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.

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.

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.

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.

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.

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.

Medical prevention and treatment of postpartum hemorrhage: a comparison of different guidelines.

BACKGROUND: Postpartum hemorrhage (PPH) remains a common cause of maternal mortality worldwide, mainly caused by uterine atony. Medical intervention plays an important part in prevention and therapies of PPH. Prophylactic interventions include the use of uterotonic drugs. We elaborated the consistency of national and international guidelines on those medical approaches. MATERIALS AND METHODS: Medical approaches in PPH were extracted from recent publications. Furthermore, the current guidelines of the World Health Organization, the FIGO and of the American, British, Canadian and German Societies of Obstetricians and Gynecologists on PPH were analyzed. RESULTS: Oxytocin is considered as therapy of first choice. However, the examined guidelines fail to give unequivocal recommendations on further uterotonics in PPH, which may partially be attributed to differing publication dates of the guidelines. CONCLUSION: International guidelines on PPH are characterized by differing recommendations. However, recent publications suggest that adhering to local guidelines significantly reduces the prevalence of severe PPH.

Postpartum hemorrhage in the developed world: whither misoprostol?

We reviewed the literature to determine the optimal medical treatment of postpartum hemorrhage caused by uterine atony. Of the available uterotonics, only misoprostol and oxytocin have undergone rigorous comparative study. Of the 2, misoprostol is inferior: 2 recent well-done randomized trials with enrollment of more than 2200 patients demonstrated that, in situations in which prophylactic oxytocin has already been utilized, additional oxytocin is as effective as or better than misoprostol in terminating bleeding, while avoiding the high rate of fever (22-58%) associated with misoprostol. The second of these trials demonstrated that misoprostol does not augment the effect of oxytocin. We conclude that in settings in which oxytocin is available, oxytocin should remain the mainstay of both prophylaxis and first-line treatment of postpartum hemorrhage caused by uterine atony. In the developed world, the use of misoprostol for postpartum hemorrhage should be infrequent.

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.

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.

Dose and side effects of sublingual misoprostol for treatment of postpartum hemorrhage: what difference do they make?

BACKGROUND: Shivering and fever are common side effects of misoprostol. An unexpectedly high rate of fever above 40°C was documented among Ecuadorian women given treatment with 800mcg of sublingual misoprostol to manage postpartum hemorrhage (PPH) (36%). Much lower rates have been reported elsewhere (0-9%). METHODS: From February to July 2010, an open-label pilot study was conducted in Quito, Ecuador to determine whether a lower dose--600mcg sublingual misoprostol--would result in a lower incidence of high fever (≥40°C). Rates of shivering and fever with 600mcg sublingual regimen were compared to previously documented rates in Ecuador following PPH treatment with 800mcg sublingual misoprostol. RESULTS: The 600mcg dose resulted in a 55% lower rate of high fever compared with the 800mcg regimen (8/50; 16% vs. 58/163; 36%; relative risk 0.45 95% CI 0.23-0.88). Only one woman had severe shivering following the 600mcg dose compared with 19 women in the 800mcg cohort (2% vs. 12%; relative risk 0.17 (0.02-1.25)). No cases of delirium/altered sensorium were reported with the 600mcg dose and women's assessment of severity/tolerability of shivering and fever was better with the lower dose. CONCLUSIONS: 600mcg sublingual misoprostol was found to decrease the occurrence of high fever among Ecuadorian women when given to treat PPH. This study however was not powered to examine the efficacy of this treatment regimen and cannot be recommended at this time. Future research is needed to confirm whether other populations, outside of Quito, Ecuador, experience unusually high rates of elevated body temperature following sublingual administration of misoprostol for treatment of PPH. If indeed similar trends are found elsewhere, larger trials to confirm the efficacy of lower dosages may be justified. TRIAL REGISTRATION: Clinical trials.gov, Registry No. NCT01080846.

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.

Delayed delivery of a twin pregnancy and uterine atony: morphological and clinical evidence.

This report presents the uncommon case of a 154-day delayed delivery in a spontaneous twin pregnancy associated with uterine atony. After abortion of the first fetus at 16 weeks, a healthy male was born at 38 weeks. Postpartum hemorrhage due to uterine atony, which was successfully treated with prostaglandins, occurred.

Umbilical vein oxytocin in the management of retained placenta: an alternative to manual removal of placenta?

PURPOSE: Retained placenta is potentially life threatening due to possible complications associated with manual removal. Our aim was to determine whether umbilical vein injection of oxytocin in saline reduces the need for manual removal of placenta. METHODS: This was a randomised controlled trial conducted at a tertiary hospital from December 2002 to March 2004. A total of 61 women delivering singletons, who had no sign of placental separation 20 min after vaginal delivery, were randomised to receive either intra-umbilical oxytocin 100 IU diluted in 30 ml of saline or controlled cord traction only. Manual removal was done if the placenta was not expelled in another 30 min in both arms. RESULTS: There was a significant reduction in the rate of subsequent manual removal of placenta (30 vs. 67.7%, p < 0.05), incidence of uterine atony (3.3 vs. 25.8%, p < 0.05) and the need for uterotonic agents (33.3 vs. 64.5%, p < 0.05) in the oxytocin group when compared with the control group. No significant differences were found in the need for blood transfusion, uterine curettage, incidence of postpartum haemorrhage and haemoglobin level reduction. CONCLUSION: Intra-umbilical vein oxytocin injection is clinically effective for the management of a retained placenta.

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.