Role of recombinant factor VIIa in the clinical management of severe postpartum hemorrhage: consensus among European experts.

OBJECTIVES: There have been significant advances in the medical management of severe postpartum hemorrhage (sPPH) over recent decades, which is reflected in numerous published guidelines. To date, many of the currently available national and international guidelines recommend recombinant factor VIIa (rFVIIa) to be used only at a very late stage in the course of sPPH, as a "last resort", before or after hysterectomy. Based on new safety data, rFVIIa has recently been approved by the European Medicines Agency (EMA) and Swissmedic for use in sPPH, if uterotonics are insufficient to achieve hemostasis, which in fact is significantly earlier in the course of postpartum hemorrhage (PPH). We therefore aimed to develop expert consensus guidance as a step toward standardizing care with the use of rFVIIa for clinicians managing women experiencing life-threatening sPPH. METHODS: The consensus process consisted of one face-to-face meeting with a group of nine experts, including eight obstetrician-gynecologists and a hematologist highly experienced in sPPH care in tertiary care perinatal centers. The panel was representative of multidisciplinary expertise in the European obstetrics community and provided consensus opinion in answer to pre-defined questions around clinical practice with rFVIIa in the management of sPPH. Recommendations have been based on current national and international guidelines, extensive clinical experience, and consensus opinion, as well as the availability of efficacy and new safety data. RESULTS: The expert panel developed 17 consensus statements in response to the 13 pre-defined questions on the use of rFVIIa in the management of sPPH including: available efficacy and safety data and the need for interdisciplinary expertise between obstetricians, anesthesiologists, and hematologists in the management of sPPH. Based on novel data, the experts recommend: (1) earlier administration of rFVIIa in patients with sPPH who do not respond to uterotonic administration to optimize the efficacy of rFVIIa; (2) the importance of hematological parameter prerequisites prior to the administration of rFVIIa to maximize efficacy; and (3) continued evaluation or initiation of further invasive procedures according to standard practice. Furthermore, recommendations on the timing of rFVIIa treatment within the sPPH management algorithm are outlined in a range of specified clinical scenarios and settings, including vaginal delivery, cesarean section, and smaller birthing units before transfer to a tertiary care center. The panel agreed that according to available, and new data, as well as real-world experience, there is no evidence that the use of rFVIIa in patients with sPPH increases the risk of thromboembolism. The authors acknowledge that there is still limited clinical effectiveness data, as well as pharmacoeconomic data, on the use of rFVIIa in sPPH, and recommend further clinical trials and efficacy investigation. CONCLUSIONS: This expert panel provides consensus guidance based on recently available data, clinical experience, and expert opinion, augmented by the recent approval of rFVIIa for use in sPPH by the EMA. These consensus statements are intended to support clinical care for sPPH and may help to provide the impetus and a starting point for updates to existing clinical practice guidelines.

[Intrahepatic cholestasis of pregnancy: French College of Obstetricians and Gynecologists guidelines for clinical practice]. / La cholestase gravidique : recommandations pour la pratique clinique du Collège national des gynécologues obstétriciens français.

OBJECTIVE: To identify strategies for reducing neonatal and maternal morbidity associated with intrahepatic cholestasis pregnancy (ICP). MATERIAL AND METHODS: The quality of evidence of the literature was assessed following the GRADE methodology with questions formulated in the PICO format (Patients, Intervention, Comparison, Outcome) and outcomes defined a priori and classified according to their importance. An extensive bibliographic search was performed on PubMed, Cochrane, EMBASE and Google Scholar databases. The quality of the evidence was assessed (high, moderate, low, very low) and a (i) strong or (ii) weak recommendations or (iii) no recommendation were formulated. The recommendations were reviewed in two rounds with external reviewers (Delphi survey) to select the consensus recommendations. RESULTS: Of the 14 questions (from 12 PICO questions and one definition question outside the PICO format), there was agreement between the working group and the external reviewers on 14 (100%). The level of evidence of the literature was insufficient to provide a recommendation on two questions. ICP is defined by the occurrence of suggestive pruritus (palmoplantar, nocturnal) associated with a total bile acid level>10µmol/L or an alanine transaminase level above 2N after ruling out differential diagnoses. In the absence of suggestive symptoms of a differential diagnosis, it is recommended not to carry out additional biological or ultrasound tests. In women with CIP, ursodeoxycholic acid is recommended to reduce the intensity of maternal pruritus (Strong recommendation. Quality of the evidence moderate) and to decrease the level of total bile acids and alanine transaminases. (Strong recommendation. Quality of the evidence moderate). S-adenosyl-methionine, dexamethasone, guar gum or activated charcoal should not be used to reduce the intensity of maternal pruritus (Strong recommendation. Quality of evidence low), and there is insufficient data to recommend the use of antihistamines (No recommendation. Quality of evidence low). Rifampicin (Weak recommendation. Very low quality of evidence) or plasma exchange (Strong recommendation. Very low quality of evidence) should not be used to reduce maternal pruritus and perinatal morbidity. Serum monitoring of bile acids is recommended to reduce perinatal morbidity and mortality (stillbirth, prematurity) (Low recommendation. Quality of the evidence low). The level of evidence is insufficient to determine whether fetal heart rate or fetal ultrasound monitoring are useful to reduce perinatal morbidity (No recommendation). Birth is recommended when bile acid level is above 99µmol/L from 36 weeks gestation to reduce perinatal morbidity, in particular stillbirth. When bile acid level is above 99µmol/L is below 100µmol/L, women should be informed that induction of labor could be considered 37 and 39 weeks gestation to reduce perinatal morbidity. (Strong recommendation. Quality of evidence low). In postpartum, total bile acids and alanine transaminases level should be checked and normalized before prescribing estrogen-progestin contraception, ideally with a low estrogen dose (risk of recurrence of pruritus and cytolysis) (Low recommendation. Quality of evidence very low). CONCLUSION: Although the quality of evidence regarding ICP gestational cholestasis remains low, there is a strong consensus in France, as shown by our Delphi study, on how to manage women with ICP. The reference first-line treatment is ursodeoxycholic acid.

[The cesarean procedure: Guidelines for clinical practice from the French College of Obstetricians and Gynecologists]. / La technique de la césarienne : recommandations pour la pratique clinique du Collège national des gynécologues obstétriciens français.

OBJECTIVE: To identify procedures to reduce maternal morbidity during cesarean. MATERIAL AND METHODS: The quality of evidence of the literature was assessed following the GRADE® method with questions formulated in the PICO format (Patients, Intervention, Comparison, Outcome) and outcomes defined a priori and classified according to their importance. An extensive bibliographic search was performed on PubMed, Cochrane and EMBASE databases. The quality of the evidence was assessed (high, moderate, low, very low) and a (i) strong or (ii) weak recommendations or (iii) no recommendation were formulated. The recommendations were reviewed in two rounds with external reviewers (Delphi survey) to select the consensus recommendations. RESULTS: Of the 27 questions, there was agreement between the working group and the external reviewers on 26. The level of evidence of the literature was insufficient to provide a recommendation on 15 questions. Preventing hypothermia is recommended to increase maternal satisfaction and comfort (weak recommendation) and to reduce neonatal hypothermia (strong recommendation). The quality of the evidence of the literature did not allow to recommend the skin disinfectant to be used nor the relevance of a preoperative vaginal disinfection nor the choice between the use or nonuse of an indwelling bladder catheterization (if micturition takes place 1 hour before the cesarean section). The Misgav-Ladach technique or its analogues should be considered rather than the Pfannenstiel technique to reduce maternal morbidity (weak recommendation) bladder flap before uterine incision should not be performed routinely (weak recommendation), but a blunt (weak recommendation) and cephalad-caudad extension of uterine incision (weak recommendation) should be considered to reduce maternal morbidity. Antibiotic prophylaxis is recommended to reduce maternal infectious morbidity (strong recommendation) without recommendation on its type or the timing of administration (before incision or after cord clamping). The administration of carbetocin after cord clamping does not significantly decrease the incidence of blood loss>1000 ml, anemia, or blood transfusion compared with the administration of oxytocin. Thus, it is not recommended to use carbetocin rather than oxytocin in cesarean. It is recommended that systematic manual removal of the placenta not to be performed (weak recommendation). An antiemetic should be administered after cord clamping in women having a planned cesarean under locoregional anaesthesia to reduce intraoperative and postoperative nausea and vomiting (strong recommendation) with no recommendation regarding choice of use one or two antiemetics. The level of evidence of the literature was insufficient to provide any recommendation concerning single or double-layer closure of the uterine incision, or the uterine exteriorization. Closing the peritoneum (visceral or parietal) should not be considered (weak recommendation). The quality of the evidence of the literature was not sufficient to provide recommendation on systematic subcutaneous closure, including in obese or overweight patients, or the use of subcuticular suture in obese or overweight patients. The use of subcuticular suture in comparison with skin closure by staples was not considered as a recommendation due to the absence of a consensus in the external review rounds. CONCLUSION: In case of cesarean, preventing hypothermia, administering antiemetic and antibiotic prophylaxis after cord clamping are the only strong recommendations. The Misgav-Ladach technique, the way of performing uterine incision (no systematic bladder flap, blunt cephalad-caudad extension), not performing routine manual removal of the placenta nor closure of the peritoneum are weak recommendations and may reduce maternal morbidity.

Guidelines for the management of urgent obstetric situations in emergency medicine, 2022

To provide recommendations on the management of urgent obstetrical emergencies outside the maternity ward. A group of 24 experts from the French Society of Emergency Medicine (SFMU), the French Society of Anaesthesia and Intensive Care Medicine (SFAR) and the French College of Gynaecologists and Obstetricians (CNGOF) was convened. Potential conflicts of interest were formally declared at the outset of the guideline development process, which was conducted independently of industry funding. The authors followed the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method to assess the level of evidence in the literature. The potential drawbacks of strong recommendations in the presence of low-level evidence were highlighted. Some recommendations with an insufficient level of evidence were not graded. Eight areas were defined: imminent delivery, postpartum haemorrhage (prevention and management), threat of premature delivery, hypertensive disorders in pregnancy, trauma, imaging, cardiopulmonary arrest, and emergency obstetric training. For each field, the expert panel formulated questions according to the PICO model (population, intervention, comparison, outcomes) and an extensive literature search was conducted. Analysis of the literature and formulation of recommendations were conducted according to the GRADE method. Fifteen recommendations on the management of obstetrical emergencies were issued by the SFMU/SFAR/CNGOF panel of experts, and 4 recommendations from formalised expert recommendations (RFE) established by the same societies were taken up to answer 4 PICO questions dealing with the pre-hospital context. After two rounds of voting and several amendments, strong agreement was reached for all the recommendations. For two questions (cardiopulmonary arrest and inter-hospital transfer), no recommendation could be made. There was significant agreement among the experts on strong recommendations to improve practice in the management of urgent obstetric complications in emergency medicine.

[Obstetrics complications of systemic lupus erythematosus and antiphospholipid syndrome: A multidisciplinary management]. / Complications obstétricales du lupus érythémateux systémique et du SAPL : une prise en charge multidisciplinaire.

The main autoimmune diseases responsible for obstetric complications are systemic lupus erythematosus and antiphospholipid syndrome. They are particularly associated with an increased risk of miscarriage, stillbirth, intrauterine growth restriction, prematurity and pre-eclampsia. Therapeutics to prevent its complications are mainly low dose aspirin and low molecular weight heparins. However, the introduction of these therapies will have to consider the benefit/risk ratio to manage pregnancy and especially delivery. Consistency of care provided by autoimmunity specialists and gynaecologist-obstetricians is extremely important and must be promoted through regular exchanges, fuelled by a mutual culture, through multidisciplinary consultation meetings.

[Management of preterm premature rupture of membranes (except for antibiotherapy): CNGOF preterm premature rupture of membranes guidelines]. / Prise en charge thérapeutique (hors antibiothérapie) de la rupture prématurée des membranes avant terme. RPC rupture prématurée des membranes avant terme CNGOF.

OBJECTIVE: To review the different parts of therapeutic management of viable preterm premature rupture of membranes (PPROM), except the antibiotherapy and birth modalities. METHODS: The Medline, Cochrane Library, and Google Scholar databases over a period from 1980 to September 2018 have been consulted. RESULTS: When the diagnostic of viable PPROM is reached, the woman should be hospitalized and signs of intrauterine infection (IUI) should be sought (Professional consensus). If cervical assessment appears necessary, speculum, digital examination or cervical ultrasound may be performed (Professional consensus). It is recommended to limit cervical evaluation regardless of the method used (Professional consensus). Initial ultrasound is recommended to determine the fetal presentation, locate the placenta, estimate the fetal weight and the residual amniotic fluid volume (Professional consensus). Performing vaginal and urinary bacteriological sampling at admission is recommended before any antibiotic (Professional consensus). In the case of positive vaginal culture, an antibiogram is necessary since it can guide antibiotherapy in the case of IUI and early onset neonatal bacterial sepsis (Professional consensus). In absence of demonstrated neonatal benefit, there is insufficient evidence to recommend or to not recommend initial tocolysis in PPROM (Grade C). If tocolysis was administered, it is recommended not to prolong it for more than 48hours (Grade C). Antenatal corticosteroid administration is recommended before 34 weeks of gestation (WG) (Grade A) and magnesium sulfate administration is recommended for women at high risk of imminent preterm birth before 32 WG (Grade A). Vitamin supplementation (vitamins C and E) is not recommended (Professional consensus), and it is recommended not to impose strict bed rest in case of PPROM (Professional consensus). In case of clinical signs of IUI with cerclage, it is recommended to remove the cerclage immediately (Professional consensus). The home care management of clinically stable PPROM after 48hours of hospital observation can be considered (Professional consensus). During the monitoring of a PPROM, it is recommended to identify elements relating to the diagnosis of IUI (Professional consensus). CONCLUSION: The level of evidence and scientific data in the literature concerning the management (except antibiotics) of PPROM are low. Initial management of viable PPROM requires hospitalization. The main objectives of the management are the detection and medical care of maternal and fetal complications.

[Preterm premature rupture of membranes: CNGOF Guidelines for clinical practice - Short version]. / Rupture prématurée des membranes avant terme : recommandations pour la pratique clinique du CNGOF ­ Texte court.

OBJECTIVE: To determine management of women with preterm premature rupture of membranes (PPROM). METHODS: Bibliographic search from the Medline and Cochrane Library databases and review of international clinical practice guidelines. RESULTS: In France, PPROM rate is 2 to 3% before 37 weeks of gestation (level of evidence [LE] 2) and less than 1% before 34 weeks of gestation (LE2). Prematurity and intra-uterine infection are the two major complications of PPROM (LE2). Compared to other causes of prematurity, PPROM is not associated with an increased risk of neonatal mortality and morbidity, except in case of intra-uterine infection, which is associated with an augmentation of early-onset neonatal sepsis (LE2) and of necrotizing enterocolitis (LE2). PPROM diagnosis is mainly clinical (professional consensus). In doubtful cases, detection of IGFBP-1 or PAMG-1 is recommended (professional consensus). Hospitalization of women with PPROM is recommended (professional consensus). There is no sufficient evidence to recommend or not recommend tocolysis (grade C). If a tocolysis should be prescribed, it should not last more than 48hours (grade C). Antenatal corticosteroids before 34 weeks of gestation (grade A) and magnesium sulfate before 32 weeks of gestation (grade A) are recommended. Antibiotic prophylaxis is recommended (grade A) because it is associated with a reduction of neonatal mortality and morbidity (LE1). Amoxicillin, 3rd generation cephalosporins, and erythromycin in monotherapy or the association erythromycin-amoxicillin can be used (professional consensus), for 7 days (grade C). However, in case of negative vaginal culture, early cessation of antibiotic prophylaxis might be acceptable (professional consensus). Co-amoxiclav, aminosides, glycopetides, first and second generation cephalosporins, clindamycin, and metronidazole are not recommended for antibiotic prophylaxis (professional consensus). Outpatient management of women with clinically stable PPROM after 48hours of hospitalization is a possible (professional consensus). During monitoring, it is recommended to identify the clinical and biological elements suggesting intra-uterine infection (professional consensus). However, it not possible to make recommendation regarding the frequency of this monitoring. In case of isolated elevated C-reactive protein, leukocytosis, or positive vaginal culture in an asymptomatic patient, it is not recommended to systematically prescribe antibiotics (professional consensus). In case of intra-uterine infection, it is recommended to immediately administer an antibiotic therapy associating beta-lactamine and aminoside (grade B), intravenously (grade B), and to deliver the baby (grade A). Cesarean delivery should be performed according to the usual obstetrical indications (professional consensus). Expectative management is recommended before 37 weeks of gestation in case of uncomplicated PPROM (grade A), even in case of positive vaginal culture for B Streptococcus, provided that an antibiotic prophylaxis has been prescribed (professional consensus). Oxytocin and prostaglandins are two possible options to induce labor in case of PPROM (professional consensus). CONCLUSION: Expectative management is recommended before 37 weeks of gestation in case of uncomplicated PPROM (grade A).

[For a targeted use of aspirin]. / Pour une prescription ciblée de l'aspirine.

The use of low-dose aspirin in pregnancy should remain a highly targeted indication since its long-term safety has not been established and should be restricted to women at high risk of vascular complications. Indications for which the benefit of aspirin has been shown are women with a history of preeclampsia responsible for a premature birth before 34 weeks, those having at least two history of preeclampsia, those with an antiphospholipid syndrome and those with lupus associated with positive antiphospholipid antibodies or renal failure. In all other cases, the level of evidence of the benefit of aspirin is insufficient to recommend its routine prescription.

Dialysis nurses for palliative care.

The palliative approach offers significant and practical care throughout the treatment of the dialysis patient until death. Varied aspects of quality of life for patients can be improved. It is possible to relieve symptoms such as sleep disorders, pain, constipation and pruritus, which, according to the present survey, are common symptoms. The treatment of dying dialysis patients or the possibility and legitimization of discontinuing treatment are complex, controversial issues with ethical and legal implications. But these issues have not yet been adequately dealt with by the nephrological community. The nurses who encounter patients daily, who constantly deal with great suffering and who lack tools to help, can lead the practice in this field within the framework of inter-disciplinary team work. In light of the obvious need for progress in this area, appropriate training courses should be considered. The implementation of the palliative approach in dialysis units could be a challenge for all of us in the coming years.

Staphylococcal infections in PD: monitoring, screening and prevention.

Peritonitis and catheter infections remain a major complication of peritoneal dialysis, accounting for much of the morbidity associated with the technique. The most common source of infection is contamination with predominantly Gram positive skin flora, Staphylococcus (S) epidermidis and S. aureus. The aims of this study were, (a) to determine the incidence of S. aureus and S. epidermidis infections in the unit, (b) to examine whether treatment of S. aureus carriers may reduce the incidence of exit site infection and (c) to examine whether improving patient education may reduce S. epidermidis peritonitis rate.

[Problems posed by the association of hemophilia A and congenital adrenal hyperplasia caused by 21-hydroxylase deficiency]. / Problèmes posés par l'association hémophilie A et hyperplasie congénitale des surrenales par déficit en 21 hydroxylase.

Association of congenital adrenal hyperplasia (21 hydroxylase deficiency) and hemophilia A in one child is reported; the authors insist about the rarity and the genetic implications of this association in case of other children.