Tranexamic Acid in the Prevention and Treatment of Postpartum Hemorrhage: A Review.

Postpartum hemorrhage (PPH) continues to be one of the leading causes of maternal morbidity and mortality worldwide. The four main causes of PPH are uterine atony, lacerations, retained placenta, and bleeding diathesis. In the patient with PPH, immediate evaluation is needed to diagnose and treat the underlying cause of hemorrhage. Uterotonic agents such as oxytocin remain first line for prevention and treatment of uterine atony. Studies have evaluated the antifibrinolytic tranexamic acid (TXA) as an adjunctive therapy in the prevention and treatment of PPH. TXA has been shown to reduce blood loss, bleeding-associated mortality, and transfusion rates in a variety of clinical settings and thus may serve a role in treating PPH. Current studies have demonstrated that TXA is an effective treatment option with limited risk of adverse events in appropriately selected patients; however, additional studies are needed to further clarify the role of TXA in the prevention of PPH.

Uterine atony prophylaxis with carbetocin versus oxytocin and the risk of major haemorrhage during caesarean section: A retrospective cohort study.

Carbetocin and oxytocin are commonly recommended agents for active management of the third stage of labour. Evidence is inconclusive whether either one more effectively reduces the occurrence of important postpartum haemorrhage outcomes at caesarean section. We examined whether carbetocin is associated with a lower risk of severe postpartum haemorrhage (blood loss ≥ 1000 ml) in comparison with oxytocin for the third stage of labour in women undergoing caesarean section. This was a retrospective cohort study among women undergoing scheduled or intrapartum caesarean section between 1 January 2010 and 2 July 2015 who received carbetocin or oxytocin for the third stage of labour. The primary outcome was severe postpartum haemorrhage. Secondary outcomes included blood transfusion, interventions, third stage complications and estimated blood loss. Outcomes were examined overall and by timing of birth, scheduled versus intrapartum, using propensity score-matched analysis. Among 21,027 eligible participants, 10,564 women who received carbetocin and 3836 women who received oxytocin at caesarean section were included in the analysis. Carbetocin was associated with a lower risk of severe postpartum haemorrhage overall (2.1% versus 3.3%; odds ratio, 0.62; 95% confidence interval 0.48 to 0.79; P < 0.001). This reduction was apparent irrespective of timing of birth. Secondary outcomes also favoured carbetocin over oxytocin. In this retrospective cohort study, the risk of severe postpartum haemorrhage associated with carbetocin was lower than that associated with oxytocin in women undergoing caesarean section. Randomised clinical trials are needed to further investigate these findings.

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.

Protocol for postpartum haemorrhage including massive transfusion.

Postpartum haemorrhage (PPH) is one of the most common causes of maternal mortality worldwide. Management of PPH depends on the severity of bleeding. If the bleeding is severe, aorta compression can reduce bleeding. It should be followed by insertion of two coarse needles for intravenous access and blood sampling for haemoglobin and haemostasis. Further on, monitoring of vital parameters, as well as provision of extra oxygen and warm crystalloids, should be performed. Uterine atony is the most common cause of PPH and local guidelines for uterotonic drug selection should be followed. Patients with ongoing bleeding should immediately receive surgical care for bleeding control. During severe ongoing bleeding, haemostasis care includes early tranexamic acid, transfusion in ratio 4:4:1 (blood:plasma:platelets), and extra fibrinogen intravenously. If not severe PPH, use goal-directed therapy. During general anaesthesia and uterine atony, stop volatile anaesthesia and change to intravenous anaesthesia.

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.

Uterine atony.

PURPOSE OF REVIEW: Postpartum hemorrhage (PPH) is the leading preventable cause of maternal morbidity and mortality worldwide. Uterine atony is identified as the underlying etiology in up to 80% of PPH. This serves as a contemporary review of the epidemiology, risk factors, pathophysiology, and treatment of uterine atony. RECENT FINDINGS: Rates of postpartum hemorrhage continue to rise worldwide with the largest fraction attributed to uterine atony. A simple 0-10 numerical rating score for uterine tone was recently validated for use during cesarean delivery and may allow for more standardized assessment in clinical and research settings. The optimal prophylactic dose of oxytocin differs depending on the patient population, but less than 5 units and as low as a fraction of one unit is needed for PPH prevention, with an increased requirements within that range for cesarean birth, those on magnesium, and advanced maternal age. Carbetocin is an appropriate alternative to oxytocin. Misoprostol shows limited to no efficacy for uterine atony in recent studies. Several uncontrolled case studies demonstrate novel mechanical and surgical interventions for treating uterine atony. SUMMARY: There is a critical, unmet need for contemporary, controlled studies to address the increasing threat of atonic PPH.

A study of uterine inertia on the spontaneous of labor using uterine electromyography.

OBJECTIVE: The purpose of this study is to analyze uterine electromyography burst patterns in patients with spontaneous labor and patients with uterine inertia. MATERIALS AND METHODS: Uterine electromyography was recorded using 4 silver/silver chloride electrodes placed periumbilical. Thirty women in the spontaneous labor were enrolled. Uterine electromyography was also recorded from patients with uterine inertia before and after oxytocin treatment. EMG bursts were characterized by analysis of multiple variables including burst frequency, duration, root mean squared, amplitude, and total power. RESULTS: There were significant reductions (P < .01) in all EMG burst characteristics. In addition, uterine electromyography parameters were all increased after oxytocin treatment and were comparable (P > .05) to patients in spontaneous labor. CONCLUSIONS: Uterine electromyography can be used effectively to distinguish patients progressing with spontaneous labor from patients that develop uterine inertia. Uterine inertia is characterized by reduced EMG activity and failure of cervical dilation. Uterine electromyography is a quantitative, non-invasive assessment tool that contributes to the diagnosis, evaluation and management of patients with spontaneous labor and uterine inertia.

Intraoperative coagulopathy during cesarean section as an unsuspected initial presentation of COVID-19: a case report.

BACKGROUND: The world's understanding of COVID-19 continues to evolve as the scientific community discovers unique presentations of this disease. This case report depicts an unexpected intraoperative coagulopathy during a cesarean section in an otherwise asymptomatic patient who was later found to have COVID-19. This case suggests that there may be a higher risk for intrapartum bleeding in the pregnant, largely asymptomatic COVID-positive patient with more abnormal COVID laboratory values. CASE: The case patient displayed D-Dimer elevations beyond what is typically observed among this hospital's COVID-positive peripartum population and displayed significantly more oozing than expected intraoperatively, despite normal prothrombin time, international normalized ratio, fibrinogen, and platelets. CONCLUSION: There is little published evidence on the association between D-Dimer and coagulopathy among the pregnant population infected with SARS-CoV-2. This case report contributes to the growing body of evidence on the effects of COVID-19 in pregnancy. A clinical picture concerning for intraoperative coagulopathy may be associated with SARS-CoV-2 infection during cesarean sections, and abnormal COVID laboratory tests, particularly D-Dimer, may help identify the patients in which this presentation occurs.

The Effect of Tranexamic Acid on Preventing Post-partum Hemorrhage Due to Uterine Atony: A Triple-blind Randomized Clinical Trial.

BACKGROUND: Postpartum haemorrhage (PPH) is an important cause of early maternal death which needs to be controlled. OBJECTIVE: This study was designed to compare the effect of intravenous tranexamic acid (TXA) and prostaglandin analogue on reducing PPH resulted from uterine atony in women undergoing C section or vaginal delivery. METHOD: A randomized, triple-blind, placebo-controlled study was conducted on 248 pregnant women with PPH due to uterine atony who were randomly assigned into two groups of TXA as the intervention group (n=124) and prostaglandin analogue as the control group (n=124). The intervention group received 4 g TXA for an hour and then 1 g over 6 hours infusion intravenously and the control group received prostaglandin analogue. RESULTS: Postoperative bleeding did not significantly differ between the two groups (68.2±6.1 ml and 69.1±175.73 ml, respectively, P =0.6). Moreover, hemoglobin declines were 1±0.4 g/dl and 1.2±0.5 g/dL in TXA and prostaglandin group respectively, indicating that the difference was not statistically significant (P =0.7). CONCLUSION: The results of the present study showed that administrating intravenous TXA had comparable effects with prostaglandin analogue on reducing PPH in women with uterine atony and in those undergoing C section or vaginal delivery. Therefore, TXA can be used instead of prostaglandin in managing such patients.

Lack of controlled studies investigating the risk of postpartum haemorrhage in cesarean delivery after prior use of oxytocin: a scoping review.

BACKGROUND: Postpartum haemorrhage (PPH) is a major cause of maternal mortality and morbidity worldwide. Experimental and clinical studies indicate that prolonged oxytocin exposure in the first or second stage of labour may be associated with impaired uterine contractility and an increased risk of atonic PPH. Therefore, particularly labouring women requiring cesarean delivery constitute a subset of patients that may exhibit an unpredictable response to oxytocin. We mapped the evidence for comparative studies investigating the hypothesis whether the risk for PPH is increased in women requiring cesarean section after induction or augmentation of labour. METHODS: We performed a systematic literature search for clinical trials in Medline, Embase, Web of Science, and the Cochrane Library (May 2016). Additionally we searched for ongoing or unpublished trials in clinicaltrials.gov and the WHO registry platform. We identified a total of 36 controlled trials investigating the exogenous use of oxytocin in cesarean section. Data were extracted for study key characteristics and the current literature literature was described narratively. RESULTS: Our evidence map shows that the majority of studies investigating the outcome PPH focused on prophylactic oxytocin use compared to other uterotonic agents in the third stage of labour. Only 2 dose-response studies investigated the required oxytocin dose to prevent uterine atony after cesarean delivery for labour arrest. These studies support the hypotheses that labouring women exposed to exogenous oxytocin require a higher oxytocin dose after delivery than non-labouring women to prevent uterine atony after cesarean section. However, the study findings are flawed by limitations of the study design as well as the outcome selection. No clinical trial was identified that directly compared exogenous oxytocin versus no oxytocin application before intrapartum cesarean delivery. CONCLUSION: Despite some evidence from dose-response studies that the use of oxytocin may increase the risk for PPH in intrapartum cesarean delivery, current research has not investigated the prepartal application of oxytocin in well controlled clinical trials. It was striking that most studies on exogenous oxytocin are focused on PPH prophylaxis in the third stage of labour without differing between the indications of cesarean section and hence the prepartal oxytocin status.

Hematoma hepático espontáneo en gestante a término durante el trabajo de parto / Spontaneous hepatic haematoma in a pregnant woman during labour

La aparición de una ruptura hepática en el transcurso de un embarazo normal es algo excepcional. A veces el diagnóstico de ruptura hepática puede ser difícil, lo que condiciona una elevada tasa de mortalidad. Aunque la ruptura hepática es más frecuente que se asocie en gestantes con síndrome de HELLP, también puede ocurrir en pacientes afectas de otras patologías hepáticas, incluso en pacientes sanas. Se debe mantener el estado de vigilancia ante cuadros clínicos sospechosos aun sin evidencia analítica de alteración hepática ni hemodinámica de hipertensión del embarazo, ya que un diagnóstico temprano facilitará el trabajo multidisciplinar que precisa el manejo de esta patología y disminuirá la morbilidad y mortalidad tanto materna como fetal (AU)

Spontaneous hepatic rupture during labour is a rare condition. Because of the difficulty in diagnosing hepatic rupture in pregnant women, it is often associated with a high mortality rate. Although pregnant women with HELLP syndrome are more prone to hepatic rupture, it can also occur with other liver pathologies and even in healthy women. We should be vigilant in case of suspicious clinical signs even if we have no evidence of preeclampsia. An early diagnosis will be the key to reducing the mortality and morbidity rate (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)

[Carbetocin and oxytocin: Prevention of postpartum hemorrhage in patients with risk factors for uterine atony]. / Carbetocina y oxitocina: prevención de hemorragia posparto en pacientes con factores de riesgo para atonía uterina.

BACKGROUND: In Mexico, during 2010, obstetric hemorrhage was second (19.6%) as a direct cause of maternal death. The aim of this paper is to evaluate the effect of oxytocin and carbetocin, in preventing postpartum hemorrhage in patients with risk factors for uterine atony. METHODS: Study type clinical trial, patients experiencing at least one of the risk factors for uterine atony included. Randomly, they were divided into two groups: one was given Oxytocin and other received Carbetocin. The following variables were determined: risk factors for uterine atony, hemoglobin and hematocrit, vital signs, trans-surgical bleeding, whether or not presented uterine atony, uresis, need for additional tonics uterus and need for blood transfusion. RESULTS: A total of 120 patients were studied in 6 months were excluded 3, 60 were treated with Carbetocin, and 57 with Oxytocin. It was determined that there is a greater number of events of uterine atony (p = 0.007, with RR 11.06) and therefore greater need for additional tonic uterus (p = 0.027, with RR 5.44) in the group of Oxytocin. There was no statistically significant difference in the other variables. CONCLUSIONS: Carbetocin is recommended as prophylaxis of obstetric hemorrhage in patients with risk factors for uterine atony.

Introducción: en México, en 2010, la hemorragia obstétrica ocupó el segundo lugar (19.6%) como causa directa de muerte materna. El objetivo de este trabajo es evaluar el efecto de la oxitocina y la carbetocina, en la prevención de hemorragia posparto en pacientes con factores de riesgo para atonía uterina. Métodos: estudio tipo ensayo clínico, se incluyeron a pacientes que presentaron al menos uno de los factores de riesgo para atonía uterina. De manera aleatoria, se dividieron en dos grupos: a uno se le administró oxitocina y el otro recibió carbetocina. Se determinaron las siguientes variables: factores de riesgo para atonía uterina, hemoglobina y hematocrito, signos vitales, sangrado transquirúrgico, si presentó o no atonía uterina, uresis, necesidad de uterotónicos adicionales y necesidad de transfusión de hemoderivados. Resultados: se estudiaron un total de120 pacientes en 6 meses, se excluyeron 3, de las cuales 60 fueron tratadas con carbetocina y 57 con oxitocina. Se determinó que existe un mayor número de eventos de atonía uterina (p = 0.007, con RR de 11.06) y, por ende, mayor necesidad de uterotónico adicional (p = 0.027, con RR de 5.44), en el grupo de la oxitocina. No hubo diferencia estadísticamente significativa en el resto de las variables. Conclusiones: Se recomienda carbetocina como profilaxis de hemorragia obstétrica en pacientes con factores de riesgo para atonía uterina.

Major obstetric hemorrhage.

Major obstetric hemorrhage is a challenge for anesthesiologists because it remains responsible for over 10% of maternal deaths in high-income countries. A standardized multidisciplinary management, described in locally validated protocols and based on international guidelines is mandatory to prevent these deaths. The first difficulty relies on the systematic underestimation of the bleeding. Collection bags must be used to facilitate the diagnosis and therefore rapid management. The etiologies in antenatal or postpartum must be well-known in order to be treated adequately. A rapid recourse to prostaglandins (sulprostone in France) may reverse uterine atony. Invasive approach with surgery or radiology should be promptly implemented (uterine artery or internal iliac artery ligations±uterus plication) and hysterectomy should then be timely considered. Simultaneously, early and aggressive resuscitation with large-bore venous accesses should be implemented for rapid and massive transfusion (4:4:1 RBC:FFP:platelets ratio), along with an early use of fibrinogen concentrates and tranexamic acid. This transfusion strategy may be then guided by thromboelastography or thromboelastometry and bedside hemoglobin measurements. Activated factor VII remains indicated only before or after hysterectomy in case of uncontrolled bleeding. Management of placentation abnormalities (placenta previa, accreta, increta, percreta) must be well mastered as these etiologies may generate cataclysmic hemorrhages that can be and have to be anticipated.

Randomized double-blind placebo-controlled trial of buccal misoprostol to reduce the need for additional uterotonic drugs during cesarean delivery.

OBJECTIVE: To determine whether buccal misoprostol during cesarean delivery in conjunction with active management of the third stage of labor reduces the need for additional uterotonic drugs. METHOD: A double-blind, randomized, placebo-controlled trial was performed in Monterrey, Mexico, between February 2008 and December 2013. Eligible women had risk factors for uterine atony and were to undergo cesarean delivery under epidural block. Using a computer-generated sequence and blocks of six, patients were randomly assigned to receive 400µg misoprostol or 800µg placebo buccally after cord clamping. Both groups received an intravenous oxytocin infusion. The primary outcome was the need for additional uterotonic drugs. Analyses were performed per protocol. Patients, investigators, and data analysts were masked to group assignment. RESULTS: A total of 120 women were included in analyses (60 in each group). At least one additional uterotonic drug was required in 24 (40%) women in the placebo group versus 6 (10%) women in the misoprostol group (relative risk 0.16; 95% confidence interval 0.06-0.44). No adverse effects due to misoprostol were recorded. CONCLUSION: Buccal misoprostol during cesarean delivery reduced the need for additional uterotonic drugs to treat uterine atony. ClinicalTrials.gov:NCT01733329.

Patterns of second-line uterotonic use in a large sample of hospitalizations for childbirth in the United States: 2007-2011.

BACKGROUND: The incidence of postpartum hemorrhage due to uterine atony has increased significantly in the United States during the past decade. For patients with refractory uterine atony after oxytocin administration, second-line uterotonics including methylergonovine maleate, carboprost, and misoprostol are recommended. In this study, we describe hospital-level patterns of second-line uterotonic use in a large, nationwide sample of admissions for childbirth in the United States. METHODS: The Premier Research Database was used to define a cohort of 2,180,916 patients hospitalized for delivery at 1 of 367 hospitals from 2007 to 2011. Mixed-effects logistic regression models were used to estimate the hospital-specific frequency of second-line uterotonic use adjusting for measured patient-level and hospital-level characteristics that might be risk factors for uterine atony. RESULTS: The median hospital-level frequency of second-line uterotonic use was 7.1% (interquartile range 5.2-% to 10.8%). In the fully adjusted model, the mean (SE) predicted probability of second-line uterotonic use was 7.02% (0.26%), with 95% of the hospitals having a predicted (SE) probability between 1.69% (0.12%) and 24.96% (1.28%). CONCLUSIONS: We observed wide interhospital variation in the use of second-line uterotonics that was not explained by patient-level or hospital-level characteristics. Studies aimed at defining the optimal pharmacologic strategies for the management of uterine atony are needed, particularly in light of the increasing incidence of atonic postpartum hemorrhage in the United States and other developed countries.