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 8/9 th chance of receiving the same dose or a 1/9 th 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 (ED 90 ) and 95% confidence interval (95% CI) were estimated using isotonic regression methods. Results:The estimated ED 90 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.

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).

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Isoflurane can provide both neuroprotection and neurotoxicity in various culture models and in rodent developing brains. Emulsified Isoflurane (EI) is an emulsion formulation of isoflurane, while its underlying molecular mechanism of developemental nerve toxicity largely remains unclear. We hypothesized that EI induced fetal neural stem cells (FNSCs) apoptosis, endoplasmic reticulum (ER) stress and c-Jun N-terminal kinase (JNK) activation.FNSCs were isolated from the cortex of SD rats during 14 days of gestation. The cell viability, cell apoptotic rates and the expression of apoptosis-related protein Caspase3, inositol requiring enzyme 1 (IRE1), poly (adenosine diphosphate-ribose) polymerase (PARP), Bax, Bcl-2, JNK, p-JNK and XBP1 were determined. Specific inhibition was performed by siRNA-targeting of JNK in FNSCs. EI could increase the p-JNK, JNK and caspase3 protein expression, the JNK pathway was activated by EI, and EI-induced apoptosis was blocked by inhibiting JNK pathway with SP600125 or JNK-small interfering RNA (siRNA), EI enhanced the level of IRE1, PARP, Bax/Bcl-2 and XBP1, which led FNSCs to apoptosis and ER stress. Meanwhile, dilatation of the ER lumens in FNSCs treated by EI for 24 h was significant. Green fluorescent protein (GFP) positive cell ratios were significantly decreased by FNSCs transfecting with JNK gene silencing. JNK was efficiently silenced in siRNA-JNK1 group.The results provided in-vitro evidence which supports that the underlying mechanisms of EI-induced apoptosis are the induction of ER stress and sequent JNK activation. Together, these data suggest that JNK inhibiting might be applied for improving therapeutic outcomes in anesthestics-induced neurotoxicity.Highlights:1. Prolonged treatment with high-dose EI decreased the survival level of FNSCs by inducing apoptosis and inhibiting proliferation via the JNK signaling pathway.2. EI induced ER stress and sequent JNK activation.3. JNK inhibiting might be applied for improving therapeutic outcomes in anesthestics-induced neurotoxicity