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Background: Labor pain perception has been demonstrated to exhibit a circadian rhythm with lower pain scores during the day compared with the night. This study aimed to determine and compare the median effective dose (ED50) of ropivacaine in parturients having epidural labor analgesia during the day vs. during the night. Methods: The study group consisted of 60 nulliparous healthy parturients who were assigned to one of two groups according to the time they requested labor analgesia: Day Group (7:01 am to 7:00 pm) and Night Group (7:01 pm to 7:00 am). A bolus of.15% ropivacaine was administered epidurally and effective analgesia was defined as the attainment of a visual analog scale (VAS) pain score ≤ 10 mm within 30 min. The dose of ropivacaine for the first parturient in each group was 18 mg. The dose for each subsequent parturient was varied with increments or decrements of 3 mg based on the response of the previous subject. The ED50 was calculated using up-down sequential analysis. Probit regression was used to estimate the relative mean potency of ropivacaine between groups. Results: The ED50 (mean [95% CI]) of ropivacaine was lower in the Day Group (17.9 [16.5-19.4] mg) than in the Night Group (20.9 [19.2-22.7] mg) (P = 0.003). The estimate of relative potency for ropivacaine for the Night Group vs. the Day Group was 0.85 (95% CI:0.56-0.98). Conclusions: Under the conditions of this study, the dose requirement for epidural ropivacaine for labor analgesia was ~ 15% greater during the night than during the day. Clinical Trials Registration: Chinese Clinical Trial Registry (No.: ChiCTR1900025269. http://www.chictr.org.cn/showprojen.aspx?proj=36993).

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BACKGROUND: The intrathecal hyperbaric bupivacaine dosage for cesarean section is difficult to predetermine. This study aimed to develop a decision-support model using a machine-learning algorithm for assessing intrathecal hyperbaric bupivacaine dose based on physical variables during cesarean section. METHODS: Term parturients presenting for elective cesarean section under spinal anaesthesia were enrolled. Spinal anesthesia was performed at the L3/4 interspace with 0.5% hyperbaric bupivacaine at dosages determined by the anesthesiologist. A spinal spread level between T4-T6 was considered the appropriate block level. We used a machine-learning algorithm to identify relevant parameters. The dataset was split into derivation (80%) and validation (20%) cohorts. A decision-support model was developed for obtaining the regression equation between optimized intrathecal 0.5% hyperbaric bupivacaine volume and physical variables. RESULTS: A total of 684 parturients were included, of whom 516 (75.44%) and 168 (24.56%) had block levels between T4 and T6, and less than T6 or higher than T4, respectively. The appropriate block level rate was 75.44%, with the mean bupivacaine volume [1.965, 95%CI (1.945,1.984)]ml. In lasso regression, based on the principle of predicting a reasonable dose of intrathecal bupivacaine with fewer physical variables, the model is "Y=0.5922+ 0.055117* X1-0.017599*X2" (Y: bupivacaine volume; X1: vertebral column length; X2: abdominal girth), with λ 0.055, MSE 0.0087, and R2 0.807. CONCLUSIONS: After applying a machine-learning algorithm, we developed a decision model with R2 0.8070 and MSE due to error 0.0087 using abdominal girth and vertebral column length for predicting the optimized intrathecal 0.5% hyperbaric bupivacaine dosage during term cesarean sections.

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PURPOSE: Carboprost may induce adverse reactions when used to treat postpartum hemorrhage. We aimed to explore the effects of intravenous infusion of low-dose remifentanil to prevent such reactions. METHODS: We enrolled parturient patients scheduled for elective cesarean section. Anesthesiologist administered combined spinal epidurals at the L3/4 interspace, with 0.5% hyperbaric bupivacaine subarachnoid space injections (1.5-2.5 ml). We randomly divided parturient patients, administered carboprost during surgery, into the remifentanil group (group R) and the control group (group C). Patients in group R received an intravenous target-controlled infusion of remifentanil (target effect-site concentration, 1.5 ng/ml) simultaneously with a carboprost tromethamine injection (250 µg). Patients in group C received a normal saline infusion with carboprost. We recorded and analyzed the incidence of carboprost-related adverse reactions (vomiting, nausea, chest congestion, flushing, hypertension, tachycardia, cough, and shivering), and assessed patient comfort using a numerical rating scale ([NRS], on which 0 was very uncomfortable and 10 was very comfortable). RESULTS: After applying inclusion and exclusion criteria, we conducted statistical analysis of the data from 70 women. The incidence of vomiting was significantly lower in group R than in group C (14.3 vs. 51.4%, p < 0.01); and the incidence of nausea, chest congestion, facial flushing, and hypertension were significantly lower in group R than in group C (all p < 0.01). Furthermore, the patients' comfort scores were significantly higher in group R than in group C (8.0 ± 1.8 vs. 3.6 ± 2.1, p < 0.01). CONCLUSION: Our results demonstrate that an intravenous low-dose remifentanil infusion can effectively prevent carboprost-related adverse reactions during cesarean delivery under combined spinal and epidural anesthesia. CLINICAL TRIAL REGISTRATION: We pre-registered this study at http://www.chictr.org.cn/showproj.aspx?proj=27707 (ChiCTR1800016292).

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BACKGROUND: During caesarean delivery under spinal anaesthesia hypotension may be managed by norepinephrine in preference to phenylephrine due a perception of less bradycardia and fewer reductions in cardiac output. OBJECTIVE: As the optimum prophylactic dose of norepinephrine is unclear, we aimed to investigate its dose-response for preventing postspinal hypotension in caesarean delivery. DESIGN: A randomised, double-blinded, dose-finding study. SETTING: Jiaxing University affiliated Women and Children Hospital, Jiaxing, China. PATIENTS: Ninety-nine patients undergoing elective caesarean delivery from 1 February to 5 August: excluding patients with ASA III or above, preeclampsia or hypertension, pre-existing or gestational diabetes, BMI more than 35 kg m, height less than 150 cm or with more than 175 cm, or with contraindications to local anaesthesia. INTERVENTIONS: Patients received 0, 0.04, 0.05, 0.06 or 0.07 µg kg min preventive norepinephrine infusions immediately after intrathecal injection of 10 mg bupivacaine with 5 µg sufentanil. MAIN OUTCOME MEASURES: The norepinephrine (Median effective dose) or (95% effective dose) ED50 and ED95, which were estimated using Probit analysis to compare haemodynamic changes associated with the different doses. RESULTS: The incidence of hypotension was 70, 47.4, 40, 20 and 15% in the 0, 0.04, 0.05, 0.06 and 0.07 µg kg min groups, respectively. The ED50, ED80 and ED95 values were 0.029 (95% CI 0.008 to 0.042 µg kg min), 0.068 (95% CI 0.055 to 0.099 µg kg min) and 0.105 µg kg min (95% CI 0.082 to 0.172 µg kg min), respectively. Apgar scores or umbilical arterial pH were similar among groups. CONCLUSION: The ED50, ED80 and ED95 were 0.029, 0.068 and 0.105 µg kg min respectively. A 0.07 µg kg min norepinephrine infusion may be optimum for preventing postspinal hypotension after intrathecal injection of 10 mg bupivacaine combined with 5 µg sufentanil. TRIAL REGISTRATION: Chinese Clinical Trial Registry (identifier: ChiCTR-TRC-1800014614).

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BACKGROUND: Ondansetron has been shown to reduce the incidence of hypotension and vasopressor requirement during spinal anesthesia for obstetric and nonobstetric surgery. However, the magnitude of this effect has not been fully quantified. In this parallel-group, randomized, double-blinded study, we determined the effective dose in 50% of subjects (ED50) of a prophylactic phenylephrine infusion for preventing hypotension in patients who received a single dose of intravenous ondansetron 4 mg or saline control before combined spinal-epidural anesthesia for elective cesarean delivery. ED50 values obtained were compared to estimate the effect of ondansetron versus placebo on vasopressor requirement. METHODS: Sixty parturients were randomly assigned to receive ondansetron (group O) or saline control (group C) 10 minutes before positioning for induction of spinal anesthesia. A prophylactic phenylephrine infusion was used to prevent hypotension. The first patient in each group received a phenylephrine infusion at the rate of 0.5 µg/kg/min. The infusion rate for each subsequent patient was varied with increments or decrements of 0.05 µg/kg/min based on the response of the previous patient, and the effective dose of the phenylephrine infusion for preventing hypotension in 50% of patients (ED50) was calculated for each group and compared using up-down sequential analysis. Probit regression was applied as a backup and sensitivity analysis was used to compare ED50 values for phenylephrine between groups by comparing calculated relative mean potency. RESULTS: The ED50 (mean [95% confidence interval (CI)]) of the rate of phenylephrine infusion was lower in group O (0.24 µg/kg/min [0.10-0.38 µg/kg/min]) compared with group C (0.32 µg/kg/min [0.14-0.47 µg/kg/min]) (P < .001). The total consumption of phenylephrine (mean ± standard deviation [SD]) until delivery was lower in group O (316.5 ± 25.9 µg) than in group C (387.7 ± 14.7 µg, P = .02). The estimate of relative median potency for phenylephrine for group O versus group C was 0.74 (95% CI, 0.37-0.95). CONCLUSIONS: Under the conditions of this study, intravenous ondansetron 4 mg reduced the ED50 of a prophylactic phenylephrine infusion by approximately 26% in patients undergoing cesarean delivery under combined spinal-epidural anesthesia.

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OBJECTIVES: The main objectives of this study were to assess the effects of cathechol-O-methyl-transferase (COMT) rs4680 and µ-opioid receptor rs1799971 polymorphisms alone or genotype combinations on chronic postsurgical pain (CPSP), acute pain, and analgesic consumption after elective cesarean delivery in a Chinese cohort. MATERIALS AND METHODS: Two hundred sixty-six patients undergoing elective cesarean delivery with a Pfannenstiel incision under spinal anesthesia were enrolled in this prospective, observational study. All patients were screened for rs4680 and rs1799971 using a peripheral venous blood sample of DNA. Postoperative pain relief was provided by IV patient-controlled analgesia with sufentanyl and tramadol for 48 hours postoperatively. Postoperative pain scores and analgesic consumption were assessed, and CPSP was evaluated 3 months after surgery in all patients. RESULTS: Twenty-nine patients (29/266; 10.9%) developed CPSP at 3 months after surgery. The risk factors for CPSP included previous cesarean delivery and higher analgesic consumptions at 24 hours and 48 hours postoperatively (P=0.032, 0.015, and 0.008, reapectively). No associations were found between CPSP and a single rs4680 and rs1799971 polymorphism, or their combinations (P>0.05). In contrast, patients with rs1799971 GG required higher patient-controlled analgesics at 24 hours and 48 hours postoperatively compared with those with other genotypes (GG>AG>AA). However, no significant effects of interactions between the 2 single nucleotide polymorphisms on analgesic consumption were observed. DISCUSSION: Our results indicate that cathechol-O-methyl-transferase rs4860 and µ-opioid receptor rs1799971 may not contribute to CPSP development after cesarean delivery. The genotype of rs1799971 affects postcesarean analgesic requirement, while the rs4680 do not. Additional larger studies are needed to confirm these findings.

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Currently, there is no consensus on how to determine the optimal dose of intrathecal bupivacaine for an individual undergoing an elective cesarean section. In this study, we developed a regression equation between intrathecal 0.5% hyperbaric bupivacaine volume and abdominal girth and vertebral column length, to determine a suitable block level (T5) for elective cesarean section patients.In phase I, we analyzed 374 parturients undergoing an elective cesarean section that received a suitable dose of intrathecal 0.5% hyperbaric bupivacaine after a combined spinal-epidural (CSE) was performed at the L3/4 interspace. Parturients with T5 blockade to pinprick were selected for establishing the regression equation between 0.5% hyperbaric bupivacaine volume and vertebral column length and abdominal girth. Six parturient and neonatal variables, intrathecal 0.5% hyperbaric bupivacaine volume, and spinal anesthesia spread were recorded. Bivariate line correlation analyses, multiple line regression analyses, and 2-tailed t tests or chi-square test were performed, as appropriate. In phase II, another 200 parturients with CSE for elective cesarean section were enrolled to verify the accuracy of the regression equation.In phase I, a total of 143 parturients were selected to establish the following regression equation: YT5 = 0.074X1 - 0.022X2 - 0.017 (YT5 = 0.5% hyperbaric bupivacaine volume for T5 block level; X1 = vertebral column length; and X2 = abdominal girth). In phase II, a total of 189 participants were enrolled in the study to verify the accuracy of the regression equation, and 155 parturients with T5 blockade were deemed eligible, which accounted for 82.01% of all participants.This study evaluated parturients with T5 blockade to pinprick after a CSE for elective cesarean section to establish a regression equation between parturient vertebral column length and abdominal girth and 0.5% hyperbaric intrathecal bupivacaine volume. This equation can accurately predict the suitable intrathecal hyperbaric bupivacaine dose for elective cesarean section.

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BACKGROUND: We aimed to test whether abdominal girth and vertebral column length were predictors of spinal hyperbaric bupivacaine spread in term parturients. METHODS: A total of 128 parturients having elective caesarean section under spinal anaesthesia were enrolled. Combined spinal-epidural anaesthesia was performed at the L3/4 interspace, confirmed by ultrasonography. Two mL of 0.5% hyperbaric bupivacaine was injected intrathecally and spinal spread assessed at three-minute intervals. If loss of discrimination of pinprick sensation at the T6 level was not obtained within 15min after injection, 5mL of 2% lidocaine was administered epidurally. Correlation and multiple linear regression were used to analyse the relationship between patient variables, including age, height, weight, abdominal girth, vertebral column length and neonatal biparietal diameter, and the spread of spinal anaesthesia. RESULTS: Two parturients were excluded. Significant univariate correlation with spinal spread existed for height, weight, abdominal girth and vertebral column length (r=-0.446, 0.201, 0.372, P<0.711, respectively, all P<0.05). Multiple linear regression analysis showed that parturients' abdominal girth and vertebral column length were the key determinants of spinal spread (both P<0.0001). The adjusted R2 was 0.742 for the regression equation between abdominal girth, vertebral column length and height of block. CONCLUSION: Parturient abdominal girth and vertebral column length have significant predictive value in determining the cephalad spread of spinal anaesthesia with hyperbaric bupivacaine in term parturients.

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BACKGROUND: Studies have shown that abdominal girth and vertebral column length have high predictive value for spinal spread after administering a dose of plain bupivacaine. we designed a study to identify the specific correlations between abdominal girth, vertebral column length and a 0.5% dosage of plain bupivacaine, which should provide a minimum upper block level (T12) and a suitable upper block level (T10) for lower limb surgeries. METHODS: A suitable dose of 0.5% plain bupivacaine was administered intrathecally between the L3 and L4 vertebrae for lower limb surgeries. If the upper cephalad spread of the patient by loss of pinprick discrimination was T12 or T10, the patient was enrolled in this study. Five patient variables and intrathecal plain bupivacaine dose were recorded. Linear regression and multiple regression analyses were performed. RESULTS: Totals of 111 patients and 121 patients who lost pinprick discrimination at T12 and T10, respectively, were analyzed in this study. Linear regression analysis showed that only abdominal girth and plain bupivacaine dose were strongly correlated (r =-0.827 for T12, r = -0.806 for T10; both p < 0.0001). Multiple linear regression analysis showed that both abdominal girth and vertebral column length were the key determinants of plain bupivacaine dose (both p < 0.0001). R(2) was 0.874 and 0.860 for the loss of pinprick discrimination at T12 and T10, respectively. CONCLUSIONS: Our data indicated that vertebral column length and abdominal girth were strongly correlated with the dosage of intrathecal plain bupivacaine for the loss of pinprick discrimination at T12 and T10. The two regression equations were YT12 = 3.547 + 0.045X1-0.044X2 and YT10 = 3.848 + 0.047X1- 0.046X2 (Y, 0.5% plain bupivacaine volume; X1, vertebral column length;and X 2, abdominal girth), which can accurately predict the minimum and suitable intrathecal bupivacaine dose for lower limb surgery to a great extent, separately.

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