The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
D T Monks - One of the best experts on this subject based on the ideXlab platform.
-
Carbetocin compared with oxytocin in non elective cesarean delivery a systematic review meta analysis and trial sequential analysis of randomized controlled trials
Canadian Journal of Anaesthesia-journal Canadien D Anesthesie, 2020Co-Authors: D N Onwochei, Preet Mohinder Singh, Adetokunbo Owolabi, D T MonksAbstract:Carbetocin has been shown to reduce the requirement for additional uterotonics in women exclusively undergoing elective Cesarean delivery (CD). The aim of this review was to determine whether this effect could also be demonstrated in the setting of non-elective CD. Medline, Embase, CINAHL, Web of Science and Cochrane databases were searched for randomized-controlled trials (RCTs) in any language comparing Carbetocin to oxytocin. Studies with data on women undergoing non-elective CD, where Carbetocin was compared with oxytocin, were included. The primary outcome was the need for additional uterotonics. Secondary outcomes included incidence of blood transfusion, estimated blood loss (mL), incidence of postpartum hemorrhage (PPH; > 1000 mL) and mean hemoglobin drop (g·dL−1 Five RCTs were included, with a total of 1,214 patients. The need for additional uterotonics was reduced with Carbetocin compared with oxytocin (odds ratio, 0.30; 95% CI, 0.11 to 0.86; I2, 90.60%). Trial sequential analysis (TSA) confirmed that the information size needed to show a significant reduction in the need for additional uterotonics had been exceeded. No significant differences were shown with respect to any of the secondary outcomes, but there was significant heterogeneity between the studies. Carbetocin reduces the need for additional uterotonics in non-elective CD compared with oxytocin. TSA confirmed that this analysis was appropriately powered to detect the pooled estimated effect. Further trials utilizing consistent core outcomes are needed to determine an effect on PPH. PROSPERO CRD42019147256, registered 13 September 2019.
-
Carbetocin reduces the need for additional uterotonics in elective caesarean delivery a systematic review meta analysis and trial sequential analysis of randomised controlled trials
International Journal of Obstetric Anesthesia, 2019Co-Authors: D N Onwochei, J Van Ross, Preet Mohinder Singh, A Salter, D T MonksAbstract:Abstract Background Carbetocin has been found to be superior to oxytocin in terms of need for additional uterotonics and prevention of postpartum haemorrhage at caesarean delivery. However, this is based on combined data from labouring and non-labouring parturients and it remains unclear how effective Carbetocin is in the purely elective setting. The aim of this review was to compare Carbetocin to oxytocin in elective caesarean delivery. Methods Medline, Embase, CINAHL, Web of Science, and the Cochrane databases were searched for randomised controlled trials in any language. The primary outcome was need for additional uterotonics. Secondary outcomes were mean blood loss, need for blood transfusion and incidence of postpartum haemorrhage >1000 mL. Results Nine studies with a total of 1962 patients were included. Trial sequential analysis confirmed that the information size (n=1692) had surpassed that required (n=1166) in order to demonstrate a statistically significant reduction in the use of additional uterotonics. Need for additional uterotonics was reduced by 53% with Carbetocin compared to oxytocin (OR 0.47, 95% CI 0.34 to 0.64; P Conclusions Carbetocin is associated with a reduced need for additional uterotonics when compared with oxytocin at elective caesarean delivery. Standardisation of bleeding-related outcomes in studies is necessary to facilitate synthesis of data in future analyses.
Dan Farine - One of the best experts on this subject based on the ideXlab platform.
-
Carbetocin at elective caesarean section a sequential allocation trial to determine the minimum effective dose in obese women
Anaesthesia, 2020Co-Authors: T Drew, Mrinalini Balki, Dan Farine, Kristi Downey, J C A CarvalhoAbstract:Postpartum haemorrhage is a leading cause of maternal death during childbirth. There is an increasing incidence of atonic postpartum haemorrhage in developed countries, and maternal obesity has been proposed as a contributing factor. The dose-response relationship of Carbetocin in obese women has not yet been determined. We conducted a double-blind, dose-finding study of Carbetocin using a biased coin up-and-down design in women with a body mass index ≥ 40 kg.m-2 undergoing elective caesarean section. The determinant for a successful response was satisfactory uterine tone, with no intra-operative need for additional uterotonic drugs. Secondary outcomes included the use of additional uterotonic drugs postoperatively, estimated blood loss and adverse effects of Carbetocin administration. Thirty women were recruited to the study. The median (IQR [range]) body mass index was 44.93 (41.5-55.2 [40-66.5]) kg.m-2 . The ED90 of Carbetocin was estimated as 62.9 (95%CI 57.0-68.7) μg using the truncated Dixon and Mood method, and 68 (95%CI 52-77) μg using the isotonic regression method. The estimated blood loss was 880 (621-1178 [75-2442]) ml. The overall rates of hypotension and hypertension after delivery were 40% and 6.7%, respectively, while nausea occurred in 26.7% of women. The ED90 for Carbetocin in obese women at elective caesarean section is lower than the dose of 100 μg currently recommended by the Society of Obstetricians and Gynaecologists of Canada, but is approximately four times higher than the previously demonstrated ED90 of 14.8 μg in women with body mass index < 40 kg.m-2 .
-
uterotonics in elective caesarean delivery a randomised non inferiority study comparing Carbetocin 20 μg and 100 μg
Anaesthesia, 2019Co-Authors: S Tabl, Mrinalini Balki, Dan Farine, Kristi Downey, George Tomlinson, Gareth Seaward, J C A CarvalhoAbstract:Postpartum haemorrhage is the leading cause of maternal mortality worldwide and prophylactic uterotonic drug administration after the delivery of the infant is advised. Carbetocin is recommended as an uterotonic, but the minimum effective dose has not been verified. We compared the efficacy of two doses of intravenous Carbetocin (20 μg and 100 μg) in women undergoing elective caesarean delivery. This was a randomised, double-blind, non-inferiority study in women at low risk of postpartum haemorrhage. Carbetocin was administered on delivery of the anterior shoulder of the neonate. Uterine tone was assessed by the obstetrician 2 min and 5 min after Carbetocin administration according to an 11-point numerical rating scale (0 = atonic uterus and 10 = firm uterus). The primary outcome was uterine tone 2 min after Carbetocin administration. The pre-specified non-inferiority margin was 1 point on the 11-point scale. Secondary outcomes included: uterine tone at 5 min; use of additional uterotonics within 24 h; blood loss; and adverse effects. Data were available for 53 women in the Carbetocin-20 group and for 55 women in the Carbetocin-100 group. The mean (SD) uterine tone at 2 min was 7.5 (1.9) in the Carbetocin-20 group and 8.0 (1.5) in the Carbetocin-100 group. The lower limit of the one-sided 95%CI for the mean difference was outside the non-inferiority margin (at -1.1; p = 0.11) meaning non-inferiority of Carbetocin 20 μg compared with Carbetocin 100 μg could not be confirmed. However, the secondary outcome measures of uterine tone at 5 min, blood loss and use of additional uterotonics were similar in both groups.
-
Carbetocin at cesarean delivery for labour arrest a sequential allocation trial to determine the effective dose
Canadian Journal of Anaesthesia-journal Canadien D Anesthesie, 2015Co-Authors: Nhathien Nguyenlu, Jose C A Carvalho, Dan Farine, Gareth Seaward, Mrinalini BalkiAbstract:The aim of this study was to estimate the effective dose 90% (ED90) of Carbetocin to provide adequate uterine tone at Cesarean delivery (CD) for labour arrest. We conducted a double-blind dose-finding study of Carbetocin using a biased-coin up-and-down design in women undergoing CD for labour arrest under epidural anesthesia. Forty healthy term pregnant women who had received at least three hours of oxytocin infusion during labour were recruited for the study. Carbetocin was administered intravenously upon delivery of the anterior shoulder of the fetus. The first patient received 20 µg, and the dose for the subsequent patient was determined according to the response of the previous patient as per the biased-coin allocation scheme using increments or decrements of 20 µg (maximum 140 µg). Uterine tone was assessed by the obstetrician and rated as satisfactory or unsatisfactory throughout the intraoperative period. The primary outcome was satisfactory uterine tone with no need for additional uterotonic drugs intraoperatively. Secondary outcomes included use of additional uterotonic drugs postoperatively in the first 24 hr, estimated blood loss, and adverse effects. The ED90 of Carbetocin to produce adequate uterine tone was estimated at 121 µg (95% confidence interval [CI]: 111 to 130; 99% CI: 108 to 133) using the truncated Dixon and Mood (DM) method. The isotonic estimator of ED90 was 140 µg; however, the observed response rate across all doses was < 90%. Also, the 95% CI of the DM estimator is likely to have lower than expected coverage, while the 99% CI may have about 90% coverage. Therefore, these results should be interpreted with caution. The overall median (range) estimated blood loss was 1,014 (104-2,436) mL. The overall incidence of hypotension and tachycardia were 45% and 57.5%, respectively. At a dose of 140 µg, the incidence of tachycardia and intraoperative arrhythmias was 76% and 14%, respectively. The ED90 of Carbetocin at CD for labour arrest, as determined in our study, should be interpreted with caution since it may be underestimated. This dose is higher than the currently recommended dose of 100 µg at elective CD and should not be used routinely given the uncertainty regarding its efficacy and the high incidence of arrhythmias at higher doses. This trial was registered at ClinicalTrials.gov, number: NCT01725243.
-
postpartum uterine response to oxytocin and Carbetocin
Journal of Reproductive Medicine, 2014Co-Authors: Hagai Amsalem, Clive J Aldrich, Marilynne Oskamp, Rory Windrim, Dan FarineAbstract:Objective To obtain quantitative data on uterine contractility postpartum and compare the response of intramuscular oxytocin to Carbetocin. Study design A prospective study using an intrauterine pressure transducer (IUPT) to measure frequency, amplitude, and duration of contractions following the administration of either oxytocin (10 U) or Carbetocin (30 microg). Results The IUPT was tolerated by all subjects and generated useful data 90% of the time in most subjects (12/16). Both drugs generated hypertonic uterine activity with contractions of similar duration. However, Carbetocin resulted in contractions of sustained higher amplitude and frequency and therefore higher uterine performance as expressed by Montevideo units. This uterotonic effect of Carbetocin lasted for 3 hours. Conclusion IUPT monitoring generated quantitative data on postpartum uterine activity. When compared to high-dose oxytocin, a low dose of Carbetocin has a more prolonged effect on uterine activity both in terms of a higher amplitude and frequency of contractions.
-
Carbetocin at elective cesarean delivery a sequential allocation trial to determine the minimum effective dose
Canadian Journal of Anaesthesia-journal Canadien D Anesthesie, 2014Co-Authors: Mubeen Khan, Mrinalini Balki, Dan Farine, Gareth Seaward, Iram Ahmed, Jose C A CarvalhoAbstract:Purpose The purpose of this study was to determine the intravenous dose of Carbetocin required to produce effective uterine contraction in 90% of females (ED90) undergoing elective Cesarean delivery (CD) under spinal anesthesia.
Patricia Griffin - One of the best experts on this subject based on the ideXlab platform.
-
Double-blind comparison of Carbetocin versus oxytocin in prevention of uterine atony after cesarean section.
American Journal of Obstetrics and Gynecology, 1999Co-Authors: Jerome Dansereau, Arvind K Joshi, Michael Helewa, Terence A Doran, Ian Lange, Edwin R Luther, Dan Farine, Miklos L Schulz, Gwendolyn L A Horbay, Patricia GriffinAbstract:Abstract Objective: The goal of this study was to compare Carbetocin, a long-acting oxytocin analog, with oxytocin in the prevention of uterine atony after cesarean section. Study Design: We enrolled 694 patients undergoing elective cesarean section in a Canadian multicenter, double-blind, randomized clinical trial. We compared the effect of a single 100 μg dose of Carbetocin with that of a standard 8-hour infusion of oxytocin. The primary outcome was the proportion of patients requiring additional oxytocic intervention for uterine atony. A variable sample size, sequential design was used. Results: The overall oxytocic intervention rate was 7.4%. The odds of treatment failure requiring oxytocic intervention was 2.03 (95% confidence interval 1.1 to 2.8) times higher in the oxytocin group compared with the Carbetocin group, respectively, 32 of 318 (10.1%) versus 15 of 317 (4.7%), P Conclusions: Carbetocin, a new drug for the prevention of uterine atony, appears to be more effective than a continuous infusion of oxytocin and has a similar safety profile. (Am J Obstet Gynecol 1999;180:670-6.)
-
double blind randomized comparison of the effect of Carbetocin and oxytocin on intraoperative blood loss and uterine tone of patients undergoing cesarean section
Journal of Perinatology, 1998Co-Authors: M Boucher, Gwendolyn L A Horbay, Patricia Griffin, Y Deschamps, C Desjardins, M Schulz, W WassenaarAbstract:OBJECTIVES A double-blind randomized study involving pregnant women undergoing cesarean section was conducted to compare the effectiveness of a single 100 micrograms intravenous injection of the long-acting oxytocin analog, Carbetocin, with that of a standard infusion of oxytocin with respect to intraoperative blood loss. The two treatments also were compared for safety and ability to maintain adequate uterine tone. STUDY DESIGN The study drug was administered to 57 women during elective cesarean section after placental delivery; blood was collected until abdominal closure. Intraoperative blood loss was calculated with a sensitive colorimetric method. Position, tone of the fundus, and vital signs were assessed up to 24 hours after the operation. The need for additional uterotonic agents was recorded. RESULTS A single 100 micrograms intravenous injection of Carbetocin was as effective as a continuous 16 hour infusion of oxytocin in controlling intraoperative blood loss after placental delivery. Mean blood loss after Carbetocin administration was 29 ml less than after oxytocin administration (p = 0.3). Subset analysis deleting two patients who received oxytocic intervention in the operating room and one extreme outlier revealed a mean blood loss of 41 ml less in the Carbetocin group (p = 0.14) with lower variances (p = 0.02). The percentage of patients with blood loss of 200 ml or less was greater with Carbetocin (79% vs 53%; p = 0.041). Carbetocin enhanced early postpartum uterine involution. The fundus was below the umbilicus in more patients who received Carbetocin at 0, 2, 3, and 24 hours on the ward (p < 0.05). There were no significant differences in uterine tone or type or amount of lochia. Additional oxytocin was used to treat three patients for postpartum hemorrhage or persistent uterine atony. All interventions were in the oxytocin group. Vital signs and hematologic values were comparable in each group, confirming similar safety profiles. CONCLUSIONS A single 100 micrograms intravenous injection of Carbetocin is as effective and more reliable than a standard continuous infusion of oxytocin in maintaining adequate uterine tone and preventing excessive intraoperative blood loss during cesarean section after delivery of the placenta. Patients receiving Carbetocin required less intervention. Carbetocin was well tolerated.
-
double blind comparison of Carbetocin versus oxytocin in preventing uterine atony post cesarean section
European Journal of Obstetrics & Gynecology and Reproductive Biology, 1996Co-Authors: Jerome Dansereau, Arvind K Joshi, Michael Helewa, Terence A Doran, Ian Lange, Edwin R Luther, Dan Farine, Miklos L Schulz, Gwendolyn L A Horbay, Patricia GriffinAbstract:Objectives : The aim of this study was to compare Carbetocin, a long-acting oxytocin analog, to oxytocin in the prevention of post-cesarean uterine atony. Material and methods : We enrolled 694 patients going for elective repeat cesarean in a Canadian multicentre double-blind randomized clinical trial. We compared the effect of a single dose of Carbetocin (100 mcg.IV) to a standard 8 h IV infusion of oxytocin. The primary outcome was the proportion of patients requiring additional uterotonic drugs. The design used a sequential analysis using the double triangular test. Results : The overall uterotonic intervention rate was 7.4%. The odds of treatment failure was 2.0 times higher in the oxytocin group compared with the Carbetocin group (respectively 10.1% vs. 4.7%, P<0.05). Interim safety analysis shows Carbetocin to be well tolerated with a safety profile similar to oxytocin. Conclusion : Carbetocin, a new drug to prevent uterine atony, appears to be more effective than a continuous infusion of oxytocin in preventing uterine atony post-Cesarean.
D N Onwochei - One of the best experts on this subject based on the ideXlab platform.
-
Carbetocin compared with oxytocin in non elective cesarean delivery a systematic review meta analysis and trial sequential analysis of randomized controlled trials
Canadian Journal of Anaesthesia-journal Canadien D Anesthesie, 2020Co-Authors: D N Onwochei, Preet Mohinder Singh, Adetokunbo Owolabi, D T MonksAbstract:Carbetocin has been shown to reduce the requirement for additional uterotonics in women exclusively undergoing elective Cesarean delivery (CD). The aim of this review was to determine whether this effect could also be demonstrated in the setting of non-elective CD. Medline, Embase, CINAHL, Web of Science and Cochrane databases were searched for randomized-controlled trials (RCTs) in any language comparing Carbetocin to oxytocin. Studies with data on women undergoing non-elective CD, where Carbetocin was compared with oxytocin, were included. The primary outcome was the need for additional uterotonics. Secondary outcomes included incidence of blood transfusion, estimated blood loss (mL), incidence of postpartum hemorrhage (PPH; > 1000 mL) and mean hemoglobin drop (g·dL−1 Five RCTs were included, with a total of 1,214 patients. The need for additional uterotonics was reduced with Carbetocin compared with oxytocin (odds ratio, 0.30; 95% CI, 0.11 to 0.86; I2, 90.60%). Trial sequential analysis (TSA) confirmed that the information size needed to show a significant reduction in the need for additional uterotonics had been exceeded. No significant differences were shown with respect to any of the secondary outcomes, but there was significant heterogeneity between the studies. Carbetocin reduces the need for additional uterotonics in non-elective CD compared with oxytocin. TSA confirmed that this analysis was appropriately powered to detect the pooled estimated effect. Further trials utilizing consistent core outcomes are needed to determine an effect on PPH. PROSPERO CRD42019147256, registered 13 September 2019.
-
Carbetocin reduces the need for additional uterotonics in elective caesarean delivery a systematic review meta analysis and trial sequential analysis of randomised controlled trials
International Journal of Obstetric Anesthesia, 2019Co-Authors: D N Onwochei, J Van Ross, Preet Mohinder Singh, A Salter, D T MonksAbstract:Abstract Background Carbetocin has been found to be superior to oxytocin in terms of need for additional uterotonics and prevention of postpartum haemorrhage at caesarean delivery. However, this is based on combined data from labouring and non-labouring parturients and it remains unclear how effective Carbetocin is in the purely elective setting. The aim of this review was to compare Carbetocin to oxytocin in elective caesarean delivery. Methods Medline, Embase, CINAHL, Web of Science, and the Cochrane databases were searched for randomised controlled trials in any language. The primary outcome was need for additional uterotonics. Secondary outcomes were mean blood loss, need for blood transfusion and incidence of postpartum haemorrhage >1000 mL. Results Nine studies with a total of 1962 patients were included. Trial sequential analysis confirmed that the information size (n=1692) had surpassed that required (n=1166) in order to demonstrate a statistically significant reduction in the use of additional uterotonics. Need for additional uterotonics was reduced by 53% with Carbetocin compared to oxytocin (OR 0.47, 95% CI 0.34 to 0.64; P Conclusions Carbetocin is associated with a reduced need for additional uterotonics when compared with oxytocin at elective caesarean delivery. Standardisation of bleeding-related outcomes in studies is necessary to facilitate synthesis of data in future analyses.
Mrinalini Balki - One of the best experts on this subject based on the ideXlab platform.
-
Carbetocin at elective caesarean section a sequential allocation trial to determine the minimum effective dose in obese women
Anaesthesia, 2020Co-Authors: T Drew, Mrinalini Balki, Dan Farine, Kristi Downey, J C A CarvalhoAbstract:Postpartum haemorrhage is a leading cause of maternal death during childbirth. There is an increasing incidence of atonic postpartum haemorrhage in developed countries, and maternal obesity has been proposed as a contributing factor. The dose-response relationship of Carbetocin in obese women has not yet been determined. We conducted a double-blind, dose-finding study of Carbetocin using a biased coin up-and-down design in women with a body mass index ≥ 40 kg.m-2 undergoing elective caesarean section. The determinant for a successful response was satisfactory uterine tone, with no intra-operative need for additional uterotonic drugs. Secondary outcomes included the use of additional uterotonic drugs postoperatively, estimated blood loss and adverse effects of Carbetocin administration. Thirty women were recruited to the study. The median (IQR [range]) body mass index was 44.93 (41.5-55.2 [40-66.5]) kg.m-2 . The ED90 of Carbetocin was estimated as 62.9 (95%CI 57.0-68.7) μg using the truncated Dixon and Mood method, and 68 (95%CI 52-77) μg using the isotonic regression method. The estimated blood loss was 880 (621-1178 [75-2442]) ml. The overall rates of hypotension and hypertension after delivery were 40% and 6.7%, respectively, while nausea occurred in 26.7% of women. The ED90 for Carbetocin in obese women at elective caesarean section is lower than the dose of 100 μg currently recommended by the Society of Obstetricians and Gynaecologists of Canada, but is approximately four times higher than the previously demonstrated ED90 of 14.8 μg in women with body mass index < 40 kg.m-2 .
-
uterotonics in elective caesarean delivery a randomised non inferiority study comparing Carbetocin 20 μg and 100 μg
Anaesthesia, 2019Co-Authors: S Tabl, Mrinalini Balki, Dan Farine, Kristi Downey, George Tomlinson, Gareth Seaward, J C A CarvalhoAbstract:Postpartum haemorrhage is the leading cause of maternal mortality worldwide and prophylactic uterotonic drug administration after the delivery of the infant is advised. Carbetocin is recommended as an uterotonic, but the minimum effective dose has not been verified. We compared the efficacy of two doses of intravenous Carbetocin (20 μg and 100 μg) in women undergoing elective caesarean delivery. This was a randomised, double-blind, non-inferiority study in women at low risk of postpartum haemorrhage. Carbetocin was administered on delivery of the anterior shoulder of the neonate. Uterine tone was assessed by the obstetrician 2 min and 5 min after Carbetocin administration according to an 11-point numerical rating scale (0 = atonic uterus and 10 = firm uterus). The primary outcome was uterine tone 2 min after Carbetocin administration. The pre-specified non-inferiority margin was 1 point on the 11-point scale. Secondary outcomes included: uterine tone at 5 min; use of additional uterotonics within 24 h; blood loss; and adverse effects. Data were available for 53 women in the Carbetocin-20 group and for 55 women in the Carbetocin-100 group. The mean (SD) uterine tone at 2 min was 7.5 (1.9) in the Carbetocin-20 group and 8.0 (1.5) in the Carbetocin-100 group. The lower limit of the one-sided 95%CI for the mean difference was outside the non-inferiority margin (at -1.1; p = 0.11) meaning non-inferiority of Carbetocin 20 μg compared with Carbetocin 100 μg could not be confirmed. However, the secondary outcome measures of uterine tone at 5 min, blood loss and use of additional uterotonics were similar in both groups.
-
in vitro comparative effect of Carbetocin and oxytocin in pregnant human myometrium with and without oxytocin pretreatment
Anesthesiology, 2016Co-Authors: Naida M Cole, Jose C A Carvalho, Magda Eriksoussi, Nivetha Ramachandran, Mrinalini BalkiAbstract:BACKGROUND: The purpose of this study was to compare in vitro contractile effects of oxytocin and Carbetocin on human term pregnant myometrium with and without oxytocin pretreatment. METHODS: This laboratory investigation was conducted on myometrial samples from women undergoing elective cesarean deliveries. The samples were dissected into four strips and suspended in individual organ bath chambers containing physiologic salt solution. After equilibration, they were pretreated with oxytocin 10 M (experimental group) or physiologic salt solution (control group) for 2 h and then subjected to dose-response testing with increasing concentrations of oxytocin or Carbetocin (10 to 10 M). The amplitude, frequency, motility index (amplitude × frequency), and area under the curve of contractions were recorded and analyzed during the equilibration and dose-response periods. Comparisons were made between oxytocin-induced and Carbetocin-induced contractions in control and oxytocin-pretreated groups. Motility index was the primary outcome measure. RESULTS: Sixty-three experiments were performed (Carbetocin, n = 31; oxytocin, n = 32) on samples from 18 women. The motility index of contractions (√g.contractions/10 min) produced by oxytocin was significantly higher than Carbetocin in both control (regression-estimated difference, 0.857; 95% CI, 0.290 to 1.425; P = 0.003) and oxytocin-pretreated (0.813; 0.328 to 1.299; P = 0.001) groups. The motility index was significantly lower in oxytocin-pretreated groups than their respective controls for both oxytocin (-1.040; -1.998 to -0.082; P = 0.03) and Carbetocin (-0.996; -1.392 to -0.560; P < 0.001). CONCLUSIONS: In vitro contractions produced by oxytocin are superior to Carbetocin in human myometrium with or without oxytocin pretreatment. Oxytocin pretreatment results in attenuation of contractions induced by both oxytocin and Carbetocin.
-
Carbetocin at cesarean delivery for labour arrest a sequential allocation trial to determine the effective dose
Canadian Journal of Anaesthesia-journal Canadien D Anesthesie, 2015Co-Authors: Nhathien Nguyenlu, Jose C A Carvalho, Dan Farine, Gareth Seaward, Mrinalini BalkiAbstract:The aim of this study was to estimate the effective dose 90% (ED90) of Carbetocin to provide adequate uterine tone at Cesarean delivery (CD) for labour arrest. We conducted a double-blind dose-finding study of Carbetocin using a biased-coin up-and-down design in women undergoing CD for labour arrest under epidural anesthesia. Forty healthy term pregnant women who had received at least three hours of oxytocin infusion during labour were recruited for the study. Carbetocin was administered intravenously upon delivery of the anterior shoulder of the fetus. The first patient received 20 µg, and the dose for the subsequent patient was determined according to the response of the previous patient as per the biased-coin allocation scheme using increments or decrements of 20 µg (maximum 140 µg). Uterine tone was assessed by the obstetrician and rated as satisfactory or unsatisfactory throughout the intraoperative period. The primary outcome was satisfactory uterine tone with no need for additional uterotonic drugs intraoperatively. Secondary outcomes included use of additional uterotonic drugs postoperatively in the first 24 hr, estimated blood loss, and adverse effects. The ED90 of Carbetocin to produce adequate uterine tone was estimated at 121 µg (95% confidence interval [CI]: 111 to 130; 99% CI: 108 to 133) using the truncated Dixon and Mood (DM) method. The isotonic estimator of ED90 was 140 µg; however, the observed response rate across all doses was < 90%. Also, the 95% CI of the DM estimator is likely to have lower than expected coverage, while the 99% CI may have about 90% coverage. Therefore, these results should be interpreted with caution. The overall median (range) estimated blood loss was 1,014 (104-2,436) mL. The overall incidence of hypotension and tachycardia were 45% and 57.5%, respectively. At a dose of 140 µg, the incidence of tachycardia and intraoperative arrhythmias was 76% and 14%, respectively. The ED90 of Carbetocin at CD for labour arrest, as determined in our study, should be interpreted with caution since it may be underestimated. This dose is higher than the currently recommended dose of 100 µg at elective CD and should not be used routinely given the uncertainty regarding its efficacy and the high incidence of arrhythmias at higher doses. This trial was registered at ClinicalTrials.gov, number: NCT01725243.
-
Carbetocin at cesarean delivery for labour arrest a sequential allocation trial to determine the effective dose administration de Carbetocine lors d un accouchement par cesarienne pour arret de la progression du travail une etude d attribution sequen
2015Co-Authors: Nhathien Nguyenlu, Carlos Almeida Carvalho, Mrinalini BalkiAbstract:Purpose The aim of this study was to estimate the effective dose 90% (ED90) of Carbetocin to provide adequate uterine tone at Cesarean delivery (CD) for labour arrest. Methods We conducted a double-blind dose-finding study of Carbetocin using a biased-coin up-and-down design in women undergoing CD for labour arrest under epidural anesthesia. Forty healthy term pregnant women who had received at least three hours of oxytocin infusion during labour were recruited for the study. Carbetocin was administered intravenously upon delivery of the anterior shoulder of the fetus. The first patient received 20 lg, and the dose for the subsequent patient was determined according to the response of the previous patient as per the biased-coin allocation scheme using increments or decrements of 20 lg (maximum 140 lg). Uterine tone was assessed by the obstetrician and rated as satisfactory or unsatisfactory throughout the intraoperative period. The primary outcome was satisfactory uterine tone with no need for additional uterotonic drugs intraoperatively. Secondary outcomes included use of additional uterotonic drugs postoperatively in the first 24 hr, estimated blood loss, and adverse effects. Results The ED90 of Carbetocin to produce adequate uterine tone was estimated at 121 lg (95% confidence interval [CI]: 111 to 130; 99% CI: 108 to 133) using the truncated Dixon and Mood (DM) method. The isotonic estimator of ED90 was 140 lg; however, the observed response rate across all doses was\90%. Also, the 95% CI of the DM estimator is likely to have lower than expected coverage, while the 99% CI may have about 90% coverage. Therefore, these results should be interpreted with caution. The overall median (range) estimated blood loss was 1,014 (104-2,436) mL. The overall incidence of hypotension and tachycardia were 45% and 57.5%, respectively. At a dose of 140 lg, the incidence of tachycardia and intraoperative arrhythmias was 76% and 14%, respectively.