The effects of remimazolam combined with sufentanil on respiration, circulation and sedation level in patients undergoing colonoscopy.

BACKGROUND: The main sedative which is propofol in painless gastroenteroscopy, has a high risk of reducing blood pressure and respiratory depression. Remimazolam (a short-acting benzodiazepine) is expected to be widely used in painless gastroenteroscopy due to its rapid onset, rapid metabolism and light respiratory and circulation inhibition. METHODS: A randomized, single-blind, parallel, controlled study, 123 outpatients who were undergoing painless colonoscopy and ramdomly divided into group A, B and C, in Hangzhou First People's Hospital, July-December 2021. All patients were intravenously injected with 5 µg sufentanil for analgesic preconditioning. The group A was induced by 0.2 mg/kg remimazolam besylate. The group B was induced by 0.25 mg/kg remimazolam besylate. And the group C was inducted by 2.0 mg /kg propofol. If the patients had limb movement or MOAA/S score > 3 and so on, remimazolam besylate was added at 2.5 mg/ time in group A and B, and propofol emulsion injection was added at 0.5 mg/kg/ time in group C. During the operation, according to the actual situation, remimazolam was per added 2.5 mg in the experimental group, and propofol was 0.5 mg/kg in the control group. Heart rate (HR), non-invasive blood pressure (BP), respiratory rate (RR), pulse oxygen saturation (SpO2), and improved vigilance/sedation score (MOAA/S) of patients was recorded from entering endoscopy room to get out of the anesthesia recovery room, also including perioperative adverse events, other medications or treatments, the time of patients waking up and leaving the hospital. RESULTS: The successful rate of induction in three groups was 100%. There was no significant difference in the sedation completion rate among the three groups (Group A:90.2%, Group B: 92.7%, Group C: 92.7%, P = 1.000). The rate of adverse events after administration: group A(27.0%) and B(36.8%) both lower than group C(71.0%),P < 0.001;There was no significant difference between group A and group B, P > 0.744;The average time from the last drug administration to meet the discharge criteria of the subjects in three groups was as follows: The average time of group A(16.2 min) and Group B(16.5 min) both shorter than group C(19.6 min), P = 0.001; There was no significant difference between group A and group B, P = 0.742. CONCLUSIONS: This study revealed that remimazolam is a safe and effective medication for colonoscopy sedation, the security of remimazolam is better than propofol, and the sedative effect with the initial dose of 0.25 mg/kg of remimazolam is optimal. TRIAL REGISTRATION: China Clinical Trial Center with registration number: 2100052615,02/11/2021.

Effect of different head-high lateral extubation on adverse reactions in the peri-extubation period of pediatric OSAS surgery under general anesthesia.

BACKGROUND: Children with OSAS are prone to various airway complications during tracheal extubation after tonsillectomy and adenoidectomy due to oropharyngeal secretions and oozing blood. However, few studies have examined the effect of position on airway complications after tracheal extubation in children with OSAS. The aim of this study was to investigate the appropriate position for extubation in children with OASA. METHODS: A total of 459 children aged 3-14 years with OSAS who underwent tonsillectomy and adenoidectomy were recruited for this study. All children were treated with the same surgical approach and standard anesthesia methods of induction of anesthesia, tracheal intubation and maintenance of anesthesia. At the end of surgery, the children were delivered to the post anesthesia care unit and randomly divided into three groups: Group A: Head-high 0° in lateral position; Group B: Head-high 15° in lateral position; Group C: Head-high 30° in lateral position. The main outcomes of this study were the pulse oxygen saturation (SpO2) and the Sedation-Agitation Scale (SAS) scores of the children after extubation, the outflow of oral-nasal secretions and the respiratory complications. Secondary outcomes were blood pressure, heart rate, end-respiratory carbon dioxide, respiratory rate, and post-operative awakening time of the children in three groups. RESULTS: Data from a total of 423 children were statistically analyzed, 141 in Group A, 142 in Group B, and 140 in Group C. The main results showed a significant decrease in choking response after extubation in Group B (46.5%) and Group C (40.7%) compared to Group A (60.3%) (P < 0.05). The SAS score for postoperative agitation was higher in Group A (4.6 [Formula: see text] 0.9) than in Group B (4.4 [Formula: see text] 0.7) and Group C (4.3 [Formula: see text] 0.6) (P < 0.05). Also the SpO2 after extubation was higher in Group B (97.2%) and Group C (97.1%) than in Group A (95.8%) (P < 0.05). In contrast, there was no difference in the occurrence of respiratory complication and postoperative agitation in children between Group B and Group C (all P > 0.05). In addition, there was no difference in the amount of oral-nasal secretions among the children in the three groups (all P > 0.05). CONCLUSION: The head-high 15° lateral position and head-high 30° lateral position can reduce the incidence of airway complications and agitation and provide safe and comfortable extubation conditions for children during the peri-extubation period after tonsillectomy and adenoidectomy, which has certain clinical guidance value. TRIAL REGISTRATION: Registration Number: NO.ChiCTR2200055835(20,01,2022) https://www.chictr.org.cn.

A comparative study of esketamine-dexmedetomidine and sufentanil-dexmedetomidine for sedation and analgesia in lung tumor percutaneous radiofrequency ablation (PRFA): a randomized double-blind clinical trial.

OBJECTIVE: To observe and evaluate the effectiveness and safety of Esketamine or Sufentanil combined with Dexmedetomidine for sedation and analgesia in lung tumor percutaneous radiofrequency ablation (PRFA) to provide a clinical basis for the optimization of sedation and analgesia in lung tumor PRFA protocols outside the operating room. METHODS: In this trial, 44 patients aged 37 to 84 undergoing lung tumor PRFA were enrolled and assigned to Group E (n = 22, Esketamine 0.2 mg/kg) or Group S (n = 22,Sufentanil 0.1 µg/kg ). Dexmedetomidine was infused intravenously as a sedative in both groups. The modified observer's assessment of alertness and sedation scale (MOAAS), physical movement pain scale, intraoperative vital signs, anesthesia recovery time, radiologist and patient satisfaction rates, incidence of respiratory depression, and incidence of postoperative nausea and vomiting were recorded. RESULTS: Although there was no significant difference in the physical movement pain scale, blood oxygen saturation or incidence of perioperative adverse events between the two groups during ablation, the MOAAS, mean arterial pressure (MAP) and heart rate (HR) were higher in Group E than in Group S. The anesthesia recovery time was shorter in Group E than in Group S, and radiologist satisfaction was better in Group E than in Group S, but there was no significant difference between the two groups in terms of patient satisfaction. CONCLUSION: Esketamine or Sufentanil combined with Dexmedetomidine is safe for lung tumor PRFA. However, in elderly patients with multiple underlying diseases, low-dose Esketamine combined with Dexmedetomidine has fewer hemodynamic effects on patients, milder respiratory depression, shorter recovery time, and better radiologist satisfaction because of its better controllability of sedation depth. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Registration number#ChiCTR ChiCTR21000500 21); Date of Registration: 16/08/2021.

Design of chitosan-based drug-loaded laminated materials with superhydrophilic/superhydrophobic properties for simultaneous effective hemostasis and antiadhesion.

Hemostatic materials play a crucial role in trauma medicine. However, existing materials have poor hemostatic efficacy and a tendency to adhere to the wound surface, limiting their clinical effectiveness. Herein, a drug-loaded, superhydrophilic/superhydrophobic laminated material (DSLM), consisting of a superhydrophobic inner layer with a micropore array, a superhydrophilic chitosan-based sponge layer loaded with hemostatic/antimicrobial drugs, and a superhydrophobic outer layer, was developed. Furthermore, the DSLM allows unidirectional flow of blood and exudates from the wound bed through the superhydrophobic inner layer while facilitating efficient drug delivery. In addition, it possesses excellent biocompatibility and antiadhesion properties, as confirmed by in vivo and in vitro experiments. Compared with traditional hemostatic materials, the DSLM remarkably increased the survival time by over threefold in the acute femoral transaction wound bleeding model, and simultaneously prevented secondary wound damage by reducing peeling force to one-eighth incomparison to pristine gauze. The DSLM holds promise as a versatile clinical biomaterial for prehospital acute trauma treatment, with its simple structure facilitating manufacturing and expanding applications in biomedicine.

Effects of glycopyrrolate and atropine for oral secretions and perioperative hemodynamics in children undergoing tonsillectomy and adenoidectomy: a prospective, single-center, randomized, double-blind, controlled trial.

Introduction: Glycopyrrolate is commonly researched as a preoperative medication or in conjunction with cholinesterase inhibitors to counteract the lingering muscarinic effects of non-depolarizing muscarinic agents. However, studies have yielded inconsistent results regarding the superiority of glycopyrrolate over other anti-cholinergic drugs, such as atropine, particularly its effect on heart rate, blood pressure (BP), and glandular secretions. This study aimed to evaluate the differences in perioperative oral secretions, hemodynamics, and recovery quality with glycopyrrolate versus those with atropine before anesthesia induction in children undergoing tonsillectomy and adenoidectomy. Methods: In this prospective, single-center, randomized, double-blind, controlled trial, a total of 103 children were randomly assigned to group A (n = 51, glycopyrrolate 0.005 mg/kg) or B (n = 52, atropine 0.01 mg/kg). The follow-up anesthetic induction and maintenance protocols were the same in both groups. Vital signs, duration of surgery, extubation time, degree of wetness around the vocal cords during tracheal intubation, weight of oral secretions, and perioperative complications were recorded. Results: No significant differences were observed in the degree of wetness around the vocal cords during tracheal intubation, as well as in the weight of oral secretions, duration of surgery, or extubation time, between the two groups. The intraoperative and postoperative heart rates were lower in group A than in group B (110.18 ± 10.58 vs. 114.94 ± 11.14, p = 0.028; 96.96 ± 10.81 vs. 103.38 ± 10.09, p = 0.002). The differences observed in the intraoperative and preoperative heart rates were lower in group A than in group B (23.84 ± 9.62 vs. 29.65 ± 8.75, p = 0.002). The differences observed in the postoperative and preoperative heart rates were lower in group A than in group B (10.63 ± 9.97 vs. 18.09 ± 9.39, p = 0.000). Conclusion: Glycopyrrolate showed a smoother change in heart rate than atropine during and after tonsillectomy and adenoidectomy, with no effect on BP or recovery quality, and did not increase oral secretions. The findings indicate that glycopyrrolate can serve as an alternative to atropine to prevent secretions in anesthesia induction for tonsillectomy and adenoidectomy in children. Trial registration: This study was registered with the Chinese Clinical Trial Registry (Registration Number: ChiCTR2200063578; Date of Registration: 12/09/2022).

The effect of low-dose esketamine on pain and post-partum depression after cesarean section: A prospective, randomized, double-blind clinical trial.

Objective: To observe and evaluate the effect of a single intravenous injection of low-dose esketamine on post-operative pain and post-partum depression (PPD) in cesarean delivery patients. Methods: A total of 210 patients undergoing elective cesarean delivery under combined spinal-epidural anesthesia were divided into an esketamine group (Group S, n = 105) and a normal saline group (Group L, n = 105) by a random number table. At 5 min after childbirth, patients in the S group were given 0.25 mg/kg esketamine, whereas patients in the L group received an equal volume of saline. The primary outcomes included post-operative pain control according to the Numerical Rating Scale (NRS) and the incidence of PPD according to the Edinburgh Post-partum Depression Scale (EPDS). The secondary outcomes included analgesia-related adverse events and Ramsay sedation scores. Results: This clinical study was a prospective, randomized, double-blind trial. A total of 210 patients were enrolled in this study. The NRS pain (cough pain) score was lower in the S group than in the L group at 24 h after surgery (P = 0.016), and there was no significant difference in resting pain and mobilization pain at 4, 8, and 48 h after surgery or resting pain at 24 h after surgery between the two groups. There was no significant difference in the prevalence of PPD between the two groups on the day before delivery, or at the first week, the second week, or the fourth week after childbirth. At 5 min after dosing, the incidence of hallucinations (P < 0.001) and dizziness (P < 0.001) was higher in the S group than in the L group. At 15 min after dosing, the incidence of dizziness (P < 0.001) and nausea (P = 0.011) was higher in the S group than in the L group. The incidence of dizziness (P < 0.001) was higher in the S group than in the L group when leaving the operating room. The Ramsay scores in Group S were lower than in Group L at 5 min (p < 0.001), 15 min (p < 0.001) after dosing and at the time of leaving the operating room (p < 0.001). Conclusion: In this study, a single intravenous injection of 0.25 mg/kg esketamine did not reduce the incidence of depression at 1, 2, or 4 w post-partum but improved pain during exercise at 24 h post-operatively under the conditions of this clinical trial. Clinical trial registration: [www.chictr.org.cn], identifier [ChiCTR2100054332].

A Comparison of Intranasal Dexmedetomidine, Esketamine or a Dexmedetomidine-Esketamine Combination for Induction of Anaesthesia in Children: A Randomized Controlled Double-Blind Trial.

Objective: To compare the efficacy of dexmedetomidine, esketamine or combined intranasal administration on the induction of inhalation anaesthesia in children. Methods: Ninety children aged 1-6 years were randomly allocated into three equal groups to be premedicated with either intranasal dexmedetomidine 2 µg/kg (Group D), esketamine 1 mg/kg (Group S), or dexmedetomidine 1 µg/kg combined with esketamine 0.5 mg/kg (Group DS). The primary endpoint was the Induction Compliance Checklist (ICC) Scale. Secondary outcomes included the sedation success rate; the modified Yale Preoperative Anxiety Scale score; the time of reaching up to two points on the University of Michigan Sedation Scale (UMSS); Parental Separation Anxiety Scale; anaesthesiologist satisfaction with induction based on the visual analogue scale; emergence agitation scale score; and adverse effects. Results: The children in the DS group showed a high degree of cooperation with inhalation anaesthesia induction, and their ICC score was significantly lower than that of the D and S groups (p = 0.001), but there was no difference between the D and S groups. The success rate of sedation was higher in Group DS (90%) than in Group D (70%) and Group S (53.3%) (p = 0.007). Anaesthesiologist satisfaction with induction was significantly higher in Group DS than in Groups D and S (p = 0.001). The incidence of emergence agitation and the Paediatric Anaesthesia Emergence Delirium (PAED) score in the DS group were lower than those in the D and S groups. Conclusions: Preoperative intranasal administration of dexmedetomidine combined with esketamine can significantly improve the cooperation of children with inhalation anaesthesia masks. It is a sedation method that has a high success rate and reduces the incidence and degree of emergence agitation.

Echinacoside Upregulates Sirt1 to Suppress Endoplasmic Reticulum Stress and Inhibit Extracellular Matrix Degradation In Vitro and Ameliorates Osteoarthritis In Vivo.

BACKGROUND: Osteoarthritis (OA) is a progressive illness that destroys cartilage. Oxidative stress is a major contributor of OA, while endoplasmic reticulum (ER) stress is the key cellular damage under oxidative stress in chondrocytes. Echinacoside (ECH) is the main extract and active substance of Cistanche, with potent antioxidative stress (OS) properties, and currently under clinical trials in China. However, its function in OA is yet to be determined. PURPOSE: We aimed to explore the specific role of ECH in the occurrence and development of OA and its underlying mechanism in vivo and in vitro. METHODS: After the mice were anesthetized, the bilateral medial knee joint meniscus resection was performed to establish the DMM model. TBHP was used to induce oxidative stress to establish the OA model in chondrocytes in vitro. Western blot and RT-PCR were used to evaluate the level of ER stress-related biomarkers such as p-PERK/PERK, GRP78, ATF4, p-eIF2α/eIF2α, and CHOP and apoptosis-related proteins such as BAX, Bcl-2, and cleaved caspase-3. Meanwhile, we used SO staining, immunofluorescence, and immunohistochemical staining to evaluate the pharmacological effects of ECH in mice in vivo. RESULTS: We demonstrated the effectiveness of ECH in suppressing ER stress and restoring ECM metabolism in vitro. In particular, ECH was shown to suppress tert-Butyl hydroperoxide- (TBHP-) induced OS and subsequently lower the levels of p-PERK/PERK, GRP78, ATF4, p-eIF2α/eIF2α, and CHOP in vitro. Simultaneously, ECH reduced MMP13 and ADAMTS5 levels and promoted Aggrecan and Collagen II levels, suggesting ECM degradation suppression. Moreover, we showed that ECH mediates its cellular effects via upregulation of Sirt1. Lastly, we confirmed that ECH can protect against OA in mouse OA models. CONCLUSION: In summary, our findings indicate that ECH can inhibit ER stress and ECM degradation by upregulating Sirt1 in mouse chondrocytes treated with TBHP. It can also prevent OA development in vivo.

Eicosapentaenoic Acid-Induced Autophagy Attenuates Intervertebral Disc Degeneration by Suppressing Endoplasmic Reticulum Stress, Extracellular Matrix Degradation, and Apoptosis.

Intervertebral disc degeneration (IDD) is a major cause of low back pain (LBP), but there is still a lack of effective therapy. Multiple studies have reported that endoplasmic reticulum (ER) stress and extracellular matrix (ECM) degradation exert an enormous function on the occurrence and development of IDD. Autophagy can effectively repair ER stress and maintain ECM homeostasis. Eicosapentaenoic acid (EPA) can specifically induce autophagy. The purpose of this study is to demonstrate that EPA can promote autophagy, reduce ECM degradation and ER stress in vitro, thereby reducing cell apoptosis, and the protective effects of EPA in an IDD-rat model in vivo. Western blot and immunofluorescence were used to detect the autophagic flux, ER stress, ECM degradation, and apoptosis in nucleus pulposus cells (NPCs) treated by EPA. We also used puncture-induced IDD rats as experimental subjects to observe the therapeutic effect of EPA on IDD. Our findings indicated that EPA can effectively improve the autophagy activity in NPCs, inhibit the endoplasmic reticulum stress process, reduce the degree of cell apoptosis, and exert protective effects on the anabolism and catabolism of ECM. In addition, in vivo investigations demonstrated that EPA ameliorated the progression of puncture-induced IDD in rats. In conclusion, this study revealed the intrinsic mechanisms of EPA's protective role in NPCs and its potential therapeutic significance for the treatment of IDD.

Downregulation of NLRP2 inhibits HUVEC viability by inhibiting the MAPK signaling pathway.

Nucleotide­binding oligomerization domain (NOD)­like receptor proteins (NLRPs) are a subfamily of NOD­like receptors (NLRs) that mainly participate in innate immunity. Among the 14 NLRPs, studies on NLRP2 are few and mostly focus on its functions in reproduction and embryonic development. To the best of the authors' knowledge, there has been no research on the function of NLRP2 in human umbilical vein endothelial cells (HUVECs). The present study knockdown the expression of NLRP2 by transfecting a short interfering (si)RNA (siNLRP2) into HUVECs and investigating its effects on HUVECs. It was identified using a Cell Counting kit­8 assay that knockdown of NLRP2 can inhibit cell proliferation in HUVECs. The results of wound healing and Transwell assays indicated that migration and invasion were also suppressed by siNLRP2 transfection in HUVECs. Flow cytometry demonstrated that siNLRP2 induced cell cycle arrest and apoptosis in HUVECs. Western blot analysis revealed that the expression levels of cell cycle and apoptosis­associated proteins were markedly changed. In addition, knockdown of NLRP2 inhibited the mitogen­activated protein kinase (MAPK) signaling pathway by elevating extracellular signal­regulated kinase phosphorylation levels and reducing proto­oncogene serine/threonine­protein kinase expression. Taken together, it was concluded that NLRP2 served an important role in maintaining cell viability, proliferation and motility in HUVECs, mainly by promoting the MAPK signaling pathway.