OBJECTIVE: Gastroscopy is one of the most commonly used diagnostic modalities for upper gastrointestinal disorders. Remazolam besylate, a new type of ultrashort-acting benzodiazepine drug, has been less studied in gastroscopy. In this study, we studied the efficacy and safety of remazolam combined with propofol for painless gastroscopy.
METHODS: This was a single-center, placebo-controlled randomized trial.
METHODS: One hundred patients undergoing painless gastroscopy were included in this study and randomly divided into 2 groups (n = 50 per group): the control group (Con group) and the remazolam group (Rem group). Sufentanil, remazolam, and propofol were used to anesthetize the patients, and then, the effects of different solutions on these patients were compared and analyzed. The patient\'s general condition, vital signs at different times, the dosage of propofol (mg) and additional times, complications, duration of gastroscopy (minutes), recovery time (minutes), length of stay in the recovery room (minutes), and adverse reactions were recorded.
RESULTS: Rem group systolic blood pressure was more stable (P < .05). The amount of additional propofol in Rem group was less (P < .05). The incidence of hypotension, bradycardia, and dizziness was lower in Rem group, as well as the time of awakening and stay in the recovery room were shorter (P < .05).
CONCLUSIONS: Remazolam combined with sufentanil and propofol has less effect on hemodynamics in painless gastroscopy, and the patients have shorter awakening times.

BACKGROUND: Remimazolam, a recently developed anesthetic characterized by its rapid and ultra-short-acting properties, exhibits pharmacological attributes that make it potentially suitable for painless surgical abortion procedures. The objective of this study was to determine the effective dose of remimazolam when administered in combination with sufentanil, with the intention of inhibiting body movement during surgical abortion. Additionally, a secondary objective was to assess the recovery profile from general anesthesia.
METHODS: The study enrolled a total of 25 healthy women aged 20 to 40, with a body mass index between 18 and 28 kg/m2, in their first trimester of pregnancy (up to 12 weeks), and American Society of Anesthesiologists status I and II. Anesthesia induction was initiated by administering sufentanil at a dose of 0.1 μg/kg. The modified Dixon up-and-down method was employed to determine the induction dose of remimazolam for each patient.
RESULTS: The 50% and 95% effective dose of remimazolam for inhibitory effects of body movement was estimated using centered isotonic regression to be 0.145 mg/kg (95% CI: 0.115, 0.207), and 0.242 mg/kg (95% CI: 0.232, 0.620), respectively. Five out of 25 (20%) experienced hiccups, with 1 patient having persistent hiccups until the end of the surgery. The mean time to first eye-opening was 51.4 ± 20.5 seconds, and the time to obey verbal command was 54.5 ± 20.6 seconds. Upon arrival at the postanesthesia care unit, 95.7% of the patients achieved a Modified Aldrete score ≥ 9.
CONCLUSIONS: The 50% and 95% effective dose of remimazolam for inhibiting body movement during surgical abortion when used in combination with 0.1 μg/kg of sufentanil were 0.145 mg/kg and 0.242 mg/kg, respectively.

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.
BACKGROUND: China Clinical Trial Center with registration number: 2100052615,02/11/2021.

OBJECTIVE: The aim of this study was to evaluate the effect of remifentanil pretreatment on sufentanil-induced cough during general anesthesia induction.
METHODS: This experimental research was conducted as a single-center, randomized, parallel-group trial.
METHODS: A total of 120 patients scheduled for elective surgery were equally randomized into two groups (remifentanil and control). The incidence and severity of coughing in both groups were recorded after sufentanil administration during general anesthesia induction. The mean arterial pressure, heart rate, and pulse oxygen saturation were recorded at T1 (before the injection of remifentanil or normal saline), T2 (1 minute after remifentanil administration), T3 (before intubation), and T4 (1 minute after intubation). Additionally, the incidences of adverse events, including dizziness, nausea, apnea, truncal rigidity, bradycardia, or other adverse effects were also recorded.
RESULTS: The incidence of sufentanil-induced cough in the remifentanil group was significantly decreased when compared with the control group (5.0% vs 35.0%, respectively; P < .001). No statistical differences were found in mean arterial pressure, heart rate, pulse oxygen saturation, and the incidences of other side effects between the two groups at T1, T2, T3, and T4 (P > .05).
CONCLUSIONS: Pretreatment with remifentanil at a dose of 0.5 mcg/kg can effectively and safely suppress the incidence and severity of sufentanil-induced coughing, providing a reference for medication during general anesthesia induction.

BACKGROUND: Postoperative pain management and cognitive function preservation are crucial for patients undergoing thoracoscopic surgery for lung cancer (LC). This is achieved using either a thoracic paravertebral block (TPVB) or sufentanil (SUF)-based multimodal analgesia. However, the efficacy and impact of their combined use on postoperative pain and postoperative cognitive dysfunction (POCD) remain unclear.
OBJECTIVE: To explore the analgesic effect and the influence on POCD of TPVB combined with SUF-based multimodal analgesia in patients undergoing thoracoscopic radical resection for LC to help optimize postoperative pain management and improve patient outcomes.
METHODS: This retrospective analysis included 107 patients undergoing thoracoscopic radical resection for LC at The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital between May 2021 and January 2023. Patients receiving SUF-based multimodal analgesia (n = 50) and patients receiving TPVB + SUF-based multimodal analgesia (n = 57) were assigned to the control group and TPVB group, respectively. We compared the Ramsay Sedation Scale and visual analog scale (VAS) scores at rest and with cough between the two groups at 2, 12, and 24 h after surgery. Serum levels of epinephrine (E), angio-tensin II (Ang II), norepinephrine (NE), superoxide dismutase (SOD), vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), and S-100 calcium-binding protein β (S-100β) were measured before and 24 h after surgery. The Mini-Mental State Examination (MMSE) was administered 1 day before surgery and at 3 and 5 days after surgery, and the occurrence of POCD was monitored for 5 days after surgery. Adverse reactions were also recorded.
RESULTS: There were no significant time point, between-group, and interaction effects in Ramsay sedation scores between the two groups (P > 0.05). Significantly, there were notable time point effects, between-group differences, and interaction effects observed in VAS scores both at rest and with cough (P < 0.05). The VAS scores at rest and with cough at 12 and 24 h after surgery were lower than those at 2 h after surgery and gradually decreased as postoperative time increased (P < 0.05). The TPVB group had lower VAS scores than the control group at 2, 12, and 24 h after surgery (P < 0.05). The MMSE scores at postoperative days 1 and 3 were markedly higher in the TPVB group than in the control group (P < 0.05). The incidence of POCD was significantly lower in the TPVB group than in the control group within 5 days after surgery (P < 0.05). Both groups had elevated serum E, Ang II, and NE and decreased serum SOD levels at 24 h after surgery compared with the preoperative levels, with better indices in the TPVB group (P < 0.05). Marked elevations in serum levels of VEGF, TGF-β1, TNF-α, and S-100β were observed in both groups at 24 h after surgery, with lower levels in the TPVB group than in the control group (P < 0.05).
CONCLUSIONS: TPVB combined with SUF-based multimodal analgesia further relieves pain in patients undergoing thoracoscopic radical surgery for LC, enhances analgesic effects, reduces postoperative stress response, and inhibits postoperative increases in serum VEGF, TGF-β1, TNF-α, and S-100β levels. This scheme also reduced POCD and had a high safety profile.

UNASSIGNED: Bronchoscopy examination is a common clinical diagnostic method. However, due to its unique operational characteristics, the procedure often induces discomfort and pain in patients. The combined use of sufentanil and nalmefene offers advantages in effectively reversing opioid-induced respiratory depression without compromising analgesic effects. However, a comprehensive analysis report on the combined use of different doses of sufentanil and nalmefene in bronchoscopy examinations has not been reported. The aim of this subject is to investigate the application effects of different doses of sufentanil combined with nalmefene in bronchoscopy.
UNASSIGNED: Using computer-based and manual methods to retrieve relevant keywords, we searched the databases of PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang from inception to the present to find studies evaluating the application effects of different doses of sufentanil combined with nalmefene in bronchoscopy examinations. The quality of the included studies was assessed, and meta-analysis was conducted using RevMan 5.3 software.
UNASSIGNED: A total of six English-language articles, involving randomized controlled trials and reviews, and comprising 774 participants, were finally included. The control group used conventional therapy, whereas the intervention group used different doses of sufentanil combined with nalmefene. Meta-analysis results indicated that compared to conventional therapy, this approach significantly improved vital signs such as systolic blood pressure [SBP; mean difference (MD) =21.44, P<1×10-5] and diastolic blood pressure (DBP; MD =22.52, P<1×10-5), heart rate (HR; MD =25.16, P<1×10-5), and oxygen saturation (SpO2; MD =30.16, P<1×10-5). A total of 4 studies focused on sedative effects, and that of sufentanil combined with nalmefene was significantly superior to conventional therapy (P<1×10-5). Analysis of adverse events showed that the combined therapy had better outcomes in terms of hypertension and tachycardia incidence compared to the control group (P<0.001, P<1×10-5), and Riker sedation-agitation scale (SAS score) was significantly reduced (P<0.05). However, there were no significant differences in other adverse events (P>0.05). Subgroup analysis showed fewer adverse reactions at 0.4 µg/kg sufentanil concentration compared to 0.2 and 0.8 µg/kg, with only hypertension differing significantly.
UNASSIGNED: In clinical practice, considering the use of sufentanil combined with nalmefene can improve patients\' experience during bronchoscopy examinations. However, it should be noted that this approach may not be suitable for all patients, and clinicians need to choose appropriate analgesic and sedative methods for bronchoscopy examinations based on patients\' conditions and individual differences. Furthermore, it is important to recognize that this study has some limitations and further research is needed to evaluate the efficacy and safety of this approach in other types of endoscopic examinations, as well as to compare the effects and safety of different drug combinations.

BACKGROUND: High doses of long-acting opioids were used to facilitate off-pump coronary artery bypass grafting procedure, which may result in opioid-related adverse events after surgery. Transcutaneous electrical acupoint stimulation (TEAS) had been reported to be effective in reducing intraoperative opioids consumption during surgery. The aim of this study is to assess whether TEAS with difference acupoints can reduce the doses of opioid analgesics.
METHODS: This was a multicenter, randomized, controlled, double-blind trial. Patients underwent off-pump coronary artery bypass grafting under general anesthesia were enrolled. Eligible patients were randomly and equally grouped into sham acupuncture group (n = 105), regional acupoints combination group (n = 105), or distal-proximal acupoints combination group (n = 105) using a centralized computer-generated randomization system. Transcutaneous electrical acupoint stimulation was applied for 30 min before anesthesia induction. The primary outcome was the doses of sufentanil during anesthesia. Secondary outcomes included the highest postoperative vasoactive-inotropic scores within 24 h, intraoperative propofol consumption, length of mechanical ventilation, duration of cardiac care unit and postoperative hospital stay, incidence of postoperative complications, and mortality within 30 days after surgery.
RESULTS: Of the 315 randomized patients, 313 completed the trial. In the modified intention-to-treat analysis, the doses of sufentanil were 303.9 (10.8) μg in the distal-proximal acupoints group, significantly lower than the sham group, and the mean difference was - 34.9 (- 64.9 to - 4.9) μg, p = 0.023. The consumption of sufentanil was lower in distal-proximal group than regional group (303.9 vs. 339.5), and mean difference was - 35.5 (- 65.6 to - 5.5) μg, p = 0.020. The distal-proximal group showed 10% reduction in opioids consumption comparing to both regional and sham groups. Secondary outcomes were comparable among three groups.
CONCLUSIONS: Transcutaneous electrical acupoint stimulation with distal-proximal acupoints combination, compared to regional acupoints combination and sham acupuncture, significantly reduced sufentanil consumption in patients who underwent off-pump coronary artery bypass grafting surgery.

UNASSIGNED: This study aimed to investigate the effect of different doses of dexmedetomidine combined with sufentanil on postoperative analgesia in developmental hip dislocation in children after Salter osteotomy.
UNASSIGNED: The clinical data of 98 children with developmental hip dislocation, who underwent Salter osteotomy in our center between January 2020 and February 2023, were selected. The children were randomly divided into four groups based on the application of patient-controlled intravenous analgesia (sufentanil + granisetron ± dexmedetomidine). All children received 1 µg/kg/day of sufentanil and 3 mg of granisetron. Group A did not receive dexmedetomidine, and Groups B, C, and D received 0.5, 0.75, and 1.0 µg/kg/day of dexmedetomidine, respectively. The pain indicators and immune factor levels of children in each group were compared.
UNASSIGNED: The heart rate (HR) and respiratory rate (RR) 2 h after operation in Groups C and D were significantly lower than those in Groups A and B (P < 0.05). The pain scores decreased over time after treatment in all groups. When compared at the same time point, children in Group D had the lowest pain scores, which were significantly lower than the other three groups (P < 0.05). The total consumption of sufentanil in Groups C and D was significantly lower than that in Group A (P < 0.05). On the first day after surgery, the children in Group D had lower levels of serum adrenocorticotropic hormone, interleukin-6, and corticosterone than those in Group A (P < 0.05).
UNASSIGNED: Administration of 1.0 µg/kg/day of dexmedetomidine combined with sufentanil in intravenous controlled analgesia after Salter osteotomy for developmental hip dislocation in children has a better analgesic effect, less consumption of sufentanil, and low incidence of opioid adverse reactions.

Non-small cell cancer (NSCLC) is the most common cancer in the world, but its effective therapeutic methods are limited. Tilianin and sufentanil alleviate various human tumors. This research aimed to clarify the functions and mechanisms of Tilianin and sufentanil in NSCLC. The functions of Tilianin and sufentanil on NSCLC cell viability, apoptosis, mitochondrial dysfunction, and immunity in vitro were examined using Cell Counting Kit-8 assay, flow cytometry, reactive oxygen species level analysis, CD8+ T cell percentage analysis, Western blot, and enzyme-linked immunosorbent assay, respectively. The molecular mechanism regulated by Tilianin and sufentanil in NSCLC was assessed using Western blot, and immunofluorescence assays. Meanwhile, the roles of Tilianin and sufentanil in NSCLC tumor growth, apoptosis, and immunity in vivo were determined by establishing a tumor xenograft mouse model, immunohistochemistry, and Western blot assays. When sufentanil concentration was proximity 2 nM, the inhibition rate of NSCLC cell viability was 50%. The IC50 for A549 cells was 2.36 nM, and the IC50 for H1299 cells was 2.18 nM. The IC50 of Tilianin for A549 cells was 38.7 μM, and the IC50 of Tilianin for H1299 cells was 44.6 μM. Functionally, 0.5 nM sufentanil and 10 μM Tilianin reduced NSCLC cell (A549 and H1299) viability in a dose-dependent manner. Also, 0.5 nM sufentanil and 10 μM Tilianin enhanced NSCLC cell apoptosis, yet this impact was strengthened after a combination of Tilianin and Sufentanil. Furthermore, 0.5 nM sufentanil and 10 μM Tilianin repressed NSCLC cell mitochondrial dysfunction and immunity, and these impacts were enhanced after a combination of Tilianin and Sufentanil. Mechanistically, 0.5 nM sufentanil and 10 μM Tilianin repressed the NF-κB pathway in NSCLC cells, while this repression was strengthened after a combination of Tilianin and Sufentanil. In vivo experimental data further clarified that 1 µg/kg sufentanil and 10 mg/kg Tilianin reduced NSCLC growth, immunity, and NF-κB pathway-related protein levels, yet these trends were enhanced after a combination of Tilianin and Sufentanil. Tilianin strengthened the antitumor effect of sufentanil in NSCLC.

UNASSIGNED: Despite the widespread use of opioids to manage severe pain, its systemic administration results in side effects. Among the subcutaneous and transdermal drug delivery systems developed to deal with adverse effects, microneedles have drawn attention due to their rapid action, high drug bioavailability, and improved permeability. SUF is an effective injectable opioid for treating severe pain. In this study, we investigated the analgesic effects of SUF using dissolvable microneedles.
UNASSIGNED: SUF polymeric dissolvable microneedles were constructed through the mold casting method and characterized by SEM and FTIR analysis. Its mechanical strength was also investigated using a texture analyzer. Fluorescence microscopy was applied in vitro to measure the penetration depth of microneedle arrays. Irritation and microchannel closure time, drug release profile, and hemocompatibility test were conducted for the validation of microneedle efficiency. Hot plate test was also used to investigate the analgesic effect of microneedle in an animal model.
UNASSIGNED: Local administration of SUF via dissolving microneedles had an effective analgesic impact. One hour after administration, there was no significant difference between the subcutaneous and the microneedle groups, and the mechanical properties were within acceptable limits.
UNASSIGNED: Microneedling is an effective strategy in immediate pain relief compared to the traditional methods.