve block that was guided by ultrasonography using the respective regimens. Time of onset, duration of motor and sensory block were recorded. Spontaneous and evoked pain score, worst pain score, additional analgesic consumption, satisfaction score and initial time of analgesic requirement of each patient were documented up to 48 hours postoperatively. RESULTS: In comparison with 0.25% ropivacaine alone, magnesium supplement prolonged the duration of sensory block (p = 0.001), as well as better evoked pain score at 6 hour postoperatively (p = 0.001). In comparison with evoked pain score (1.6/10) in group of 0.375% ropivacaine, magnesium plus 0.25% ropivacaine presented a little higher score (2.5/10) at 6 hour postoperatively (p = 0.001), while lower worst pain score (p = 0.001) and less postoperative total analgesic consumption (p = 0.002). CONCLUSIONS: The regimen of adding 200mg MgSO4 to 0.25% ropivacaine for sciatic nerve block yields equal analgesic effect in comparison with 0.375% ropivacaine. These findings have suggested that supplemental MgSO4 could not improve analgesic quality except reducing the total amount of local anesthetics requirement in diabetic toe amputations with sciatic nerve blocks.