Median effective dose of spinal ropivacaine in combined spinal and epidural anesthesia for emergency cesarean delivery following failed vaginal delivery with epidural labor analgesia: a single-blind, sequential dose-finding study.

PURPOSE: This study aimed to estimate the median effective dose of intrathecal isobaric ropivacaine without opioid required for adequate cesarean delivery anesthesia after epidural labor analgesia. METHODS: Patients aged 20-40 years with American Society of Anesthesiology scores of I-II, body mass index ≤ 36, who underwent emergency cesarean delivery after failed vaginal delivery with epidural analgesia of a duration ≤ 6 h were included in the study. After removal of the epidural used for labor analgesia, a new combined spinal epidural was performed, and a dose of intrathecal isobaric ropivacaine without opioid was administered. The dose was determined using up-down methodology, with the starting patient's dose set to 12 mg. Adequate anesthesia, defined as a pinprick level no lower than T6 at 5 min after ropivacaine administration, resulted in the next patient receiving a dose of ropivacaine 1 mg higher, and inadequate anesthesia 1 mg lower. The primary outcome was the median (95% confidence interval (CI)) dose of spinal ropivacaine required for adequate cesarean delivery anesthesia. RESULTS: Of the 46 patients included in the study, 40 were analyzed. The median spinal ropivacaine dose was 8.11 mg (95% CI 7.29-8.93 mg) by the Dixon and Mood method and 8.06 mg (95% CI 6.93-9.00 mg) by isotonic regression. Two patients had high spinal anesthesia. CONCLUSION: Our findings suggest that for 50% of patients undergoing cesarean delivery after failed vaginal delivery with epidural analgesia, an 8-mg spinal dose of isobaric ropivacaine without opioid provides an anesthesia level no lower than T6 at 5 min.

ED50 and ED95 of Remimazolam Tosilate Combined with Different Doses of Fentanyl in Elderly Patients for Painless Gastroscopy.

Background: The novel short-acting benzodiazepine drug, remimazolam tosilate, has been employed for sedation during endoscopic procedures. The optimal loading dosage of remimazolam tosilate in gastroscopy for elderly patients when co-administered with fentanyl remains unclear. Therefore, the primary objective of our research was to ascertain the median effective dose (ED50) and the 95% effective dose (ED95) of remimazolam tosilate in combination with various fentanyl dosages for elderly patients undergoing painless gastroscopy. Methods: Seventy-five patients aged ≥65 years and American Society of Anesthesiologists (ASA) class I-III were recruited to undergo elective painless gastroscopy. All patients were randomized assigned to group F1, group F2, and group F3, and were injected intravenously with different doses of fentanyl (0.5 ug/kg, 1 ug/kg, and 1.5 ug/kg) 3 minutes prior to the administration of remimazolam tosilate, respectively. The initial preset dose of remimazolam tosilate was 0.3 mg/kg in group F1, 0.2 mg/kg in group F2, 0.15 mg/kg in group F3. The dose gradient was 0.02 mg/kg per group according to the up-and-down sequential method. Probibt regression model was employed to determine the ED50 and ED95 of remimazolam tosilate. Results: The ED50 of remimazolam tosilate in group F3 was lower than that in group F1 and F2 (0.095 [0.088-0.108] mg/kg vs 0.162 [0.153-0.171] mg/kg; 0.258 [0.249-0.266] mg/kg, p < 0.05). The ED95 of remimazolam tosilate was 0.272 mg/kg (95% CI: 0.264-0.295 mg/kg) in group F1, 0.175 mg/kg (95% CI: 0.167-0.200 mg/kg) in group F2 and 0.109 mg/kg (95% CI: 0.101-0.135 mg/kg) in group F3. The total dosage of remimazolam tosilate decreased gradually with the increasing of fentanyl (p < 0.001). The frequency of injection pain was higher in group F1 compared to groups F2 and F3 (p < 0.05). The patients in group F3 had a lower incidence of hypotension than in groups F1 and F2 (p < 0.05). There was no respiratory depression, intraoperative consciousness, dizziness or delirium in the three groups. Conclusion: The concurrent use of fentanyl reduces the dosage of remimazolam tosilate required for sedative gastroscopy in elderly patients in a dose-dependent manner. Moreover, 1.5 ug/kg fentanyl combined with remimazolam tosilate may reduce the incidence of hypotension and injection pain. These findings should be confirmed in a large-scale study.

Dose-response study of propofol combined with two different doses of esketamine for laryngeal mask airway insertion in women undergoing hysteroscopy.

Objective: To prospectively determine the median effective dose (ED50) of propofol for inhibiting a response to laryngeal mask airway (LMA) insertion when combined with different doses of esketamine in female patients. Methods: A total of 58 female patients (aged 20-60 years, ASAⅠ-Ⅱ) scheduled for elective hysteroscopy were enrolled and randomly divided into 2 groups, one of which was administered 0.2 mg/kg of esketamine (K1 group, n = 28) and the other 0.3 mg/kg of esketamine (K2 group, n = 30). The 2 groups received the corresponding doses of esketamine intravenously, followed by an intravenous injection of propofol (injection time was 30 s). The initial dose of propofol was 2 mg/kg, and the dose ratio of propofol in the adjacent patients was 0.9. If a positive reaction occurred due to LMA insertion, the dose ratio in the next patient was increased by 1 gradient; if not, the dose ratio was decreased by 1 gradient. The ED50, 95 % effective dose (ED95) and 95 % confidence interval (CI) of propofol for inhibiting a response to LMA insertion in the 2 esketamine groups were calculated using probit analysis. Results: The ED50 of propofol for inhibiting a response to LMA insertion in female patients was 1.95 mg/kg (95 % CI, 1.82-2.08 mg/kg) in the K1 group and 1.60 mg/kg (95 % CI, 1.18-1.83 mg/kg) in the K2 group. The ED95 of propofol for inhibiting a response to LMA insertion in female patients was 2.22 mg/kg (95 % CI, 2.09-2.86 mg/kg) in the K1 group and 2.15 mg/kg (95 % CI, 1.88-3.09 mg/kg) in the K2 group. Conclusion: Propofol combined with 0.3 mg/kg of esketamine has low ED50 and ED95 effective doses for inhibiting an LMA insertion response in female patients undergoing hysteroscopy and surgery. There were no significant adverse effects, but the additional dose of propofol and airway pressure were significantly higher than those in the group administered 0.2 mg/kg of esketamine. Based on the results, we recommend the combination of propofol with 0.2 mg/kg esketamine for optimal conditions during LMA insertion in women undergoing hysteroscopy.

Median Effective Dose of Ciprofol Combined With Sufentanil for Inhibiting the Upper Gastrointestinal Endoscopic Placement Reaction in Elderly Patients.

Objective: Ciprofol is a new sedative anesthetic drug that can be used for gastrointestinal endoscopy and induction of general anesthesia, but the appropriate dosage for use in elderly patients has not been determined. Sufentanil is a commonly used opioid in clinical practice, and this study was designed to induce anesthesia in elderly patients using sufentanil in combination with ciprofol. However, the optimal dosage of ciprofol when it is co-administered with sufentanil has not yet been established. This study was designed to find the median effective dose (ED50) and 95% confidence interval (95% CI) of ciprofol for intravenous anesthesia when combined with sufentanil. Methods: We studied 57 patients who were scheduled to undergo a diagnostic upper gastrointestinal endoscopy. According to age, it was divided into two groups: 65∼74 years old (group A) and over 75 years old (group B). Using the modified Dixon sequence test method, intravenous bolus of 0.1 µg/kg sufentanil was given 3 min before ciprofol is administered, the initial dose of ciprofol was 0.4 mg/kg, the upper gastrointestinal endoscopy was placed after reaching the depth of sedation, and vital signs and adverse events were recorded at each perioperative time point (T0-T7). Results: In the group A, when combined with 0.1 µg/kg sufentanil, the ED50 of ciprofol to inhibiting responses to insertion of upper gastrointestinal endoscopy was 0.23 mg/kg, and the 95% CI was 0.09∼0.30 mg/kg; in the group B, the ED50 was 0.18 mg/kg, and the 95% CI was 0.13∼0.22 mg/kg. Conclusion: The ED50 of ciprofol in combination with sufentanil (0.1 µg/kg) for upper gastrointestinal endoscopy in elderly patients: 0.23 mg/kg in group A and 0.18 mg/kg in group B.

The Median Effective Dose of Dexmedetomidine for the Inhibition of Emergence Delirium in Preschool Children Undergoing Tonsillectomy and/or Adenoidectomy: A Retrospective Dose-response Trial.

The incidence of emergence delirium (ED) is higher in preschool children undergoing tonsillectomy and/or adenoidectomy. The purpose of this study was to determine the median effective dose (ED50) of dexmedetomidine (DEX) for the inhibition of ED in preschool children by using probit regression analysis. A total of 140 anesthesia records were retrieved and divided into seven groups based on the infusion rate of DEX: .2, .25, .3, .35, .4, .45, and .5 µg·kg-1·h-1. The Pediatric Anesthesia Emergence Delirium Scale (PAEDS) was used to assess ED in preschool children, and ED was defined as a PAEDS score ≥ 10. Probit regression analysis revealed that the ED50 and ED95 of DEX were .31 µg·kg-1·h-1 (95% CI: .29-.35) and .48 µg·kg-1·h-1 (95% CI: .44-.56), respectively. Probit(p) = -2.84 + 9.28 × ln (Dose), (χ2 = 1.925, P = .859). The PAEDS score was significantly increased in the ED group, and the rate of bradycardia was significantly decreased in the ED group compared with the without ED group (27.3% vs 54.1%, P = .02). DEX can effectively inhibit the ED in preschool children undergoing tonsillectomy and/or adenoidectomy, however, bradycardia was the main complication.

Exploring the Median Effective Dose of Ciprofol for Anesthesia Induction in Elderly Patients: Impact of Frailty on ED50.

Purpose: Explore the median effective dose of ciprofol for inducing loss of consciousness in elderly patients and investigate how frailty influences the ED50 of ciprofol in elderly patients. Patients and Methods: A total of 26 non-frail patients and 28 frail patients aged 65-78 years, with BMI ranging from 15 to 28 kg/m2, and classified as ASA grade II or III were selected. Patients were divided into two groups according to frailty: non-frail patients (CFS<4), frail patients (CFS≥4). With an initial dose of 0.3 mg/kg for elderly non-frail patients and 0.25 mg/kg for elderly frail patients, using the up-and-down Dixon method, and the next patient's dose was dependent on the previous patient's response. Demographic information, heart rate (HR), oxygen saturation (SpO2), mean blood pressure (MBP), and bispectral index (BIS) were recorded every 30 seconds, starting from the initiation of drug administration and continuing up to 3 minutes post-administration. Additionally, the total ciprofol dosage during induction, occurrences of hypotension, bradycardia, respiratory depression, and injection pain were recorded. Results: The calculated ED50 (95% confidence interval [CI]) and ED95 (95% CI) values for ciprofol-induced loss of consciousness were as follows: 0.267 mg/kg (95% CI 0.250-0.284) and 0.301 mg/kg (95% CI 0.284-0.397) for elderly non-frail patients; and 0.263 mg/kg (95% CI 0.244-0.281) and 0.302 mg/kg (95% CI 0.283-0.412) for elderly frail patients. Importantly, no patients reported intravenous injection pain, required treatment for hypotension, or experienced significant bradycardia. Conclusion: Frailty among elderly patients does not exert a notable impact on the median effective dose of ciprofol for anesthesia induction. Our findings suggest that anesthesiologists may forego the necessity of dosage adjustments when administering ciprofol for anesthesia induction in elderly frail patients.

Combined sedation in pediatric magnetic resonance imaging: determination of median effective dose of intranasal dexmedetomidine combined with oral midazolam.

BACKGROUND: The exact median effective dose (ED50) of intranasal dexmedetomidine combined with oral midazolam sedation for magnetic resonance imaging (MRI) examination in children remains unknow and the aim of this study was to determine the ED50 of their combination. METHODS: This is a prospective dose-finding study. A total of 53 children aged from 2 months to 6 years scheduled for MRI examination from February 2023 to April 2023 were randomly divided into group D (to determine the ED50 of intranasal dexmedetomidine) and group M (to determine the ED50 of oral midazolam). The dosage of dexmedetomidine and midazolam was adjusted according to the modified Dixon's up-and-down method, and the ED50 was calculated with a probit regression approach. RESULTS: The ED50 of intranasal dexmedetomidine when combined with 0.5 mg∙kg- 1 oral midazolam was 0.39 µg∙kg- 1 [95% confidence interval (CI) 0.30 to 0.46 µg∙kg- 1] while the ED50 of oral midazolam was 0.17 mg∙kg- 1 (95% CI 0.01 to 0.29 mg∙kg- 1) when combined with 1 µg∙kg- 1 intranasal dexmedetomidine. The sedation onset time of children with successful sedation in group D was longer than in group M (30.0[25.0, 38.0]vs 19.5[15.0, 35.0] min, P < 0.05). No other adverse effects were observed in the day and 24 h after medication except one dysphoria. CONCLUSION: This drug combination sedation regimen appears suitable for children scheduled for MRI examinations, offering a more precise approach to guide the clinical use of sedative drugs in children. TRIAL REGISTRATION: Chinese Clinical Trial Registry, identifier: ChiCTR2300068611(24/02/2023).

Median effective dose of intranasal dexmedetomidine for satisfactory mask induction in children undergoing examination under anaesthesia for retinoblastoma - A prospective up and down sequential allocation study.

Background and Aims: Inhalational technique is used to induce anaesthesia in children without intravenous access. We aimed to determine the median effective dose (ED50) of intranasal dexmedetomidine to ensure satisfactory mask acceptance during inhalation induction in children with retinoblastoma undergoing examination under anaesthesia. Methods: A prospective sequential allocation study was conducted in children aged 1-60 months divided into Group A (1-18 months) and Group B (18-60 months). Children were administered dexmedetomidine intranasally as premedication. Sedation was assessed using the modified Observer Assessment of Alertness and Sedation Scale until induction. Successful mask acceptance was defined as a cooperative or asleep child during inhalational induction. The starting dose of dexmedetomidine was 1 µg/kg. The next dose varied by 0.2 µg/kg depending on the outcome of this case. According to the Dixon up-and-down method, the mean of midpoints of the failure-success sequence was calculated to obtain the ED50 values. Results: The ED50 of intranasal dexmedetomidine for satisfactory mask acceptance was 0.7 µg/kg (95% confidence interval [CI]: 0.54-0.86) in Group A (n = 23) and 0.96 µg/kg (95% CI: 0.83-1.08) in Group B (n = 25) (P = 0.020). The mean (standard deviation) duration of anaesthesia was 33.5 (14.9) minutes in group A versus 23.5 (8.48) minutes in Group B (P = 0.007). Conclusion: ED50 was lower in children younger than 18 months than in older children. There was no difference in the time to discharge from the post-anaesthesia care unit despite the procedure being longer in smaller children.

Effect of intravenous lidocaine on the ED50 of propofol induction dose in elderly patients undergoing painless gastroscopy: a prospective, randomized, double-blinded, controlled study.

BACKGROUND: Intravenous lidocaine could be a potential alternative adjuvant to propofol-based sedation for gastroscopy in elderly patients. This study aimed to evaluate the effect of intravenous lidocaine on the median effective dose (ED50) of propofol induction dose in elderly patients undergoing painless gastroscopy. METHODS: The study included 70 patients aged ≥ 60 years undergoing painless gastroscopy with 64 randomly assigned to either group L (2% lidocaine 1.5 mg/kg, n = 31) or group N (equal volume normal saline, n = 33). All patients received propofol induction following 0.1 µg/kg intravenous sufentanil. The Dixon "up-and-down" sequential method was used, with a 1.5 mg/kg initial induction dose of propofol followed by a 0.1 mg/kg sequential variable dose. The primary endpoint was the ED50 of the propofol induction dose. The total propofol dose, recovery time, adverse events, and local anesthetic intoxication reactions were also recorded. RESULTS: The ED50 of propofol induction dose was 0.670 (95% confidence interval [CI] 0.216-0.827) mg/kg in group L and 1.118 (95% CI 0.803-1.232) mg/kg in group N. There was a statistically significant difference between the two groups (p < 0.001). The incidence of hypotension and propofol injection pain were lower in group L than in group N (p < 0.05). Furthermore, the orientation recovery time in group L was shorter compared to group N (p < 0.05). None of the participants in group L observed local anesthetic intoxication reactions after receiving lidocaine. CONCLUSIONS: The administration of intravenous lidocaine to elderly patients undergoing painless gastroscopy resulted in a significant 40% reduction in the ED50 of propofol induction dose, which may be related to the decreased incidence of hypotension and injection pain, as well as the improved post-gastroscopy orientation recovery. TRIAL REGISTRATION: ChiCTR, ChiCTR2200065530. Registered on 08 November 2022.

Median effective dose of remimazolam combined with sufentanil for inhibition of nasopharyngeal airway insertion reaction in elderly patients / 临床麻醉学杂志

Objective To calculate median effective dose(ED50)of remimazolam combined with sufentanil for inhibition of nasopharyngeal airway insertion reaction in elderly patients.Methods Thirty-eight patients,aged≥65 years,BMI 18-25 kg/m2,ASA physical statusⅠ-Ⅲ,undergoing elective cata-ract surgery under nasopharyngeal airway were selected.Patients received intravenous sufentanil injections of 0.1 μg/kg,followed by intravenous remimazolam injection 3 minutes later,then nasopharyngeal airway in-sertion after 2 minutes.The initial dose of remimazolam was 0.2 mg/kg and adjusted by 0.01 mg/kg,based on the modified Dixon sequential method.A positive reaction was defined as head shaking,choking,body movement,an increase in HR＞20%of the basal value,or an increase in SBP or DBP＞20%of the basal value at the time of nasopharyngeal airway placement.The procedure was stopped after seven crossovers.The ED50,95%effective dose(ED95)of remimazolam,and 95%confidence intervals(CI)were calculated by probabilistic unit(Probit)regression analysis.Results When combined with sufentanil,the ED50 and ED95 of remimazolam for inhibition of nasopharyngeal airway insertion in elderly patients was 0.193 mg/kg(95%CI 0.191-0.195 mg/kg)and 0.209 mg/kg(95%CI 0.205-0.213 mg/kg),respectively.Conclusion The ED50 of remimazolam combined with sufentanil for inhibition of nasopharyngeal airway in-sertion reaction in elderly patients were 0.193 mg/kg(95%CI 0.191-0.195 mg/kg).

Effect of gender on dose-effect relationship of remimazolam combined with alfentanil in painless gastroscopy / 沈阳医学院学报

Objective:To evaluate the effect of gender on dose-effect relationship of remimazolam combined with alfentanil in painless gastroscopy.Methods:Subjects who planned to undergo elective painless gastroscopy,aged 18-60 years old,body mass index 19-24 kg/m2,American Society of Anesthesiologists physical status Ⅰ or Ⅱ,were enrolled.They were divided into male group and female group.The first subject in both groups received afentanil 5 μg/kg and remimazolam 0.2 mg/kg,and was implanted into a gastroscope 2 minutes later.Positive reactions were defined as body movement,coughing,swallowing and frowning during gastroscopy placement and examination.Remimazolam 0.05 mg/kg was used as a dose gradient by using modified Dixon's up-and-down method.The dose of the next subject was adjusted according to whether the subject had a positive reaction.If there was a positive reaction,the dose of the next subject was increased by one level of gradient,otherwise,the dose was decreased by one level of gradient,and so on.The process was terminated at the seventh intersection point of positive-negative reaction.And 50% effective dose(ED50),95% effective dose(ED95)and 95% confidence interval(CI)of remimazolam for inhibiting gastroscopic implantation reaction was calculated by Probit method.Results:A total of 46 subjects were included,with 23 subjects in each group.There was no significant difference in general data between the two groups.The ED50 of afentanil combined with remimazolam was 0.193 mg/kg(95% CI:0.145-0.286),and the ED95 was 0.293 mg/kg(95% CI:0.237-0.903)in male group.The ED50 of afentanil combined with remimazolam was 0.215 mg/kg(95% CI:0.155-0.293),and the ED95 was 0.316 mg/kg(95% CI:0.261-0.968)in female group.The ED50 and ED95(P＜0.05).Conclusion:When combined with 5 μg/kg of afentanil,remimazolam is more effective in inhibiting responses to gastroscopy inserting in male subjects than in female subjects.

Effect of propofol or different doses of remimazolam on median effective dose of sufentanil for suppressing tracheal intubation response in elderly patients / 中国现代医生

@#Objective To investigate the effect of propofol or different doses of remimazolam on effective dose(ED50)of sufentanil in elderly patients with tracheal intubation response by sequential method.Methods Elderly patients,American Society of Anesthesiologists(ASA)Ⅰ and Ⅱ,aged 65-80 years,undergoing elective surgery under general anesthesia with endotracheal intubation from October to December 2022 were selected and randomly divided into 4 groups:Group P(propofol 2mg/kg)and group R1,R2 and R3(remimazolam 0.2,0.3 and 0.4mg/kg)were administered intravenously.During anesthesia induction,sufentanil was given with the dose set by Dixon sequential method,followed by intravenous injection of propofol or corresponding dose of remimazolam and cisatracurium 0.15mg/kg.Tracheal intubation was performed when train of four(TOF)count was 0.If the tracheal intubation response is positive,the sufentanil dose of the next patient is increased by 1 concentration gradient,otherwise,the sufentanil dose is decreased by 1 concentration gradient,and the ratio between adjacent concentrations is 1∶1.1,until 7 turning points appear and the study is terminated.Probit regression analysis was used to calculate the median ED50 and 95%effective dose(ED95)of sufentanil for suppressing tracheal intubation response in elderly patients,and the corresponding 95%CI.The incidence of hypotension,bradycardia,injection pain and other adverse reactions were recorded.Results A total of 113 elderly patients were included in this study,including 24,28,30 and 31 patients in P,R1,R2 and R3 groups,respectively.The ED50 and ED95 and corresponding 95%CI of sufentanil for suppressing tracheal intubation response in elderly patients with propofol 2 mg/kg or remimazolam 0.2,0.3,0.4mg/kg were:The ED50 and ED95 of group P were 0.236μg/kg(95%CI:0.218-0.256)and 0.266μg/kg(95%CI:0.250-0.398),respectively.The ED50 and ED95 of group R1 were 0.284μg/kg(95%CI:0.265-0.309)and 0.329μg/kg(95%CI:0.306-0.478),respectively.The ED50 and ED95 of R2 group were 0.239μg/kg(95%CI:0.221-0.260)and 0.282μg/kg(95%CI:0.261-0.415),respectively.The ED50 and ED95 of R3 group were 0.198μg/kg(95%CI:0.182-0.211)and 0.231μg/kg(95%CI:0.216-0.303),respectively.The incidence of hypotension,bradycardia and injection pain in R1,R2 and R3 groups were lower than those in P group(P<0.05).The ED50 of sufentanil in group R2 was similar to that in group P,but the incidence of hypotension and injection pain in group R2 was lower than that in group P.Conclusion With the increase of the dose of remimazolam,the ED50 of sufentanil to inhibit tracheal intubation reaction in elderly patients gradually decreased,and in the case of similar ED50,the incidence of hypotension,bradycardia and injection pain induced by remimazolam was lower than that induced by propofol,so remimazolam induction was more advantageous in general anesthesia for tracheal intubation in elderly patients.

Expression,purification and immunogenicity evaluation of recombinant HPV58 virus-like particles / 中国生物制品学杂志

@#Objective To prepare recombinant human papillomavirus 58 L1 protein virus-like particles(HPV58 LI VLPs)in Pichia pastoris and immunize mice with the purified product to evaluate the immunogenicity of HPV58 L1 VLPs.Methods The HPV58 L1 multi-copy expression plasmid was constructed and transformed into Pichia pastoris KM71.The highly expressed Pichia pastoris engineering strain was screened and cultured in 5 L fermenter.The expressed HPV58 L1 VLPs were isolated and purified,which were then used to immunize 80 female BALB/c mice at different doses by intraperitoneal injection.After four weeks,the immune effect was evaluated by median effective dose(ED_(50)).Results Restriction analysis results showed that HPV58 L1 expression vectors were constructed correctly.Western blot,amino acid sequencing and transmission electron microscopy(TEM) results showed that HPV58 L1 protein was correctly expressed in Pichia pastoris and could self-assemble into VLPs at a diameter of about 50 nm.After purification by ion exchange and size exclusion chromatography,the HPV58 L1 VLPs reached a purity above 95%,and the ED_(50) in mouse model was 0.009 μg.Conclusion Recombinant HPV58 L1 VLPs with good immunogenicity were successfully prepared by using Pichia pastoris.

Modified Dixon sequential method to determine the effective dose of alfentanil compounded with propofol for day-case hysteroscopy.

Background: Propofol combined with alfentanil is suitable for intravenous anesthesia for day-case hysteroscopy. Objective: To investigate the median effective dose (ED50) and 95% effective dose (ED95) of alfentanil compounded with propofol for day-case hysteroscopy. Design: In all, 29 patients who volunteered for painless hysteroscopy in 2022 were recruited. 1.5 mg/kg propofol was given as a sedative to all patients. The trial was conducted using the modified Dixon sequential method, with an initial dose of 10 µg/kg of alfentanil, and the subject's alfentanil dose depended on whether the prior hysteroscopy had failed, which was defined as inadequate cervical dilatation and hysteroscope placement with the patient exhibiting body movement, frowning, or a MOAA/S score >1. If the hysteroscopy failed (i.e. a positive response), the subsequent subject's alfentanil dosage was raised, and conversely (i.e. a negative response), the dose was decreased, with the adjacent dose ratio always being 1:1.2. The formal test begins with the first crossover wave and lasts until seven crossover waves materialize. Methods: The probit method was used to calculate the ED50, ED95, and corresponding 95% confidence intervals (CIs) of alfentanil compounded with propofol for hysteroscopy. Results: The ED50 and ED95 of alfentanil combined with propofol for day-case hysteroscopy were 5.701 (95% CI: 3.841-7.069) µg/kg and 8.817 (95% CI: 7.307-20.868) µg/kg, respectively. Conclusion: Alfentanil at 8.817 µg/kg in conjunction with propofol is a successful and safe approach for day-case painless hysteroscopy. Trial registration: The trial registry name: Modified sequential method to determine the half-effective dose of alfentanil compounded with propofol for ambulatory hysteroscopy. The URL of registration is https://www.chictr.org.cn/showproj.html?proj=171786, where the full trial protocol can be accessed. Registration number: ChiCTR2200061619.

Alfentanil combined with propofol is suitable for day-case hysteroscopy Why was this study done? Hysteroscopy is a procedure in which a hysteroscope is placed after the cervix is dilated to observe lesions in the uterine cavity. This study explores the effective dose of alfentanil combined with propofol for day-case (i.e., patients admitted and discharged on the same day) hysteroscopy to provide patients with comforting anesthesia (i.e., pain relief) during hysteroscopy. What did the researchers do? The research team recruited 29 patients who volunteered for painless hysteroscopy in 2022. All patients received alfentanil and propofol for intravenous anesthesia. If anesthesia was not effective, subsequent subjects increased the dose of anesthetic medication, and vice versa, the dose was decreased. According to this method, we can find the optimal dose of anesthetic drugs in hysteroscopy. What did the researchers find? The effective dose of alfentanil combined with propofol in patients undergoing painless hysteroscopy was 8.817 µg/kg. What do the findings mean? Alfentanil at 8.817 µg/kg in conjunction with propofol is a successful and safe approach for day-case painless hysteroscopy.

The median effective dose of propofol combined with butorphanol during artificial abortion: a randomized controlled trial.

Objective: Propofol-opioids are the most common drug combination and can reduce the dose of propofol and the incidence of adverse events in painless artificial abortion. We hypothesized that butorphanol may reduce the median effective dose (ED50) of propofol, propofol injection pain, and postoperative uterine contraction pain. Methods: This was a randomized, double-blind, controlled study. A total of 54 female patients, who had ASA I or II, aged 18-49 years, undergoing painless artificial abortion, were randomly assigned into two groups, namely, Group P (propofol) and Group PB (propofol plus 10 µg/kg butorphanol). According to the pre-experiment, the initial dose of propofol for the P and PB groups was 3 and 2.5 mg/kg, respectively, with a dose gradient of 0.25 mg/kg. The ED50 of propofol was analyzed using probit regression analysis. The total propofol dose consumed, recovery time, and anesthesia-related adverse events were also recorded. Results: There were 25 and 29 patients in the P and PB groups, respectively. The ED50 (95% CI) of propofol for artificial abortion were 2.477 (2.186-2.737) and 1.555 (1.173-1.846) mg/kg in the P and PB groups, respectively. The total propofol dose consumed was (150.7 ± 21.7) mg and (110.4 ± 28.2) mg in the P and PB groups, respectively (P < 0.001). Compared with the P group, injection-site pain (76 vs. 20.7%) and uterine contraction pain (72 vs. 6.9%) in the PB group had a significant decrease (P < 0.001). Conclusion: Combination of propofol with 10 µg/kg butorphanol reduced the ED50 of propofol and decreased the incidence of propofol injection-site pain and postoperative uterine contraction pain during painless artificial abortion compared with propofol alone. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=166610, identifier: ChiCTR2200059795.

The Effect of Dezocine on the Median Effective Dose of Sufentanil-Induced Respiratory Depression in Patients Undergoing Spinal Anesthesia Combined with Low-Dose Dexmedetomidine.

Purpose: The application of sedation and analgesia in spinal anesthesia has many benefits, but the risk of respiratory depression (RD) caused by opioids cannot be ignored. We aimed to observe the effect of dezocine, a partial agonist of µ-receptor, on the median effective dose (ED50) of sufentanil-induced RD in patients undergoing spinal anesthesia combined with low-dose dexmedetomidine. Patients and Methods: Sixty-two patients were randomly assigned to dezocine group (DS) and control group (MS). After spinal anesthesia, mask oxygen (5 L/min) and dexmedetomidine (0.1 ug/kg) were given. Five minutes later, patients in the DS group received an Intravenous (IV) bolus of sufentanil and 0.05mg/kg dezocine, while patients in the MS group only received an IV bolus of sufentanil. Results: ED50 of DS group was 0.342 ug/kg, 95% confidence interval (CI) was (0.269, 0.623) ug/kg, and the ED50 of MS group was 0.291 ug/kg, 95% CI was (0.257, 0.346) ug/kg. There was no difference in the type and treatment measures of RD and hemodynamic changes between the two groups, and no serious adverse reactions occurred in either group. Conclusion: Dezocine can improve RD induced by sufentanil in patients with spinal anesthesia combined with low-dose dexmedetomidine, and increase the safety window of sufentanil use.

Median effective dose (ED50) of esketamine combined with propofol for children to inhibit response of gastroscope insertion.

BACKGROUND: Propofol is the most commonly used drug for procedural sedation during gastroscopy. However, independent use of propofol can lead to increased dosage and additional side effects. Esketamine was found to be exceptional in combination with propofol for painless gastroscopy. No studies have calculated the median effective dose (ED50) of esketamine combined with propofol in pediatric painless gastroscopy. Here, we designed a research to study the ED50 of esketamine combined with propofol using the Dixon and Massey up-and-down sequential method for inhibiting the response of gastroscope insertion. METHODS: Children who met the inclusion and exclusion criteria were included in this study. Propofol and esketamine were used as anesthetics for painless gastroscopy in children. To explore the ED50, the initial propofol dose was set at 3 mg/kg in all children. The first child was given an esketamine dose of 0.1 mg/kg, followed by 30 s of slow bolus injection propofol. If anesthesia induction failed (coughing or body movement of children during gastroscope insertion), the esketamine dose was elevated in the next child, with a interval difference of 0.05 mg/kg. Otherwise, if the anesthesia induction was successful, the next dosage was reduced by 0.05 mg/kg. The study was stopped if nine crossover inflection points were reached. The ED50 of esketamine was calculated using probit regression, and the blood pressure, pulse oxygen saturation, heart rate, recovery time, and side effects were recorded in all children. RESULTS: A total of 26 children were included in this study. The ED50 of esketamine combined with 3 mg/kg propofol was 0.143 mg/kg (95% CI 0.047-0.398 mg/kg). The total consumption of propofol was 16.04 ± 5.37 mg. The recovery time was 16.38 ± 8.70 min. Adverse effects recorded were delayed awakening in two cases and increased oral secretions of another child during the examination inducing cough and hypoxemia (86% was the lowest). DISCUSSION: The ED50 of esketamine was 0.143 mg/kg when combined with 3 mg/kg propofol for successful sedation in pediatric gastroscope insertion. This sub-anaesthetic dose of esketamine was safe and efficacious with few complications in pediatric painless gastroscopy. TRIAL REGISTRATION: The study was registered at the Chinese Clinical Trial Registry ( www.chictr.org.cn ; registration number: ChiCTR2100052830 on 06/11/2021).

Median effective dose of esketamine for intranasal premedication in children with congenital heart disease.

BACKGROUND: Esketamine is commonly used as a premedication for its sedation effect. However, the proper dosage for intranasal use in children with congenital heart disease (CHD) has not been determined. This study aimed to estimate the median effective dose (ED50) of esketamine for intranasal premedication in children with CHD. METHODS: Thirty-four children with CHD who needed premedication in March 2021 were enrolled. Intranasal esketamine was initiated at a dose of 1 mg/kg. Based on the outcome of sedation in the previous patient, the dose for the subsequent patient was either increased or reduced by 0.1 mg/kg, which was adjusted between each child. Successful sedation was defined as a Ramsay Sedation Scale score ≥ 3 and Parental Separation Anxiety Scale score ≤ 2. The required ED50 of esketamine was calculated using the modified sequential method. Non-invasive blood pressure, heart rate, saturation of peripheral oxygen, sedation onset time, and adverse reactions were recorded at 5 min intervals after drug administration. RESULTS: The 34 children enrolled had a mean age of 22.5 ± 16.4 (4-54) months and a mean weight of 11.2 ± 3.6 (5.5-20.5) kg; American Society of Anesthesiologists classification I-III. The ED50 of intranasal S(+)-ketamine (esketamine) required for preoperative sedation in pediatric patients with CHD was 0.7 (95% confidence interval: 0.54-0.86) mg/kg, and the mean sedation onset time was 16.39 ± 7.24 min. No serious adverse events, such as respiratory distress, nausea, and vomiting were observed. CONCLUSIONS: The ED50 of intranasal esketamine was 0.7 mg/kg, which was safe and effective for preoperative sedation in pediatric patients with CHD. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry Network (ChiCTR2100044551) on 24/03/2021.

Median Effective Dose of Remifentanil for the Prevention of Pain Caused by the Injection of Rocuronium: An Age-Stratified Study.

INTRODUCTION: Rocuronium intravenous pain is common in induction of general anesthesia. The aim of our study was to determine the median effective dose (ED50) of prophylactic intravenous remifentanil for the prevention of rocuronium injection pain and to explore the effect of age on the ED50. METHODS: Eighty-nine adult patients undergoing elective general anesthesia, ASA I or II, regardless of gender or weight, were stratified according to age: group R1 18-44 years, group R2 45-59 years, and group R3 60-80 years. The initial dose of prophylactic remifentanil before rocuronium injection was set at 1 µg/kg lean body weight (LBW). The remifentanil doses were adjusted according to the degree of injection pain using the Dixon sequential method, with a ratio of 1.1 between adjacent doses. Injection pain was graded, and the occurrence of injection pain and adverse reactions were recorded. The ED50 and 95% confidence intervals (CIs) of remifentanil were calculated using the Dixon-Massey formula. Patients were asked whether they recalled feeling any injection pain in the post-anesthesia care unit (PACU). RESULTS: The ED50 (95% CIs) of prophylactic remifentanil for the prevention of rocuronium injection pain were 1.266 µg/kg (1.186-1.351 µg/kg), 1.188 µg/kg (1.065-1.324 µg/kg), and 1.070 µg/kg (1.014-1.129 µg/kg) LBW in group R1, group R2, and group R3, respectively. No adverse reactions to remifentanil occurred in any group. In PACU, 84.6, 86.7, and 85.7% of patients who experienced injection pain had memories of the pain in group R1, group R2, and group R3, respectively. CONCLUSIONS: Prophylactic intravenous remifentanil can prevent rocuronium injection pain, and its ED50 decreases with age, with 1.266 µg/kg (18-44 years), 1.188 µg/kg (45-59 years), and 1.070 µg/kg LBW (60-80 years), respectively. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05217238 (registration date 18 Dec 2021).

ED50 and ED95 of Propofol Combined with Different Doses of Intravenous Lidocaine for First-Trimester Uterine Aspiration: A Prospective Dose-Finding Study Using Up-and-Down Sequential Allocation Method.

Purpose: This study aimed to test the effect of different doses of intravenous lidocaine on the median effective dose (ED50) and 95% effective dose (ED95) of propofol-induction dose and identify the optimal dose. Patients and Methods: Patients undergoing first-trimester uterine aspiration were screened and randomly enrolled into the following groups: saline (L0), 0.5 mg/kg lidocaine (L0.5), 1.0 mg/kg lidocaine (L1.0), and 1.5 mg/kg lidocaine (L1.5). Anesthesia was induced with 1.0 µg/kg fentanyl. Prepared lidocaine or saline solution was injected later according to allocation, followed by propofol. The dose of propofol for each patient was determined using the up-and-down sequential study design. The primary end point was the ED50 and ED95 of the propofol-induction dose. The total propofol doses, awakening time, and adverse events were recorded. Results: The ED50 (95% confidence interval) of propofol was significantly lower in groups L1.0 and L1.5 than group L0 (1.6 [1.5-1.7] mg/kg and 1.8 [1.6-1.9] mg/kg, versus 2.4 [2.3-2.5] mg/kg, respectively; p<0.001). There was no significant difference in ED50 between groups L1.0 and L1.5 (p>0.05). However, surprisingly, the ED50 was significantly higher in group L0.5 than L0 (2.8 [2.6-3.0] mg/kg vs 2.4 [2.3-2.5] mg/kg; p<0.05). The total doses of propofol in groups L1.0 and L1.5 were lower than those in groups L0 and L0.5 (p<0.05). The systolic blood pressure (SBP) decline after anesthesia induction in group L0.5 was greater than that in group L0 (p<0.01). The incidence of respiratory depression in group L0.5 was greater than that in groups L0 and L1.0 (p<0.05). Conclusion: In patients who underwent first-trimester uterine aspiration, intravenous lidocaine 1.0 mg/kg prior to propofol injection significantly reduced the ED50 of propofol induction dose without severe side effects, equivalent to the effect of 1.5 mg/kg dose. We recommend 1.0 mg/kg as the optimal dose.