Randomized clinical trial of continuous transversus thoracis muscle plane block for patients undergoing open heart valve replacement surgery.

The optimal analgesia regimen after open cardiac surgery is unclear. The aim of this study was to investigate the beneficial effects of continuous transversus thoracis muscle plane (TTMP) blocks initiated before surgery on open cardiac surgery outcomes. A group of 110 patients were randomly allocated to either receive bilateral continuous TTMP blocks (TTP group) or no nerve block (SAL group). The primary endpoint was post-operative pain at 4, 8, 16, 24, 48 and 72 h after extubation at rest and exercise. The secondary outcome measures included analgesia requirements (sufentanil and flurbiprofen axetil administration), time to extubation, incidence of reintubation, length of stay in the ICU, incidence of post-operative nausea and vomiting (PONV), time until return of bowel function, time to mobilization, urinary catheter removal and length of hospital stay. The length of stay in the ICU and length of hospital stay were significantly longer in the SAL group than in the TTP group. NRS scores at rest and exercise were significantly lower in the TTP group than in the SAL group at all time points. The TTP group required significantly less intraoperative and post-operative sufentanil and post-operative dynastat consumption than the SAL group. Time to extubation, time to first flatus, time until mobilization and time until urinary catheter removal were significantly earlier in the TTP group than in the SAL group. The incidence of PONV was significantly lower in the TTP group. Bilateral continuous TTMP blocks provide effective analgesia and accelerate recovery in patients undergoing open heart valve replacement surgery.

Low-dose sufentanil does not affect tolerance to LBNP-induced central hypovolemia or blood pressure responses during the cold pressor test.

Hemorrhage is a leading cause of death in the pre-hospital setting. Since pain often accompanies a hemorrhagic insult, the administered pain medication must not interfere with critical autonomic regulation of arterial blood pressure and vital organ perfusion. The purpose of this study was to test two unique hypotheses: a) sublingual sufentanil (Dsuvia) impairs tolerance to progressive central hypovolemia, and b) sublingual sufentanil attenuates pain sensation and the accompanying cardiovascular responses to a noxious stimulus. Twenty-nine adults participated in this double-blinded, randomized, crossover, placebo-controlled trial. Following sublingual administration of sufentanil (30 µg) or placebo, participants completed a progressive lower-body negative pressure (LBNP) challenge to tolerance, followed by a cold pressor test (CPT) after LBNP recovery. Addressing the first aim, tolerance to LBNP was not different between trials (p = 0.495). Decreases in systolic blood pressure from baseline to the end of LBNP also did not differ between trials (time: p<0.001, trial p=0.477, interaction p=0.587). Finally, increases in heart rate from baseline to the end of LBNP did not differ between trials (time: p < 0.001, trial p= p=0.626, interaction p = 0.424). Addressing the second aim, sufentanil attenuated perceived pain (p < 0.001) in response to the CPT, though the magnitude of the change in mean blood pressure during the CPT (p = 0.078) was not different between trials. These data demonstrate that sublingual sufentanil does not impair tolerance to progressive central hypovolemia. Additionally, sublingual sufentanil attenuates perceived pain, but not the accompanying mean blood pressure responses to the CPT.

Tilianin enhances the antitumor effect of sufentanil on non-small cell lung cancer.

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.

The use of intranasal sufentanil and/or s-ketamine for treatment of procedural pain in children in an ambulatory setting: A retrospective observational study.

BACKGROUND: Minor but painful medical procedures are often handled at the operating room. If safe and effective treatment options are available many procedures may be performed outside of the operating room. OBJECTIVE(S): The objective of this study is to assess the adverse events of intranasal s-ketamine and/or sufentanil alone or as part of a multimodal analgesic regime for medical procedures outside of the operating room. Secondary outcomes included analgesic effect, doses and indications for use. DESIGN: Retrospective observational study. SETTING: Tertiary care paediatric hospital. PATIENTS: Children 1 year up till 18 years. INTERVENTION(S): Intranasal (IN) sufentanil (S), intranasal s-ketamine (K) or the free combination of the two drugs (SK). MAIN OUTCOME MEASURE(S): The frequency of adverse events including serious adverse events reported by intervention. RESULTS: Between 2004 and 2014, 2185 medical procedures were registered, including 652 procedures with IN SK, 1469 procedures with IN S and 64 procedures with IN K. The children's median age was 5.6 years (range 1.0-17.9). Medical procedures with at least one adverse event were 18% with IN SK, 25% with IN K and 18% with IN S. Common adverse events included episodes of vomiting (9%), nausea (8%) and dizziness (3%). In two patients receiving IN S, serious adverse events occurred. One patient had respiratory depression and bronchospasm and another patient with cerebral palsy had a seizure. Both were handled immediately and did not result in any sequelae. The median doses of intranasal sufentanil were 38% lower when combined with s-ketamine (IN SK free combination: sufentanil dose 0.5 µg/kg (range 0.2-1.3) and s-ketamine dose 0.5 mg/kg (range 0.2-1.5). IN S monotherapy, sufentanil dose 0.8 µg/kg (range 0.2-2.7)). Similar analgesic effect was reported for S and SK. CONCLUSIONS: Intranasal sufentanil and/or s-ketamine are feasible for the treatment of procedural pain in an ambulatory setting with appropriate per- and post-procedural observations and trained staff.

Effect of pretreatment with a small dose of esketamine on sufentanil-induced cough during anesthesia induction: a randomized controlled trial.

BACKGROUND: Sufentanil-induced cough is common during the induction of anesthesia. The objective of this study was to determine whether pretreatment with a small dose of esketamine is effective in treating sufentanil-induced cough. METHODS: 220 patients were screened, and 200 patients who had scheduled elective surgery and were between 18 and 70 years old were randomly divided into two groups. Before sufentanil was administered, esketamine group (group K) was injected with 0.15 mg/kg esketamine at 5 s, and control group (group C) was administered with the same volume. Within 1 min after sufentanil(0.4ug/kg) injection during induction, cough incidence and severity were evaluated. After sufentanil was injected, we recorded its hemodynamic changes and side effects. RESULTS: In the esketamine group (group K) and control group (group C), there was an incidence of cough of 5 and 34%, respectively. The esketamine group (group K) had a significantly lower incidence and severity of cough compared to the control group (group C) immediately after sufentanil injection (P < 0.05). MAP and HR did not differ significantly between the two groups during three different times of general anesthesia induction (P > 0.05). CONCLUSION: In our study, we found that sufentanil-induced cough was significantly reduced by pretreatment with 0.15 mg/kg esketamine, but with no significant changes in the hemodynamic status. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2200063821, registered date: 17/09/2022), http://www.chictr.org.cn.

90% effective volume of 0.1% ropivacaine combined with 0.4 µg/ml sufentanil for epidural labour analgesia with push pump at a rate of 400 mL/hr and a bolus interval of 30 min: a double-blind sequential dose-finding study.

BACKGROUND: It was reported that either shorter programmed intermittent epidural bolus (PIEB) intervals or high-speed bolus can produce more extensive epidural spread. We hypothesized that a combination of shortened time interval and increased speed of epidural bolus might further improve analgesic effect and therefore reduce the hourly volume for epidural labour analgesia. METHODS: This double-blind dose-finding study used a biased coin up-and-down sequential allocation method to determine the 90% effective bolus volume of ropivacaine combined with sufentanil while using the push pump at a rate of 400 mL/hr and interval of 30 min to provide effective analgesia without breakthrough pain. We used 0.1% ropivacaine with 0.4 µg/mL sufentanil, with bolus volumes ranging from 3 to 6 mL. The first patient was assigned a volume of 3 mL, and the remaining volumes were assigned according to the biased coin-up-and-down method. RESULTS: The estimated 90% effective volume (EV90) of ropivacaine combined with sufentanil for epidural labour analgesia at a time interval of 30 min was 4.88 mL (95% confidence interval 4.83-5.38). CONCLUSIONS: The optimum bolus volume of ropivacaine with sufentanil while using push pump at a time interval of 30 min is approximately 5 mL. It could probably further reduce the hourly bolus volume for epidural labour analgesia.

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.

50% efficacy dose of intravenous lidocaine in supressing sufentanil-induced cough in children: a randomised controlled trial.

BACKGROUND: Opioids such as sufentanil are used as anaesthetics due to their rapid action and superior analgesic effect. However, sufentanil induces a huge cough in paediatric patients. In contrast, intravenous (IV) lidocaine suppresses opioid-induced cough in children, but its use is limited due to anaesthetists' concern about its toxicity. Therefore, this study aimed to evaluate the effect of dose-dependent IV lidocaine on sufentanil-induced cough (SIC) in paediatric patients. METHODS: A total of 188 patients aged 3-12 years scheduled for elective tonsillectomy with or without adenoidectomy were enrolled and divided into four groups depending on different dose of lidocaine: A (0 mg.kg-1), B (1 mg.kg-1), C (1.5 mg.kg-1), and D (2 mg.kg-1). The primary outcome was the SIC grade observed during the induction of general anaesthesia. The secondary outcomes were the incidence of SIC, mean arterial pressure, and heart rate at T0, T1, T2, T3, T4, and T5. RESULTS: The SIC grade was significantly different between groups A and D (P = 0.04) and between groups B and D (P = 0.03). Moreover, the incidence of SIC in groups A, B, C, and D was 81%, 87%, 68%, and 64%, respectively, and the difference between groups B and C (P = 0.03) and between groups B and D (P = 0.0083) was statistically significant. No statistical differences were observed in the hemodynamic parameters between the groups. The incidence of severe cough was statistically different between group D and group A (P < 0.0001), between group D and group B (P < 0.0001), and between group D and group C (P < 0.0001) respectively. CONCLUSIONS: Lidocaine suppresses SIC in a dose-dependent manner without severe adverse events. IV lidocaine can be used in paediatric patients safely and efficiently, and the median effective dose was 1.75 mg/kg. TRIAL REGISTRATION: This study was approved by the Institutional Review Board of Yichang Central People's Hospital (HEC-KYJJ-2020-038-02), The trial was registered at www.chictr.org.cn (ChiCTR2100053006).

Effects of adding low-dose esketamine to sufentanil and propofol sedation during cervical conization: a single-centre, randomized controlled trial.

BACKGROUND: Cervical conization is a brief but painful procedure that can be performed under sufficient sedation with propofol and opioids. However, this sedation approach comes with a high risk of sedation-related adverse events (SRAEs). Esketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, causes less cardiorespiratory depression than opioids. The aim of this study was to assess the efficacy and safety of adding a low dose of esketamine to propofol and sufentanil sedation as an opioid-reduced regimen. METHODS: A total of 122 consecutive patients with ASA I-II, body mass index < 30, and STOP-BANG score < 3 who underwent cervical conization were enrolled and randomly divided into Group S and Group ES. Using a closed-loop target-controlled infusion (TCI) pump with a target bispectral index (BIS) value of 60 ± 5, patients in Group S were sedated with 0.2 mcg·kg-1 sufentanil and propofol, while patients in Group ES were sedated with 0.15 mg·kg-1 esketamine, 0.1 mcg·kg-1 sufentanil and propofol. The primary outcome was the incidence and severity of SRAEs, while the secondary outcomes included effectiveness of sedation, awakening time, psychotomimetic side effects, postoperative pain, postoperative nausea and vomiting, and patient and gynaecologist satisfaction. RESULTS: Data from 120 patients were analysed. The incidence of composite SRAEs was significantly higher in Group S than in Group ES (85.0% vs. 56.7%, P < 0.05). Furthermore, the severity of SRAEs was higher in Group S than in Group ES (P < 0.001). There were no significant differences in the effectiveness of sedation, awakening time, psychotomimetic side effects, postoperative pain, postoperative nausea and vomiting, or patient and gynaecologist satisfaction between the two groups. CONCLUSION: Adding low-dose esketamine to propofol and sufentanil sedation reduces the incidence and severity of SRAEs in patients undergoing cervical conization, with equal sedation efficacy, recovery quality, and no additional psychomimetic side effects. TRIAL REGISTRATION: ChiCTR2000040457 , 28/11/2020.

Comparisons of fentanyl and sufentanil on recovery time after inguinal hernia repair in children: a randomized clinical trial.

BACKGROUND: Inguinal hernia repair is a common pediatric procedure. We studied postoperative recovery times in children undergoing laparoscopic inguinal hernia repair with anesthesia induced by fentanyl versus sufentanil. METHODS: We performed a pilot randomized clinical trial between February and December 2022. Eligible children were assigned into two age groups, 2-6 and 6-12 years old groups. Then, children in each age group were randomly assigned into either the fentanyl (2 µg/kg) or sufentanil (0.2 µg/kg) group for anesthesia induction. Baseline characteristics were collected. The primary outcome was the postoperative recovery time, which was recorded as the time period from extubation to a Steward recovery score reaching 6. Secondary outcomes included surgical duration, anesthetic duration, intubation duration, and intraoperative hemorrhage. RESULTS: There were 300 children, with 75 children in each group. In the 2-6 years old group, children who received fentanyl had statistically significantly shorter postoperative recovery times than children who received sufentanil (0.9 ± 0.4 versus 1.5 ± 0.3 h, P < 0.001). However, in the 6-12 years old group, children who received fentanyl had statistically significantly longer postoperative recovery times than children who received sufentanil (1.2 ± 0.4 versus 0.8 ± 0.4 h, P < 0.001). Baseline characteristics and secondary outcomes were comparable between two groups. CONCLUSIONS: Anesthesia induction with fentanyl or sufentanil resulted in different postoperative recovery times after laparoscopic inguinal hernia repair in children in different age groups. More studies are required to determine the appropriate induction anesthetic in children of different ages. TRIAL REGISTRATION: The study protocol was retrospectively registered online at the Chinese Clinical Trial Registry (registration number ChiCTR2300072177, retrospectively registered on 06/06/2023).

Catheter Tip-Associated Mass With Continuous Infusion of Sufentanil for Persistent Spinal Pain Syndrome Type 2: A Case Report Including Histopathologic Examination and Review of the Associated Basic and Clinical Research.

OBJECTIVES: Intrathecal opioids delivered by implanted pumps are used to treat malignant or nonmalignant chronic pain. In this study, we 1) review a case in which intrathecal infusions of sufentanil along with other adjuvants were used and after an extended period led to an intrathecal mass and 2) compared and contrasted the potential mechanisms for these phenomena. MATERIALS AND METHODS: A woman aged 66 years with a history of scoliosis and multiple spine surgeries was treated with an implantable drug delivery system for treating persistent pain after laminectomy. The patient received intrathecal medication comprising sufentanil, bupivacaine, and clonidine. RESULTS: Intrathecal therapy over approximately ten years served to reduce pain and improve function over the treatment period. After the extended treatment interval, the patient developed an intrathecal mass that was associated with impairment. The mass was surgically removed. Systematic histopathology revealed the space-occupying mass to largely comprise fibroblasts and some inflammatory cells embedded in a collagen mass located proximally to the catheter tip. CONCLUSIONS: To our knowledge, this is the first published case report of sufentanil causing this complication. The science and mechanism of intrathecal catheter tip-associated mass formation and associated clinical research correlates are reviewed in detail, and explanations for this phenomenon are proposed based on histochemical analysis of the patient's pathology findings.

Effects of Remifentanil Pretreatment on Sufentanil-induced Cough Suppression During the Induction of General Anesthesia.

PURPOSE: The aim of this study was to evaluate the effect of remifentanil pretreatment on sufentanil-induced cough during general anesthesia induction. DESIGN: 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. FINDINGS: 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.

The Study of Remazolam Combined With Propofol on Painless Gastroscopy: A Randomized Controlled Trial.

PURPOSE: 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. DESIGN: 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. FINDINGS: 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.

The impact of sufentanil versus remifentanil on surgical site wound healing in caesarean section primiparas undergoing epidural anaesthesia: A systematic meta-analysis.

Caesarean section (C-section) is a prevalent obstetric surgical procedure, with the choice of analgesic agents playing a pivotal role in postoperative recovery. This systematic meta-analysis aimed to compare the effects of sufentanil (ST) and remifentanil (RT) on postoperative wound healing in caesarean section primiparas undergoing epidural anaesthesia. A comprehensive search was conducted across multiple databases, adhering to PRISMA guidelines, yielding eight randomized controlled trials (RCTs) for inclusion. The primary outcome was wound healing assessment using the REEDA (redness, edema, ecchymosis, discharge, approximation) scale on the third, fifth and tenth postoperative days. The meta-analysis encompassed 691 primiparas. A significant difference in wound healing was observed between ST and RT on the third (I2 = 99%; Random: SMD: 6.75, 95% CIs: 3.11-10.39, p < 0.01) and fifth days (I2 = 99%; Random: SMD: 3.63, 95% CIs: 1.56-5.70, p < 0.01) postcaesarean section. However, no significant difference was noted on the tenth day (I2 = 5%; Random: SMD: 0.00, 95% CIs: -0.45-0.45, p = 0.35). Sufentanil and remifentanil exhibit differential effects on early postoperative wound healing in caesarean section primiparas undergoing epidural anaesthesia. While both opioids are effective analgesics, sufentanil demonstrates a more pronounced impact on wound healing during the immediate postoperative days. Clinicians should consider these findings when selecting an opioid for pain management in this patient population.

Comparison of Analgesic Effects and Adverse Events of Hydromorphone PCIA Versus Sufentanil PCIA: A Retrospective Analysis.

PURPOSE: The aim of this study was to compare the analgesic effect and adverse events of hydromorphone patient-controlled intravenous analgesia (PCIA) without background dose versus sufentanil PCIA with background dose in patients after surgery. DESIGN: A retrospective analysis. METHODS: From June 2020 to May 2021, 1,594 eligible postoperative patients who received PCIA were included in this study. According to the types of opioids, patients were divided into two groups: the sufentanil group and the hydromorphone group. The Numerical Rating Scale, Functional Activity Scale, and Level of Sedation were used to evaluate the analgesic effects between the two groups. In addition, total patient-controlled analgesia (PCA) use, effective number of PCA compressions, and adverse effects of PCIA were compared between the two groups. FINDINGS: At 24 hours (h) after surgery, the Functional Activity Scale score in the sufentanil group was higher than that in the hydromorphone group (P < .05). Compared with the sufentanil group, total PCA use, total number of PCA compressions and effective number of PCA consumptions were significantly decreased in the hydromorphone group during a 48 hours period (P < .05). There were no statistical differences in Numerical Rating Scale score, Level of Sedation score, and adverse events between two groups at 24 hours and 48 hours after surgery. CONCLUSIONS: Compared with sufentanil PCIA with a background dose, under a similar analgesic effect, hydromorphone PCIA without a background dose provided lower PCA use. Our findings may provide useful evidence for more future studies related to postoperative analgesia.

Mu-opioid receptor alleviated ferroptosis in hepatic ischemia-reperfusion injury via the HIF-1α/KCNQ1OT1 axis.

Ferroptosis is the ideal therapeutic target for hepatic ischemia and reperfusion injury (HIRI). The µ opioid receptor (MOR) is associated with ferroptosis in HIRI. We aimed to determine the ferroptosis-related therapeutic mechanism of MOR in HIRI. A model of HIRI was established in BALB/c mice. Primary hepatocytes isolated from mice were stimulated by hypoxia/reoxygenation (H/R). Changes in histopathology were determined by H&E staining. Alterations in ferroptosis were evaluated by malondialdehyde (MDA), iron, glutathione (GSH), ACSL4, GPX4, and mitochondrial morphology. ALT and AST were used to determine hepatic function. First, we found that hepatic ischemia/reperfusion (I/R) induced the destruction of hepatic tissue structure and dead hepatocytes and determined that ferroptosis occurred in vivo and in vitro. During HIRI, the expression levels of HIF-1α and KCNQ1OT1 were significantly upregulated. We demonstrated that sufentanil improved the damage in the liver and hepatocytes undergoing I/R. Importantly, sufentanil inhibited ferroptosis in HIRI. In addition, sufentanil downregulated the expression levels of HIF-1α and KCNQ1OT1 in HIRI. Increases in HIF-1α and KCNQ1OT1 reversed the role of sufentanil in ferroptosis and HIRI. Subsequently, we determined that HIF-1α could activate the transcription of KCNQ1OT1 by binding to its promoter. In addition, KCNQ1OT1 was demonstrated to enhance ACSL4 stability by interacting with SRSF1. Finally, we observed that KCNQ1OT1 downregulation protected hepatocytes from hepatic I/R and inhibited ferroptosis. KCNQ1OT1 upregulation aggravated ferroptosis and hepatic injury during I/R. However, decreases in ACSL4 and SRSF1 reversed the harmful role of KCNQ1OT1 upregulation in HIRI. MOR alleviated ferroptosis in HIRI via the HIF-1α/KCNQ1OT1 axis.

Spinal microRNA-134-5p targets glutamate receptor ionotropic kainate 3 to modulate opioid induced hyperalgesia in mice.

Background: Fentanyl and its analogs are extensively used for pain relief. However, their paradoxically pronociceptive effects often lead to increased opioids consumption and risk of chronic pain. Compared to other synthetic opioids, remifentanil has been strongly linked to acute opioid hyperalgesia after exposure [remifentanil-induced hyperalgesia (RIH)]. The epigenetic regulation of microRNAs (miRNAs) on targeted mRNAs has emerged as an important pathogenesis in pain. The current research aimed at exploring the significance and contributions of miR-134-5p to the development of RIH. Methods: Both the antinociceptive and pronociceptive effects of two commonly used opioids were assessed, and miRNA expression profiles in the spinal dorsal horn (SDH) of mice acutely exposed to remifentanil and remifentanil equianalgesic dose (RED) sufentanil were screened. Next, the candidate miRNA level, cellular distribution, and function were examined by qPCR, fluorescent in situ hybridization (FISH) and Argonaute-2 immunoprecipitation. Furthermore, bioinformatics analysis, luciferase assays, miRNA overexpression, behavioral tests, golgi staining, electron microscopy, whole-cell patch-clamp recording, and immunoblotting were employed to investigate the potential targets and mechanisms underlying RIH. Results: Remifentanil induced significant pronociceptive effects and a distinct miRNA-profile from sufentanil when compared to saline controls. Among top 30 differentially expressed miRNAs spectrum, spinal miR-134-5p was dramatically downregulated in RIH mice but remained comparative in mice subjected to sufentanil. Moreover, Glutamate Receptor Ionotropic Kainate 3 (Grik3) was a target of miR-134-5p. The overexpression of miR-134-5p attenuated the hyperalgesic phenotype, excessive dendritic spine remodeling, excitatory synaptic structural plasticity, and Kainate receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) in SDH resulting from remifentanil exposure. Besides, intrathecal injection of selective KA-R antagonist was able to reverse the GRIK3 membrane trafficking and relieved RIH. Conclusion: The miR-134-5p contributes to remifentanil-induced pronociceptive features via directly targeting Grik3 to modulate dendritic spine morphology and synaptic plasticity in spinal neurons.

Opioid infusions at different times of the day produce varying degrees of opioid-induced hyperalgesia.

BACKGROUND: Opioids are metabolised by enzymes the activities of which vary with the circadian rhythm. We examined whether opioid infusions administered at different times of the day produce varying degrees of opioid-induced hyperalgesia (OIH) in animal experiments and clinical studies. METHODS: Male Sprague-Dawley rats received remifentanil infusions (1 µg kg-1·min-1 for 1 h) at Zeitgeber times (ZT) 0, 4, 8, 12, 16, or 20 h. Rhythmicity of mechanical hypersensitivity was assayed after the infusion. Mechanical hypersensitivity, drug concentration, and metabolic enzyme activity of Wistar rats that received sufentanil (10 µg kg-1; four consecutive i.p. injections at 15-min intervals) or remifentanil infusion at ZT0 or ZT8 were assayed. Sixty patients who underwent abdominal laparoscopic surgery under general anaesthesia received remifentanil infusion (0.15 µg kg-1 min-1) and sufentanil injection (0.2 µg kg-1) at induction and skin incision, respectively. Postoperative pressure pain sensitivity, pain Numeric Rating Scale (NRS), drug concentrations, and nonspecific esterase activity were assessed. RESULTS: Sprague-Dawley rats that received remifentanil infusion exhibited a robust rhythmic paw withdrawal threshold (JTK_CYCLE: P=0.001, Q=0.001, Phase=26). Wistar rats infused with remifentanil or sufentanil at ZT8 exhibited greater OIH (P<0.001) than those infused at ZT0, with higher blood concentrations (P<0.001) and lower metabolic enzyme activities (P=0.026 and P=0.028, respectively). Patients in the afternoon group exhibited higher pressure pain sensitivity at forearm (P=0.002), higher NRS (P<0.05), higher drug concentrations (sufentanil: P=0.037, remifentanil: P=0.005), and lower nonspecific esterase activity (P=0.024) than the morning group. CONCLUSIONS: Opioid infusions administered at different times of day produced varying degrees of OIH, possibly related to circadian rhythms of metabolic enzyme activities. CLINICAL TRIAL REGISTRATION: NCT05234697.

Labour analgesia by single shot spinal for any parturient?-A retrospective one-year single centre audit.

BACKGROUND: Single shot spinal (SSS) provides effective analgesia for multiparous parturients during advanced labour. Its utility in early labour or primiparous parturients may be limited by the insufficient duration of action. Regardless, SSS may offer a reasonable labour analgesia option in certain clinical scenarios. In this retrospective study, we analyse the failure rate of SSS analgesia by assessing pain after the SSS and by determining the need for additional analgesic interventions in primiparous or early-stage multiparous parturients compared to multiparous parturients in advanced labour (cervix ≥6 cm). METHODS: Following institutional ethical board approval, the patient files of all parturients receiving SSS analgesia during a 12-month period in a single centre were analysed for any recorded notes regarding recurrent pain or subsequent analgesia interventions (a new SSS, epidural, pudendal or paracervical bloc) as a marker for insufficient analgesia. RESULTS: A total of 88 primiparous and 447 multiparous parturients (cervix <6 cm: N = 131; cervix ≥6 cm: N = 316) received SSS analgesia. The odds ratio for the insufficient duration of analgesia was 1.94 (1.08-3.48) in primiparous and 2.08 (1.25-3.46) in early-stage multiparous parturients compared to advanced multiparous labour (p < .01). Primiparous and early-stage multiparous parturients were also 2.20 (1.15-4.20) and 2.61 (1.50-4.55) times more likely, respectively, to receive new peripheral and/or neuraxial analgesic interventions during delivery (p < .01). CONCLUSIONS: SSS appears to provide adequate labour analgesia for the majority of parturients in whom it is used, including nulliparous and early-stage multiparous parturients. It remains a reasonable option in certain clinical scenarios, including resource-limited settings where epidural analgesia is unavailable.

Alternatives to remifentanil for the analgesic component of total intravenous anaesthesia: a narrative review.

Propfol-remifentanil-based total intravenous anaesthesia has dominated recent clinical practice due to its favourable pharmacokinetic profile. Interruption in remifentanil supply has presented an opportunity to diversify or even avoid the use of opioids and consider adjuncts to propofol-based total intravenous anaesthesia. Propofol, while a potent hypnotic, is not an effective analgesic. The administration of opioids, along with other adjuncts such as α-2 adrenoceptor agonists, magnesium, lidocaine, ketamine and nitrous oxide provide surgical anaesthesia and avoids large doses of propofol being required. We provide an overview of both target-control and manual infusion regimes for the alternative opioids: alfentanil, sufentanil and fentanyl. The optimal combination of hypnotic-opioid dose, titration sequence and anticipated additional postoperative analgesia required depend on the chosen combination. In addition, we include a brief discussion on the role of non-opioid adjuncts in total intravenous anaesthesia, suggested doses and expected reduction in propofol dose.