Purpose The aim of this study was to determine the intravenous dose of carbetocin required to produce effective uterine contraction in 95% of women (ED 95 ) undergoing elective Cesarean delivery under spinal anesthesia. Methods One hundred and twenty term pregnant women at low risk for postpartum hemorrhage (PPH) undergoing elective Cesarean delivery under spinal anesthesia were randomly allocated to receive carbetocin in doses of 20, 40, 60, 80, or 100 lg iv upon delivery of the fetus. The obstetrician evaluated the efficacy of uterine tone as satisfactory or unsatisfactory, and in case of unsatisfactory tone, additional uterotonics were administered as per routine institutional practice. The primary outcome measure was satisfactory uterine tone at two minutes after carbetocin administration, and the secondary outcomes were the estimated blood loss, need for additional uterotonic agents within 24 hr, and side effects. Results Overall satisfactory uterine tone at two minutes was observed in 94.2% (113/120) of the women, and there was no difference across the different study groups. It was not possible to calculate the ED 95 of carbetocin due to the even distribution of women with unsatisfactory uterine tone at two minutes across all dose groups (P = 0.60). Additional uterotonics within 24 hr were required in 13% (16/120) of the women. Side effects were similar across all dose groups, with an overall 42.5% incidence of hypotension following the administration of carbetocin. Conclusions In women at low risk for PPH undergoing elective Cesarean delivery under spinal anesthesia, carbetocin is similarly effective in doses of 20-100 lg. There is a high incidence of hypotension associated with carbetocin in these doses. Further dose-finding studies are warranted, including doses lower than 20 lg. This trial was registered at www.clinicaltrials.gov (NCT01428817). RésuméObjectif L'objectif de cette étude était de déterminer la dose intraveineuse de carbétocine nécessaire à produire une contraction utérine efficace chez 95 % des femmes (DE 95

General anaesthesia for obstetric surgery has distinct characteristics that may contribute towards a higher risk of accidental awareness during general anaesthesia. The primary aim of this study was to investigate the incidence, experience and psychological implications of unintended conscious awareness during general anaesthesia in obstetric patients. From May 2017 to August 2018, 3115 consenting patients receiving general anaesthesia for obstetric surgery in 72 hospitals in England were recruited to the study. Patients received three repetitions of standardised questioning over 30 days, with responses indicating memories during general anaesthesia that were verified using interviews and record interrogation. A total of 12 patients had certain/ probable or possible awareness, an incidence of 1 in 256 (95%CI 149-500) for all obstetric surgery. The incidence was 1 in 212 (95%CI 122-417) for caesarean section surgery. Distressing experiences were reported by seven (58.3%) patients, paralysis by five (41.7%) and paralysis with pain by two (16.7%). Accidental awareness occurred during induction and emergence in nine (75%) of the patients who reported awareness. Factors associated with accidental awareness during general anaesthesia were: high BMI (25-30 kg.m -2 ); low BMI (<18.5 kg.m -2 ); out-of-hours surgery; and use of ketamine or thiopental for induction. Standardised psychological impact scores at 30 days were significantly higher in awareness patients (median (IQR [range]) 15 (2.7-52.0 [2-56]) than in patients without awareness 3 (1-9 [0-64]), p = 0.010. Four patients had a provisional diagnosis of post-traumatic stress disorder. We conclude that direct postoperative questioning reveals high rates of accidental awareness during general anaesthesia for obstetric surgery, which has implications for anaesthetic practice, consent and follow-up.

Topics: Obstetric Hemorrhage, Pharmacology C arbetocin is a synthetic analogue of oxytocin that binds to the oxytocin receptors in the myometrium and causes an increase in the concentration of calcium. This promotes uterine contractility with an onset of action in <2 minutes, similar to oxytocin. The chief difference between oxytocin and carbetocin is the prolonged uterotonic activity of carbetocin, which is related to its increased plasma half-life (40 min, which is 10 times longer than oxytocin's plasma half-life). This study attempted to determine the minimum effective intravenous dose of carbetocin for adequate production of uterine contractions in 95% of women [effective dose (ED) 95 ] at low risk for postpartum hemorrhage undergoing elective cesarean section under spinal anesthesia. Determination of the ED 95 was based on assessments of satisfactory uterine tone 2 minutes after administration. Secondly, the authors aimed to identify differences in the need for additional uterotonics, estimated blood loss, and side effects across carbetocin dosage groups. Finally, the authors aimed to identify clinical factors associated with inadequate uterine tone at 2 minutes.A double-blind, randomized, controlled trial was conducted between November 2010 and April 2011. Patients were randomized by a computer-generated list to receive a single intravenous dose of 80, 90, 100, 110, or 120 mg of carbetocin (16 patients/group; n = 80). Baseline blood pressure and heart rate were represented as the mean of 3 readings taken 2 minutes apart. A subarachnoid puncture was performed in the sitting position at the L2-L3 or L3-L4 interspace, and adequate spinal anesthesia was achieved with 12-13 mg of 0.75% hyperbaric bupivacaine, fentanyl 10 mg, and morphine 100 mg injected over 60 seconds. Immediately following delivery, the anesthesiologist administered the carbetocin study solution. The obstetrician then assessed uterine firmness and graded tone as satisfactory or unsatisfactory every minute for 5 minutes following administration. Satisfactory tone was determined to have been achieved when no additional uterotonic agents were needed.Eighty-seven percent (70/80) of women experienced satisfactory uterine contraction at 2 minutes after carbetocin administration with no significant difference found across the groups. This lack of difference made it impossible to create a dose-response curve to calculate the ED 95 of carbetocin for elective cesarean section. The analysis of the need for additional uterotonic medication within 24 hours was also consistent across doses; 9 women overall required additional therapy (11%), all within 4 hours. These agents were required in 60% (6/10) of the women who presented with unsatisfactory uterine tone at 2 minutes and 2% (3/70) of those with satisfactory tone. The mean estimated blood loss was similar across groups with an overall mean of 648.6 mL. No significant differences in side effects were found across the groups; hypotension occurred frequently (55% of all patients) with flushing (36% of all ...

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