Oxytocin infusion for maintenance of uterine tone under prophylactic phenylephrine infusion for prevention of post-spinal hypotension in cesarean delivery: a prospective randomised double-blinded dose-finding study.

BACKGROUND: Prior studies have shown that, when administered as an intravenous bolus to prevent uterine atony, prophylactic phenylephrine infusion increased the dose requirement of oxytocin and second-line uterotonics. For the prevention of uterine atony, oxytocin should be delivered by continuous infusion. Here, we aimed to determine the ED50 and ED90 parameters (the effective doses for 50 and 90% patients without uterine atony) of oxytocin for co-infusion with prophylactic phenylephrine during cesarean delivery. METHODS: In this prospective randomized double-blinded dose-finding study, one hundred patients were divided into four groups to receive 2.5, 5.0, 7.5, or 10 IU/h oxytocin infusion, after the umbilical cord was clamped during the study period. The uterine tone was evaluated and defined as either adequate or inadequate. Probit regression analysis was applied to calculate the ED50 and ED90 of oxytocin infusion. Uterine tone, the percentage of patients who needed additional oxytocin bolus, second-line uterotonics, side effects, estimated blood loss, and neonatal outcomes were monitored. RESULTS: The estimated ED50 and ED90 values of the oxytocin infusion doses for the prevention of uterine atony were 1.9 IU/h (95% CI -4.6-3.8) IU/h and 9.3 IU/h (95% CI 7.3-16.2) IU/h, respectively. Across groups, there was a significant linear trend between the infusion dose and the percentage of patients who required additional oxytocin (p-value = 0.002). No differences were observed in the incidence of side effects and neonatal outcomes. CONCLUSION: Under the conditions of this study, the ED90 of oxytocin infusion for the prevention of uterine atony was 9.3 IU/h, which is higher than the current recommendation. This finding is helpful for clinical practice, because of the routine use of phenylephrine in cesarean delivery. Further studies are needed to determine the appropriate initial bolus of oxytocin after neonatal delivery. TRIAL REGISTRATION: The study was registered on the Chinese Clinical Trial Register (register no. ChiCTR2200059556 ).

A randomized double-blinded study assessing the dose-response of ropivacaine with dexmedetomidine for maintenance of labor with epidural analgesia in nulliparous parturients.

Background: The combination of ropivacaine and dexmedetomidine has been used as an epidural analgesic for inducing labor. However, there is limited data regarding the administration of epidural analgesia for labor maintenance, hence, this study aimed to determine the optimum concentration through dose-response curves of ropivacaine plus dexmedetomidine, which could be used along with the Programmed Intermittent Epidural Bolus (PIEB) technique. Methods: One hundred parturients were randomized into 4 groups who were administered four different doses of ropivacaine (dexmedetomidine at 0.4 µg mL-1): 0.04%, 0.06%, 0.08%, and 0.1%. The primary outcome that was determined included the proportion of patients experiencing breakthrough pain during their 1st stage of labor. Breakthrough pain was described as a visual analog scale [VAS] score of >30 mm, requiring supplemental epidural analgesia after the administration of at least one patient-controlled bolus. The effective concentration of analgesia that was used for labor maintenance in 50% (EC50) and 90% (EC90) of patients were calculated with the help of probit regression. Secondary outcomes included epidural block characteristics, side effects, neonatal outcomes, and patient satisfaction. Results: The results indicated that the proportion of patients without breakthrough pain was 45% (10/22), 55% (12/22), 67% (16/24), and 87% (20/23) for 0.04%, 0.06%, 0.08%, and 0.10% doses of the analgesic that were administered, respectively. The EC50 value was 0.051% (95% confidence interval [CI], 0.011%-0.065%) while the EC90 value was recorded to be 0.117% (95% CI, 0.094%-0.212%). Side effects were similar among groups. Conclusion: A ropivacaine dose of 0.117% can be used as epidural analgesia for maintaining the 1st stage of labor when it was combined with dexmedetomidine (0.4 µg mL-1) and the PIEB technique. Clinical Trial Register: https://www.chictr.org.cn/index.aspx, identifier ChiCTR2200059557.

Comparison of epidural dexmedetomidine to fentanyl in reducing ropivacaine dose in Programmed Intermittent Epidural Bolus plus Patient Controlled Epidural Analgesia during labor: A randomized, double-blind, controlled study.

Background: Dexmedetomidine has been documented to reduce the dose of both intrathecal local anesthetic during cesarean delivery, and the concentration of ropivacaine needed for inducing analgesia during labor. However, few studies have compared adjuvant dexmedetomidine to fentanyl on how they impact the dose of ropivacaine required during labor. The aim of the current study was to evaluate the efficacy of epidural dexmedetomidine at doses of 0.3, 0.4, or 0.5 and 2 µg/ml of fentanyl (the traditional clinical concentration), when added to epidural 0.125% ropivacaine. Methods: This was a randomized, double-blinded study that comprised one hundred eighty-eight patients, allocated into four groups receiving either epidural fentanyl at 2 µg/ml, or dexmedetomidine at 0.3, 0.4, or 0.5 µg/ml for labor analgesia. The primary outcome was the amount of ropivacaine necessary per hour. Secondary outcomes included visual analogue pain scale (VAS), motor block (Bromage Scale), side effects, patient satisfaction, and neonatal outcomes. Results: At the completion of the study, data from 165 participants were analyzed. The mean hourly amount of epidural ropivacaine administered was 16.2 ± 3.3, 14.0 ± 3.1, 13.1 ± 3.7 and 12.1 ± 2.5 ml/h in the 2 µg/ml fentanyl group, and the 0.3, 0.4 and 0.5 µg/ml dexmedetomidine groups, respectively. There was a significant difference among groups in the mean hourly consumption of epidural ropivacaine (P < 0.0001 for 1 way ANOVA). The frequency of PCEA (patient-controlled epidural analgesia) was significantly higher in the fentanyl group than in the three dexmedetomidine groups (P < 0.001), and similar among the dexmedetomidine groups. The mean values of the VAS among all groups were similar over time, P > 0.05. The incidence of pruritus in the fentanyl group was 17.5%, whereas no patient experienced pruritus in any of the dexmedetomidine groups, P < 0.0001. Conclusion: The study demonstrated that epidural dexmedetomidine (0.3 and 0.4 µg/ml) was superior to standard dose epidural fentanyl in reducing the mean hourly amount of ropivacaine administered, and minimizing opioid-related side effects. Further large and multicenter studies would be necessary to confirm the benefits of dexmedetomidine, and potentially serve as an alternative to opioids for routine use in labor analgesia. Clinical trial registration: [http://www.chictr.org.cn/showproj.aspx?proj=62846], identifier [ChiCTR2000039067].

Prophylactic Phenylephrine Increases the Dose Requirement of Oxytocin to Treat Uterine Atony During Cesarean Delivery: A Double-Blinded, Single-Center, Randomized and Placebo-Controlled Trial.

Purpose: Studies involving mouse models and human uterine smooth muscle cells have shown that phenylephrine inhibits uterine contractions in non-pregnant mice and human in vitro cell via cyclic adenosine monophosphate (cAMP) signaling. However, there has been no limited exploration to date of the effect of phenylephrine on uterine contractions in clinical practice. This study aimed to compare the dose requirement of oxytocin with or without the infusion of prophylactic phenylephrine to prevent post spinal hypotension during cesarean delivery under combined spinal and epidural anesthesia. Methods: This was a double-blinded, single-center, randomized, control study. One hundred and sixty pregnant patients provided informed consent and were randomly allocated to the phenylephrine (phenylephrine infusion) and control (saline infusion) groups. Patients randomized to the phenylephrine group received an intravenous prophylactic phenylephrine infusion at a fixed rate of 0.5 µg/kg/min. The control group received a saline placebo at the same rate and used the same apparatus for delivery. After neonatal delivery and clamping of the umbilical cord, patients received a standard institutional oxytocin protocol. The primary outcome measure was the total dose of oxytocin administered during CD. Secondary outcomes including the proportion (%) of patients requiring a secondary uterotonic agent and estimated blood loss (EBL) in the first 24 h after surgery. Results: The median oxytocin dose administered was significantly higher in the phenylephrine group than in the control group [6.9 ± 2.5 international standardized units (IU) vs. 5.4 ± 2.4 IU, p = 0.0004]. The number of patients that required a secondary uterotonic agent was significantly higher in the phenylephrine group than in the control group (24.2% vs. 9.1%; p = 0.034). The EBL in the first 24-h postoperatively was similar between the two groups (467 ± 47 ml vs. 392 ± 38 ml; p = 0.22). Conclusions: Prophylactic infusion of phenylephrine used to prevent post-spinal hypotension during CD was associated with a higher dose of oxytocin. This has important clinical implications, as the suboptimal use of oxytocin is associated with an increased risk of postpartum hemorrhage and increased maternal morbidity and mortality. Further studies are now needed to confirm these findings.