Early and systematic administration of fibrinogen concentrate in postpartum haemorrhage following vaginal delivery: the FIDEL randomised controlled trial.

OBJECTIVE: To assess the benefits and safety of early human fibrinogen concentrate in postpartum haemorrhage (PPH) management. DESIGN: Multicentre, double-blind, randomised placebo-controlled trial. SETTING: 30 French hospitals. POPULATION: Patients with persistent PPH after vaginal delivery requiring a switch from oxytocin to prostaglandins. METHODS: Within 30 minutes after introduction of prostaglandins, patients received either 3 g fibrinogen concentrate or placebo. MAIN OUTCOME MEASURES: Failure as composite primary efficacy endpoint: at least 4 g/dl of haemoglobin decrease and/or transfusion of at least two units of packed red blood cells within 48 hours following investigational medicinal product administration. Secondary endpoints: PPH evolution, need for haemostatic procedures and maternal morbidity-mortality within 6 ± 2 weeks after delivery. RESULTS: 437 patients were included: 224 received FC and 213 placebo. At inclusion, blood loss (877 ± 346 ml) and plasma fibrinogen (4.1 ± 0.9 g/l) were similar in both groups (mean ± SD). Failure rates were 40.0% and 42.4% in the fibrinogen and placebo groups, respectively (odds ratio [OR] = 0.99) after adjustment for centre and baseline plasma fibrinogen; (95% CI 0.66-1.47; P = 0.96). No significant differences in secondary efficacy outcomes were observed. The mean plasma FG was unchanged in the Fibrinogen group and decreased by 0.56 g/l in the placebo group. No thromboembolic or other relevant adverse effects were reported in the Fibrinogen group versus two in the placebo group. CONCLUSIONS: As previous placebo-controlled studies findings, early and systematic administration of 3 g fibrinogen concentrate did not reduce blood loss, transfusion needs or postpartum anaemia, but did prevent plasma fibrinogen decrease without any subsequent thromboembolic events. TWEETABLE ABSTRACT: Early systematic blind 3 g fibrinogen infusion in PPH did not reduce anaemia or transfusion rate, reduced hypofibrinogenaemia and was safe.

Traces pilot pharmacokinetic study dataset.

The dataset displays the pharmacokinetics data obtained from the TRACES pilot study. The nine patients included were undergoing haemorrhagic caesarean section (blood loss > 800 mL) and receiving a single i.v dose of tranexamic acid (0.5, 1 or 2 g over 1 min). The dataset gathers the tranexamic acid blood and urinary concentrations. With these first elements, a pharmacokinetic compartment model was built as described in Gilliot et al. and the individual pharmacokinetic parameters were estimated. In parallel, the patients anthropometric, biological, and clinical characteristics were collected. The correlation between the patient data and the estimated individual pharmacokinetic parameters were tested. The correlation tests revealed that the dose, the height, the body weight, and the ideal bodyweight had and impact on the volume of distribution of tranexamic acid. According to these results, these latter covariates were explored using a multi-regression analysis in Gilliot et al.

[Normal childbirth: physiologic labor support and medical procedures. Guidelines of the French National Authority for Health (HAS) with the collaboration of the French College of Gynaecologists and Obstetricians (CNGOF) and the French College of Midwives (CNSF) - Mother's wellbeing and regional or systemic analgesia for labor]. / Accouchement normal : accompagnement de la physiologie et interventions médicales. Recommandations de la Haute Autorité de Santé (HAS) avec la collaboration du Collège National des Gynécologues Obstétriciens Français (CNGOF) et du Collège National des Sages-Femmes de France (CNSF) ­ Bien être maternel et prise en charge médicamenteuse de la douleur.

INTRODUCTION: These guidelines deal with the parturient wellbeing in terms of hydration and regional and systemic pain management during labour. METHOD: Guidelines were established based on literature analysis and experts consensus. RESULTS: Clear liquids consumption is permitted all along labor and postpartum, without volume limitation, in patients at low risk of general anesthesia (grade B). The consumption of solid foods is not recommended during the active stage of labor (consensus agreement). It is recommended to promote on regional analgesia to prevent inhalation (grade A). Pain relief using regional analgesia is a part of normal childbirth. It is recommended to provide regional analgesia to parturient who wish these technics. Regional analgesia is the safest and most effective analgesic method for the mother (grade A) and the child (grade B). It is recommended to inform women on the analgesic technics, to respect their choice and consider the right for a parturient to change her strategy in obstetrical circumstances or in cases of untractable pain (consensus agreement). It is recommended to perform a "low-dose" regional analgesia that respects the experience of childbirth (grade A) and maintain it with a patient controlled epidural analgesia technics (grade A). There is no minimum cervical dilation to allow epidural analgesia (grade A). In cases of rapid labor or after delivery for revision, spinal or combined spinal epidural can be used (grade C). Epidural has not to be ended before birth (consensus agreement). Blood pressure and fetal heart rate must be monitored every 3minutes after induction and/or each 10mL bolus then hourly (consensus agreement). Systematic and preventive fluid loading is not needed if only due to regional analgesia (grade B). Deambulation or postures are allowed in the absence of motor block and must be traced and do not alter the distribution of the regional analgesia (grade C). The postures of childbirth do not alter regional analgesia spread (NP2). There is no effect low dose regional analgesia on the duration of obstetric labor, nor the rate of instrumental births or caesarean section (NP1). Systematic use of oxytocin due to epidural analgesia is neither useful nor recommended (AE). Regional analgesia has no side effect on the fetus or newborn (NP1). If regional analgesia is contraindicated or during the waiting time, alternatives analgesic drugs (entonox, nalbuphine and tramadol or pudendal block) can be used but their analgesic efficiency remains mediocre to moderate and they are associated with adverse maternal and especially neonatal side effects (NP2). Remifentanil, ketamine and volatile anesthetics are excluded from these recommendations. CONCLUSION: The present guidelines were established to update wellbeing of normal parturient during normal labor: hydration is recommended and low dose patient-controlled regional (epidural and spinal) analgesia is the most effective and safest analgesic method.

Hypothesis for a partially non urinary elimination of tranexamic acid in haemorrhagic caesarean section: Traces pilot pharmacokinetic study: Pharmacokinetics of tranexamic acid in obstetrics.

BACKGROUND: In previous studies, the choice of doses of tranexamic acid was empirically defined as no pharmacokinetic study had been conducted in haemorrhagic caesarean section. OBJECTIVE: The objective was to build a pharmacokinetic model in patients receiving a single 0.5, 1 or 2 g intravenous bolus. METHOD: A preliminary monocentric open study was performed in the Lille centre. Blood samples and one urinary sample were collected in the 6 h following the injection. Nine patients were included. Tranexamic acid concentration was measured using liquid chromatography system coupled with tandem mass spectrometry. We used Monolix 2019R1 for population pharmacokinetic modelling. A structural model was constructed followed by the investigation of potential covariates. RESULTS: Data were best described with a two-compartment model with a double first-order elimination from the central compartment. The model was improved when the variable ideal weight per dose was affected as a covariate for the apparent volume of distribution. Assuming a dose of 1 g and a height of 160 cm, the pharmacokinetic parameters were estimated at 10.26 L.h-1 for total clearance, 11.5 L for the volume of the central compartment, 15.8 L for the volume of the second compartment, a diffusional clearance of 30.36 L.h-1 , and a urinary excretion fraction of 25.8%. CONCLUSIONS: The population pharmacokinetic model of tranexamic acid in haemorrhagic caesarean section was successfully established in our tiny sample of patients. The results of this preliminary TRACES pharmacokinetic study suggested that elimination of tranexamic acid is partially non urinary in contrast with healthy patients.

Core outcome sets for prevention and treatment of postpartum haemorrhage: an international Delphi consensus study.

OBJECTIVE: To develop core outcome sets (COS) for studies evaluating interventions for (1) prevention and (2) treatment of postpartum haemorrhage (PPH), and recommendations on how to report the COS. DESIGN: A two-round Delphi survey and face-to-face meeting. POPULATION: Healthcare professionals and women's representatives. METHODS: Outcomes were identified from systematic reviews of PPH studies and stakeholder consultation. Participants scored each outcome in the Delphi on a Likert scale between 1 (not important) and 9 (critically important). Results were discussed at the face-to-face meeting to agree the final COS. Consensus at the meeting was defined as ≥ 70% of participants scoring the outcome as critically important (7-9). Lectures, discussion and voting were used to agree how to report COS outcomes. MAIN OUTCOME MEASURES: Outcomes from systematic reviews and consultations. RESULTS: Both Delphi rounds were completed by 152/205 (74%) participants for prevention and 143/197 (73%) for treatment. For prevention of PPH, nine core outcomes were selected: blood loss, shock, maternal death, use of additional uterotonics, blood transfusion, transfer for higher level of care, women's sense of wellbeing, acceptability and satisfaction with the intervention, breastfeeding, and adverse effects. For treatment of PPH, 12 core outcomes were selected: blood loss, shock, coagulopathy, hysterectomy, organ dysfunction, maternal death, blood transfusion, use of additional haemostatic intervention, transfer for higher level of care, women's sense of wellbeing, acceptability and satisfaction with the intervention, breastfeeding, and adverse effects. Recommendations were developed on how to report these outcomes where possible. CONCLUSIONS: These COS will help standardise outcome reporting in PPH trials. TWEETABLE ABSTRACT: Core outcome sets for PPH: nine core outcomes for PPH prevention and 12 core outcomes for PPH treatment.

[Human Resources for Unplanned Activities in Obstetrics and Gynecology. Consensus statements by the CNGOF, CARO, CNSF, FFRSP, SFAR, SFMP and SFN]. / Ressources humaines pour les activités non programmées en gynécologie-obstétrique. Propositions élaborées par le CNGOF, le CARO, le CNSF, la FFRSP, la SFAR, la SFMP et la SFN.

OBJECTIVE: To determine a minimum threshold of human resources (midwives, obstetricians and gynecologists, anesthesiology and intensive care units, pediatricians) to ensure the safety and quality of unplanned activities in Obstetrics and Gynecology. MATERIALS AND METHODS: Consultation of the MedLine database, the Cochrane Library and the recommendations of authorities. Meetings of representative members in different modes of practice (university, hospital, liberal) under the aegis of and belonging to the French College of Obstetricians and Gynecologists (CNGOF), the French Society of Anesthesia and Resuscitation (SFAR), the French Society of Neonatalogy (SFN), the French Society of Perinatal Medicine (SFMP), the French College of Midwives (CNSF), the French Federation of Perinatal Care Networks (FFRSP) with elaboration of a re-read text by external experts, in particular by the members of the Boards of Directors of these authorities and of Club of Anesthesiology-Intensive Care Medicine in Obstetrics (CARO). RESULTS: Different minimum thresholds for each category of caregivers were proposed based on the number of births/year. These proposed minimum thresholds can be modulated upwards according to the types (level I, IIA, IIB or III) or the activity (existence of an emergency reception service, maternal-fetal and/or surgical activity of resort or referral). Due to peak activity and the possibility of unpredictable concomitance of urgent medical procedures, it is necessary that organizations plan to use resource persons. The occupancy rate of the target beds of a maternity ward must be 85%. CONCLUSION: These proposed minimum thresholds are intended to help caregivers providing non-scheduled perinatal as well as Obstetrics and Gynecology care to make the most of the human resources allocated to institutional bodies to ensure their safety and quality.

Postauthorization safety study of Clottafact® , a triply secured fibrinogen concentrate in acquired fibrinogen deficiency: a prospective observational study.

BACKGROUND AND OBJECTIVES: A postauthorization safety study was performed between 2009 and 2012 to describe the use of Clottafact® in acquired fibrinogen deficiency in real-life medical practice in France. MATERIALS AND METHODS: One hundred and fifty patients were planned for 28 days of prospective follow-up after infusion. The analysis of this observational study was descriptive and performed according to the type of treatment (curative or preventive) and the origin of the bleed. RESULTS: One hundred and fifty-six patients (16-87 years) were included in 13 centres and treated in five different medical bleeding situations: postpartum (59), other gynaecological/obstetrical (6), trauma (34), liver (13), cardiovascular (23) and other various bleeding situations (21). The mean follow-up time was 18·9 ± 12·3 days. Two patients presented adverse drug reactions: one a pulmonary embolism and the other a four-site venous thromboembolic episode. All were serious with a dubious causal relationship with the study treatment. Efficacy data were collected as a secondary objective. In 150 patients receiving curative treatment, 117 of 159 infusions (73·6%) were considered as successful by the investigators, 35 as moderate (22%) and seven as no response (4·4%). CONCLUSION: The Clottafact® safety profile observed during the study matched the known profile of fibrinogen during use.

Evaluation of a new technique of prophylactic cervical cerclage simplified from the Shirodkar cerclage: A pilot study.

INTRODUCTION: In terms of prophylactic cerclage, the simplest and most commonly used technique is the McDonald cervical cerclage. Cervico-isthmic cerclage techniques may have better results, but are more difficult to achieve. A simplified Shirodkar technique would have the advantage of being "cervical high" while remaining easy to achieve. OBJECTIVE: To compare the results of high cervical cerclage, according to a simplified Shirodkar technique, with those of a classic McDonald cerclage, in the case of women at high risk of prematurity in an exploratory study. METHODS: A comparative, retrospective study of prophylactic cerclage was conducted according to one or the other technique performed in a university hospital from 2006 to 2013. Women were included only if they had a history of at least two late miscarriages and/or premature delivery before 33 weeks. The primary outcome was the rate of delivery before 35 weeks. RESULTS: Our study involved 38 women: 24 in the McDonald cerclage group and 14 in the simplified Shirodkar cerclage group. The two groups were comparable for their obstetric and general characteristics. The percentage of preterm deliveries before 35 weeks was similar in both groups (7.1% and 25.0% in the Shirodkar and McDonald groups respectively; P=0.17). No significant difference was observed in the rate of surgical complications or hospitalizations during the pregnancies. CONCLUSION: In this study, we were unable to demonstrate an advantage to using the simplified Shirodkar technique - high cervical cerclage - compared with use of the McDonald technique - classical cerclage.

Are there any additional mechanisms for haemolysis in HELLP syndrome?

HELLP syndrome is a microangiopathy that leads to severe maternal complications. The objective of this study was to identify any additional mechanisms that could have contributed to HELLP syndrome-induced haemolysis. This is a pilot, prospective and observational study that lasted 9months. All patients with HELLP syndrome treated at academic tertiary care women hospital accepted to participate. Sixteen patients were included. In ten patients (63%), schizocytes were detected following a blood smear test. Six patients (38%) were diagnosed with a partial expression deficiency of proteins regulating the complement system (CD 55 or CD 59). In nine patients (56%), an activation of the complement classical pathway was detected. In two patients (13%), an ADAMTS 13 activity below 30% was detected. Three patients (19%) were diagnosed with a folate deficiency and one (6%) with an antiphospholipid syndrome. All patients developed maternal or fetal morbidity including nine (56%) an acute kidney injury. All patients but one had at least one additional mechanism that could contribute to haemolysis, besides a simple physical injury. Larger studies should be promoted to understand haemolysis in HELLP syndrome.

Postpartum haemorrhage related early increase in D-dimers is inhibited by tranexamic acid: haemostasis parameters of a randomized controlled open labelled trial.

BACKGROUND: Beneficial effects of tranexamic acid (TA) have been established in surgery and trauma. In ongoing postpartum haemorrhage (PPH), a moderate reduction of blood loss was observed in a previously published randomized controlled trial. Analysis of haemostasis parameters obtained from samples collected as part of this study are presented. METHODS: Women with PPH >800 ml after vaginal delivery were assigned to receive either TA (4 g over 1 h, then 1 g per h over six h) (TA) or not (H). A non-haemorrhagic group (NH), <800 ml blood loss, was included as postpartum reference. At four time-points (enrolment, +30 min, +2 h, +6 h), haemostasis was assessed. Haemostasis assays were performed blinded to group allocation. Data were expressed as median [interquartiles] and compared with non-parametric tests. RESULTS: In H compared with NH group, D-dimers increase (3730 ng ml(-1) [2468-8493] vs 2649 [2667-4375]; P=0.0001) and fibrinogen and factor II decrease were observed at enrolment and became maximal 2 h later. When comparing TA to H patients, the increase in Plasmin-Antiplasmin-complexes at +30 min (486 ng ml(-1) [340-1116] vs 674 [548-1640]; P=0.03) and D-dimers at +2 h (3888 ng ml(-1) [2688-6172] vs 7495 [4400-15772]; P=0.0001) was blunted. TA had no effect on fibrinogen decrease. CONCLUSIONS: This study provides biological evidence of an early increase in D-dimers and plasmin-antiplasmin complexes associated with active post-partum haemorrhage and its attenuation by the early use of a clinically effective high dose of TA, opening the perspective of dose ranging studies to determinate the optimal dose and timing in this setting. CLINICAL TRIAL REGISTRATION: ISRCTN09968140.

Systematic prophylactic oxytocin injection and the incidence of postpartum hemorrhage: A before-and-after study.

OBJECTIVE: Assess the impact of routine injection of 5 units of oxytocin as soon as the anterior shoulder is delivered on the incidence of postpartum haemorrhage (PPH) in a context of daily practice. MATERIALS AND METHODS: Single-centre before-and-after study evaluating the effect of a change in the protocol for PPH prevention as applied in our obstetrical unit. During the first period, oxytocin (5 units) was to be injected only in case of PPH risk factors. During the second period, the injection was systematic. RESULTS: In the "before" study period, there were 1953 patients vaginal deliveries and 843 (43%) oxytocin injections, with a protocol compliance of 85%. In the "after" study period, 2018 women had vaginal deliveries and 1911 (95%) had an oxytocin injection (protocol compliance: 95%). The whole study period was associated with a reduced risk of moderate haemorrhage (13.4% vs. 9.2%, P<0.001), but no significant reduced risk of severe haemorrhage was observed (2.1% vs. 2.0%, P=0.79). After logistic regression, the study period remained associated with a significant reduction in the risk of moderate PPH (OR=0.72 [0.58-0.89]). CONCLUSION: Routine injection of 5 units of oxytocin makes it possible to reduce the risk of moderate PPH, but it does not affect the risk of severe PPH.

[Aortic dissection in pregnancy]. / Dissection aortique et grossesse.

During pregnancy, the occurrence of aortic dissection is a rare event immediately threatening fetal and maternal prognosis. Its occurrence is more common in cases of connective tissue disease. But the absence risk factor shall not exclude or delay diagnosis. We must learn to think about it, because the prognosis is highly dependent on time management. The clinical presentation of this medical and surgical emergency varies, and pregnancy adds its own symptoms. We have to ask without hesitation that echocardiography or chest CT be performed since these diagnostic methods are both reliable and available.

Recombinant human FVIIa for reducing the need for invasive second-line therapies in severe refractory postpartum hemorrhage: a multicenter, randomized, open controlled trial.

BACKGROUND: Case reports on recombinant human factor VIIa (rhuFVIIa) use in women with severe postpartum hemorrhage (PPH) showed encouraging results, but no randomized controlled trial (RCT) is available. PATIENTS AND METHODS: Eighty-four women with severe PPH unresponsive to uterotonics were randomized to receive one early single rhuFVIIa infusion (n = 42) or standard care (no rhuFVIIa; n = 42). The primary efficacy outcome measure was the reduction of the need for specific second-line therapies, such as interventional hemostatic procedures, for blood loss and transfusions. The primary safety outcome measure was the number of deaths and thrombotic events during the 5 days following rhuFVIIa infusion. RESULTS: rhuFVIIa was associated with a reduction in the number of patients who needed second-line therapies compared with controls (standard care). Specifically, 39/42 (93%) patients in the standard care arm received second-line therapies and 22/42 (52%) patients in the rhuFVIIa arm (absolute difference, 41%; range, 18-63%; relative risk RR, 0.56 [0.42-0.76]). The delivery mode (vaginal or Cesarean section) did not affect the primary outcome. No death occurred. Two venous thrombotic events were recorded in the rhuFVIIa arm: one ovarian vein thrombosis and one deep vein thrombosis with a non-severe pulmonary embolism. CONCLUSION: This open RCT in women with severe PPH refractory to uterotonics shows that rhuFVIIa reduces the need for specific second-line therapies in about one in three patients, with the occurrence of non-fatal venous thrombotic events in one in 20 patients.

Tranexamic acid for the prevention and treatment of postpartum haemorrhage.

Postpartum haemorrhage (PPH) is a major cause of maternal mortality, accounting for one-quarter of all maternal deaths worldwide. Uterotonics after birth are the only intervention that has been shown to be effective for PPH prevention. Tranexamic acid (TXA), an antifibrinolytic agent, has therefore been investigated as a potentially useful complement to this for both prevention and treatment because its hypothesized mechanism of action in PPH supplements that of uterotonics and because it has been proved to reduce blood loss in elective surgery, bleeding in trauma patients, and menstrual blood loss. This review covers evidence from randomized controlled trials (RCTs) for PPH prevention after caesarean (n=10) and vaginal (n=2) deliveries and for PPH treatment after vaginal delivery (n=1). It discusses its efficacy and side effects overall and in relation to the various doses studied for both indications. TXA appears to be a promising drug for the prevention and treatment of PPH after both vaginal and caesarean delivery. Nevertheless, the current level of evidence supporting its efficacy is insufficient, as are the data about its benefit:harm ratio. Large, adequately powered multicentre RCTs are required before its widespread use for preventing and treating PPH can be recommended.

[Efficacy and safety of tranexamic acid administration for the prevention and/or the treatment of post-partum haemorrhage: a systematic review with meta-analysis]. / Efficacité et sécurité de l'acide tranexamique en prévention et/ou en traitement de l'hémorragie du post-partum : une revue systématique de la littérature avec méta-analyse.

OBJECTIVE(S): Assess the efficacy and safety of tranexamic acid administration for the prevention and/or the treatment of postpartum haemorrhage. STUDY DESIGN: Systematic review with meta-analysis. MATERIAL AND METHODS: Systematic review of the literature with the aim of identifying prospective, randomised, controlled trials that assessed the effect of tranexamic acid on peripartum blood loss and transfusion requirement in three clinical contexts: (i) prevention of post-partum haemorrhage in case of elective caesarean section, (ii) prevention of post-partum haemorrhage in case of vaginal delivery, (iii) treatment of post-partum haemorrhage. RESULTS: Prophylactic administration of tranexamic acid reduced blood loss (mean difference for intraoperative blood loss: -177.9mL, IC 95%: -189.51 to -166.35, total blood loss: -183.94, IC 95%: -198.29 to -169.60), and the incidence of severe post-partum haemorrhage (OR: 0.49, IC 95%: 0.33 to 0.74). None of the published trials assessed the effect of tranexamic acid on blood products administration or transfusion requirement. Only one study assessed and reported the efficacy of tranexamic acid when administered as a treatment for postpartum haemorrhage. A significant reduction in blood loss was reported within 30 minutes after randomisation (P=0.03) and confirmed after 6 hours (median: 170mL (58-323) vs 221mL (110-543), P=0.04). None of the included studies adequately studied the incidence of side effects after tranexamic acid administration. CONCLUSION: Although tranexamic acid administration seemed to significantly reduce blood loss and the incidence of severe post-partum haemorrhage, further prospective trials are needed to confirm the efficacy and safety of tranexamic administration in the treatment of postpartum haemorrhage. Those studies should assess the pharmacokinetic profile and the safety of this drug in pregnant women.

[Clinical and pharmacological procedures for the prevention of postpartum haemorrhage in the third stage of labor]. / Prévention clinique et pharmacologique de l'hémorragie du post-partum lors de la troisième phase du travail.

OBJECTIVES: To describe the clinical and pharmacological procedures for the prevention of Postpartum Haemorrhage (PPH). MATERIALS AND METHODS: We searched the Medline and the Cochrane Library (1st December 2004 to 1st March 2014) and we checked the international guidelines. RESULTS: Vaginal birth: only the use of uterotonics reduces the incidence of PPH. Oxytocin is the treatment of choice if it is readily available (grade A). Oxytocin can be used either after the shoulders expulsion or rapidly after the placental delivery (grade B). A dose of 5 or 10IU must be administrated IV over at least 1minute or directly by an intramuscular injection (professional agreement) except in women with documented cardiovascular disease in which the duration of the IV perfusion should be over at least 5minutes (professional agreement). Mechanical procedures have no significant impact on PPH. The decision to use a collector bag is left to the medical team (professional agreement). A systematic complementary oxytocin perfusion is not recommended (professional agreement). Caesarean delivery: There is no evidence to recommend a particular type of caesarean technique to prevent PPH (professional agreement) but a lower uterine section is recommended (grade B). All types of incision expansion may be used (professional agreement). A controlled cord traction is associated with lower blood losses than manual removal of the placenta (grade B). A dose of 5 or 10IU can be injected (IV) over 1minute, and over 5minutes in women with cardiovascular disease (professional agreement). Carbetocin reduces the incidence of PPH but there is presently no inferiority study comparing oxytocin and carbetocin so that oxytocin remains the gold standard therapy to prevent PPH in C-section (professional agreement).

[Anesthetic management of severe or worsening postpartum hemorrhage]. / Prise en charge anesthésique d'une hémorragie du post-partum sévère ou résistant au traitement médical.

INTRODUCTION: Risk factors of maternal morbidity and mortality during postpartum hemorrhage (PPH) include non-optimal anesthetic management. As the anesthetic management of the initial phase is addressed elsewhere, the current chapter is dedicated to the management of severe PPH. METHODS: A literature search was performed using PubMed and Medline databases, and the Cochrane Library, for articles published from 2003 up to and including 2013. Several keywords related to anesthetic and critical care practice, and obstetrical management were used, in various combinations. Guidelines from several societies and organisations were also read. RESULTS: When PPH worsens, one should ask for additional team personnel (professional consensus). Patients should be monitored for heart rate, blood pressure, skin and mucosal pallor, bleeding at skin puncture sites, diuresis and the volume of genital bleeding (grade B). Because of the possible rapid worsening of coagulapathy, patients should undergo regular evaluation of coagulation status (professional consensus). Prevention and management of hypothermia should be considered (professional consensus), by warming intravenous fluids and blood products, and by active body warming (grade C). Antibiotics should be given, if not already administered at the initial phase (professional consensus). Vascular fluids must be given (grade B), the choice being left at the physician discretion. Blood products transfusion should be decided based on the clinical severity of PPH (professional consensus). Priority is given to red blood cells (RBC) transfusion, with the aim to maintain Hb concentration>8g/dL. The first round of products could include 3 units of RBC (professional consensus), and the following round 3 units of RBC, and 3 units of fresh frozen plasma (FFP). The FFP:RBC ratio should be kept between 1:2 and 1:1 (professional consensus). Depending on the etiology of PPH, the early administration of FFP is left at the discretion of the physician (professional consensus). Platelet count should be maintained at>50 G/L (professional consensus). During massive PPH, fibrinogen concentration should be maintained at>2g/L (professional consensus). Fibrinogen can be given without prior fibrinogen measurement in case of massive bleeding (professional consensus). General anesthesia should be considered in case of hemodynamic instability, even when an epidural catheter is in place (professional consensus). CONCLUSION: The anesthetic management aims to restore and maintain optimal respiratory state and circulation, to treat coagulation disorders, and to allow invasive obstetrical and radiologic procedures. Clinical and instrumental monitoring are needed to evaluate the severity of PPH, to guide the choice of therapeutic options, and to assess treatments efficacy.

6% Hydroxyethyl starch (130/0.4) vs Ringer's lactate preloading before spinal anaesthesia for Caesarean delivery: the randomized, double-blind, multicentre CAESAR trial.

BACKGROUND: Vasopressor administration is recommended to prevent hypotension during spinal anaesthesia (SA) for elective Caesarean delivery. We aimed to test the superior efficacy and ensure safety of a hydroxyethyl starch (HES) vs a Ringer's lactate (RL) preloading, when combined with a phenylephrine-based prophylaxis. METHODS: A total of 167 healthy parturients undergoing elective Caesarean delivery under SA were included in this multicentre, randomized, double-blind study. Patients received 500 ml of 6% HES (130/0.4)+500 ml of RL (HES group) or 1000 ml of RL (RL group) i.v. before SA. After SA, i.v. phenylephrine boluses were titrated when systolic arterial pressure (SAP) was below 95% of baseline. The primary outcome was the incidence of maternal hypotension (SAP <80% of baseline). RESULTS: The incidence of both hypotension and symptomatic hypotension (i.e. with dizziness, nausea/vomiting, or both) was significantly lower in the HES group vs the RL group: 36.6% vs 55.3% (one-sided P=0.025) and 3.7% vs 14.1%. There was no significant difference in total phenylephrine requirements [median (range): 350 (50-1800) vs 350 (50-1250) µg]. The decrease in maternal haemoglobin value the day after surgery was similar in the two groups [1.2 (1.0) vs 1.0 (0.9) g dl(-1)]. There was no detectable placental transfer of HES in six umbilical cord blood samples analysed in the HES group. Neonatal outcomes were comparable between the groups. CONCLUSIONS: Compared with a pure RL preloading, a mixed HES-RL preloading significantly improved prevention of both hypotension and symptomatic hypotension based on early phenylephrine bolus administration and did not induce adverse effects. CLINICAL TRIAL REGISTRATION: NCT00694343 (http://clinicaltrials.gov).