Sequential Allocation Method Research Articles

Effect of different doses of esketamine on the median effective concentration of propofol for inhibiting body movement during hysteroscopy

The objective of this study is to investigate the effects of various doses of esketamine on the median effective concentration (EC50) of propofol required for inhibiting body movement during hysteroscopy. Additionally, this research aims to explore the pharmacodynamic interactions between esketamine and propofol. Prospective, double-blind, up-down sequential allocation study. Operating room, post-anesthesia care unit (PACU), and general ward. A total of 90 patients were allocated into three groups in a randomized, double-blinded manner as follows: 0.1 mg/kg esketamine combined with propofol intravenous injection (EP0.1) group, 0.2 mg/kg esketamine combined with propofol intravenous injection (EP0.2) group, 0.3 mg/kg esketamine combined with propofol of intravenous injection (EP0.3) group. For the initial patient in each group, the starting effector target concentration of propofol was set at 4 µg/ml. Each patient received an initial intravenous injection of 0.04 mg/kg midazolam, followed by the administration of the appropriate dose of esketamine. Ten seconds after the esketamine injection, propofol was administered intravenously to achieve the target concentration. In accordance with the sequential method principle, the concentration of propofol for the subsequent patient was adjusted based on the response of the previous patient. Effective inhibition of body movement was defined as the absence of any involuntary body movements throughout the entire surgical process. If the previous patient exhibited body movements, the propofol concentration for the next patient was increased by 0.5 µg/ml; conversely, if no movements were observed, it was decreased by 0.5 µg/ml. The up-down sequential allocation method and probit regression were used to calculate the EC50 of propofol. Hospital Anxiety and Depression Scale-Anxiety (HADS-A) and Depression (HADS-D) score, adverse events, hemodynamic changes, demographic data and clinical characteristics. The EC50 of propofol was 3.849 μg/ml (95% CI: 3.419–4.281) in the EP0.1 group, 3.641 μg/ml (95% CI: 2.807−4.200) in the EP0.2 group, and 3.417 μg/ml (95% CI: 2.845–3.852) in the EP0.3 group. These findings suggest that esketamine can dose-dependently reduce the EC50 of propofol. Esketamine can dose-dependently reduce the EC50 of propofol in hysteroscopy, while concurrently lowering patients’ HADS-A and HADS-D scores 24 h post-operation. It is concluded that the optimal dose of esketamine, when combined with propofol for hysteroscopy, is 0.3 mg/kg.

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

BackgroundIt 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.MethodsThis 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.ResultsThe 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).ConclusionsThe 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 median effective concentration of epidural ropivacaine with different doses of dexmedetomidine for motor blockade: an up-down sequential allocation study.

Recent studies have shown that dexmedetomidine can be safely used in peripheral nerve blocks and spinal anesthesia. Epidural administration of dexmedetomidine produces analgesia and sedation, prolongs motor and sensory block time, extends postoperative analgesia, and reduces the need for rescue analgesia. This investigation seeks to identify the median effective concentration (EC50) of ropivacaine for epidural motor blockade, and assess how incorporating varying doses of dexmedetomidine impacts this EC50 value. Prospective, double-blind, up-down sequential allocation study. Operating room, post-anesthesia care unit, and general ward. One hundred and fifty patients were allocated into five groups in a randomized, double-blinded manner as follows: NR (normal saline combined with ropivacaine) group, RD0.25 (0.25 μg/kg dexmedetomidine combined with ropivacaine) group, RD0.5 (0.5 μg/kg dexmedetomidine combined with ropivacaine) group, RD0.75 (0.75 μg/kg dexmedetomidine combined with ropivacaine) group, RD1.0 (1.0 μg/kg dexmedetomidine combined with ropivacaine) group. The concentration of epidural ropivacaine for the first patient in each group was 0.5%. Following administration, the patients were immediately placed in a supine position for observation, and the lower limb motor block was assessed every 5 min using the modified Bromage score within 30 min after drug administration. According to the sequential method, the concentration of ropivacaine in the next patient was adjusted according to the reaction of the previous patient: effective motor block was defined as the modified Bromage score > 0 within 30 min after epidural administration. If the modified Bromage score of the previous patient was >0 within 30 min after drug administration, the concentration of ropivacaine in the next patient was decreased by 1 gradient. Conversely, if the score did not exceed 0, the concentration of ropivacaine in the next patient was increased by 1 gradient. The up-down sequential allocation method and probit regression were used to calculate the EC50 of epidural ropivacaine. Adverse events, hemodynamic changes, demographic data and clinical characteristics. The EC50 of epidural ropivacaine required to achieve motor block was 0.677% (95% CI, 0.622-0.743%) in the NR group, 0.624% (95% CI, 0.550-0.728%) in the RD0.25 group, 0.549% (95% CI, 0.456-0.660%) in the RD0.5 group, 0.463% (95% CI, 0.408-0.527%) in the RD0.75 group, and 0.435% (95% CI, 0.390-0.447%) in the RD1.0 group. The EC50 of the NR group and the RD0.25 group were significantly higher than that of the RD0.75 and the RD1.0 groups, and the EC50 of the RD0.5 group was significantly higher than that of the RD1.0 group. The EC50 of epidural ropivacaine required to achieve motor block was 0.677% in the NR group, 0.624% in the RD0.25 group, 0.549% in the RD0.5 group, 0.463% in the RD0.75 group, and 0.435% in the RD1.0 group. Dexmedetomidine as an adjuvant for ropivacaine dose-dependently reduce the EC50 of epidural ropivacaine for motor block and shorten the onset time of epidural ropivacaine block. The optimal dose of dexmedetomidine combined with ropivacaine for epidural anesthesia was 0.5 μg/kg.

Minimum effective dose of intrathecal hyperbaric bupivacaine for cesarean section with and without prophylactic norepinephrine infusion: Randomized triple-blinded trial.

Vasopressor usage can affect the rostral spread of intrathecal drug and, hence, its requirement during cesarean delivery. Although a decreased spread is evidenced with phenylephrine, there is no data for norepinephrine usage. The present study aimed to evaluate the minimum effective dose of intrathecal hyperbaric bupivacaine for cesarean section with and without prophylactic norepinephrine infusion. Patients scheduled for elective cesarean section under combined spinal-epidural block were randomized to receive intravenous infusion of norepinephrine (0.05 μg/kg/min) or normal saline (placebo), initiated immediately after intrathecal injection. Postspinal hypotension in either group (systolic arterial pressure ≤0.8 baseline) was treated with norepinephrine 4 μg rescue. Dose of intrathecal hyperbaric bupivacaine (0.5%) was decided for individual patients using up-and-down sequential allocation method. Primary outcome measure was the minimum effective dose of intrathecal hyperbaric bupivacaine (0.5%) defined as ED50, while secondary observations included spinal block characteristics and neonatal outcomes. Demographic parameters were statistically similar between both groups (P > 0.05). ED50 of intrathecal hyperbaric bupivacaine was 7.8 mg (95% confidence interval [CI]: 6.7-8.8) and 7.4 mg (95% CI: 6.1-8.7) for normal saline and norepinephrine group respectively (P = 0.810). Block characteristics were similar between both groups as was neonatal APGAR score, but umbilical artery base excess was greater for norepinephrine versus normal saline group (-4.4 ± 3.6 vs. -6.5 ± 2.4, P = 0.038). Use of prophylactic norepinephrine (0.05 μg/kg/min) during cesarean delivery does not require adjustment of intrathecal hyperbaric bupivacaine.

ED50 of ciprofol combined with different doses of remifentanil during upper gastrointestinal endoscopy in school-aged children: a prospective dose-finding study using an up-and-down sequential allocation method.

This study aimed to determine the 50% effective dose (ED50) of ciprofol when combined with different doses of remifentanil for upper gastrointestinal endoscopy of school-age children and to evaluate its safety. This study involved school-aged children who were scheduled to undergo upper gastrointestinal endoscopy under deep sedation. The children were randomly assigned to two groups: remifentanil 0.3μg/kg (R0.3) and remifentanil 0.5μg/kg (R0.5). Anesthesia was induced with remifentanil, followed by ciprofol. The dose of ciprofol for each patient was determined using the Dixon up-down sequential method. If the MOAA/S score was ≤1 and the child did not exhibit significant movement or coughing during the endoscopy process, sedation was considered successful. The first patient in each group received 0.5mg/kg ciprofol. The dose of ciprofol was adjusted by 0.05mg/kg based on the response of the previous patient. The primary outcome was the ED50 of the ciprofol-induction dose. The total ciprofol doses, onset times, awakening times, and adverse reactions were recorded. 1) The Dixon method was used to collect crossovers data from each group, and the ED50 values of the R0.3 and R0.5 groups were calculated to be 0.390mg/kg (95% CI 0.356-0.424mg/kg) and 0.332mg/kg (95% CI 0.291-0.374mg/kg), respectively. The ED50 of ciprofol in the R0.3 group was significantly higher than that in the R0.5 group (p < 0.05). 2) The onset time and recovery time of the R0.5 group were shorter than those of the R0.3 group (p < 0.05). When the two groups were compared, the total dose of ciprofol in the R0.5 group decreased (p < 0.05). 3) Compared with the R0.3 group, the incidence of respiratory depression during induction in the R0.5 group increased (p < 0.05). This study explored the ED50 of ciprofol combined with different doses of remifentanil for successful sedation in upper gastrointestinal examinations in school-aged children. Compared to the use of remifentanil 0.3μg/kg, the combination of ciprofol with remifentanil 0.5μg/kg significantly reduced the ED50 required to prevent body movement or cough during endoscope insertion but increased the incidence of respiratory depression.

Comparison of the ED50 of prophylactic butorphanol in preventing morphine-induced pruritus with or without palonosetron: a prospective, double-blinded, randomized dose–response trial using an up-down sequential allocation method

Background Butorphanol has been used to reduce the incidence and severity of neuraxial morphine-induced pruritus. Palonosetron is a commonly used antiemetic for the prevention of postoperative nausea and vomiting. The aim of our study was to compare the effective dose in 50% of subjects (ED50) of intravenous butorphanol infusion with or without a single intravenous bolus of palonosetron for preventing pruritus induced by epidural administration of morphine. Methods A total of 120 parturients were randomly assigned to receive an intravenous bolus injection of palonosetron plus continuous infusion of butorphanol (Group P + B) or an intravenous bolus of saline plus continuous infusion of butorphanol (Group B) after epidural administration of morphine. The antipruritic effect was graded as satisfactory (numerical rating scale (NRS) of pruritus ≤3) or unsatisfactory (NRS >3) within 48 h after morphine treatment. The first patient in each group received butorphanol infusion at a rate of 4 µg/kg/h. The infusion dose for each subsequent patient in the corresponding group was increased by 0.2 µg/kg/h after an unsatisfactory response or decreased by 0.2 µg/kg/h after a satisfactory response. The ED50 was calculated for each group and compared using up-down sequential analysis. Results The ED50 (mean [95% confidence interval (CI)]) of the dose of intravenous butorphanol infusion for preventing moderate to severe pruritus was lower in Group P + B (3.29 µg/kg/min [3.25–3.34 µg/kg/min]) than in Group B (3.57 µg/kg/min [3.47–3.67 µg/kg/min]) (p < 0.05). Conclusions Under the conditions of the present study, a prophylactic use of 0.25 mg palonosetron reduced the ED50 of prophylactic infusion of butorphanol by approximately 8% to achieve a satisfactory antipruritic effect after epidural morphine for post-caesarean analgesia.

Labor Analgesia Initiation With Dural Puncture Epidural Versus Conventional Epidural Techniques: A Randomized Biased-Coin Sequential Allocation Trial to Determine the Effective Dose for 90% of Patients of Bupivacaine.

The dural puncture epidural (DPE) technique has a faster onset, better sacral spread, and improved bilateral coverage when compared to the conventional epidural (EPL) technique. Whether these qualities translate into a lower bupivacaine dose to provide initial analgesia is unknown. We sought to determine the effective dose of bupivacaine to achieve initial (first 30 minutes) labor analgesia in 90% of patients (ED90) with the DPE and EPL techniques, using a biased-coin, sequential allocation method. A total of 100 women of mixed parity with term, singleton gestation at ≤5 cm dilation with no major comorbidities were randomized to receive a DPE or an EPL technique. An experienced anesthesiologist performed these techniques and administered an allocated dose of plain bupivacaine diluted with isotonic sterile 0.9% saline to a total volume of 20 mL via the EPL catheter. Bupivacaine doses for each subject were determined by the response of the previous subject, using a biased-coin sequential allocation method, with success defined by a numeric rating scale (NRS) < 3 at 30 minutes. Outcome assessments were performed by an investigator blinded to the technique and bupivacaine dose. Sensory and motor blockade and maternal or fetal side effects were recorded every 5 minutes for the first 30 minutes. The ED90 of bupivacaine with each technique was estimated using centered isotonic regression. A total of 95 women were included in the final analysis. The ED90 of bupivacaine was estimated at 29.30 mg (90% confidence interval [CI], 28.55-31.56) with a DPE technique and 45.25 mg (90% CI, 42.80-52.03) with an EPL technique. Using a biased-coin, sequential allocation method, the DPE technique requires less bupivacaine to achieve effective initial analgesia (ED90) when compared to the EPL technique.

Intrathecal dexmedetomidine as an adjuvant to plain ropivacaine for spinal anesthesia during cesarean section: a prospective, double-blinded, randomized trial for ED50 determination using an up-down sequential allocation method

BackgroundIntrathecal dexmedetomidine, as an adjuvant to local anesthetics, has been reported to improve the quality of spinal anesthesia and reduce the required local anesthetic dose. However, the optimal dosage regimen for intrathecal dexmedetomidine combined with plain ropivacaine for cesarean section (CS) remains undetermined. The present study aimed to determine the median effective dose (ED50) of intrathecal dexmedetomidine as an adjuvant to plain ropivacaine for spinal anesthesia during CS.MethodsSixty parturients undergoing CS were randomly assigned to either group: plain ropivacaine 8 mg (Group Rop8) or plain ropivacaine 10 mg (Group Rop10). The initial dosage of intrathecal dexmedetomidine in each group was 5 µg. The effective dose was defined as a bilateral sensory block at the level of T6 or above to pinprick attained within 10 min after intrathecal injection, without the need for supplementary intraoperative epidural anesthesia. Effective or ineffective responses were determined, followed by a 1 µg increment or decrement in the dose of intrathecal dexmedetomidine for the next parturient using up-down sequential allocation. ED50 were calculated using probit regression.ResultsThe ED50 of intrathecal dexmedetomidine with plain ropivacaine was 5.9 µg (95% confidence interval [CI], 4.9–7.4 µg) in Group Rop8 and 3.1 µg (95% CI, 0.1–4.8 µg) in Group Rop10 (P < 0.05). Hemodynamic stability, side effects, patient satisfaction and neonatal outcomes were comparable between the two groups.ConclusionsThe present data suggested that the ED50 of intrathecal dexmedetomidine as an adjuvant to 8 mg and 10 mg plain ropivacaine in spinal anesthesia during cesarean section was approximately 6 µg and 3 µg, respectively.Trial registrationChinese Clinical Trial Registry, identifier: ChiCTR2200055928.

Calculation of effective dose of phenylephrine bolus for treatment of post-spinal hypotension in pre-eclamptic patients undergoing caesarean section – a non-randomised controlled trial

BackgroundPatients with pre-eclampsia require smaller vasopressor doses compared with those with normotension for management of post-spinal hypotension during caesarean section. However, the literature has little evidence as to the phenylephrine dose required for patients with pre-eclampsia. MethodsFifty patients, with either pre-eclampsia or normotension, and developing post-spinal hypotension during caesarean section under spinal anaesthesia, were studied. Women in both groups did not receive prophylactic vasopressors. The first patient in each group received phenylephrine 50 µg to treat the first episode of hypotension, defined as fall of systolic blood pressure ≥20% from baseline or an absolute value <100 mmHg. If hypotension was corrected within one minute it was considered a ‘success’. The doses for the subsequent patients were determined by responses to all previous patients, according to a variation of Narayana’s rule for the up-down sequential allocation method. ResultsThe 95% effective dose (ED95) and 50% effective dose (ED50) of phenylephrine was 41.7 µg (95% CI 33.8 to 49.6 µg) and 29.1 µg (95% CI 26.0 to 32.2 µg) respectively in the pre-eclampsia group, and 64.9 µg (95% CI 54.1 to 75.7 µg) and 47.3 µg (95% CI 39.7 to 54.9 µg) respectively in the normotensive group. The proportionate reduction in phenylephrine dose ranged from 33% (95% CI 18 to 44%) to 40% (95% CI 19 to 52%). ConclusionPatients with pre-eclampsia may need a 33% to 40% reduction in the first phenylephrine bolus dose, compared with patients with normotension, for the treatment of the first episode of post-spinal hypotension.

A comparison of eight optimization methods applied to a wind farm layout optimization problem

Abstract. Selecting a wind farm layout optimization method is difficult. Comparisons between optimization methods in different papers can be uncertain due to the difficulty of exactly reproducing the objective function. Comparisons by just a few authors in one paper can be uncertain if the authors do not have experience using each algorithm. In this work we provide an algorithm comparison for a wind farm layout optimization case study between eight optimization methods applied, or directed, by researchers who developed those algorithms or who had other experience using them. We provided the objective function to each researcher to avoid ambiguity about relative performance due to a difference in objective function. While these comparisons are not perfect, we try to treat each algorithm more fairly by having researchers with experience using each algorithm apply each algorithm and by having a common objective function provided for analysis. The case study is from the International Energy Association (IEA) Wind Task 37, based on the Borssele III and IV wind farms with 81 turbines. Of particular interest in this case study is the presence of disconnected boundary regions and concave boundary features. The optimization methods studied represent a wide range of approaches, including gradient-free, gradient-based, and hybrid methods; discrete and continuous problem formulations; single-run and multi-start approaches; and mathematical and heuristic algorithms. We provide descriptions and references (where applicable) for each optimization method, as well as lists of pros and cons, to help readers determine an appropriate method for their use case. All the optimization methods perform similarly, with optimized wake loss values between 15.48 % and 15.70 % as compared to 17.28 % for the unoptimized provided layout. Each of the layouts found were different, but all layouts exhibited similar characteristics. Strong similarities across all the layouts include tightly packing wind turbines along the outer borders, loosely spacing turbines in the internal regions, and allocating similar numbers of turbines to each discrete boundary region. The best layout by annual energy production (AEP) was found using a new sequential allocation method, discrete exploration-based optimization (DEBO). Based on the results in this study, it appears that using an optimization algorithm can significantly improve wind farm performance, but there are many optimization methods that can perform well on the wind farm layout optimization problem, given that they are applied correctly.

95% effective volume of ropivacaine for ultrasound‑guided supra‑inguinal fascia iliaca compartment block

BackgroundHip arthroplasty is effective in treating hip diseases, such as osteoarthritis and hip fracture, but it often brings severe trauma and pain. In recent years, ultrasound-guided supra-inguinal fascia iliaca compartment block(S-FICB) has become a widely used nerve block method for analgesia in hip arthroplasty.MethodsFifty-three patients preparing for hip arthroplasty were prospectively enrolled. S-FICB was performed under ultrasound guidance, and inject 0.33% ropivacaine into the space. Using the biased-coin design (BCD) sequential allocation method. The initial volume of 0.33% ropivacaine was 30ml. In case of failure, the next patient received a higher volume (defined as the previous volume with an increment of 1.2 mL). If the previous patient had a successful block, the next patient was randomized to a lower volume (defined as the previous volume with a decrement of 1.2 mL), with a probability of b = 0.05, or the same volume, with a probability of 1 − b = 0.95. The study was stopped when 45 successful blocks were achieved.ResultsForty-five patients (84.9%) were blocked successfully. The 95% effective volume (EV95) was 34.06ml (95%CI 33.35 ~ 36.28ml). There were 31 patients with non-fracture in this study. The quadriceps muscle strength decreased in only two patients. Moreover, they both received 34.8ml of ropivacaine for S-FICB. Twenty-two patients had hip fractures. There were 3 patients (14%) with failed blocks and 19 patients (86%) with successful blocks. However, all fracture patients experienced less pain after S-FICB.ConclusionEV95 of 0.33% ropivacaine for ultrasound-guided S-FICB was 34.06ml.Trial registrationThe trial was registered at the Chinese Clinical Trial Registry (registration number: ChiCTR2100052214, registration date: 2021 October 22).

Optimal Propofol Concentration at Effect Site for Esophagogastroduodenoscopy under Moderate to Deep Sedation with Target-controlled Infusion

Background: The target-controlled infusion (TCI) of propofol is being increasingly used for moderate-to-deep sedation during esophagogastroduodenoscopies (EGDs). Objective: To determine the target effect-site concentration (Cet) of propofol required for EGD scope insertions during sedation using TCI. Materials and Methods: Dixon’s up-and-down sequential allocation method was used with patients scheduled for elective EGD at Srinagarind Hospital, Thailand. The patients were divided into Group A aged 18 to 64 years and Group B aged over 65 years. Anesthesia was induced with propofol via TCI (Schnider model). The propofol Cet commenced at 3 mcg/mL and 2 mcg/mL in Groups A, and B, respectively. The response during an EGD scope insertion determined the Cet for the next patient, with intervals of 0.3 mcg/mL. Calculations of the effective concentration without response during EGD scope insertion in 50% and 95% of patients (EC50 and EC95) values of propofol, with 95% confidence intervals (CIs), were performed using the isotonic regression method. Results: Twenty-one and nineteen patients were enrolled in Groups A, and B, respectively. In Group A, the EC50 of propofol for EGD was 3.30 mcg/mL (95% CI 3.05 to 3.55), while the EC95 was 3.75 mcg/mL (95% CI 3.34 to 4.16). In the case of Group B, the EC50 was 3.05 mcg/mL (95% CI 2.75 to 3.35) and the EC95 was 3.05 mcg/mL (95% CI 2.92 to 3.18). Hypotension occurred in 52.3% and 31.5% of patients in group A, and B, respectively. Conclusion: The appropriate Cet of propofol for anesthesia during EGD using TCI is 3.75 mcg/mL for patients aged 18 to 64 years, and 3.05 mcg/mL for patients aged 65 years and over. Hypotension is the most common adverse event of moderate-to-deep sedation with propofol using TCI. Keywords: Sedation; Esophagogastroduodenoscopy; Propofol; Target-controlled infusion

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

PurposeThis 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 MethodsPatients 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.ResultsThe 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).ConclusionIn 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.

Moderate sedation with single-dose remimazolam tosilate in elderly male patients undergoing transurethral resection of the prostate with spinal anesthesia: a prospective, single-arm, single-centre clinical trial

BackgroundRemimazolam tosilate (RT) is a newly listed benzodiazepine for sedation and anesthesia featuring quick onset of effects, short maintenance and recovery times, which is currently under research. This trial was conducted to determine the median effective dose (ED50) and the 95% effective dose (ED95) of single-dose remimazolam for moderate sedation in elderly patients undergoing transurethral resection of the prostate (TURP) under spinal anesthesia, and to evaluate its efficacy and safety.MethodsThirty male patients aged 65–80 years old were recruited for selective TURP. Remimazolam was administered intravenously to pain-free patients (VAS score < 1) within 1 min of successful spinal anesthesia by the same anesthesiologist. We used modified Dixon’s up-and-down sequential allocation method to determine the ED50 and ED95 of the agent with an initial dosage of 0.1 mg/kg. Successful sedation was defined as an MOAA/S score ≤ 3 and above 1. A score of > 3 was deemed as failed sedation. Recruitment continued until ten independent pairs (from successful sedation to failed sedation) would give a reliable estimation of the ED50 and ED95 of RT and their 95% confidence intervals.ResultsThe ED50 of remimazolam was 0.063 (95% C.I. 0.045–0.073) mg/kg. Its ED95 was 0.079 (95% C.I. 0.07–0.137) mg/kg. Remimazolam was safe in its application.ConclusionsA single-dose of RT proves to be safe for assisted sedation during TURP in elderly male patients under spinal anesthesia with a lower incidence of adverse events. Its ED50 and ED95 were 0.063 mg/kg and 0.079 mg/kg, respectively.Trial registrationhttp://www.chictr.org.cn (ChiCTR2100051912).

Optimization of programmed intermittent epidural bolus volume for different concentrations of ropivacaine in labor analgesia: a biased coin up-and-down sequential allocation trial

Background and objectivesTo date, programmed intermittent epidural bolus (PIEB) has been widely used in obstetric analgesia, while no optimal PIEB regimen has been proposed. This study aimed to assess effective analgesia in 90% of women (EV90) with different concentrations of ropivacaine (0.075% and 0.1%) combined with 0.5 µg/mL sufentanil, at an interval of 40 min using the biased coin design-up-and-down method (BCD-UDM), and to explore whether there is a difference in EV90 with the increase of ropivacaine concentration.MethodsIn total, 103 primiparous women were assigned to two groups, including group A (n = 52) and group B (n = 51). Parturients in group A were treated with 0.075% ropivacaine and 0.5 µg/mL sufentanil, while those in group B were treated with 0.1% ropivacaine and 0.5 µg/mL sufentanil. Used the biased coin up-and-down sequential allocation method to determine the EV90. The secondary outcomes were sensory block level, motor block, and adverse events (hypotension, urinary retention, and pruritus).ResultsThe results revealed that EV90 was 10 mL (95% confidence interval (CI):8.03–11.54) in group A, and EV90 was 9 mL (95% CI:7.49–10.51) in group B by the isotonic regression method. The highest level of the sensory block was T8, and the lowest was T12. No case of hypotension was recorded,and only 4 parturients complained of motor block.ConclusionWith an interval of 40 min, the optimal PIEB bolus volume of 0.075% ropivacaine and 0.5 µg/mL sufentanil was 10 mL, 0.1% ropivacaine and 0.5 µg/mL sufentanil was 9 mL. Moreover, the PIEB volume decreased along with the higher concentration of ropivacaine.Trial registrationChiCTR registration number: ChiCTR2000040917. Registration date: December 15, 2020.

ED50 and ED95 of propofol combined with different doses of esketamine for children undergoing upper gastrointestinal endoscopy: A prospective dose-finding study using up-and-down sequential allocation method.

Propofol and esketamine are routine anaesthetics used in sedation or general anaesthesia for paediatric procedures. Coadministration could reduce the dose of either propofol or esketamine required and lower the incidence of drug-related adverse events. We designed a four-arm randomized controlled trial in children undergoing diagnostic upper gastrointestinal endoscopy to investigate the dose of propofol with different doses of esketamine inducing appropriate depth of anaesthesia in 50% patients (median effective dose, ED50 ). After getting the approval of the research ethics committee and informed consent, 92 paediatric patients planning for upper gastrointestinal endoscopy were divided into four groups randomly: esketamine 0, 0.25, 0.5 and 1mg/kg groups (n=23/group). Propofol doses followed the Dixon and Massey up-and-down method with different starting and interval doses between groups. During the first attempt of endoscope insertion, if patients' reactions prevented the insertion, it would be considered as a failure. The awakening time, total propofol doses, as well as the perioperative and post-procedure adverse events were evaluated and recorded for each patient. The ED50 (median, 95% confidence interval) of propofol was significantly greater in esketamine 0 and 0.25mg/kg groups in comparison with the esketamine 0.5 and 1mg/kg groups (4.1 [3.3-4.9]; 3.1 [2.5-3.8] mg/kg vs. 1.8 [1.1-2.4]; 0.8 [0.2-1.3] mg/kg, respectively, p<.05). The total doses of propofol in esketamine 0.5 and 1mg/kg groups were statistically lower than these in esketamine 0 and 0.25mg/kg group (p<.01). The mean blood pressure was lower in the esketamine 0mg/kg group than that in 1mg/kg group after administration and during the procedure (p<.01). The esketamine 1mg/kg group showed a higher incidence of vomiting and visual disturbances than the other three groups (p<.001). In children who accomplished diagnostic paediatric upper gastrointestinal endoscopy under deep sedation/anaesthesia, the total dosage of propofol needed was reduced significantly in esketamine 0.5 and 1mg/kg groups with a corresponding reduce in propofol-related hemodynamic changes. However, a higher incidence of esketamine-related adverse effects was found in esketamine 1mg/kg group.

A randomized trial to determine the minimum effective lidocaine volume for median nerve block using hydrodissection

Ultrasound-guided hydrodissection with 5% dextrose in water (DW5) creates a peri-nervous compartment, separating the nerve from the neighboring anatomical structures. The aim of this randomized study was to determine the minimum volume of lidocaine 2% with epinephrine 1:200,000 required when using this technique to achieve an effective median nerve block at the elbow in 95% of patients (MEAV95). Fifty-two patients scheduled for elective hand surgery received an ultrasound-guided circumferential perineural injection of 4 ml DW5 and an injection of local anesthetic (LA) following a biased coin up-and-down sequential allocation method. A successful block was defined as a light touch completely suppressed on the two distal phalanges of the index finger within a 30-min evaluation period. The MEAV95 of lidocaine 2% with epinephrine was 4 ml [IQR 3.5–4.0]. Successful median nerve block was obtained in 38 cases (82.6%) with median onset time of 20.0 [10.0–21.2] minutes (95% CI 15–20). The analgesia duration was 248 [208–286] minutes (95% CI 222–276). Using an ultrasound-guided hydrodissection technique with DW5, the MEAV95 to block the median nerve at the elbow with 2% lidocaine with epinephrine was 4 ml [IQR 3.5–4.0]. This volume is close to that usually recommended in clinical practice.Trial registration clinicaltrials.gov. NCT02438657, Date of registration: May 8, 2015.

Median Effective Dose of Dexmedetomidine Inducing Bradycardia in Elderly Patients Determined by Up-and-Down Sequential Allocation Method.

Purpose: When dexmedetomidine is used in elderly patients, high incidence of bradycardia is reported. Given age-related physiological changes in this population, it is necessary to know the safety margin between the loading dose of dexmedetomidine and bradycardia. Therefore, we conducted this study to investigate the median effective dose (ED50) of dexmedetomidine causing bradycardia in elderly patients.Methods: Thirty patients with ages over 65 years undergoing elective general surgery were enrolled. The Dixon and Massay sequential method were applied to determine the loading dose of dexmedetomidine, starting from 1.0 µg/kg. The dose for the follow-up subjects increased or decreased according to the geometric sequence with the common ratio 1.2, based on the 'negative' or 'positive' response of the previous subject. Positive mean that the subject developed bradycardia during the test. Hemodynamic data including heart rate and systolic blood pressure were recorded. The level of sedation was assessed with the Observer Assessment of Alertness and Sedation Scale (OAA/S).Results: Bradycardia occurred in 13 patients (43.3%). The ED50 of dexmedetomidine causing bradycardia was 1.97 µg/kg (95% CI, 1.53-2.53 µg/kg). OAA/S scores at 10 min after the beginning of the dexmedetomidine infusion and 10 min after the termination of dexmedetomidine administration showed no significant differences between the positive and negative groups (P > 0.05).Conclusion: The ED50 of dexmedetomidine causing bradycardia in our cohort was higher than clinical recommended dose. A higher loading dose appears acceptable for a faster onset of sedation under careful hemodynamic monitoring.Trial registration: ChiCTR 15006368.

The Intraoperative Median Effective Dose of Oxytocin for Preventing Uterine Atony in Parturients with a Prior History of Caesarean Delivery.

While oxytocin is commonly used for the prevention of uterine atony, its pharmacology may be affected by a prior history of caesarean delivery. The objective of this study was to determine the 50% effective dose (ED50) of bolus oxytocin after caesarean delivery in parturients with and without prior caesarean delivery. This was a parallel-group, double-blind, dose-response study using Dixon's up-and-down sequential allocation method to estimate the ED50 of bolus-administered oxytocin in parturients having caesarean delivery under combined spinal-epidural anaesthesia (CSE). Twenty-seven parturients with a history of prior caesarean delivery (With-PCD group) and 26 parturients with no such history (Without-PCD group) were enrolled. Oxytocin was administered as an intravenous bolus at a starting dose of 0.5 units, which was then increased or decreased by 0.25 units at a time. Uterine tone was assessed by the obstetrician as either 'adequate' or 'inadequate' 3 min after delivery of the fetus. Adverse effects, administration of additional uterotonic agents, and estimated blood loss were recorded. The ED50 of oxytocin was greater in the With-PCD group than in the Without-PCD group (0.95 units [95% CI 0.82-1.08] vs. 0.55 units [95% CI 0.38-0.73], P < 0.001). The overall incidence of adverse effects was higher in the With-PCD group than in the Without-PCD group (33.3% vs. 7.7%, P = 0.02). The initial bolus dose of oxytocin needed to prevent uterine atony was higher in parturients with prior caesarean delivery than in parturients without prior caesarean delivery. Uterine scarring may contribute to the increased oxytocin requirements of the former group. ChiCTR1900023474; investigator: Wei CN; date of registration: 30 May 2019.

Dose dependent reduction in median effective concentration (EC50) of ropivacaine with adjuvant dexmedetomidine in labor epidural analgesia: An up-down sequential allocation study

Study objectiveAdjuvant dexmedetomidine can be used to reduce the required concentration of ropivacaine for labor epidural analgesia. However, the potency of dexmedetomidine has not been fully studied. The purpose of this study was to determine the median effective concentration (EC50) of ropivacaine with adjuvant dexmedetomidine. DesignProspective, double-blind, up-down sequential allocation study. SettingAcademic medical center specializing in the care of women and children. PatientsOne hundred and fifty healthy, term parturients requesting labor epidural analgesia were randomly assigned to 1 of 5 different concentrations of dexmedetomidine: 0 μg/ml, 0.3 μg/ml, 0.4 μg/ml, 0.5 μg/ml, or 0.6 μg/ml. InterventionsThe study solution for the first patient in each group included the randomly assigned concentration of dexmedetomidine in 0.1% ropivacaine. Subsequent patients in each randomization group received the assigned concentration of dexmedetomidine in a new concentration of ropivacaine as determined by the up-down allocation methodology. Effective analgesia was defined as pain on the visual analogue scale of<3 at30 min after administration of local anesthetic. The up-down sequential allocation method and probit regression were used to calculate the EC50 of epidural ropivacaine. MeasurementsThe primary outcome was pain 30 min after administration of local anesthetic via epidural catheter. Exploratory outcomes included side effects, neonatal outcomes, and obstetric outcomes. Main resultsThe EC50 values for ropivacaine in dexmedetomidine 0.4 μg/ml, 0.5 μg/ml, and 0.6 μg/ml (0.044% [95% CI 0.036% to 0.045%], 0.035% [95% CI 0.031% to 0.041%], and 0.039% [95% CI 0.034% to 0.045%], respectively) were lower compared to ropivacaine in dexmedetomidine 0 μg/ml and 0.3 μg/ml (0.086% [95% CI 0.081% to 0.092%], and, 0.069% [95% CI 0.056% to 0.076%], respectively). Differences between EC50 values for ropivacaine in dexmedetomidine 0.4 μg/ml, 0.5 μg/ml, and 0.6 μg/ml were not statistically significant. Results of our exploratory analyses did not reveal differences in side effects, neonatal outcomes, or obstetric outcomes. ConclusionsIn this study, the lowest concentration of dexmedetomidine in ropivacaine with the greatest clinical effect was 0.4 μg/ml, which is important because there may be no additional analgesic benefit of dexmedetomidine greater than 0.4 μg/ml.