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Previous studies have reported the recommended dosage of remimazolam alone for achieving loss of consciousness (LoC). However, the effect of analgesics on the dosage of remimazolam for successful sedation remains unclear. This study evaluated the impact of fentanyl on the effective dose of remimazolam-induced sedation in female patients undergoing elective hysteroscopic surgery. Two hundred female patients were randomly allocated into two groups, receiving with or without fentanyl (1ug/kg) during anesthetic induction. Within each group, patients were randomized to receive one of four doses (0.1, 0.2, 0.3, and 0.4 mg/kg) of remimazolam for sedation. Modified Observer's Assessment of Alertness/Sedation (MOAA/S) was evaluated during anesthetic induction. Success was defined when the patient did not respond to painful trapezius squeeze and no requirement for rescue doses. Estimate of ED50 and ED95 with 95% confidence interval (CI) was performed by probit regression. The ED50 and ED95 values of remimazolam for patients receiving fentanyl (1 ug/kg) were 0.097 (95% CI, 0.072-0.120) mg/kg and 0.254 (95% CI, 0.203-0.345) mg/kg, respectively. For patients not receiving fentanyl, the ED50 and ED95 values of remimazolam were 0.181 (95% CI, 0.149-0.215) mg/kg and 0.475 (95% CI, 0.377-0.687) mg/kg, respectively. The estimated relative median potency of remimazolam in patients, with and without fentanyl administration, was determined to be 0.534 (95% CI, 0.327-0.737). The administration of fentanyl reduced the effective dose of remimazolam-induced sedation by 50% in female patients undergoing elective hysteroscopic surgery. The recommended ED95 dose for remimazolam-induced sedation was 0.254 mg/kg under the condition of this study. ChiCTR2400079842; https://www.chictr.org.cn/showproj.html?proj=216480: HUANG, Date of registration: January 15, 2024.

Transcranial Direct Current Stimulation (tDCS) is a method of non-invasive brain stimulation that has been frequently used in experimental and clinical pain studies. However, the molecular mechanisms underlying tDCS-mediated pain control, and most important its placebo component, are not completely established. In this pilot study, we investigated in vivo the involvement of the endogenous μ-opioid system in the global tDCS-analgesia experience. Nine healthy volunteers went through positron emission tomography (PET) scans with [11C]carfentanil, a selective μ-opioid receptor (MOR) radiotracer, to measure the central MOR activity during tDCS in vivo (non-displaceable binding potential, BPND)--one of the main analgesic mechanisms in the brain. Placebo and real anodal primary motor cortex (M1/2mA) tDCS were delivered sequentially for 20 minutes each during the PET scan. The initial placebo tDCS phase induced a decrease in MOR BPND in the periaqueductal gray matter (PAG), precuneus, and thalamus, indicating activation of endogenous μ-opioid neurotransmission, even before the active tDCS. The subsequent real tDCS also induced MOR activation in the PAG and precuneus, which were positively correlated to the changes observed with placebo tDCS. Nonetheless, real tDCS had an additional MOR activation in the left prefrontal cortex. Although significant changes in the MOR BPND occurred with both placebo and real tDCS, significant analgesic effects, measured by improvements in the heat and cold pain thresholds, were only observed after real tDCS, not the placebo tDCS. This study gives preliminary evidence that the analgesic effects reported with M1-tDCS, can be in part related to the recruitment of the same endogenous MOR mechanisms induced by placebo, and that such effects can be purposely optimized by real tDCS.

In this randomized trial involving nulliparous women at term, the rate of cesarean delivery was not higher among women who were given intrathecal analgesia early in labor than among those given systemic analgesia early in labor. Women who received intrathecal analgesia early also had better pain control and a shorter time to delivery. The rate of cesarean delivery was not higher among women who were given intrathecal analgesia early in labor than among those given systemic analgesia early in labor. The American College of Obstetricians and Gynecologists recommends that “when feasible, obstetrical practitioners should delay the administration of epidural anesthesia in nulliparous women until the cervical dilatation reaches at least 4.0 to 5.0 cm and that other forms of analgesia should be used until that time.” 1 This recommendation is based on studies that found an association between the initiation of epidural analgesia early in labor and an increased rate of cesarean delivery. 2 , 3 The nature of this association is uncertain. Neuraxial analgesia may directly or indirectly influence the progress of labor. Alternatively, the request for analgesia early in labor may . . .

AbstractObjectiveRegional techniques minimize anesthetic requirements and their effects may be beneficial. There is a lack of consensus and evidence concerning alternative analgesia strategies for cranial neurosurgery. This study was designed to evaluate the effect of scalp block with or without dexmedetomidine combined with general anesthesia on hemodynamic stability, opioid consumption and postoperative pain in patients undergoing elective craniotomy. MethodsOne hundred five patients undergoing elective craniotomy for tumor dissection were randomly divided into three groups to receive scalp block as an adjuvant to general anesthesia: with either 40 ml ropivacaine 0.5 % (Group R), 40 ml ropivacaine 0.5 % plus dexmedetomidine 1 μg/kg (Group RD) or 40 ml saline as a placebo (Group C). After a standard induction sequence using propofol, fentanyl and a single dose of rocuronium, patients were intubated. Bilateral scalp block was given immediately after induction. Anesthesia was maintained with propofol and remifentanil infusion. Five minutes before head pinning scalp block was performed by blocking the supraorbital, supratrochlear, auriculotemporal, occipital, and postauricular branches of the greater auricular nerves. All patients were monitored with electrocardiogram, invasive blood pressure, pulse oximetry and BIS monitoring. Primary outcomes measures were overall hemodynamic variables during surgery and intravenous fentanyl and remifentanil consumption. Mean arterial pressure (MAP) and heart rate (HR) were recorded at seven time-points: scalp block (T1-baseline), pin fixation (T2), skin incision (T3), drilling (T4), dura matter incision (T5), dura matter closure (T6) and skin closure (T7). For all time points it was recorded the mean value after 3 consecutive measures with 5 min interval. Secondary outcome was postoperative pain intensity using visual analog scale 24 and 48 h after surgery. VAS scores, fentanyl and remifentanil were evaluated using Kruskal-Wallis test. MAP and HR were compared by One-Way repeated measures Anova (GLMM) using time as random efect and by One-Way Anova using time as fxed efect. ResultsMean arterial pressure was significant lower at skin closure compared to baseline in group R (p < 0,001) and in group RD (p < 0,001). Patients in group RD showed significant lower heart rate at dura matter incision, dura matter closure and skin closure compared to baseline, pin fixation and skin incision time points (p < 0,001) and reported significantly less heart rate than group C (p < 0,001) and group R (p < 0,001) during dura matter incision, dura matter closure and skin closure time points. Patients in group RD receive significant lower fentanyl than group R (p < 0,01). The intraoperative consumption of remifentanil was significant higher in control group compared to group R (p < 0,01) and to group RD (p < 0,001). Additionally, remifentanil consumption was significant lower in group RD as compared to group R (p < 0,001). Postoperative pain had no statistically differences between the three groups at 24 h and 48 h after craniotomy (Preop VAS: p = 0,915, VAS 24: p = 0,284, VAS 48, p = 0,385). No adverse effects were noted. ConclusionOur study indicated that addition of dexmedetomidine to scalp block with ropivacaine 0.5% provided significantly better perioperative hemodynamic stability during elective craniotomy. Moreover, scalp block with or without dexmedetomidine reduced fentanyl and remifentanil consumption, but it didn’t significantly prolonged analgesia in patients undergoing elective craniotomy.

This study was aimed to systematically evaluate the effects of fentanyl and sufentanil on intraoperative cerebral oxygen saturation changes and postoperative cognitive function in elderly patients undergoing open surgery. Ninety-six elderly patients who had undergone open surgery under general anesthesia were randomly divided into fentanyl group (F group, anesthesia by fentanyl, 4 g/kg) and sufentanil group (S group, anesthesia by sufentanil, 0.4 µg/kg). There were no significant differences between the F group and S group in the general characteristics of patients. Compared to the F group, the S group had a better effect on suppressing the stress response, maintaining a stable hemodynamic status and achieving better anesthesia effects. The anesthesia recovery time of the S group was significantly shorter than that of the F group. There was no significant difference between the two groups in the intraoperative and postoperative agitation. Patient’s waking time and extubation time were significantly shorter in the S group than the F group. The VAS scores in the S group were significantly lower than those in the F group at each time point. The Ramsay scores in the S group were significantly higher than those in the F group at each time point. The cerebral oxygen saturation (SctO 2 ) levels in both groups were significantly increased following anesthesia induction and intubation compared to that of the awake state ( P  < 0.05), and SctO 2 was significantly decreased during the surgery in both groups. The changes in SctO 2 levels were not significantly different between the two groups ( P  > 0.05). The SctO 2 level was significantly higher during surgery than that after intubation. Compared with the F group, the relative value of SctO 2 decline in the S group was smaller. Compared to the day before surgery, the Montreal Cognitive Assessment (MoCA) scores of both groups were significantly reduced after surgery. At 1 day post-surgery, the MoCA scores of the S group were significantly higher and the incidence of postoperative cognitive dysfunction (POCD) was significantly lower compared to the F group. POCD occurred in three patients (6.2%) in the S group, and the ratio was significantly lower than that in the F group (11.9%) ( P  < 0.05). It showed a consistent trend with the SctO 2 status during the surgery. The relative value of SctO 2 decline in the S group was significantly smaller than that in the F group. The reduction of cognitive function in the S group was significantly lower than that in the F group. These results indicate that the changes in SctO 2 are a good prediction of the incidence of POCD.

Background Breakthrough cancer pain (BTcP) has a negative impact on patients’ quality of life, general activities, and is related to worse clinical outcomes. Fentanyl inhalant is a hand-held combination drug-device delivery system providing rapid, multi-dose (25μg/dose) administration of fentanyl via inhalation of a thermally generated aerosol. This multicenter, randomized, placebo-controlled, multiple-crossover, double-blind study evaluated the efficacy, safety, and tolerability of fentanyl inhalant in treating BTcP in opioid-tolerant patients. Methods The trial was conducted in opioid-tolerant cancer patients with 1 ~ 4 BTcP outbursts per day. Each patient was treated and observed for 6 episodes of BTcP (4 with fentanyl inhalant, 2 with placebo). During each episode of targeted BTcP, patients were allowed up to six inhalations, with an interval of at least 4 min between doses. Primary outcome was the time-weighted sum of PID (pain intensity difference) scores at 30 min (SPID30). Results A total of 335 BTcP episodes in 59 patients were treated. The mean SPID30 was -97.4 ± 48.43 for fentanyl inhalant-treated episodes, and -64.6 ± 40.25 for placebo-treated episodes ( p  < 0.001). Significant differences in PID for episodes treated with fentanyl inhalant versus placebo was seen as early as 4 min and maintained for up to 60 min. The percentage of episodes reported PI (pain intensity) scores ≤ 3, a ≥ 33% or ≥ 50% reduction in PI scores at 30 min, PR30 (pain relief scores at 30 min) and SPID60 favored fentanyl inhalant over placebo. Only 4.4% of BTcP episodes required rescue medication in fentanyl inhalant group. Most AEs were of mild or moderate severity and typical of opioid drugs. Conclusion Treatment with fentanyl inhalant was shown to be a promising therapeutic option for BTcP, with significant pain relief starting very soon after dosing. Confirmation of effectiveness requires a larger phase III trial. Trial registration ClinicalTrials.gov: NCT05531422 registered on 6 September 2022 after major amendment, NCT04713189 registered on 14 January 2021.

Background and Objectives: Although vitreoretinal surgery (VRS) is most commonly performed under regional anaesthesia (RA), in patients who might be unable to cooperate during prolonged procedures, general anaesthesia (GA) with intraprocedural use of opioid analgesics (OA) might be worth considering. It seems that the surgical pleth index (SPI) can be used to optimise the intraprocedural titration of OA, which improves haemodynamic stability. Preventive analgesia (PA) is combined with GA to minimise intraprocedural OA administration. Materials and Methods: We evaluated the benefit of PA combined with GA using SPI-guided fentanyl (FNT) administration on the incidences of PIPP (postprocedural intolerable pain perception) and haemodynamic instability in patients undergoing VRS (p < 0.05). We randomly assigned 176 patients undergoing VRS to receive GA with SPI-guided FNT administration alone (GA group) or with preventive topical 2% proparacaine (topical anaesthesia (TA) group), a preprocedural peribulbar block (PBB) using 0.5% bupivacaine with 2% lidocaine (PBB group), or a preprocedural intravenous infusion of 1.0 g of metamizole (M group) or 1.0 g of paracetamol (P group). Results: Preventive PBB reduced the intraprocedural FNT requirement without influencing periprocedural outcomes (p < 0.05). Intraprocedural SPI-guided FNT administration during GA resulted in PIPP in 13.5% of patients undergoing VRS and blunted the periprocedural effects of preventive intravenous and regional analgesia with respect to PIPP and haemodynamic instability. Conclusions: SPI-guided FNT administration during GA eliminated the benefits of preventive analgesia in the PBB, TA, M, and P groups following VRS.

The authors sought to quantify the clinical impacts of granisetron, ketamine, dexmedetomidine, and lidocaine combined with fentanyl, for procedural sedation and analgesia in cystoscopy and for bladder catheter tolerance. This double-blind trial recruited four stratified blocked randomized eligible groups of patients (n = 120) formerly identified as needing cystoscopy, each receiving one of the above four anesthetic agents. Dexmedetomidine-sedated subjects experienced less pain from 5 to 120 minutes after the beginning of procedure, and next the ketamine manifested a better pain relief experienced. Sedation score was found to be rather more satisfactory in the early-mentioned from 15 to 55 minutes and at 90 and 105 minutes after procedure. The mean opioid use was observed lower in the dexmedetomidine treated patients and next in the ketamine administered patients. Considering the findings emanating from the study and the lack of complications that need to be treated, dexmedetomidine and ketamine afforded superior pain relief, greater sedation, and less postoperative opioid use in patients undergoing cystoscopy, and thus, they could be suggested to be combined with fentanyl during outpatient cystoscopy.

Endotracheal intubation elicits huge spectrum of stress responses which are hazardous in high-risk patients. Numerous drugs and techniques have been applied to attenuate the stress responses. In this double-blind study, one hundred and forty-five patients over 20 years old, ASA physical status I and II, undergoing elective surgeries requiring general anaesthesia with endotracheal intubation were included. Patients were randomly divided into three groups which fentanyl 2 mcg/kg was given at either 1, 2, 3 minutes before intubation. All groups received midazolam 0.05 mg/kg, lidocaine 0.5 mg/kg, propofol 2 mg/kg and rocuronium 1 mg/kg before intubation. Haemodynamic parameters were recorded for 10 minutes after induction. Two-level longitudinal hierarchical linear models were used for data interpretation and P < 0.05 was considered statistically significant. The study demonstrated significantly lower haemodynamic responses in the group who received fentanyl 2 minutes before intubation (P < 0.05). Confounding factors such as smoking, hypertension, diabetes mellitus and preoperative intravenous fluid supplement were analysed. In conclusion, fentanyl injection 2 minutes before intubation is recommended in order to obtain the most stable haemodynamic status.

To compare the effects of intravenous fentanyl and lidocaine on hemodynamic changes following endotracheal intubation in patients requiring Rapid Sequence Intubation (RSI) in the emergency department (ED). A single-centered, prospective, simple non-randomized, double-blind clinical trial was conducted on 96 patients who needed RSI in Edalatian ED. They were randomly divided into three groups (fentanyl group (F), lidocaine group (L), and fentanyl plus lidocaine (M) as our control group). M was administered with 3 μgr/kg intravenous fentanyl and 1.5 μgr/kg intravenous lidocaine, F was injected with 3g/kg intravenous fentanyl and L received 1.5mg/kg intravenous lidocaine prior to endotracheal intubation. Heart rate (HR) and mean arterial pressure (MAP) were assessed four times with the chi-square test: before, immediately after, 5 and 10 min after intubation. Intervention was discontinued for five people due to unsuccessful CPR. HR was notably different in F, L and M groups during four time courses (p<0.05). Comparison of MAP at measured points in all groups exhibited no significant difference (p>0.05). In fentanyl group both HR and MAP increased immediately after intubation, and significantly decreased 10 min after intubation (p<0.05). Overall, the result of this study shows that lidocaine effectively prevents MAP and HR fluctuations following the endotracheal intubation. According to our findings, lidocaine or the combination of fentanyl and lidocaine are able to diminish hemodynamic changes and maintain the baseline conditions of the patient, thus could act more effectively than fentanyl alone.