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Background Maternal hypotension after spinal anaesthesia occurs at a high rate during caesarean delivery and can lead to adverse maternal or foetal outcomes. The aim of this study was to determine the optimal dose of spinal ropivacaine for caesarean section with or without intravenous single bolus of S-ketamine and to observe the rates of hypotension associated with both methods. Methods Eighty women undergoing elective caesarean delivery were randomly allocated into either a ropivacaine only or ropivacaine with intravenous S-ketamine group. If the upper sensory level of the patient reached T6 and the visual analogue scale (VAS) scores remained below 3 points before delivery, the next patient had a 1/9th chance of receiving a lower dose or an 8/9th chance of receiving the same dose as the previous patient. If the patient had VAS scores of more than 2 points or needed an extra epidural rescue bolus before delivery, a higher dose was used for the next patient. The primary outcome was the successful use of spinal ropivacaine to maintain patient VAS score of < 3 points before delivery and the incidence of post-spinal hypotension in both groups. Secondary outcomes included the rates of hypotension-related symptoms and interventions, upper sensory level of anaesthesia, level of sedation, neonatal outcomes, Edinburgh Postnatal Depression Scale scores at admission and discharge, and post-operative analgesic effect. The 90% effective dose (ED90) and 95% confidence interval (95% CI) were estimated by isotonic regression. Results The estimated ED90 of ropivacaine was 11.8 mg (95% CI: 11.7–12.7) with and 14.7 mg (95% CI: 14.6–16.0) without intravenous S-ketamine, using biased coin up-down sequential dose-finding method. The rates of hypotension and associated symptoms were significantly lower in S-ketamine group than in the ropivacaine only group. Conclusions A spinal dose of ropivacaine 12 mg with a single intravenous 0.15 mg/kg bolus dose of S-ketamine may significantly reduce the risk of hypotension and induce sedation before delivery. This method may be used with appropriate caution for women undergoing elective caesarean delivery and at a high risk of hypotension or experiencing extreme nervousness. Trial registration http://www.chictr.org.cn ( ChiCTR2000040375 ; 28/11/2020).

Hysteroscopy is a minimally invasive procedure that can nonetheless elicit considerable pain, especially during cervical dilation. While fentanyl is widely used for analgesia, its application is limited by side effects such as respiratory depression. Esketamine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, has emerged as a promising alternative due to its potent analgesic effects and safer profile. This study aimed to determine and compare the effective dose 90 (ED90) of these drugs for preventing physical movements and to evaluate their efficacy and safety. This two-part, prospective, randomized, double-blind trial enrolled patients scheduled for hysteroscopy. In Part 1, the ED90 of intravenous fentanyl (0.25-2.00 μg/kg) and esketamine (0.15-0.50 mg/kg) was determined using a sequential allocation biased-coin design (SABCD). The SABCD was implemented independently for each drug, with a targeted enrollment of 60 participants per group; ultimately, 56 participants per group were included in this dose-finding phase. In Part 2, clinical outcomes and adverse events were compared in an additional set of 56 patients per group, all of whom received the predetermined ED90 of their assigned drug. The ED90 of fentanyl was 1.424 μg/kg (95% confidence interval [CI]: 1.322-1.618 μg/kg), compared to 0.423 mg/kg (95% CI: 0.368-0.569 mg/kg) for esketamine. The two groups exhibited comparable efficacy in physical movements inhibition and total propofol consumption. However, the esketamine group demonstrated a markedly improved safety and recovery profile. Specifically, patients receiving esketamine reported significantly less propofol injection pain (fentanyl group vs esketamine group, 25% vs 7.1%; relative risk [RR], 0.4; 95% CI: 0.2-0.8; = 0.019), experienced significantly faster emergence from anesthesia (7.0 [5.0, 9.5] vs 6.0 [5.0, 8.0]; median difference [MD], -1.0; 95% CI: -2.0-0; = 0.029), and maintained better hemodynamic stability. Crucially, the incidence of respiratory depression was significantly lower in the esketamine group (26.8% vs 3.6%; RR, 0.2; 95% CI: 0.06-0.6; = 0.001). Furthermore, the esketamine group showed a significantly greater reduction in Hospital Anxiety and Depression Scale (HADS) scores at the one-month follow-up than the fentanyl group (4.0 [3.0, 4.0] vs 2.0 [1.0, 2.0]; MD, -2.0; 95% CI: -2.0--2.0; < 0.001). At equipotent ED90 doses, esketamine provides analgesia equivalent to fentanyl during hysteroscopy, while conferring additional advantages, such as reduced injection pain, faster emergence, superior cardiorespiratory stability, and potential psychological benefits. Chinese Clinical Trial Registry ChiCTR2500106429.

Postoperative pain significantly impairs recovery in elderly patients. Oxycodone is widely used in the postoperative period due to its favorable safety profile and low risk of respiratory depression. To determine the minimum effective dose of intravenous oxycodone, administered in combination with postoperative patient-controlled intravenous analgesia, that achieves at least 90% efficacy in elderly patients undergoing video-assisted thoracoscopic surgery. We enrolled participants aged 65 and older who underwent thoracoscopic lobectomy. Oxycodone was administered 30 minutes before the completion of the surgical procedure. The initial dose was 0.02 mg/kg. Subsequent dose adjustments were determined based on the previous patient's response using a biased coin design. The dose interval was 0.01 mg/kg. A positive response was defined as an NRS score ≤ 3 at cough 2 hours postoperatively. The study was terminated after 45 successful responses. Secondary endpoints included postoperative pain assessed at various time points up to hospital discharge, adverse events, sedation levels, and the occurrence of chronic pain during the postoperative period. A total of sixty patients were enrolled. Among elderly patients undergoing elective VATS with multimodal analgesia, the ED90 of oxycodone was 0.104 mg/kg (95% CI: 0.095-0.108 mg/kg). The supplementary analysis focused on patients who received at least 0.09 mg/kg of oxycodone. After adjusting for imbalanced baseline characteristics, the incidence of chronic pain in the 0.09 mg/kg dose group was significantly higher than in the 0.10 mg/kg dose group (P = 0.007). For thoracoscopic lobectomy in elderly individuals aged >65 years, the ED90 of oxycodone was 0.104 mg/kg (95% CI: 0.095-0.108 mg/kg).

This study employed probit regression analysis to determine the 90% effective dose (ED ) of oliceridine when combined with propofol for day-case hysteroscopy. 100 patients undergoing hysteroscopic surgery were randomized to receive intravenous oliceridine (0.01, 0.015, 0.02, 0.025, or 0.03 mg kg ) 3 minutes preoperatively. Propofol was administered intravenously at 2 mg kg induction and maintained at 6 mg kg h . Successful anesthesia was defined as absence of body movement during cervical dilation. Parameters recorded included the success rate, propofol consumption, total surgical duration, recovery time, postoperative pain, and adverse events. The ED of oliceridine for suppressing response to cervical dilation was 0.025 (95% confidence interval, CI, 0.020-0.050) mg kg . The incidence of propofol injection pain in the 0.01, 0.015, 0.02, 0.025, and 0.03 mg kg oliceridine groups (80%, 80%, 45%, 40%, and 30%, respectively) were significantly different (P = 0.001). There was no difference in the propofol requirements, time to anesthesia emergence, and visual analog scores(VAS) at 30 minutes postoperation among groups. No serious adverse events occurred in any patient. For healthy adult women undergoing day-case hysteroscopy, oliceridine 0.025 mg kg combined with propofol provides effective and safe anesthesia.

Epidural analgesia in the latent phase of the first stage of labor has been recognized and accepted by anesthesiologists worldwide. However, there is no unified consensus on the exact dosage of sufentanil with the combination of ropivacaine in the induction of epidural analgesia in the early first stage of labor. In this sequential dose-finding study, the 90% effective dose (ED90) of sufentanil for epidural administration in the early first stage of labor was estimated to minimize the adverse effects of using higher doses. Forty parturients with cervical dilatation of 2 to 4 cm who requested epidural analgesia were enrolled in this study. Parturients received 15 mL of a combination of ropivacaine 13 mg and the test dose of sufentanil. The initial dose of sufentanil in epidural administration was 1 μg, and the dose of sufentanil for the next parturient was based on the response of the preceding participant as per a biased coin up-and-down design. The primary outcome was the dose of sufentanil that resulted in successful epidural administration by maintaining the parturients’ visual analog scale scores at ≤30 mm in the first 15, 30, and 45 minutes of induction. The ED90 and 95% CIs were estimated using isotonic regression methods and bootstrapping. The estimated ED90 of sufentanil in epidural administration in the early first stage of labor was 1.91 μg (95% CI, 1.82–2.35 μg) in this sequential dose-finding study. Sufentanil at a dosage of 2 μg is recommended for the administration of epidural analgesia in parturients in the early first stage of labor. ChiCTR.org.cn identifier: 1900021683.

Background: Because it has been reported that racemic ketamine had a local anesthetic-sparing effect when used for epidural analgesia this would suggest the likelihood of a potential advantage (less pruritus) over opioid drugs. Esketamine has greater analgesic efficacy than racemic ketamine, but the optimum dosage regimen for epidural use is undetermined. The aim of this study was to determine the ED 90 of epidural esketamine when coadministered with 0.075% ropivacaine for labor analgesia. Methods: A total of 65 laboring nulliparous patients were enrolled in this study from 16 March 2022 to 15 October 2022. The patients were randomly assigned to receive 0, 0.25, 0.5, 0.75 or 1.0 mg/mL esketamine with 0.075% ropivacaine epidurally. An effective response to the epidural loading dose was defined as numerical rating scale pain score ≤3 at 30 min after the end of the epidural loading dose (10 mL of the ropivacaine 0.075% solution with the added esketamine). The ED 90 of epidural esketamine coadministered with 0.075% ropivacaine with 95% confidence intervals for labor analgesia was determined using probit regression. Secondary outcomes and side effects were recorded. Results: The estimated value of ED 90 with 95% CIs for epidural esketamine with 0.075% ropivacaine was 0.983 (0.704–2.468) mg/mL. The characteristics of sensory and motor block, consumption of ropivacaine per hour, duration of first or second stage, Apgar scores did not differ among the five groups. The incidence of mild dizziness in Group esketamine 1.0 mg/mL was significantly higher than that in other groups ( p < 0.05). No statistical differences were found in other side effects among groups. Conclusion: The ED 90 value of epidural esketamine coadministered with 0.075% ropivacaine for labor analgesia in nulliparous parturients was about 1.0 mg/mL. Furthermore, our results suggested that epidural esketamine would cause dose-dependent mild dizziness especially at doses up to 1.0 mg/mL. As a single epidural additive, esketamine may not be suitable for labor analgesia. Future studies may investigate the appropriate dosage of esketamine at slightly higher concentrations of local anesthetics or larger initial volume of analgesia, or explore other potential advantages of esketamine. Clinical Trial Registration: ( https://www.chictr.org.cn/bin/project/edit?pid=159764 ), identifier (ChiCTR2200057662).

A single dose of epidural hydromorphone has been suggested as an alternative method for providing analgesia after caesarean section (CS). Nevertheless, the optimal dosage of epidural hydromorphone for postoperative pain relief following CS has yet to be determined. This trial included 30 singleton primiparous women undergoing scheduled caesarean delivery, who were recruited to determine doses of epidural hydromorphone using the modified Dixon sequential method. The initial hydromorphone dose was 0.75 mg, with adjustments based on the efficacy of the preceding participant's dose over 12 hours. Various parameters such as blood pressure, heart rate, respiratory rate, visual analog scale (VAS) pain score, postoperative adverse reactions, and patient satisfaction with analgesic effect were recorded at each time point. The VAS scores were categorized as positive (score >3) or negative (score ≤3). Participants received a single epidural injection of 0.2% ropivacaine 20 mg along with a study dose of hydromorphone. The median effective dose (ED50), 90% effective dose (ED90), and corresponding 95% confidence intervals (CIs) of hydromorphone with ropivacaine for analgesia after caesarean section were calculated using the probit method. The ED90 and ED50 in our population were 1.105 mg (95% CI: 0.825-2.324 mg) and 0.659 mg (95% CI: 0.434-0.883 mg), respectively. Epidural hydromorphone can be safely used for postoperative analgesia in patients undergoing caesarean section, and the analgesic effect is satisfactory when the dosage is appropriate.

Vasopressors remain an important strategy for managing spinal anesthesia-induced hypotension in women with preeclampsia. The aim of this study was to investigate the ED90s and efficacy ratio of phenylephrine and norepinephrine in managing spinal anesthesia-induced hypotension in women with preeclampsia during cesarean delivery. 60 women with preeclampsia, who underwent cesarean delivery, were randomly assigned to receive either a continuous intravenous infusion of phenylephrine or norepinephrine following spinal anesthesia. The initial dosage of phenylephrine or norepinephrine for the first women was 0.5 or 0.05 μg/kg/min, respectively, and subsequent infusion dosages were adjusted based on their efficacy in preventing spinal anesthesia-induced hypotension (defined as a systolic blood pressure less than 80% of the baseline level). The incremental or decremental doses of phenylephrine or norepinephrine were set at 0.1 or 0.01 μg/kg/min. The primary outcomes were the ED90s and efficacy ratio of phenylephrine and norepinephrine infusions for preventing spinal anesthesia-induced hypotension prior to delivery. The results obtained from isotonic regression analysis revealed that the ED90 values of the phenylephrine and norepinephrine group for preventing spinal anesthesia-induced hypotension were 0.597 (95% CI: 0.582-0.628) and 0.054 (95% CI: 0.053-0.056) μg/kg/min, respectively, with an efficacy ratio of 11.1:1. The results of Probit regression analysis revealed that the ED90 values were determined to be 0.665 (95% CI: 0.576-1.226) and 0.055 (95% CI: 0.047-0.109) μg/kg/min, respectively, with an efficacy ratio of 12.1:1. The administration of 0.6 μg/kg/min phenylephrine and 0.05 μg/kg/min norepinephrine has been found to effectively manage a 90% incidence of spinal anesthesia-induced hypotension in women with preeclampsia.

To determine the 90 percent effective dose (ED90) of intrathecal sufentanil combined with ropivacaine 2.5 mg for labor analgesia and observe its safety for parturients and neonates. We conducted a prospective, double-blind, biased coin up-and-down study. We injected a fixed 2.5 mg ropivacaine combined with a designated dose of sufentanil intrathecally to observe the labor analgesic effect. The initial dose of sufentanil was assigned 1.0 μg, and the remaining doses were assigned as per the biased coin up-and-down method. The criterion of successful response was defined as VAS ≤ 30 mm after intrathecal injection at 10 min. Safety was evaluated in terms of maternal and neonatal outcomes. The ED90 dose of intrathecal sufentanil combined with ropivacaine 2.5 mg (0.1%, 2.5 mL) was 2.61 μg (95% CI, 2.44 to 2.70 μg) by isotonic regression. No respiratory depression, hypotension, or motor block was observed. Thirty-one (77.5%) parturients complained of pruritus, and 14 (35.0%) suffered nausea and vomiting. Three neonates reported a 1 min Apgar score of ≤7, and none reported a 5 min Apgar score of ≤7. The ED90 of intrathecal sufentanil combined with ropivacaine 2.5 mg for labor analgesia was 2.61 μg. The dose is safe for parturients and neonates.

Although the optimal infusion dose of norepinephrine combined with crystalloid coload for preventing spinal anesthesia-induced hypotension (SAIH) for cesarean delivery has been established, the infusion regimen of norepinephrine combined with colloid coload has not been fully quantified. The objective of this study was to compare and determine the median effective dose (ED ) and 90% effective dose (ED ) of norepinephrine infusion combined with crystalloid coload versus colloid coload for preventing SAIH during cesarean delivery. Two hundred parturients were randomly assigned to receive norepinephrine infusion at 0.02, 0.04, 0.06, 0.08, or 0.10 µg/kg/min in combination with 10 mL/kg crystalloid coload or colloid coload to prevent SAIH. The study period was defined as the interval from the commencement of intrathecal injection to delivery of the neonate. The primary outcome was non-occurrence of hypotension, defined as systolic blood pressure (SBP) less than 80% of the baseline before delivery. The ED and ED of norepinephrine infusion dose were determined using probit regression analysis. By calculating the 95% confidence intervals (CIs) of relative median potency to determine whether the prophylactic infusion of norepinephrine requirement was different between the two groups. The derived ED and ED of norepinephrine infusion combined with crystalloid coload were 0.030 (95% CIs 0.020 to 0.038) and 0.097 (95% CIs 0.072 to 0.157) µg/kg/min, respectively. The ED and ED of norepinephrine infusion combined with colloid coload were 0.021 (95% CIs 0.013 to 0.029) and 0.070 (95% CIs 0.053 to 0.107) µg/kg/min, respectively. The estimate of relative median potency for norepinephrine between the two groups was 1.37 (95% CIs 0.94 to 2.23). Under the conditions of this study, 10 mL/kg colloid coload reduced the dose of prophylactic norepinephrine infusion by approximately 30% in parturients during spinal anesthesia for cesarean delivery compared with the crystalloid coload.