ED90 of Sufentanil in Epidural Initiation for Labor Analgesia in Latent Phase and Active Phase During the First Labor Stage.

BACKGROUND: The standard solutions for epidural labor analgesia include both local anesthetics and opioids. The concept of the standard epidural use of local anesthetics in labor analgesia has shifted from high concentrations to high volumes with low concentrations. However, the optimal dosage of opioids needed to initiate and maintain epidural labor analgesia in different phases during the first labor stage has rarely been studied. OBJECTIVE: The present study aimed to determine the optimal sufentanil dose for epidural initiation in the latent and active phases during the first stage of labor. STUDY DESIGN: A prospective, double-blind, sequential dose-finding study. SETTING: A Class A tertiary obstetrics and gynecology hospital. METHODS: The study included 80 nulliparae with cervical dilatation of 2-4 cm and 5-6 cm, with 40 nulliparae in each group. A research dose of sufentanil combined with ropivacaine 13 mg in epidural initiation with a volume of 15 mL was administered to the puerperant. A 1-microgram sufentanil dose and a 2.5-micrograms sufentanil dose were used for the first puerperant of each group. The dose of sufentanil for the subsequent puerperant was determined by the response of the previous puerperant according to the biased coin up-and-down design in each trial. The primary outcome was a visual analog scale score of <= 3 at 15, 30, and 45 minutes after epidural administration, including the given dose of sufentanil. According to the response of each puerperant, the 90% effective doses and their 95% confidence intervals were estimated by isotonic regression and bootstrapping according to the response of each puerperant. RESULTS: The 90% effective doses of sufentanil for puerperants were 1.91 micrograms (95% confidence intervals 1.82-2.35 micrograms) and 4.90 micrograms (95% confidence intervals 4.82-5.35 micrograms) in epidural initiation in the latent and active phases, respectively. The 90% effective doses were 62.5% (95% confidence intervals 50.8-64.0%) lower in the latent phase than that in the active phase during the first stage of labor. LIMITATIONS: Both spontaneous labor and induced labor were included in this study, and the degree of pain in these 2 types of labor is different. Further, only nulliparae were recruited in the study. CONCLUSIONS: Different sufentanil doses should be adopted in epidural initiation in different phases during the first stage of labor due to the large differences in the demand for sufentanil.

Optimum dose of spinal ropivacaine with or without single intravenous bolus of S-ketamine during elective cesarean delivery: a randomized, double-blind, sequential dose-finding study.

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).

Norepinephrine intravenous prophylactic bolus versus rescue bolus to prevent and treat maternal hypotension after combined spinal and epidural anesthesia during cesarean delivery: a sequential dose-finding study.

BACKGROUND: As a relatively new drug in obstetrical anesthesia, norepinephrine is less likely to induce bradycardia and decrease cardiac output, which makes it a potential alternative to phenylephrine. The purpose of this study was to determine the optimal norepinephrine bolus dose needed to either prevent or reverse hypotension after the use of combined spinal and epidural (CSE) anesthesia in 90% of women during elective cesarean delivery (CD). METHODS: Eighty women undergoing elective CD were randomly allocated into either a prophylactic group or a rescue group in this dose finding study. If the women's systolic blood pressure (SBP) was maintained above 80% of their baseline, the next patient had an 8/9th chance of receiving the same dose or a 1/9th chance of receiving a lower dose. If the patient's SBP was not maintained, a higher dose was used for next patient. The primary outcome was the successful use of the norepinephrine bolus dose to maintain SBP above 80% of the baseline until after delivery. Secondary outcomes included nausea, vomiting, breathlessness, dizziness, hypertension, bradycardia due to hypotension and supplemental use of atropine and norepinephrine, upper sensory level of anesthesia, umbilical vein (UV) blood gases, and 1- and 5-minute Apgar scores. The 90% effective dose (ED90) and 95% confidence interval (95% CI) were estimated using isotonic regression methods. RESULTS: The estimated ED90 of the norepinephrine prophylactic bolus was 10.85 µg (95% CI, 9.20-11.67 µg) and that of the norepinephrine rescue bolus was 12.3 µg (95% CI, 10.0-12.8 µg) using isotonic regression methods. CONCLUSIONS: For norepinephrine, either a prophylactic bolus dose of 11 µg or a rescue bolus dose of 12 µg was recommended for clinical practices.