Effect of volatile versus propofol anaesthesia on major complications and mortality after cardiac surgery: a multicentre randomised trial.

BACKGROUND: The comparative effectiveness of volatile anaesthesia and total intravenous anaesthesia (TIVA) in terms of patient outcomes after cardiac surgery remains a topic of debate. METHODS: Multicentre randomised trial in 16 tertiary hospitals in China. Adult patients undergoing elective cardiac surgery were randomised in a 1:1 ratio to receive volatile anaesthesia (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was a composite of predefined major complications during hospitalisation and mortality 30 days after surgery. RESULTS: Of the 3123 randomised patients, 3083 (98.7%; mean age 55 yr; 1419 [46.0%] women) were included in the modified intention-to-treat analysis. The composite primary outcome was met by a similar number of patients in both groups (volatile group: 517 of 1531 (33.8%) patients vs TIVA group: 515 of 1552 (33.2%) patients; relative risk 1.02 [0.92-1.12]; P=0.76; adjusted odds ratio 1.05 [0.90-1.22]; P=0.57). Secondary outcomes including 6-month and 1-yr mortality, duration of mechanical ventilation, length of ICU and hospital stay, and healthcare costs, were also similar for the two groups. CONCLUSIONS: Among adults undergoing cardiac surgery, we found no difference in the clinical effectiveness of volatile anaesthesia and propofol-based TIVA. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IOR-17013578).

Microglia sustain anterior cingulate cortex neuronal hyperactivity in nicotine-induced pain.

BACKGROUND: Long-term smoking is a risk factor for chronic pain, and chronic nicotine exposure induces pain-like effects in rodents. The anterior cingulate cortex (ACC) has been demonstrated to be associated with pain and substance abuse. This study aims to investigate whether ACC microglia are altered in response to chronic nicotine exposure and their interaction with ACC neurons and subsequent nicotine-induced allodynia in mice. METHODS: We utilized a mouse model that was fed nicotine water for 28 days. Brain slices of the ACC were collected for morphological analysis to evaluate the impacts of chronic nicotine on microglia. In vivo calcium imaging and whole-cell patch clamp were used to record the excitability of ACC glutamatergic neurons. RESULTS: Compared to the vehicle control, the branch endpoints and the length of ACC microglial processes decreased in nicotine-treated mice, coinciding with the hyperactivity of glutamatergic neurons in the ACC. Inhibition of ACC glutamatergic neurons alleviated nicotine-induced allodynia and reduced microglial activation. On the other hand, reactive microglia sustain ACC neuronal excitability in response to chronic nicotine, and pharmacological inhibition of microglia by minocycline or liposome-clodronate reduces nicotine-induced allodynia. The neuron-microglia interaction in chronic nicotine-induced allodynia is mediated by increased expression of neuronal CX3CL1, which activates microglia by acting on CX3CR1 receptors on microglial cells. CONCLUSION: Together, these findings underlie a critical role of ACC microglia in the maintenance of ACC neuronal hyperactivity and resulting nociceptive hypersensitivity in chronic nicotine-treated mice.

What is the impact of perioperative cerebral oxygen desaturation on postoperative delirium in old population: a systemic review and meta-analysis.

BACKGROUND: Perioperative cerebral oxygen saturation (ScO2) has been reported to associate with postoperative delirium (POD) which is a common postoperative complication, however, the results were inconclusive. Therefore, we aimed to conduct an up-to-date review and meta-analyze the relationship between perioperative ScO2 and POD. METHODS: We systematically searched PubMed, Embase and Web of science through January 13, 2022. The pooled results were estimated through a random-effects model meta-analysis and expressed as odds ratios (ORs) and standard mean differences (SMDs), accompanied with 95% confident intervals (CIs). RESULTS: Finally, of 467 searched articles, ten articles were included. A total of six studies reported the baseline ScO2 value and the pooled result showed that preoperative baseline ScO2 was lower in POD groups (SMD = - 0.41, 95% CI - 0.64 to - 0.18). And beyond that, the pooled OR across four literatures about preoperative low ScO2 on POD was 3.44 (95% CI 1.69, 7.02). In contrast, insignificant differences were detected in baseline/lowest ScO2 value during intraoperative and postoperative period. Additionally, there were no statistically significant associations for intraoperative and postoperative low ScO2 effect on POD risk. Meta-regress analysis has found no significant impact factors. CONCLUSIONS: Based on current evidence, POD patients have a lower ScO2, and ScO2 desaturation may increase POD incidence, indicating the role of ScO2 underlying pathological mechanisms. For generalizability of evidence, we should rely on high-quality, considering more comprehensively longitudinal, interdisciplinary studies.

Intraoperative Flurbiprofen Treatment Alters Immune Checkpoint Expression in Patients Undergoing Elective Thoracoscopic Resection of Lung Cancer.

OBJECTIVES: This study aimed to determine the effect of intraoperative administration of flurbiprofen on postoperative levels of programmed death 1 (PD-1) in patients undergoing thoracoscopic surgery. MATERIALS AND METHODS: In this prospective double-blind trial, patients were randomized to receive intralipid (control group, n = 34, 0.1 mL/kg, i.v.) or flurbiprofen axetil (flurbiprofen group, n = 34, 50 mg, i.v.) before induction of anesthesia. PD-1 levels on T cell subsets, inflammation, and immune markers in peripheral blood were examined before the induction of anesthesia (T0) and 24 h (T1), 72 h (T2), and 1 week (T3) after surgery. A linear mixed model was used to determine whether the changes from baseline values (T0) between groups were significantly different. RESULTS: The increases in the percentage of PD-1(+)CD8(+) T cells observed at T1 and T2 in the control group were higher than those in the flurbiprofen group (T1: 12.91 ± 1.65 vs. 7.86 ± 5.71%, p = 0.031; T2: 11.54 ± 1.54 vs. 8.75 ± 1.73%, p = 0.004), whereas no differences were observed in the changes in the percentage of PD-1(+)CD4(+) T cells at T1 and T2 between the groups. Moreover, extensive changes in the percentage of lymphocyte subsets and inflammatory marker concentrations were observed at T1 and T2 after surgery and flurbiprofen attenuated most of these changes. CONCLUSIONS: Perioperative administration of flurbiprofen attenuated the postoperative increase in PD-1 levels on CD8(+) T cells up to 72 h after surgery, but not after this duration. The clinical relevance of changes in PD-1 levels to long-term surgical outcome remains unknown.

Renin-angiotensin-system, a potential pharmacological candidate, in acute respiratory distress syndrome during mechanical ventilation.

While effective treatments for acute respiratory distress syndrome (ARDS) are lacking, mechanical lung ventilation can sustain adequate gas exchange in critically ill patients with respiratory failure due to ARDS. However, as a result of the phenomenon of ventilator-induced lung injury (VILI), there is an increasing need to seek beneficial pharmacological therapies for ARDS. Recent studies have suggested the renin-angiotensin system (RAS), which consists of the ACE/Ang-II/AT1R axis and ACE2/Ang-(1-7)/MasR axis, plays a dual role in the pathogenesis of ARDS and VILI. This review highlights the deleterious action of ACE/Ang-II/AT1R axis and the beneficial role of ACE2/Ang-(1-7)/MasR axis, as well as AT2R, in VILI and ARDS, and also discusses the possibility of targeting RAS components with pharmacological interventions to improve outcomes in ARDS.

Effect of Transversus Abdominis Plane Block on Postoperative Pain after Colorectal Surgery: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: To assess the analgesic efficacy of transversus abdominis plane (TAP) block in patients undergoing colorectal surgery (CRS). MATERIALS AND METHODS: The databases of PubMed, ISI Web of Science, and Embase were searched, and randomized controlled studies (RCTs) that compared TAP block to control for relief of postoperative pain in patients who underwent CRS were included. Outcomes, including postoperative pain at rest and with movement, morphine use, postoperative nausea and vomiting, and the length of hospital stay, were analyzed using STATA software. The weighted mean differences (WMDs) with 95% confidence intervals (95% CIs) or relative risk with 95% CI were used to present the strength of associations. RESULTS: A total of 7 RCTs with 511 patients were included. The results of this study suggested that TAP block significantly relieved postoperative pain during postanesthetic recovery after CRS at rest and during movement (WMDs were -0.98 [95% CI -1.57 to -0.38] and -0.68 [-1.07 to -0.30], respectively), and also decreased pain intensity during movement 24 h after CRS (WMD: -0.57 [95% CI -1.06 to -0.08]). TAP block significantly reduced opioid consumption within 24 h when compared to controls, with a WMD of 15.66 (95% CI -23.93 to -7.39). However, TAP block did not shorten the length of hospital stay. CONCLUSIONS: TAP block was an effective approach for relief of postoperative pain and reduced postoperative consumption of morphine. More RCTs with large sample sizes are required to confirm these findings.

Flurbiprofen axetil increases arterial oxygen partial pressure by decreasing intrapulmonary shunt in patients undergoing one-lung ventilation.

PURPOSES: In the present study, we investigated whether flurbiprofen axetil (FA) alleviates hypoxemia during one-lung ventilation (OLV) by reducing the pulmonary shunt/total perfusion (Q s/Q t) ratio, and examined the relationship between the Q s/Q t ratio and the thromboxane B2 (TXB2)/6-keto-prostaglandin F1α (6-K-PGF1α) ratio. METHODS: Sixty patients undergoing esophageal resection for carcinoma were randomly assigned to groups F and C (n = 30 for each group). FA and placebo were administered i.v. 15 min before skin incision in groups F and C, respectively. The partial pressure of arterial oxygen (PaO2) was measured and the Q s/Q t ratio was calculated. Serum TXB2, 6-K-PGF1α, and endothelin (ET) were measured by radioimmunoassay. The relationship between TXB2/6-K-PGF1α and Q s/Q t was investigated. RESULTS: Compared with group C, PaO2 was higher and the Q s/Q t ratio was lower during OLV in group F (P < 0.05). After treatment with FA, both serum TXB2 and 6-K-PGF1α decreased significantly (P < 0.05) but the TXB2/6-K-PGF1α ratio increased significantly (P < 0.01). Increases in the TXB2/6-K-PGF1α ratio were correlated with reductions in the Q s/Q t ratio during OLV in group F (r = -0.766, P < 0.01). There was no significant difference in serum ET between groups F and C. CONCLUSIONS: Treatment with FA reduced the Q s/Q t ratio and further increased the PaO2 level during OLV, possibly due to upregulation of the vasoactive agent TXB2/6-K-PGF1α ratio.

Single-dose, bilateral paravertebral block plus intravenous sufentanil analgesia in patients with esophageal cancer undergoing combined thoracoscopic-laparoscopic esophagectomy: a safe and effective alternative.

OBJECTIVE: Paravertebral block (PVB) has been shown to be an ideal aid for analgesia after thoracic or abdominal surgery. The authors studied the safety and efficacy of the single-dose and bilateral ultrasound-guided (USG)-PVB before combined thoracoscopic-laparoscopic esophagectomy (TLE) along with intravenous sufentanil analgesia as a method of pain relief in comparison with intravenous sufentanil as a sole analgesic agent. DESIGN: Prospective, randomized study. SETTING: Single university hospital. PARTICIPANTS: Fifty-two patients undergoing TLE. INTERVENTIONS: A USG-PVB was performed before surgery using a solution of 30 mL of 0.5% ropivacaine by 3 injections of 10 mL each at the right T5 and bilateral T8 (PVB group, n=26) or the saline injection of 10 mL at every site (control group, n=26). MEASUREMENTS AND MAIN RESULTS: Successful PVBs were achieved in all patients of the PVB group. Intraoperative mean remifentanil usage and end-tidal sevoflurane concentration were lower in the PVB group (p<0.001). Hemodynamic parameters were stable in both groups. Postoperative pain scores both at rest and on coughing were lower during the first 8 hours in the PVB group than those in the control group (p<0.05). Cumulative sufentanil consumption delivered by patient-controlled analgesia (PCA) was significantly lower in the PVB group at all time points (p<0.05). Postoperative pulmonary function was better at the third postoperative day in the PVB group (p<0.05), with quicker hospital discharge and lower hospital costs (p<0.05). CONCLUSIONS: The single-dose and bilateral PVB given before TLE combined with sufentanil may provide better postoperative analgesia and early discharge in patients undergoing TLE.

Effect of electro-acupuncture stimulation of Ximen (PC4) and Neiguan (PC6) on remifentanil-induced breakthrough pain following thoracal esophagectomy.

The clinical analgesic effect of electro-acupuncture (EA) stimulation (EAS) on breakthrough pain induced by remifentanil in patients undergoing radical thoracic esophagectomy, and the mechanisms were assessed. Sixty patients (ASAIII) scheduled for elective radical esophagectomy were randomized into three groups: group A (control) receiving a general anesthesia only; group B (sham) given EA needles at PC4 (Ximen) and PC6 (Neiguan) but no stimulation; and group C (EAS) electrically given EAS of the ipsilateral PC4 and PC6 throughout the surgery. The EAS consisting of a disperse-dense wave with a low frequency of 2 Hz and a high frequency of 20 Hz, was performed 30 min prior to induction of general anesthesia and continued through the surgery. At the emergence, sufentanil infusion was given for postoperative analgesia with loading dose of 7.5 µg, followed by a continuous infusion of 2.25 µg/h. The patient self-administration of sufentanil was 0.75 µg with a lockout of 15 min as needed. Additional breakthrough pain was treated with dezocine (5 mg) intravenously at the patient's request. Blood samples were collected before (T1), 2 h (T2), 24 h (T3), and 48 h (T4) after operation to measure the plasma ß-EP, PGE2, and 5-HT. The operative time, the total dose of sufentanil and the dose of self-administration, and the rescue doses of dezocine were recorded. Visual Analogue Scale (VAS) scores at 2, 12, 24 and 48 h postoperatively and the incidence of apnea and severe hypotension were recorded. The results showed that the gender, age, weight, operative time and remifentanil consumption were comparable among 3 groups. Patients in EAS group had the lowest VAS scores postoperatively among the three groups (P<0.05). The total dose of sufentanil was 115±6.0 µg in EAS group, significantly lower than that in control (134.3±5.9 µg) and sham (133.5±7.0 µg) groups. Similarly, the rescue dose of dezocine was the least in EAS group (P<0.05) among the three groups. Plasma ß-EP levels in EAS group at T3 (176.90±45.73) and T4 (162.96±35.00 pg/mL) were significantly higher than those in control (132.33±36.75 and 128.79±41.24 pg/mL) and sham (136.56±45.80 and 129.85±36.14 pg/mL) groups, P<0.05 for all. EAS could decrease the release of PGE2. Plasma PGE2 levels in EAS group at T2 and T3 (41±5 and 40±5 pg/mL respectively) were significantly lower than those in control (64±5 and 62±7 pg/mL) and sham (66±6 and 62±6 pg/mL) groups. Plasma 5-HT levels in EAS group at T2 (133.66±40.85) and T3 (154.66±52.49 ng/mL) were significantly lower than those in control (168.33±56.94 and 225.28±82.03) and sham (164.54±47.53 and 217.74±76.45 ng/mL) groups. For intra-group comparison, plasma 5-HT and PGE2 levels in control and sham groups at T2 and T3, and ß-EP in EAS group at T3 and T4 were significantly higher than those at T1 (P<0.05); PGE2 and 5-HT levels in EAS group showed no significant difference among the different time points (P>0.05). No apnea or severe hypotension was observed in any group. It was concluded that intraoperative ipsilateral EAS at PC4 and PC6 provides effective postoperative analgesia for patients undergoing radical esophagectomy with remifentanil anesthesia and significantly decrease requirement for parental narcotics. The underlying mechanism may be related to stimulation of the release of endogenous ß-EP and inhibition of inflammatory mediators (5-HT and PGE2).

Cigarette smoking is linked to an increased risk of delirium following arthroplasty in patients suffering from osteoarthritic pain.

AIMS: Postoperative delirium (POD) is a common postoperative complication, and the potential relationship between cigarette smoking and POD is still unclear. The current study evaluated the relationship between preoperative smoking status in patients suffering from osteoarthritic pain and POD after total knee arthroplasty (TKA). METHODS: A total of 254 patients who had undergone unilateral TKA were enrolled between November 2021 and December 2022, with no gender limitation. Preoperatively, patients' visual analog scale (VAS) scores at rest and during movement, hospital anxiety and depression (HAD) scores, pain catastrophizing scale (PCS) scores and smoking status were collected. The primary outcome was the incidence of POD, which was evaluated by the confusion assessment method (CAM). RESULTS: A total of 188 patients had complete datasets for final analysis. POD was diagnosed in 41 of 188 patients (21.8%) who had complete data for analysis. The incidence of smoking was significantly higher in Group POD than in Group Non-POD (22 of 41 patients [54%] vs. 47 of 147 patients [32%], p < 0.05). The postoperative hospital stays were also longer than those of Group Non-POD (p < 0.001). Multiple logistic regression analysis showed that preoperative smoking (OR: 4.018, 95% CI: 1.158-13.947, p = 0.028) was a risk factor for the occurrence of POD in patients with TKA. The length of hospital stay was correlated with the occurrence of POD. CONCLUSIONS: Our findings suggest that patients who smoked preoperatively were at increased risk of developing POD following TKA.

Corrigendum: Flurbiprofen used in one-lung ventilation improves intraoperative regional cerebral oxygen saturation and reduces the incidence of postoperative delirium.

[This corrects the article DOI: 10.3389/fpsyt.2022.889637.].

Angiotensin II type 2 receptor pharmacological agonist, C21, reduces the inflammation and pain hypersensitivity in mice with joint inflammatory pain.

Primary and secondary hyperalgesia develop in response to chronic joint inflammation due to peripheral and central mechanisms. Synovial macrophage and spinal microglia are involved in pain sensitization in arthritis. The level of angiotensin II type 2 receptor (AT2R) is related to the severity of arthritis. This study aimed to determine the role of AT2R in primary and secondary hyperalgesia in joint inflammatory pain in mice. After intra-articular CFA injection, primary hyperalgesia in the ipsilateral knee joint was measured by pressure application meter and gait analysis, secondary hypersensitivity in ipsilateral hind-paw was measured by von-Frey and Hargreaves tests following a combination of global AT2R-deficient (Agtr2-/-) mice and AT2R pharmacological agonist C21. Synovial macrophage and spinal microglia were collected for flow cytometry. Morphological reconstruction of microglia was detected by immunostaining. AT2R expression was investigated by quantitative polymerase chain reaction and western blot. Neuronal hyperactivity was evaluated by c-Fos and CGRP immunostaining. We found that pain hypersensitivity and synovial inflammation in Agtr2-/- mice were significantly exacerbated compared with wild-type mice; conversely, systemically administrated C21 attenuated both of the symptoms. Additionally, spinal microglia were activated, and an abundant increase of spinal AT2R was expressed on activated microglia in response to peripheral joint inflammation. Intrathecally-administrated C21 reversed the secondary hypersensitivity, accompanied by alleviation of spinal microglial activation, spinal neuronal hyperactivity, and calcitonin gene-related peptide content. These findings revealed a beneficial role of AT2R activating stimulation against pain hypersensitivity in joint inflammatory pain via direct modulation of synovial macrophage and spinal microglial activity.

Continuous Serratus Anterior Plane Block Improved Early Pulmonary Function After Lung Cancer Surgical Procedure.

BACKGROUND: Serratus anterior plane block (SAPB) has been proven to be an efficient way to control postoperative pain. This study explored whether the use of continuous SAPB in combination with flurbiprofen could improve early pulmonary function in lung cancer patients undergoing video-assisted thoracoscopic surgery (VATS). METHODS: From July 2019 to April 2020, patients who scheduled for elective lung resection undergoing VATS were randomly allocated to receive patient-controlled SAPB in combination with intravenous flurbiprofen or patient-controlled intravenous analgesia. Postoperative pulmonary function variables, including forced expiratory volume in 1 second, and forced vital capacity were collected before and 24, 48, and 72 hours after Surgical Procedure. Pain intensity was measured at rest and on coughing. Comfort scores during breathing exercises, postoperative pulmonary complications, and adverse events were recorded. RESULTS: A substantial reduction in lung function was exhibited in both groups after Surgical Procedure (P < .001), but lung function variables in the continuous SAPB group were significantly higher (P < .001) throughout the postoperative period up to 72 hours, regardless of the surgical procedure type. Meanwhile, there were significant differences of pain intensity at rest and on coughing between the groups (P < .001). The incidence of pneumonia, pulmonary atelectasis, hypoxemia, vomiting, and the comfort score in the continuous SAPB group was significantly lower (P < .05). CONCLUSIONS: Postoperative acute pain treatment with continuous SAPB in combination with flurbiprofen enhanced pulmonary function and reduced postoperative pulmonary complications in lung cancer patients undergoing VATS.

Effect of Perineural Dexamethasone with Ropivacaine in Continuous Serratus Anterior Plane Block for Postoperative Analgesia in Patients Undergoing Video-Assisted Thoracoscopic Surgery.

Purpose: The goal of this study was to evaluate the analgesic efficiency of dexamethasone with ropivacaine in continuous serratus anterior plane block (cSAPB) after video-assisted thoracoscopic surgery (VATS). Patients and Methods: Sixty-six patients who underwent VATS were randomized into two groups. All patients received cSAPB postoperatively, and patients in Group RD received 20 mL of 0.375% ropivacaine plus 0.1 mg/kg dexamethasone followed by an infusion of 0.2% ropivacaine plus 0.02 mg/kg/hour dexamethasone at a rate of 5 mL/h in patient-controlled analgesia (PCA) pump. Patients in Group R received 20 mL of 0.375% ropivacaine with normal saline followed by an infusion of 5 mL/h of 0.2% ropivacaine in PCA pump. Fifty milligrams of tramadol was given as rescue medication when the visual analog scale (VAS) score was ≥4 at rest. The primary outcomes were the sum of pressing number within 48 hours postoperatively and the time to the first patient-controlled bolus. The secondary outcomes were VAS scores, the incidence of rescue analgesia, wound infection and nausea/vomiting. Results: Within 48 hours postoperatively, the sum of pressing number was more in Group R (18.33 ± 3.149 vs 16.09 ± 3.292, P = 0.006), and the Log Rank Test showed a significant difference in time to the first patient-controlled bolus (P = 0.006). After the PCA infusion finished, there were significantly lower VAS scores in Group RD at 60 and 72 hours postoperatively (P < 0.001). Additionally, the incidence of rescue analgesia in Group R was significantly more than that in Group RD (P < 0.001). No incision infection was observed in any patient. Conclusion: The cSAPB with ropivacaine plus dexamethasone prolonged the duration of analgesia and motor blockade, reduced pain intensity and rescued analgesia requirements after the end of PCA infusion for patients undergoing VATS, which provide further improvement to continuous perineural block.

Flurbiprofen used in one-lung ventilation improves intraoperative regional cerebral oxygen saturation and reduces the incidence of postoperative delirium.

Background: We previously demonstrated that flurbiprofen increased arterial oxygen partial pressure and reduced intrapulmonary shunts. The present study aims to investigate whether flurbiprofen improves intraoperative regional cerebral oxygen saturation (rScO2) and reduces the incidence of postoperative delirium (POD) in elderly patients undergoing one-lung ventilation (OLV). Methods: One hundred and twenty patients undergoing thoracoscopic lobectomy were randomly assigned to the flurbiprofen-treated group (n = 60) and the control-treated group (n = 60). Flurbiprofen was intravenously administered 20 minutes before skin incision. The rScO2 and partial pressure of arterial oxygen (PaO2) were recorded during the surgery, and POD was measured by the Confusion Assessment Method (CAM) within 5 days after surgery. The study was registered in the Chinese Clinical Trial Registry with the number ChiCTR1800020032. Results: Compared with the control group, treatment with flurbiprofen significantly improved the mean value of intraoperative rScO2 as well as the PaO2 value (P < 0.05, both) and significantly reduced the baseline values of the rScO2 area under threshold (AUT) (P < 0.01) at 15, 30, and 60 min after OLV in the flurbiprofen-treated group. After surgery, the POD incidence in the flurbiprofen-treated group was significantly decreased compared with that in the control group (P < 0.05). Conclusion: Treatment with flurbiprofen may improve rScO2 and reduce the incidence of POD in elderly patients undergoing thoracoscopic one-lung ventilation surgery for lung cancer. Clinical trial registration: http://www.chictr.org/cn/, identifier ChiCTR1800020032.

Dexmedetomidine alleviates anxiety-like behavior in mice following peripheral nerve injury by reducing thehyperactivity of glutamatergic neurons in the anterior cingulate cortex.

BACKGROUND: Treatment of chronic pain is challenged by concurrent anxiety symptoms. Dexmedetomidine is known to produce sedation, analgesia, and anxiolysis. However, the neural mechanism of dexmedetomidine-elicited anxiolysis remains elusive. Here, we aimed to test the hypothesis that the anterior cingulate cortex might be involved in dexmedetomidine-induced anxiolysis in pain. METHODS: A common peroneal nerve ligation mouse model was used to test the dexmedetomidine-induced analgesia and anxiolysis by assessing mechanical allodynia, open-field, light-dark transition, and acoustic startle reflex tests. In vivo calcium signal fiber photometry and ex vivo whole-cell patch-clamp recordings were used to measure the excitability of glutamatergic neurons in anterior cingulate cortex. Modulation of glutamatergic neurons was performed by chemogenetic inhibition or activation via viral injection. RESULTS: Compared with vehicle, dexmedetomidine (4 µg/kg) alleviated mechanical allodynia (P < 0.001) and anxiety-like behaviors (P < 0.001). The glutamatergic neurons' excitability after dexmedetomidine administration was lower than that of the vehicle group (P = 0.001). Anxiety-like behaviors were rescued by inhibiting glutamatergic neurons in the model mice. Nociception-related anxiety-like behavior was induced by activation of glutamatergic neurons, which was rescued by dexmedetomidine. CONCLUSIONS: The reduction in glutamatergic neuronal activity in anterior cingulate cortex may be involved in dexmedetomidine-elicited anxiolysis in chronic pain.

Efficacy and safety of remimazolam besylate in bronchoscopy for adults: A multicenter, randomized, double-blind, positive-controlled clinical study.

Background: With the development of fiberoptic bronchoscopy in the diagnosis and treatment of various pulmonary diseases, the anesthesia/sedation requirements are becoming more demanding, posing great challenges for patient safety while ensuring a smooth examination/surgery process. Remimazolam, a brand-new ultra-short-acting anesthetic, may compensate for the shortcomings of current anesthetic/sedation strategies in bronchoscopy. Methods: This study was a prospective, multicenter, randomized, double-blind, parallel positive controlled phase 3 clinical trial. Subjects were randomized to receive 0.2 mg/kg remimazolam besylate or 2 mg/kg propofol during bronchoscopy to evaluate the efficacy and safety of remimazolam. Results: A total of 154 subjects were successfully sedated in both the remimazolam group and the propofol group, with a success rate of 99.4% (95%CI of the adjusted difference -6.7 × 10%-6% to -5.1 × 10%-6%). The sedative effect of remimazolam was noninferior to that of propofol based on the prespecified noninferiority margin of -5%. Compared with the propofol group, the time of loss of consciousness in the remimazolam group (median 61 vs. 48s, p < 0.001), the time from the end of study drug administration to complete awakening (median 17.60 vs. 12.80 min, p < 0.001), the time from the end of bronchoscopy to complete awakening (median 11.00 vs. 7.00 min, p < 0.001), the time from the end of study drug administration to removal of monitoring (median 19.50 vs. 14.50 min, p < 0.001), and the time from the end of bronchoscopy to removal of monitoring (median 12.70 vs. 8.60 min, p < 0.001) were slightly longer. The incidence of Adverse Events in the remimazolam group and the propofol group (74.8% vs. 77.4%, p = 0.59) was not statistically significant, and none of them had Serious Adverse Events. The incidence of hypotension (13.5% vs. 29.7%, p < 0.001), hypotension requiring treatment (1.9% vs. 7.7%, p = 0.017), and injection pain (0.6% vs. 16.8%, p < 0.001) were significantly lower in the remimazolam group than in the propofol group. Conclusion: Moderate sedation with 0.2 mg/kg remimazolam besylate is effective and safe during bronchoscopy. The incidence of hypotension and injection pain was less than with propofol, but the time to loss of consciousness and recovery were slightly longer. Clinical Trial Registration: clinicaltrials.gov, ChiCTR2000039753.

Flurbiprofen axetil enhances analgesic effect of fentanyl associated with increase in ß-endorphin levels.

PURPOSE: To examine the analgesic effect of preoperative administration of flurbiprofen axetil and that of postoperative administration of a combination of flurbiprofen axetil and fentanyl, as well as perioperative plasma ß-endorphin (ß-EP) levels in patients undergoing esophagectomy. METHODS: Forty-five patients were randomly divided into three groups: group A: 100 mg flurbiprofen axetil preoperative, 10 µg/kg fentanyl + 10 ml placebo postoperative; group B: 100 mg flurbiprofen axetil preoperative, 10 µg/kg fentanyl + 100 mg flurbiprofen axetil postoperative; group C: 10 ml placebo preoperative, 10 µg/kg fentanyl + 10 ml placebo postoperative. Postoperative analgesia was achieved by intravenous infusion containing flurbiprofen axetil and/or fentanyl at 2.0 ml/h (total volume, 100 ml) using infusion pumps. The ß-EP was measured at preanesthesia (T(1)), the end of surgery (T(2)), 24 h (T(3)), and 48 h (T(4)) after surgery. Visual analog scale scores (VAS) at T3, T4 (at rest), and rescue analgesic tramadol requirement was recorded. RESULTS: The VAS of group B was significantly lower than group A and C (P < 0.01) at T(3) and T(4). The ß-EP levels at T(2)-T(4) in group A did not differ significantly from those at T(1) (P > 0.05); however, the ß-EP levels in group B at T(3)-T(4) increased significantly (P < 0.05), while those in group C increased at T(2) and decreased at T(4) (P < 0.05). The ß-EP levels in group B at T(3) and T(4) were the highest as compared to its levels in groups A and C (P < 0.01). Tramadol consumption in group B was significantly lower than in groups A and C (P < 0.01). CONCLUSION: These results show that flurbiprofen axetil enhances the analgesic effect of fentanyl associated with increase in ß-EP levels.

The Role of Serratus Anterior Plane Block During in Video-Assisted Thoracoscopic Surgery.

Although thoracoscopy has characteristics such as a small surgical incision and low stress response, post-surgical pain after a thoracoscopic operation is no less than that after a thoracotomy. Moreover, poor post-surgical pain management is likely to cause an increased incidence of postoperative pulmonary complications (PPCs) and chronic post-surgical pain. The serratus anterior plane block (SAPB) is a regional anesthesia method whereby local anesthetics (LAs) are injected into the serratus anterior space to block the lateral cutaneous branch of the intercostal nerve, long thoracic nerve, and dorsal thoracic nerve. The block range of the SAPB covers the incisions of video-assisted thoracoscopic surgery (VATS) and the site of the chest tube, which are often located in the antero-lateral chest wall. Therefore, the SAPB can achieve effective analgesia in VATS. For example, 0.125% to 0.25% levobupivacaine (20-25 ml) is widely used for thoracic surgery, which can achieve effective analgesia and avoid adverse reactions. Moreover, it has advantages compared with thoracic segmental epidural block (TEA) and thoracic paravertebral block (TPVB), such as simple operation, increased safety, fewer complications, and hemodynamic stability. In addition, adequate analgesia is helpful for pulmonary function recovery and reduces the incidence of PPCs. This article introduces the anatomical mechanism of the SAPB, diverse operation approaches, how to choose drugs and adjuvants, and the resulting impacted area range. It summarizes the advantages and disadvantages of the SAPB compared with other analgesic methods and posits that the SAPB is beneficial to the recovery of postoperative lung function, which provides more options for postoperative analgesia after VATS.