Weight-based oxytocin infusion for preventing uterine atony during caesarean delivery in non-labouring patients: A dose-response study.

Postpartum haemorrhage remains a significant cause of maternal morbidity and mortality with the commonest reason being uterine atony. For prevention of uterine atony during caesarean delivery, oxytocin is advocated as a first line drug. There is however no published data regarding utility of a weight-based oxytocin infusion. The present study evaluated dose-response relationship for oxytocin infusion when used as weight-based regimen. A total of 55 non-labouring patients without risk factors for uterine atony and scheduled for caesarean delivery under spinal anaesthesia were enrolled. Randomization was done to receive oxytocin infusion in a dose of 0.1, 0.15, 0.2, 0.25 or 0.3 IU kg-1  h-1 (n = 11 each), initiated at the time of cord clamping and continued until the end of surgery. Successful outcome was defined as attaining an adequate uterine response at 4 min of initiation of infusion and maintained till end of surgery. Oxytocin associated hypotension, tachycardia, ST-T changes, nausea/vomiting, flushing and chest pain were also observed. A significant linear trend for adequate intraoperative uterine tone was seen with increasing dose of weight-based oxytocin infusion (P < 0.001). The effective dose in 90% population (ED90) was 0.29 IU kg-1  h-1 (95% CI = 0.25-0.42). Amongst the oxytocin associated side effects, a significant linear trend was seen between increasing dose of oxytocin infusion and hypotension as well as nausea/vomiting (p = 0.016 and 0.023 respectively). Thus, oxytocin infusion during caesarean delivery may be used as per the patient's body weight.

Costs of the use of carbetocin in the prevention of uterine atony following delivery of the infant by Caesarean section - retrospective multicenter study.

OBJECTIVES: The aim of this study was to compare the costs of using carbetocin in the prevention of uterine atony following delivery of the infant by Cesarean section (C-section) under epidural or spinal anesthesia with standard methods of prevention (SMP). MATERIAL AND METHODS: This retrospective multicenter study was based on data from three medical centers. A questionnaire was developed to gather patient records on consumption and costs of resources related to C-section, prevention of uterine atony and postpartum hemorrhage (PPH) treatment. Six subpopulations were considered, depending on patient characteristics. The analysis covered two perspectives: that of the hospital and of the public payer. RESULTS: The subpopulations were homogenous, which was a premise for pooling the data. The use of carbetocin in the prevention of uterine atony following Cesarean section generates savings for hospital in comparison with SMP (oxytocin) in 5 of 6 subpopulations. The biggest savings were observed amongst patients who experienced severe PPH and reached 2.6-6.2 thousand PLN per patient. Costs of services related to C-section borne by the hospitals were higher than the refund received from a public payer. The greatest underestimation reached 12.1 thousand PLN per patient. Nevertheless, loss generated by this underfunding was lower in carbetocin versus oxytocin group. CONCLUSIONS: The use of carbetocin instead of SMP gives hospitals an opportunity to make savings as well as to reduce losses resulting from the underfunding of the services provided by the National Health Fund.

The ED90 of prophylactic oxytocin infusion after delivery of the placenta during cesarean delivery in laboring compared with nonlaboring women: an up-down sequential allocation dose-response study.

BACKGROUND: Prophylactic administration of oxytocin as a part of active management of the third stage of labor reduces the risk of postpartum hemorrhage. Prophylactic oxytocin is often administered as an infusion rather than a bolus. The aim of the current up-down sequential allocation dose-response study was to test the hypothesis that parturients who receive intrapartum exogenous oxytocin therapy, and who subsequently undergo cesarean delivery for labor dystocia, will have a higher estimated effective dose in 90% of paturients (ED90) for oxytocin infusion in the third stage of labor compared with nonlaboring parturients. METHODS: The study design was a single-blinded, dual-arm, dose-response study using a 9:1 biased-coin sequential allocation method to estimate the ED90 of an infusion of prophylactic oxytocin in women undergoing cesarean delivery with neuraxial anesthesia. The experimental (laboring) group included women scheduled for intrapartum cesarean delivery after prior exposure to exogenous oxytocin, and the control (nonlaboring) group included women scheduled for elective cesarean delivery. The starting infusion rate was 18 IU/h, with an incremental dose of 2 IU/h. The outcome was satisfactory uterine tone 4 minutes after delivery as judged by the obstetrician. Secondary outcomes included requirement for additional uterotonic agents and maternal side effects (e.g., nausea and vomiting, ST-segment depression). Dose-response data for each group were evaluated by a log-logistic function and ED90 estimates derived from the fitted equations using the delta method. RESULTS: Thirty-eight and 32 subjects participated in the nonlaboring and laboring groups, respectively. The oxytocin ED90 was significantly greater for the laboring group (44.2 IU/h [95% confidence interval (CI), 33.8-55.6]) compared with that for the nonlaboring group (16.2 IU/h [95% CI, 13.1-19.3]; difference in dose 28 IU/h [95% CI of difference, 26-29, P < 0.001]). Significantly more women in the laboring group (34%) than in the nonlaboring group (8%) required supplemental uterotonic agents (difference 26% [95% CI of the difference, 7%-44%, P = 0.008]). The overall incidence of side effects was greater in the laboring group (69%) than in the nonlaboring group (34%; difference 25% [95% CI of the difference, 10%-59%, P = 0.004]). CONCLUSIONS: Women with prior exposure to exogenous oxytocin require a higher initial infusion rate of oxytocin to prevent uterine atony after cesarean delivery than women without prior exposure.

[Comparison of carbetocin and oxytocin effectiveness for prevention of postpartum hemorrhage after caesarean delivery]. / Porównanie skutecznosci dzialania karbetocyny i oksytocyny w profilaktyce krwotoku poporodowego po cieciu cesarskim.

OBJECTIVES: The aim of the study was to compare the effectiveness of carbetocin and oxytocin for prevention of postpartum hemorrhage (PPH) after caesarean section. MATERIAL AND METHODS: We analyzed data from 279 patients who received 100 µg of carbetocin intravenously or 10 IU of oxytocin into the uterine muscle as a rudimentary treatment for prevention of PPH. RESULTS: Blood loss was statistically significantly higher (p=0.0136) in the entire study group as compared to the oxytocin group, and in cases when additional uterotonics were administered (p=0.0090). Also, we observed a statistically significantly correlation between the need for additional treatment and patient BMI. Patients with pre-pregnancy BMI of ≥25 more often required additional medicaments after administration of carbetocin as compared to oxytocin (p=0.0077). We noted a statistically significantly higher rate of using additional treatment (p<0.05) after administering oxytocin into the uterine muscle as compared to intravenously given carbetocin (75% vs. 33%, respectively). CONCLUSIONS: 1. Carbetocin is more effective than oxytocin in the prevention of PPH and significantly reduces the necessity to administer therapeutic uterotonics during caesarean delivery. 2. Higher rates of additional treatment with uterotonics after the administration of carbetocin as compared to oxytocin in a group of patients after2 or more cesarean sections and women with BMI of ≥25 require further studies in a target-selected larger sample size. 3. Based on our findings, it is not possible to conclude that 100 µg of intravenous carbetocin is more effective than 10 IU of oxytocin given to the uterine muscle during caesarean delivery to prevent PPH.

Weight-based versus fixed dose oxytocin infusion for preventing uterine atony during cesarean section in laboring patients: A randomized trial.

OBJECTIVE: We compared efficacy of weight-based (0.4 IU/kg/h) versus fixed-dose (34 IU/h) oxytocin infusion during cesarean section. METHODS: The oxytocin infusion in either group (n = 32 each) was initiated upon cord clamping. Primary outcome measure was adequacy of uterine tone at 4 min after initiating oxytocin infusion. Oxytocin associated side effects were also observed. RESULTS: Significantly less oxytocin was used with the weight-based versus fixed-dose regimen (16.3 [11.2-22.4] IU vs 20.4 [15.8-26.9] IU; P = 0.036). Incidence of adequate uterine tone was clinically greater but not significantly different with the weight-based versus fixed-dose regimen (81.3% vs 71.9%; P = 0.376). The weight-based regimen was associated with clinically lesser, although not statistically significant need for rescue oxytocin (25% vs 46.9%; P = 0.068) and additional uterotonic (9.4% vs 15.6%; P = 0.708); as well as oxytocin associated side effects (hypotension [34.4% vs 46.9%; P = 0.309], nausea/vomiting [18.8% vs 40.6%; P = 0.055], and ST-T changes [0% vs 3.1%; P = 1.000]). CONCLUSION: Weight-based oxytocin was not significantly different from the fixed-dose regimen in terms of uterotonic efficacy or associated side-effects, despite significantly lower doses being used. Use of weight-based oxytocin infusion (0.4 IU/kg/h) can be considered in clinical practice. TRIAL REGISTRATION: Clinical Trial Registry of India (ctri.nic.in, number. CTRI/2021/01/030642).

Risk factors for uterine atony/postpartum hemorrhage requiring treatment after vaginal delivery.

OBJECTIVE: We sought to identify risk factors for uterine atony or hemorrhage. STUDY DESIGN: We conducted a secondary analysis of a 3-arm double-blind randomized trial of different dose regimens of oxytocin to prevent uterine atony after vaginal delivery. The primary outcome was uterine atony or hemorrhage requiring treatment. In all, 21 potential risk factors were evaluated. Logistic regression was used to identify independent risk factors using 2 complementary predefined model selection strategies. RESULTS: Among 1798 women randomized to 10, 40, or 80 U of prophylactic oxytocin after vaginal delivery, treated uterine atony occurred in 7%. Hispanic (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.3-3.4), non-Hispanic white (OR, 1.6; 95% CI, 1.0-2.5), preeclampsia (OR, 3.2; 95% CI, 2.0-4.9), and chorioamnionitis (OR, 2.8; 95% CI, 1.6-5.0) were consistent independent risk factors. Other risk factors based on the specified selection strategies were obesity, induction/augmentation of labor, twins, hydramnios, anemia, and arrest of descent. Amnioinfusion appeared to be protective against uterine atony (OR, 0.53; 95% CI, 0.29-0.98). CONCLUSION: Independent risk factors for uterine atony requiring treatment include Hispanic and non-Hispanic white ethnicity, preeclampsia, and chorioamnionitis.

Carbetocin in comparison with oxytocin in several dosing regimens for the prevention of uterine atony after elective caesarean section in the Netherlands.

PURPOSE: The aim of the study was to compare the prophylactic effects of carbetocin with those of oxytocin for the prevention of uterine atony in patients undergoing elective caesarean section (CS) in the Netherlands. The primary endpoint was the need for additional uterotonic medication. METHODS: Each of the five participating Dutch hospitals treated 50-100 term patients with 100 µg of intravenous carbetocin on prescription. Each centre retrieved charts of 250 patients treated with oxytocin according to the hospital's policy for the prevention of uterine atony (oxytocin bolus 5 IU, bolus 10 IU or bolus 5 IU followed by 10 IU in 2 h). RESULTS: In the carbetocin group 462 subjects were included and in the oxytocin group 1,122. The proportion of subjects needing additional uterotonic treatment was 3.1 % (95 % CI 1.7-5.1 %) after carbetocin and 7.2 % (5.8-8.9 %) after oxytocin; relative risk 0.41 (0.19-0.85); p = 0.0110. Carbetocin was most effective compared with the oxytocin 5 IU bolus subgroup with less need for additional uterotonic medication (3.1 vs. 9.3 %, p = 0.0067) and blood transfusions (2.2 vs. 3.6 %, p = 0.0357). CONCLUSIONS: Compared with oxytocin, prophylaxis of uterine atony with carbetocin after an elective CS diminished the need for additional uterotonics by more than 50 %.

Development of clinical risk-prediction models for uterine atony following vaginal and cesarean delivery.

BACKGROUND: Uterine atony is the most common cause of postpartum hemorrhage and is associated with substantial morbidity. Prospectively identifying women at increased risk of atony may reduce the incidence of subsequent adverse events. We sought to develop and evaluate clinical risk-prediction models for uterine atony following vaginal and cesarean delivery, using prespecified risk factors identified from systematic review. METHODS: Using retrospective data from vaginal and cesarean deliveries occurring at a single institution between 2010 and 2019, antepartum and intrapartum risk-prediction models for uterine atony, defined by supplementary uterotonic administration in addition to prophylactic oxytocin infusion, were developed using logistic regression. The C-statistic quantified the ability of the model to discriminate between cases and controls. RESULTS: Data were available for 4773 atony cases and 23 933 controls. The antepartum model included 20 risk factors and exhibited moderate discriminatory ability (C-statistic 0.61, 95% confidence interval 0.60 to 0.62). The intrapartum model included 27 risk factors and showed improved discriminatory ability (C-statistic 0.68, 95% confidence interval 0.67 to 0.69). CONCLUSIONS: We identified antepartum and intrapartum risk-prediction models to quantify patients' risk of uterine atony. Models performed similarly for all delivery modes, races, and ethnic groups. Future work should further improve these models through inclusion of more comprehensive prediction data.

Calcium chloride for the prevention of uterine atony during cesarean delivery: A pilot randomized controlled trial and pharmacokinetic study.

STUDY OBJECTIVE: To assess the feasibility, patient tolerance, pharmacokinetics, and potential effectiveness of a randomized controlled trial protocol investigating intravenous calcium chloride for the prevention of uterine atony during cesarean delivery. DESIGN: Double-blind, randomized controlled pilot trial with nested population pharmacokinetic analysis. SETTING: This study was performed at Lucile Packard Children's Hospital, from August 2018 to September 2019. PATIENTS: Forty patients with at least two risk factors for uterine atony at the time of cesarean delivery. INTERVENTIONS: One gram of intravenous calcium chloride (n = 20 patients) or a saline placebo control (n = 20 patients), in addition to standard care with oxytocin, upon umbilical cord clamping. MEASUREMENTS: The primary efficacy-related outcome was the presence of uterine atony defined as the use of a second-line uterotonic medication, surgical interventions for atony, or hemorrhage with blood loss >1000 mL. Blood loss, uterine tone numerical rating scores, serial venous blood calcium levels, hemodynamics, and potential side effects were also assessed. MAIN RESULTS: The study protocol proved feasible. The incidence of atony was 20% in parturients who received calcium compared to 50% in the placebo group (relative risk 0.38, P = 0.07, 95% CI 0.15-1.07, NNT 3.3). Calcium recipients tolerated the drug infusion well, with no adverse events and an equal incidence of potential side effects in the calcium and placebo groups. Ionized calcium concentration rose significantly in all patients who received calcium infusion, from baseline 1.18 mmol/L to peak levels 1.50-1.60 mmol/L. One-compartment population pharmacokinetics established clearance of 0.93 (95% CI 0.63-1.52) L/min and volume of distribution 76 (95% CI 49-94) L. CONCLUSIONS: In this pilot study, investigators found that intravenous calcium chloride was well-tolerated by the 20 patients assigned to receive the study drug and may be effective in prevention of uterine atony. A 1-g dose was sufficient to substantially increase calcium levels without any critically elevated lab values or concern for adverse side effects. These encouraging findings warrant further investigation of calcium as a novel agent to prevent uterine atony with an adequately powered clinical trial. Clinical trial registry NCT03867383 https://clinicaltrials.gov/ct2/show/NCT03867383.

Five unit bolus oxytocin at cesarean delivery in women at risk of atony: a randomized, double-blind, controlled trial.

BACKGROUND: I.v. bolus oxytocin is used routinely during cesarean delivery to prevent postpartum hemorrhage. Its adverse hemodynamic effects are well known, resulting in a recent change in dose from 10 IU to 5. Whether a 5 IU bolus has any advantages over infusion alone is unclear. We tested the hypothesis that a 5 IU i.v. bolus of oxytocin before the initiation of a continuous infusion decreases the need for additional uterotonic drugs in the first 24 hours after delivery in women with risk factors for uterine atony undergoing cesarean delivery, compared with infusion alone. METHODS: A prospective, randomized, double-blind, controlled trial was conducted in 143 subjects undergoing cesarean delivery with at least 1 risk factor for uterine atony. Subjects received 5 IU bolus of oxytocin or normal saline i.v. over 30 seconds after umbilical cord clamping. All subjects received an infusion of 40 IU oxytocin in 500 mL normal saline over 30 minutes, followed by 20 IU in 1 L over 8 hours. The primary outcome was the need for additional uterotonics in the first 24 hours after delivery. Secondary outcomes included uterine tone as assessed by the surgeon (5-point Likert scale: 0 = "floppy," 4 = "rock hard"), estimated blood loss, side effects of bolus administration, and the oxytocin bolus-placental delivery interval. RESULTS: There was no difference in the need for additional uterotonic drugs in the first 24 hours between groups. There was a significant difference in uterine tone immediately after placental delivery (P < 0.01) (2.8 in the oxytocin group [95% confidence interval 2.6-3.0] vs 2.2 in the saline group [95% confidence interval 1.8-2.5]), which disappeared after 5 minutes. There were no differences in observed or reported side effects between groups. CONCLUSIONS: We found that a 5 IU i.v. bolus of oxytocin added to an infusion did not alter the need for additional uterotonic drugs to prevent or treat postpartum hemorrhage in the first 24 hours in women undergoing cesarean delivery with risk factors for uterine atony, despite causing an initial stronger uterine contraction. Our study was not powered to find a difference in side effects between groups. These results suggest that an oxytocin infusion may be adequate without the need for a bolus, even in high-risk patients.

Up-down determination of the ED(90) of oxytocin infusions for the prevention of postpartum uterine atony in parturients undergoing Cesarean delivery.

INTRODUCTION: Use of the lowest effective dose of oxytocin may reduce side effects. This study was designed to determine the effective dose (ED)(90) of oxytocin infusion for an elective Cesarean delivery (CD) to prevent uterine atony. METHODS: The participants were ASA I and II, non-obese, non-labouring adult women undergoing an elective CD at term with a singleton gestation. The spinal anesthetic technique was standardized, and a blinded infusion of oxytocin was administered after delivery. The obstetrician rated the uterine contraction as either satisfactory or unsatisfactory. The initial dose of oxytocin infusion was 0.4 IU.min(-1), and the dose for the next subject was based on the response of the preceding subject as per a biased-coin design up-down sequential method. The ED(90) was calculated using Firth's penalized likelihood estimation. RESULTS: Fifty subjects were screened, eight subjects were excluded, and two patients were withdrawn. Seven of the 40 subjects had uterine tone that was judged unsatisfactory by the obstetrician and required additional uterotonic medications. The ED(90), i.e., the dose at which 90% of women were judged to have satisfactory uterine tone, was 0.29 IU.min(-1) (95% confidence interval [CI] 0.15-0.43 IU.min(-1)). DISCUSSION: In this study, we found the ED(90) of oxytocin required to prevent uterine atony and postpartum hemorrhage after an elective CD to be 0.29 IU.min(-1)-approximately 15 IU of oxytocin in 1 L of intravenous fluid administered over a one-hour period-(95% CI 0.15-0.43 IU.min(-1)). This oxytocin infusion dose is 30% less than the clinical infusions currently in use. It remains to be seen whether this dosing will be required for higher risk individuals or for labouring parturients undergoing non-elective CD. (Clinical Trial gov. NCT00785395).

Postpartum hemorrhage in Suriname: A national descriptive study of hospital births and an audit of case management.

BACKGROUND: Postpartum hemorrhage (PPH) is the leading cause of direct maternal mortality globally and in Suriname. We aimed to study the prevalence, risk indicators, causes, and management of PPH to identify opportunities for PPH reduction. METHODS: A nationwide retrospective descriptive study of all hospital deliveries in Suriname in 2017 was performed. Logistic regression analysis was applied to identify risk indicators for PPH (≥ 500ml blood loss). Management of severe PPH (blood loss ≥1,000ml or ≥500ml with hypotension or at least three transfusions) was evaluated via a criteria-based audit using the national guideline. RESULTS: In 2017, the prevalence of PPH and severe PPH in Suriname was 9.2% (n = 808/8,747) and 2.5% (n = 220/8,747), respectively. PPH varied from 5.8% to 15.8% across the hospitals. Risk indicators associated with severe PPH included being of African descent (Maroon aOR 2.1[95%CI 1.3-3.3], Creole aOR 1.8[95%CI 1.1-3.0]), multiple pregnancy (aOR 3.4[95%CI 1.7-7.1]), delivery in Hospital D (aOR 2.4[95%CI 1.7-3.4]), cesarean section (aOR 3.9[95%CI 2.9-5.3]), stillbirth (aOR 6.4 [95%CI 3.4-12.2]), preterm birth (aOR 2.1[95%CI 1.3-3.2]), and macrosomia (aOR 2.8 [95%CI 1.5-5.0]). Uterine atony (56.7%, n = 102/180[missing 40]) and retained placenta (19.4%, n = 35/180[missing 40]), were the main causes of severe PPH. A criteria-based audit revealed that women with severe PPH received prophylactic oxytocin in 61.3% (n = 95/155[missing 65]), oxytocin treatment in 68.8% (n = 106/154[missing 66]), and tranexamic acid in 4.9% (n = 5/103[missing 117]). CONCLUSIONS: PPH prevalence and risk indicators in Suriname were similar to international and regional reports. Inconsistent blood loss measurement, varied maternal and perinatal characteristics, and variable guideline adherence contributed to interhospital prevalence variation. PPH reduction in Suriname can be achieved through prevention by practicing active management of the third stage of labor in every birth and considering risk factors, early recognition by objective and consistent blood loss measurement, and prompt treatment by adequate administration of oxytocin and tranexamic acid according to national guidelines.

The Median Effective Dose of Oxytocin Needed to Prevent Uterine Atony During Cesarean Delivery in Elderly Parturients.

PURPOSE: Oxytocin is the first-line agent to prevent and treat uterine atony during cesarean delivery (CD). We compared the effective dose in 50% of the parturients (ED50) of a prophylactic oxytocin bolus during CD in young (<35 years) and old parturients (≥35 years) using Dixon's up-and-down method. PATIENTS AND METHODS: Twenty-eight young parturients (young group) and 25 old parturients (old group) undergoing CD under combined spinal-epidural anesthesia were enrolled. The initial oxytocin bolus was 0.5 IU, with increments or decrements of 0.25 IU. Maternal adverse effects, requirement for additional uterotonic agents, and estimated blood loss were recorded. RESULTS: The ED50 for oxytocin in the old group was higher than that in the young group (1.41 IU; 95% confidence interval, 0.63-2.19) vs 0.66 IU (0.04-1.29), P < 0.001). The total oxytocin dose in the old group was higher than in the young group (5.9 ± 2.9 vs 4.1 ± 2.1 IU, P = 0.01). The estimated blood loss in the older group and young group was 401.2 ± 204.5 mL and 289.3 ± 104.6 mL, respectively (P =0.01). The overall prevalence of adverse effects was higher in the old group than in the young group (68.0% vs 21.4%, P < 0.001). CONCLUSION: The initial bolus and total requirement of oxytocin for preventing uterine atony were higher in old parturients than in young parturients during CD. Advanced maternal age may necessitate higher doses of oxytocin.

Utilization of carbetocin for prevention of postpartum hemorrhage after cesarean section: a randomized clinical trial.

PURPOSE: A randomized study involving pregnant women was conducted to compare the effectiveness of a single intravenous (IV) injection of carbetocin with that of a standard 2-h oxytocin IV infusion with respect to intraoperative blood loss in the prevention of uterine atony after cesarean section (CS). The two treatments also were compared for safety and ability to maintain adequate uterine tone and to reduce the incidence and severity of postpartum hemorrhage (PPH) in women at risk for this condition. METHODS: Between 1 September 2007 and 5 January 2008, we enrolled 104 patients with at least one risk factor for PPH undergoing CS in a randomized, controlled clinical trial. We compared the effect of a single 100 microg IV dose of carbetocin with that of a standard 2-h ten international units (IU) IV infusion of oxytocin. The primary outcome was the proportion of patients requiring additional oxytocic intervention for uterine atony. Fiftytwo women received 100 microg carbetocin IV immediately after placental delivery, while 52 women received 10 IU oxytocin IV infusion. Complete blood count was collected at entry and 24 h postpartum. All outcome measures, including the need for additional uterotonic agents or uterine massage, and blood loss, were analyzed using chi-square, Fisher exact, and Student's t tests. RESULTS: A single 100 microg IV injection of carbetocin was as effective as a continuous 2-h infusion of oxytocin in controlling intraoperative blood loss after placental delivery. Mean blood loss after carbetocin administration was 30 ml less than after oxytocin administration (P = 0.5). The percentage of patients with blood loss < or =500 ml was greater with carbetocin (81 vs. 55%; P = 0.05). Carbetocin enhanced early postpartum uterine involution. The fundus was below the umbilicus in more patients who received carbetocin at 0, 2, 6, and 24 h on the ward (P < 0.05). The main additional uterotonic agent used was a further administration of oxytocin (20 IU in physiological solution 500 ml at an infusion rate of 200 ml/h). In the carbetocin group, 20 of the 52 women (38.4%) required at least one uterine massage compared to 30 of the 52 women (57.7%) in the oxytocin group (P < 0.01). Overall, uterotonic intervention was clinically indicated in two of the women (3.8%) receiving carbetocin compared to five of the women (9.6%) given an IV oxytocin infusion (P < 0.01). The odds ratio of treatment failure requiring oxytocic intervention was 1.83 (95% confidence interval, CI, 0.9-2.6) times higher in the oxytocin group compared with the carbetocin group. CONCLUSIONS: Carbetocin makes possible to obtain, with a single IV injection, results equivalent to those of oxytocin on the maintenance of uterine tonicity and the limitation of blood losses, in the peri- and in the post-operative period, during a delivery by CS. It has in addition a comparable tolerance. Even in our series adverse events are practically of the same type and similar frequency in both study groups. Thus, the effectiveness of carbetocin consists, thanks to its long half-life, on an unique injection, whereas oxytocin requires repeated injections or a perfusion of several hours, with a variability of the administered doses.

Oxytocin in cesarean-sections. What's new?

Oxytocin is the uterotonic agent of choice in the prevention and treatment of postpartum uterine atony. Nevertheless, there is no consensus on the optimal dose and rate for use in cesarean sections. The use of high bolus doses (e.g., 10IU of oxytocin) can determine deleterious cardiovascular changes for the patient, especially in situations of hypovolemia or low cardiac reserve. Furthermore, high doses of oxytocin for prolonged periods may lead to desensitization of oxytocin receptors in myometrium, resulting in clinical inefficiency.

Impact of a third stage of labor oxytocin protocol on cesarean delivery outcomes.

BACKGROUND: There are currently no standard recommendations regarding the dose, rate, or duration of intravenous oxytocin administration for the active management of the third stage of labor in the USA. In 2008, we initiated a standardized postpartum oxytocin protocol for active management of the third stage of labor. In cesarean deliveries, upon clamping of the umbilical cord, an oxytocin infusion of 18 U/h was started and adjusted upward if there was ongoing uterine atony. The aim of this study was to compare intraoperative data on oxytocin dose, estimated blood loss, supplemental uterotonic use and vasopressor use before and after the implementation of this protocol. We hypothesized that implementation of the protocol would result in lower intraoperative oxytocin doses without increasing estimated blood loss. METHODS: In this retrospective study, patient characteristics, estimated blood loss, vasopressor administration, and supplemental uterotonic use during two time periods were compared: the two-month interval before initiation of the oxytocin protocol and the two-month interval after initiation. Data were compared using the chi-squared test, t-test, or Mann-Whitney U test as appropriate. P < 0.05 was considered significant. RESULTS: Data for 901 deliveries were analyzed. The amount of intraoperative oxytocin administered decreased after implementation of the protocol (median difference 8.4 U, 95% CI 7.4 to 9.4). Although there was an increase in estimated blood loss, there were no differences in the percentage of patients experiencing intraoperative blood loss >1000 mL or the need for additional uterotonic mediations between the two time periods. CONCLUSIONS: We found that the use of an oxytocin management protocol reduced the amount of intraoperative oxytocin administered without increasing the rate of postpartum hemorrhage or the need for additional uterotonics. Clinicians may consider using a rate of 18 U/h as a starting point for administration of oxytocin to achieve adequate uterine tone in healthy parturients for prevention of postpartum hemorrhage.

What is new in postpartum hemorrhage? Best articles from the past year.

This month, we focus on current research in postpartum hemorrhage. Dr. Rouse discusses five recent publications, and each is concluded with a "bottom line" that is the take-home message. The complete reference for each can be found in on this page, along with direct links to the abstracts.

Uso de carbetocina frente al uso de oxitocina en pacientes intervenidas por cesárea con alto riesgo de atonía uterina / Use of Carbetocin versus Oxytocin in Cesareans with High Risk of Uterine Atony

Introducción: la utilización adecuada de medicamentos uterotónicos es fundamental en el manejo de la hemorragia obstétrica. Objetivo: describir los efectos de la carbetocina y su comparación con la oxitocina como primera elección para prevenir la hemorragia obstétrica en pacientes cesareadas con riesgo de atonía uterina. Métodos: se realizó un estudio prospectivo, comparativo y transversal, en el 2016, donde se incluyeron 165 pacientes embarazadas que ingresaron para interrupción del embarazo por cesárea, las cuales tenían factores de riesgo de atonía uterina. Se formaron dos grupos: el A, con 110 pacientes que recibieron oxitocina a dosis de 10 U por vía intravenosa, y el B, con 55 pacientes a las que se les administraron 100 mg de carbetocina después del nacimiento. Resultados: ambos grupos resultaron similares en la edad. En el grupo A, el promedio de edad fue de 27,5 años, y en el B, de 28,1 años. Se encontró una adecuada contractilidad en 83 pacientes del grupo A (75,45 por ciento) y en 53 del grupo B (96,36 por ciento). El grupo que recibió carbetocina requirió menor cantidad de maniobras o medicamentos adicionales. El sangrado transoperatorio fue, en promedio, de 845 ± 124,8 mL, para el grupo A, y de 709 ± 275,21 mL para el grupo B, en 21 pacientes del grupo A fue mayor de 1 000 mL y en 12 del grupo B. Conclusiones: las pacientes que recibieron carbetocina tuvieron resultados mejores en la contractilidad uterina. La necesidad de maniobras y medicamentos adicionales así como en la magnitud del sangrado y por tanto menor cantidad de transfusiones de hemoderivados(AU)

Introduction: the proper use of uterotonic drugs is fundamental in the management of obstetric hemorrhage. Objective: describe the effects of carbetocin and its comparison with oxytocin as the first choice to prevent obstetric hemorrhage in patients who are at risk for uterine atony. Methods: aprospective, comparative and cross-sectional study was conducted in 2016, which included 165 pregnant patients admitted for cesarean section, who had risk factors for uterine atony. Two groups were formed: A, with 110 patients receiving oxytocin at a dose of 10 U intravenously, and B, with 55 patients given 100 mcg of carbetocin after birth. Results: both groups were similar in age. In group A, the mean age was 27.5 years, and in B, 28.1 years. Adequate contractility was found in 83 patients in group A (75.45 percent) and 53 patients in group B (96.36 percent). The group receiving carbetocin required fewer maneuvers or additional medications. The intraoperative bleeding was, on average, 845 ± 124.8 mL in group A and 709 ± 275.21 mL in group B. It was more than 1,000 mL in 21 patients in group A and 12 patients in group B. Conclusions: patients who received carbetocin had better results in uterine contractility. The need for maneuvers and additional drugs was lesser as well as the magnitude of bleeding and therefore less transfusions of blood products(AU)

Uso de carbetocina frente al uso de oxitocina en pacientes intervenidas por cesárea con alto riesgo de atonía uterina / Use of Carbetocin versus Oxytocin in Cesareans with High Risk of Uterine Atony

Introducción: la utilización adecuada de medicamentos uterotónicos es fundamental en el manejo de la hemorragia obstétrica. Objetivo: describir los efectos de la carbetocina y su comparación con la oxitocina como primera elección para prevenir la hemorragia obstétrica en pacientes cesareadas con riesgo de atonía uterina. Métodos: se realizó un estudio prospectivo, comparativo y transversal, en el 2016, donde se incluyeron 165 pacientes embarazadas que ingresaron para interrupción del embarazo por cesárea, las cuales tenían factores de riesgo de atonía uterina. Se formaron dos grupos: el A, con 110 pacientes que recibieron oxitocina a dosis de 10 U por vía intravenosa, y el B, con 55 pacientes a las que se les administraron 100 mg de carbetocina después del nacimiento. Resultados: ambos grupos resultaron similares en la edad. En el grupo A, el promedio de edad fue de 27,5 años, y en el B, de 28,1 años. Se encontró una adecuada contractilidad en 83 pacientes del grupo A (75,45 por ciento) y en 53 del grupo B (96,36 por ciento). El grupo que recibió carbetocina requirió menor cantidad de maniobras o medicamentos adicionales. El sangrado transoperatorio fue, en promedio, de 845 ± 124,8 mL, para el grupo A, y de 709 ± 275,21 mL para el grupo B, en 21 pacientes del grupo A fue mayor de 1 000 mL y en 12 del grupo B. Conclusiones: las pacientes que recibieron carbetocina tuvieron resultados mejores en la contractilidad uterina. La necesidad de maniobras y medicamentos adicionales así como en la magnitud del sangrado y por tanto menor cantidad de transfusiones de hemoderivados(AU)

Introduction: the proper use of uterotonic drugs is fundamental in the management of obstetric hemorrhage. Objective: describe the effects of carbetocin and its comparison with oxytocin as the first choice to prevent obstetric hemorrhage in patients who are at risk for uterine atony. Methods: aprospective, comparative and cross-sectional study was conducted in 2016, which included 165 pregnant patients admitted for cesarean section, who had risk factors for uterine atony. Two groups were formed: A, with 110 patients receiving oxytocin at a dose of 10 U intravenously, and B, with 55 patients given 100 mcg of carbetocin after birth. Results: both groups were similar in age. In group A, the mean age was 27.5 years, and in B, 28.1 years. Adequate contractility was found in 83 patients in group A (75.45 percent) and 53 patients in group B (96.36 percent). The group receiving carbetocin required fewer maneuvers or additional medications. The intraoperative bleeding was, on average, 845 ± 124.8 mL in group A and 709 ± 275.21 mL in group B. It was more than 1,000 mL in 21 patients in group A and 12 patients in group B. Conclusions: patients who received carbetocin had better results in uterine contractility. The need for maneuvers and additional drugs was lesser as well as the magnitude of bleeding and therefore less transfusions of blood products(AU)

Higher-dose oxytocin and hemorrhage after vaginal delivery: a randomized controlled trial.

OBJECTIVE: Higher-dose oxytocin is more effective than lower-dose regimens to prevent postpartum hemorrhage after cesarean delivery. We compared two higher-dose regimens (80 units and 40 units) to our routine regimen (10 units) among women who delivered vaginally. METHODS: In a double-masked randomized trial, oxytocin (80 units, 40 units, or 10 units) was administered in 500 mL over 1 hour after placental delivery. The primary outcome was a composite of any treatment of uterine atony or hemorrhage. Prespecified secondary outcomes included outcomes in the primary composite and a decline of 6% or more in hematocrit. A sample size of 600 per group (N=1,800) was planned to compare each of the 80-unit and 40-unit groups to the 10-unit group. At planned interim review (n=1,201), enrollment in the 40-unit group was stopped for futility and enrollment continued in the other groups. RESULTS: Of 2,869 women, 1,798 were randomized as follows: 658 to 80 units; 481 to 40 units; and 659 to 10 units. Most characteristics were similar across groups. The risk of the primary outcome in the 80-unit group (6%; relative risk [RR] 0.93, 95% confidence interval [CI] 0.62-1.40) or the 40-unit group (6%; RR 0.94, 95% CI 0.61-1.47) was not different compared with the 10-unit group (7%). Treatment with additional oxytocin after the first hour was less frequent with 80 units compared with 10 units (RR 0.41, 95% CI 0.19-0.88), as was a 6% or more decline in hematocrit (RR 0.83, 95% CI 0.69-0.99); both outcomes declined with increasing oxytocin dose. Outcomes were similar between the 40-unit and 10-unit groups. CONCLUSION: Compared with 10 units, 80 units or 40 units of prophylactic oxytocin did not reduce overall postpartum hemorrhage treatment when administered in 500 mL over 1 hour for vaginal delivery. Eighty units decreased the need for additional oxytocin and the risk of a decline in hematocrit of 6% or more. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00790062. LEVEL OF EVIDENCE: I.