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International audience; BackgroundThe optimal dose of tranexamic acid to inhibit hyperfibrinolysis in postpartum haemorrhage is unclear. Tranexamic Acid to Reduce Blood Loss in Hemorrhagic Cesarean Delivery (TRACES) was a double-blind, placebo-controlled, randomised, multicentre dose-ranging study to determine the dose–effect relationship for two regimens of intravenous tranexamic acid vs placebo.MethodsWomen experiencing postpartum haemorrhage during Caesarean delivery were randomised to receive placebo (n=60), tranexamic acid 0.5 g (n=57), or tranexamic acid 1 g i.v. (n=58). Biomarkers of fibrinolytic activation were assayed at five time points, with inhibition of hyperfibrinolysis defined as reductions in the increase over baseline in D-dimer and plasmin–antiplasmin levels and in the plasmin peak time.ResultsIn the placebo group, hyperfibrinolysis was evidenced by a mean increase over baseline [95% confidence interval] of 93% [68–118] for D-dimer level at 120 min and 56% [25–87] for the plasmin–antiplasmin level at 30 min. A dose of tranexamic acid 1 g was associated with smaller increases over baseline (D-dimers: 38% [13–63] [P=0.003 vs placebo]; plasmin–antiplasmin: –2% [–32 to 28] [P=0.009 vs placebo]). A dose of tranexamic acid 0.5 g was less potent, with non-significant reductions (D-dimers: 58% [32–84] [P=0.06 vs placebo]; plasmin–antiplasmin: 13% [18–43] [P=0.051]). Although both tranexamic acid doses reduced the plasmin peak, reduction in plasmin peak time was significant only for the 1 g dose of tranexamic acid.ConclusionsFibrinolytic activation was significantly inhibited by a dose of intravenous tranexamic acid 1 g but not 0.5 g. Pharmacokinetic–pharmacodynamic modelling of these data might identify the best pharmacodynamic monitoring criteria and the optimal tranexamic acid dosing regimen for treatment of postpartum haemorrhage.

General Relativity (GR) exists in different formulations, which are equivalent in pure gravity. Once matter is included, however, observable predictions generically depend on the version of GR. In order to quantify the resulting ambiguity, we employ metric-affine gravity, which encompasses as special cases the metric, Palatini, Einstein-Cartan and Weyl formulations. We first discuss the interaction of fermions with torsion and non-metricity, also commenting on projective symmetry. With a view towards the Standard Model, we then construct a generic model of (complex) scalar, fermionic and gauge fields coupled to GR and derive an equivalent metric theory, which features numerous new interaction terms. As a first observable consequence, we point out that a gravitational mechanism for producing dark matter in the form of singlet fermions can be used to distinguish between metric gravity and other formulations of GR., Comment: 52 pages, 2 figures, 2 appendices

Pre-viable premature rupture of membranes (pre-viable PROM) is a rare event occurring in less than 1% of pregnancies. Nevertheless, it can be responsible for severe maternal complications, the risk of which needs to be balanced with the possibility to prolong the pregnancy up to viable gestational age. Maternal sepsis was reported in 1%-5% of women who received conservative management and prophylactic antibiotics, but information on maternal mortality is lacking. Our objective was to identify maternal deaths in women who had pre-viable PROM, describe the characteristics of the women, explore preventability factors within the care they received, and estimate the lethality of pre-viable PROM.We identified all maternal deaths associated with pre-viable PROM from the 2001-2015 French National Confidential Enquiry into Maternal Deaths (NCMM). Data on women's characteristics and the care they received were extracted from the ENCMM database. The lethality was determined after estimating the total number of pregnant women with pre-viable PROM from the national hospital discharge database.Between 2001 and 2015, we identified seven maternal deaths associated with pre-viable PROM, representing 0.6% of all maternal deaths over this period (ie, maternal mortality ratio 0.06/100 000 live births). Six maternal deaths were attributed to sepsis after genital infection by Gram-negative bacilli and one to postpartum hemorrhage due to placenta accreta. Four of these seven cases were considered preventable. The main preventability factors were delayed diagnosis, delayed fetal extraction, and inappropriate antibiotic treatment. The estimated lethality was 4.5/10 000 women with pre-viable PROM.Maternal death associated with pre-viable PROM is rare but possible. Most of these deaths seem preventable, with areas for improvement related to earlier diagnosis and better treatment of uterine infections, which can evolve rapidly.

General Relativity (GR) exists in different formulations. They are equivalent in pure gravity but generically lead to distinct predictions once matter is included. After a brief overview of various versions of GR, we focus on metric-affine gravity, which avoids any assumption about the vanishing of curvature, torsion or non-metricity. We use it to construct an action of a scalar field coupled non-minimally to gravity. It encompasses as special cases numerous previously studied models. Eliminating non-propagating degrees of freedom, we derive an equivalent theory in the metric formulation of GR. Finally, we give a brief outlook to implications for Higgs inflation., 49 pages, 5 figures, 3 appendices; v2: minor improvements and references added, matches published version

Resume La grossesse et le post-partum sont des periodes ou le risque d’embolie pulmonaire est augmente du fait d’une hypercoagulabilite, d’une stase veineuse et de traumatismes vasculaires eventuels. La physiopathologie de l’embolie pulmonaire fait intervenir une redistribution de la perfusion responsable d’hypoxemie et dans les formes graves une hypertension arterielle pulmonaire responsable de dilatation et d’ischemie du ventricule droit. Certaines parturientes (syndrome des antiphospholipides, mutation du facteur V ou du facteur II) sont particulierement a risque. Ce risque peut etre apprecie a l’aide de score (Dargaud, Strathege) qui permet d’adapter la strategie de prevention. Le seuil des D-dimeres permettant d’eliminer le diagnostic augmente avec l’evolution de la grossesse. La realisation d’un angioscanner thoracique est possible, malgre la grossesse, de meme que l’IRM. Le traitement repose sur les HBPM qui ne passent pas la barriere placentaire. Les antivitamines K sont contre-indiques au cours de la grossesse. La fibinolyse au cours des formes graves est exceptionnelle mais possible ainsi que le recours a l’ECMO.

Resume La mortalite maternelle de cause infectieuse a represente, au cours du triennium 2013–2015, 10 % des causes directes de deces et 12,7 % des causes indirectes. Parmi les 21 deces de causes infectieuses, compare au triennium precedent, les morts maternelles par infection d’origine genitale ont double avec 11 deces pour la periode 2013–2015. Il s’agit pour six cas de toxi-infections puerperales dont quatre dues au Streptocoque A beta hemolytique et pour cinq cas de sepsis secondaires a une infection intra-uterine a Bacille Gram Negatif. Les morts maternelles indirectes par infection d’origine extra-genitale representent 10 deces dans ce triennium dont quatre infections grippales et trois complications infectieuses d’un etat d’immunosuppression (pour deux patientes sur infection a VIH non controlee et pour une patiente sur encephalite a CMV au cours d’un traitement par immunosuppresseurs). Sur ces 21 deces par infection, 6 morts maternelles directes et 9 morts maternelles indirectes ont ete jugees peut-etre ou probablement evitables. Pour ces 15 dossiers, les facteurs d’evitabilite lies au contenu des soins sont les plus frequents (13 fois) : defaut ou retard diagnostique a l’origine d’un retard au traitement medical et/ou obstetrical, absence de vaccination contre la grippe. Des facteurs d’evitabilite lies a l’organisation des soins sont retrouves dans six dossiers (lieu de prise en charge inadapte, transfert fait avec retard ou defaut de communication entre equipes) ainsi que des facteurs lies a la patiente dans cinq cas, le plus souvent par vulnerabilite sociale impactant les interactions avec le systeme de sante.

Resume La grossesse et le post-partum constituent une periode a tres haut risque thromboembolique veineux qui semble se prolonger bien au-dela des classiques 6–8 semaines apres l’accouchement. L’embolie pulmonaire (EP) reste une des trois principales causes de mort maternelle (MM) directe dans la plupart des pays developpes. Entre 2013 et 2015, 23 deces maternels ont ete causes par une complication thromboembolique veineuse (TEV) (20 embolies pulmonaires et 3 thrombophlebites cerebrales), soit 8,8 % des morts maternelles et un ratio de mortalite maternelle de 1,0 pour 100 000 naissances vivantes (IC 95 % 0,6–1,4). Ce resultat est stable sur 10 ans. Concernant le moment du deces, 1 deces est survenu apres une 1 IVG, 35 % (8/23) pendant une grossesse evolutive (dont quatre avant 22 SA), et 61 % (14/23) apres un accouchement. Parmi les 23 deces par TEV, 17 % (5/23) sont survenus en dehors d’une structure de soins (domicile, voie publique). L’âge moyen etait de 32,3 ans et 7 femmes (30 %) etaient âgees de ≥ 35 ans. Six patientes etaient obeses (27 %). Le taux d’evitabilite est de 34,8 % (contre 50 % en 2007–2009 et en 2010–2012), reparti en « peut-etre evitables » (sept cas) ou « probablement evitables » (un cas). Les facteurs d’evitabilite sont l’inadequation des soins dans 34,8 % des cas (8/23), des facteurs organisationnels dans un cas (1/23) et un defaut d’interaction de la patiente avec le systeme de soins dans deux cas (2/23). Tous deces confondus (evitables et non evitables), les soins ont ete consideres comme non optimaux dans 59 %. Cette proportion est superieure au taux d’evitabilite car certains soins consideres comme sous optimaux n’ont pas eu d’influence sur certains deces consideres comme inevitables.

Between 2013 and 2015, six maternal deaths were due to hypertensive disorders. During this period, the maternal mortality ratio was 0.2/100,000 live births. Hypertensive disorders were responsible for 2% of maternal deaths in France and for 5% of direct maternal mortality. All these deaths happened after the delivery. Mode of delivery was a cesarean section when the hypertensive complication started before the delivery (4/6; 67%). Three had DIC during the immediate post-partum. Five women were under 35 years old. Only one had a BMI over 30. Four out of six patients were primiparous. One woman was Afro-Caribbean. Medical care was estimated non-optimal in 100% of the cases. In three cases, it was prenatal care and in three cases it was obstetrical care during delivery; anesthesia and intensive care were suboptimal in five cases. Eighty percent of these deaths seemed to be preventable. The main causes of suboptimal management were inappropriate or insufficient obstetrical and/or anesthetic treatments, and delayed optimal treatment. The analysis of these maternal deaths offers the opportunity to stress major points to optimize medical management in case of hypertensive disorders during pregnancy such as management of eclampsia (use of magnesium sulfate) or recognition of DIC when HELLP syndrome is diagnosed.

Background Pregnant women are at increased risk of hypoxaemia during general anaesthesia. Our aim was to determine the incidence and the risk factors that contribute to hypoxaemia in this setting. Methods Every woman 18 yr or older who underwent a non-elective Caesarean section under general anaesthesia was eligible to participate in this multicentre observational study. The primary endpoint was the incidence of hypoxaemia defined as the SpO2 ≤95%. The secondary endpoint was the incidence of difficult intubation defined as more than two attempts or failed intubation. Results During the study period, 895 women were prospectively included in 17 maternity hospitals, accounting for 79% of women who had general anaesthesia for non-elective Caesarean section. Maternal hypoxaemia was observed in 172 women (19%; confidence interval [CI], 17–22%). Risk factors associated with hypoxaemia in the multivariate analysis were difficult or failed intubation (adjusted odds ratio [aOR]=19.1 [8.6–42.7], P 35 kg m−2 (aOR=0.53 [0.28–0.998], P=0.0495). Intubation was difficult in 40 women (4.5%; CI, 3.3–6%) and failed intubation occurred in five women (0.56%; CI, 0.1–1%). In the multivariate analysis, use of a hypnotic drug other than propofol was associated with difficult or failed intubation (aOR=25 [2–391], P=0.02). A propensity score confirmed that propofol was associated with a significant decreased risk of difficulty or failure to intubate (P Conclusions Hypoxaemia during Caesarean sections was observed in 19% of women and was significantly associated with difficult or failed intubation. The use of propofol may protect against the occurrence of difficult intubation.

Rapid assessment of hemostasis during postpartum hemorrhage (PPH) is essential to allow characterization of coagulopathy, to estimate bleeding severity, and to improve outcome. Point of care (POC) coagulation monitors could be of great interest for early diagnosis and treatment of coagulation disorders in PPH.Women with ongoing PPH500 mL who clinically required an assessment of coagulation with thromboelastography (TEG) were included. The primary aim of this retrospective observational cohort study was to assess the predictive accuracy of TEG parameters for the diagnosis of coagulation disorders (hypofibrinogenemia ≤2 g/L, thrombocytopenia ≤80,000/mm, prothrombin ratio ≤50%, or activated partial thromboplastin time ratio ≥1.5) during PPH. The analyzed TEG parameters were Kaolin-maximum amplitude (K-MA), Kaolin-maximum rate of thrombus generation using G (K-MRTGG), functional fibrinogen-maximum amplitude (FF-MA), and functional fibrinogen-maximum rate of thrombus generation using G (FF-MRTGG). Secondary aims of this study were (1) comparison of the time delay between classical parameters and velocity curve-derived parameters (K-MA versus K-MRTGG and FF-MA versus FF-MRTGG) and (2) evaluation of the accuracy of TEG parameters to predict severe hemorrhage estimated by calculated blood losses.Ninety-eight patients were included with 98 simultaneous TEG analyses and laboratory assays. All parameters had an excellent predictive performance. For the Kaolin assay, no significant difference was evidenced between K-MA and K-MRTGG for the predictive performance for hypofibrinogenemia ≤2 g/L and/or thrombocytopenia ≤80,000/mm (respective area under the curve [AUC], 0.970 vs 0.981). For the functional fibrinogen assay, no significant difference was evidenced between FF-MA and FF-MRTGG for the predictive performance for hypofibrinogenemia ≤2 g/L (respective AUC, 0.988 vs 0.974). For both assays, the time to obtain results was shorter for the velocity parameters (K-MRTGG: 7.7 minutes [2.4 minutes] versus K-MA: 24.7 minutes [4.2 minutes], P.001; FF-MRTGG: 2.7 minutes [2.7 minutes] versus FF-MA: 14.0 minutes [4.3 minutes], P.001). All TEG parameters derived from the Kaolin and functional fibrinogen assays and Clauss fibrinogen were significantly predictive of severe PPH2500 mL.During PPH, when coagulation assessment is indicated, TEG provides a rapid and reliable detection of hypofibrinogenemia ≤2 g/L and/or thrombocytopenia ≤80,000/mm. No difference in performance was evidenced between the velocity-derived parameters (K-MRTGG and FF-MRTGG) and the classical parameters (K-MA and FF-MA). However, velocity-derived parameters offer the advantage of a shorter time to obtain results: FF-MRTGG parameter is available within ≤5 minutes. POC assessment of hemostasis during PPH management may help physicians to diagnose clotting disorders and to provide appropriate hemostatic support.

International audience; Objective: To provide national guidelines for the management of women with severe preeclampsia. Design: A consensus committee of 26 experts was formed. A formal conflict of interest (COI) policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Methods: The last SFAR and CNGOF guidelines on the management of women with severe preeclampsia was published in 2009. The literature is now sufficient for an update. The aim of this expert panel guidelines is to evaluate the impact of different aspects of the management of women with severe preeclampsia on maternal and neonatal morbidities separately. The experts studied questions within 7 domains. Each question was formulated according to the PICO (Patients Intervention Comparison Outcome) model and the evidence profiles were produced. An extensive literature review and recommendations were carried out and analyzed according to the GRADE® methodology. Results: The SFAR/CNGOF experts panel provided 25 recommendations: 8 have a high level of evidence (GRADE 1±), 9 have a moderate level of evidence (GRADE 2±), and for 7 recommendations, the GRADE method could not be applied, resulting in expert opinions. No recommendation was provided for 3 questions. After one scoring round, strong agreement was reached between the experts for all the recommendations. Conclusions: There was strong agreement among experts who made 25 recommendations to improve practices for the management of women with severe preeclampsia.

To provide national guidelines for the management of women with severe preeclampsia.A consensus committee of 26 experts was formed. A formal conflict of interest (COI) policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized.The last SFAR and CNGOF guidelines on the management of women with severe preeclampsia was published in 2009. The literature is now sufficient for an update. The aim of this expert panel guidelines is to evaluate the impact of different aspects of the management of women with severe preeclampsia on maternal and neonatal morbidities separately. The experts studied questions within 7 domains. Each question was formulated according to the PICO (Patients Intervention Comparison Outcome) model and the evidence profiles were produced. An extensive literature review and recommendations were carried out and analyzed according to the GRADE® methodology.The SFAR/CNGOF experts panel provided 25 recommendations: 8 have a high level of evidence (GRADE 1±), 9 have a moderate level of evidence (GRADE 2±), and for 7 recommendations, the GRADE method could not be applied, resulting in expert opinions. No recommendation was provided for 3 questions. After one scoring round, strong agreement was reached between the experts for all the recommendations.There was strong agreement among experts who made 25 recommendations to improve practices for the management of women with severe preeclampsia.

Objective: To study the effect of a low (0.5g) or a standard (1g) tranexamic acid (TA) dose compared to placebo on clinical and biological endpoints in women experiencing postpartum hemorrhage (PPH) Design: TRACES trial is a double-blind, randomized, placebo-controlled, dose-ranging study Setting: 8 women hospitals in France. Population: Women experiencing PPH > 800 mL during caesarean section. Method: After informed consent, patients were randomized to receive either TA 0.5g (n=57), TA 1g (n=58), or a placebo (n=60). Data were collected at 8 time-points. Main outcome measures: Efficacy: additional blood loss after study drug, maternal morbidity, safety, biology: D-dimers, plasmin-antiplasmin complexes (PAP), simultaneous-generation-thrombin-plasmin-potential. Results: Compared to 1g dose, 0.5g TA was less effective to reduce additional blood loss (300 mL [95% confidence interval (95%CI) 68 to 630] vs 134 mL [95%CI50 to 419] (p=0.042)). Compared to placebo, 1g TA, but not 0.5g, inhibited hyperfibrinolysis as shown by plasmin generation potential, % increase in D-dimers from injection to 120 minutes (93% [95%CI 68 to 118] vs 58% [ 95%CI 32 to 84] (p=0.06) vs 38% [95%CI 13 to 63] (p=0.003) and % increase in PAP from injection to 30 minutes (56% [95%CI 25 to 87] vs 13% [ 95%CI 18 to 43] (p=0,051) vs -2% [95%CI -32 to 28] (p=0.009)). Conclusions: In this study, fibrinolysis inhibition was more sustained after the administration of 1g TA compared to 0.5g TA or a placebo. Further pharmacokinetic-pharmacodynamic modelling will be needed to determine the optimal TA dose to be administered in PPH. NCT 02797119

Objective To provide national guidelines for the management of women with severe pre-eclampsia. Design A consensus committee of 26 experts was formed. A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE(r)) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised. Methods The last SFAR and CNGOF guidelines on the management of women with severe pre-eclampsia were published in 2009. The literature is now sufficient for an update. The aim of this expert panel guidelines is to evaluate the impact of different aspects of the management of women with severe preeclampsia on maternal and neonatal morbidities separately. The experts studied questions within 7 domains. Each question was formulated according to the PICO (Patients Intervention Comparison Outcome) model and the evidence profiles were produced. An extensive literature review and recommendations were carried out and analysed according to the GRADE(r) methodology. Results The SFAR/CNGOF experts panel provided 25 recommendations: 8 have a high level of evidence (GRADE 1+/−), 9 have a moderate level of evidence (GRADE 2+/−), and for 7 recommendations, the GRADE method could not be applied, resulting in expert opinions. No recommendation was provided for 3 questions. After one scoring round, strong agreement was reached between the experts for all the recommendations. Conclusions There was strong agreement among experts who made 25 recommendations to improve practices for the management of women with severe pre-eclampsia.

International audience; BACKGROUND : In this prospective study, we describe the electroencephalographic (EEG) profiles in children anesthetized with sevoflurane or propofol.METHODS : Seventy-three subjects (11 years, range 5-18) were included and randomly assigned to two groups according to the anesthetic agent. Anesthesia was performed by target-controlled infusion of propofol (group P) or by sevoflurane inhalation (group S). Steady-state periods were performed at a fixed randomized concentration between 2, 3, 4, 5, and 6 μg.ml-1 of propofol in group P and between 1, 2, 3, 4, and 5% of sevoflurane in group S. Remifentanil was continuously administered throughout the study. Clinical data, Bispectral Index (BIS), and raw EEG were continuously recorded. The relationship between BIS and anesthetic concentrations was studied using nonlinear regression. For all steady-state periods, EEG traces were reviewed to assess the presence of epileptoid signs, and spectral analysis of raw EEG was performed.RESULTS : Under propofol, BIS decreased monotonically and EEG slowed down as concentrations increased from 2 to 6 μg.ml-1 . Under sevoflurane, BIS decreased from 0% to 4% and paradoxically rose from 4% to 5% of expired concentration: this increase in BIS was associated with the occurrence of fast oscillations and epileptoid signs on the EEG trace. Propofol was associated with more delta waves and burst suppression periods compared to sevoflurane.CONCLUSION : Under deep anesthesia, the BIS and electroencephalographic profiles differ between propofol and sevoflurane. For high concentrations of sevoflurane, an elevated BIS value may be interpreted as a sign of epileptoid patterns or EEG fast oscillations rather than an insufficient depth of hypnosis.

International audience; Introduction: - Open fetal myelomeningocele (MMC) surgery is currently the standard of care option for prenatal MMC repair. We described the population referred to our center and reviewed outcome after open fetal MMC repair.Material and methods: - All patients referred to our center for MMC were reviewed from July 2014 to June 2020. For all the patients who underwent fetal MMC repair, surgical details, maternal characteristics and data from the neonatal to the three-years-old evaluations were collected.Results: - Among the 126 patients referred to our center, 49.2% were eligible and 27.4% (n=17) of them underwent fetal MMC repair. Average gestational age at fetal surgery was 24+6 weeks. There was no case of fetal complication and the only maternal complication was one case of transfusion. We recorded 70% of premature rupture of membranes and 47% of premature labor. Average gestational age at delivery was 34+2 weeks and no patient delivered before 30 weeks. There was no case of uterine scar dehiscence or maternal complication during cesarean section. After birth, 59% of the children had a hindbrain herniation reversal. At 1-year-old, 42% were assigned a functional level of one or more better than expected according to the prenatal anatomic level and 25% required a ventriculoperitoneal shunt. At 3-year-old, all the children attended school and 75% were able to walk with orthotics or independently.Conclusion: - Open fetal surgery enables anatomical repair of the MMC lesion, a potential benefit on cerebral anomalies and motor function, with a low rate of perinatal and maternal complications.

International audience; Abstract Objective Obesity has significant implications for the health of pregnant women. However, few studies have quantified its association with maternal mortality or examined the relevant underlying causes and the role of care, although this remains the most severe maternal outcome. Our objectives were to quantify the risk of maternal death by prepregnancy body mass index and to determine whether obesity affected the quality of care of the women who died. Desing This is a national population-based case–control study in France. Cases were 364 maternal deaths from the 2007–2012 National Confidential Enquiry. Controls were 14,681 parturients from the nationally representative 2010 perinatal survey. We studied the association between categories of prepregnancy BMI and maternal death by multivariable logistic regression, estimating adjusted odds ratios and 95% confidence intervals, overall and by specific causes of death. Individual case reviews assessed the quality of care provided to the women who died, by obesity status. Results Compared with women with normal BMI, underweight women (

International audience; To provide national guidelines for the management of women with severe pre-eclampsia. Design: A consensus committee of 26 experts was formed. A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE(r)) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised. The last SFAR and CNGOF guidelines on the management of women with severe pre-eclampsia were published in 2009. The literature is now sufficient for an update. The aim of this expert panel guidelines is to evaluate the impact of different aspects of the management of women with severe preeclampsia on maternal and neonatal morbidities separately. The experts studied questions within 7 domains. Each question was formulated according to the PICO (Patients Intervention Comparison Outcome) model and the evidence profiles were produced. An extensive literature review and recommendations were carried out and analysed according to the GRADE(r) methodology. The SFAR/CNGOF experts panel provided 25 recommendations: 8 have a high level of evidence (GRADE 1+/−), 9 have a moderate level of evidence (GRADE 2+/−), and for 7 recommendations, the GRADE method could not be applied, resulting in expert opinions. No recommendation was provided for 3 questions. After one scoring round, strong agreement was reached between the experts for all the recommendations. Conclusions: There was strong agreement among experts who made 25 recommendations to improve practices for the management of women with severe pre-eclampsia.

Objective To provide national guidelines for the management of women with severe pre-eclampsia. Design A consensus committee of 26 experts was formed. A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised. Methods The last SFAR and CNGOF guidelines on the management of women with severe pre-eclampsia were published in 2009. The literature is now sufficient for an update. The aim of this expert panel guidelines is to evaluate the impact of different aspects of the management of women with severe preeclampsia on maternal and neonatal morbidities separately. The experts studied questions within 7 domains. Each question was formulated according to the PICO (Patients Intervention Comparison Outcome) model and the evidence profiles were produced. An extensive literature review and recommendations were carried out and analysed according to the GRADE® methodology. Results The SFAR/CNGOF experts panel provided 25 recommendations: 8 have a high level of evidence (GRADE 1+/−), 9 have a moderate level of evidence (GRADE 2+/−), and for 7 recommendations, the GRADE method could not be applied, resulting in expert opinions. No recommendation was provided for 3 questions. After one scoring round, strong agreement was reached between the experts for all the recommendations. Conclusions There was strong agreement among experts who made 25 recommendations to improve practices for the management of women with severe pre-eclampsia.

Pregnancy and postpartum represent periods at very high risk of venous thromboembolism disease which appears to extend well beyond the classic 6-8 weeks after childbirth. Pulmonary embolism (PE) is still one of the three leading causes of direct maternal death (MM) in most developed countries. Between 2013 and 2015, 23 maternal deaths were caused by a venous thromboembolic complication (VTE) (20 pulmonary embolism and 3 cerebral thrombophlebitis), representing 8.8 % of maternal deaths and a Maternal Mortality Ratio of 1.0 per 100,000 live births (95 % CI 0.6-1, 4) which is stable over the last 10 years. Regarding the timing of death, 1 death occurred after abortion, 35 % (8/23) during an ongoing pregnancy (including four before 22 WG), and 61 % (14/23) after childbirth. Among the 23 deaths from VTE, 17 % (5/23) occurred outside a healthcare center (home, street). The mean age was 32.3 and 7 women (30 %) were≥35 years old. Six patients were obese (27 %). The preventability rate is 34.8 % (compared to 50 % in 2007-2009 and 2010-2012), The preventability factors involve the inadequacy of care in 34.8 % of cases (8/23), organizational factors in one case (1/23) and a lack of interaction of the patient with the health care system in two cases (2/23). Care was considered non-optimal in 59 % of these deaths. This proportion is higher than the preventability rate because suboptimal care sometimes did not influence the final outcome.

Over the 2013-2015 period, maternal mortality due to infections accounted for 10 % of direct maternal deaths and 13 % of indirect maternal deaths. Among the 21 deaths from infection, and compared to the last triennium, maternal deaths from genital infection doubled with 11 deaths during the 2013-2015 period. This included 6 cases of puerperal toxic shock syndrome, 4 of which due to Streptococcus A, and 5 cases of sepsis caused by intrauterine infection due to Gram-Negative Bacillus. Indirect maternal deaths due to infections from extragenital sources represented 10 deaths in this triennium, including four influenza infections and three infectious complications of an immunosuppressive state (uncontrolled HIV infection for two patients and CMV encephalitis during an immunosuppressive treatment for one patient). Of these 21 deaths by infectious causes, 6 direct maternal deaths and 9 indirect maternal deaths were considered preventable. The most common preventable factors were those related to medical management (13 times): diagnostic failure or delayed diagnosis leading to a delayed medical treatment, absence of influenza vaccination. The other contributory factors were related to the organization of healthcare (delayed transfer, lack of communication between clincians) as well as factors related to patient social vulnerability.

Between 2013 and 2015, six maternal deaths were due to hypertensive disorders. During this period, the maternal mortality ratio was 0.2/100,000 live births. Hypertensive disorders were responsible for 2% of maternal deaths in France and for 5% of direct maternal mortality. All these deaths happened after the delivery. Mode of delivery was a cesarean section when the hypertensive complication started before the delivery (4/6; 67%). Three had DIC during the immediate post-partum. Five women were under 35 years old. Only one had a BMI over 30. Four out of six patients were primiparous. One woman was Afro-Caribbean. Medical care was estimated non-optimal in 100% of the cases. In three cases, it was prenatal care and in three cases it was obstetrical care during delivery; anesthesia and intensive care were suboptimal in five cases. Eighty percent of these deaths seemed to be preventable. The main causes of suboptimal management were inappropriate or insufficient obstetrical and/or anesthetic treatments, and delayed optimal treatment. The analysis of these maternal deaths offers the opportunity to stress major points to optimize medical management in case of hypertensive disorders during pregnancy such as management of eclampsia (use of magnesium sulfate) or recognition of DIC when HELLP syndrome is diagnosed.

Performing a feticide as part of termination of late pregnancy is recommended in many countries. Feticide avoids a live birth of a severely affected premature newborn and prevents fetal pain. There are limited data on feticide procedures since only a few countries in the world authorize late termination of pregnancy. The objective of this review was to assess the most appropriate feticide procedure based on published data during the last thirty years. Administration of an initial fetal analgesia followed by a lethal lidocaine injection through the umbilical cord, under ultrasound guidance, appears to be the most effective, safe and ethical way to perform feticide. According to the current knowledge regarding the risk of fetal pain and survival of extremely preterm infants, a feticide should be discussed as early as 20-22 weeks of gestation.

In type III hereditary angioedema (HAE type III), the phenotype is the same as type I and type II disease, but the level and function of C1-esterase inhibitor (C1-INH) is normal. Hereditary angioedema type III has been described as an oestrogen-sensitive form because it can be triggered or aggravated by exposure to high oestrogen levels as seen during pregnancy, especially when associated with Factor XII mutation. This case report describes the evolution and management of repeated angioedema attacks during pregnancy in a woman with HAE, with normal levels and function of C1-INH (type III); and a mis-sense mutation of factor XII. The physiopathology and genetic features, the unpredictability of clinical manifestations and the management during pregnancy and delivery are discussed.

Resume La mortalite maternelle de cause infectieuse a represente au cours de la periode 2010–2012, 5 % des causes directes de deces et 16 % des morts maternelles indirectes. Parmi les 22 deces releves de causes infectieuses, 6 morts maternelles ont ete attribuees a une infection a porte d’entree genitale confirmant la diminution depuis 10 ans des morts maternelles directes par infection. A l’inverse, les morts maternelles indirectes par infection, a porte d’entree extragenitale, ont double au cours de la meme periode avec 16 deces au cours du dernier triennium, domines par les infections respiratoires hivernales en particulier grippales : la pandemie grippale A (H1N1) de 2009–2010 est, au cours de la periode etudiee, la premiere cause de mortalite maternelle indirecte par infection. Les principaux agents infectieux a l’origine des deces de cause infectieuse directe sont les Streptococcus pyogenes , Escherichia Coli et Clostridium perfringens , responsables de chocs toxi-infectieux, de sepsis graves, secondaires pour plusieurs cas a une cellulite ou une fasciite necrosante. Sur les 6 deces par infection directe, 4 ont ete juges peut-etre evitables en raison de soins inadaptes : retard ou defaut diagnostique, traitement medical et/ou chirurgical initie avec retard ou inadapte. Parmi les 16 morts maternelles indirectes par infection, le virus grippal A(H1N1) et le Streptococcus pneumoniae complique de purpura fulminans ont ete le plus souvent en cause : l’absence de vaccination antigrippale au cours de la grossesse, le retard diagnostique et a l’initiation en urgence d’un traitement specifique sont les principaux facteurs d’evitabilite retrouves dans 70 % des dossiers expertises.

Background Pupillometry has shown promising results for assessing nociception in anesthetized patients. However, its benefits in clinical practice are not demonstrated. The aim of this prospective randomized study was to evaluate the impact of intraoperative pupillometry monitoring on perioperative opioid consumption in major gynecologic surgery. Methods After receiving ethics committee approval and written consent of patients, American Society of Anesthesiologists status I to II women undergoing gynecologic surgery were included in this single-blinded, prospective, parallel-arm randomized study. General anesthesia was standardized with propofol–remifentanil target-controlled infusion. Patients were randomly assigned into two groups. In the pupillometry group, remifentanil administration was guided by pupillary diameter changes. In the standard group, remifentanil administration was left to the discretion of the anesthesiologist. The primary outcome was intraoperative remifentanil consumption. Results Fifty-five patients were analyzed. Remifentanil consumption was markedly decreased in the pupillometry group (3.8 [3.4 to 4.8 µg · kg–1 · h–1] vs. 7.9 µg · kg–1 · h–1 [6.5 to 9.0 µg · kg–1 · h–1] in the standard group; difference = 4.2 µg · kg–1 · h–1 [95% CI, 3.0 to 5.3 µg · kg–1 · h–1]; P < 0.001). Cumulative 0- to 12-h morphine consumption was reduced in the pupillometry group (two-way repeated measures ANOVA 0.3 ± 0.1 vs. 0.4 ± 0.2 mg/kg; P = 0.048). A telephone survey 3 months after surgery revealed that 15 of 29 patients in the standard group still experienced procedure-related pain versus 3 of 23 in the pupillometry group (chi-square P = 0.037). No adverse events associated with pupillometry were observed during the study. Conclusions The use of pupillometry to guide intraoperative analgesia reduced intraoperative remifentanil consumption and postoperative morphine requirements. The possible consequences of decreasing intraoperative remifentanil in terms of chronic pain require further investigation.

Objectives To evaluate feasibility of performing benign gynecologic pathology low pressure (7 mmHg) laparoscopy (LPL) with AirSeal® system and to study benefits in terms of postoperative pain, when compared to a standard insufflation group (15 mmHg). Materials and methods In this prospective randomized pilot study, 60 patients had laparoscopy for gynecologic benign pathology: 30 with 7 mmHg and AirSeal system, and 30 with 15 mmHg standard insufflator. The primary endpoint was incidence of shoulder pain. A postoperative questionnaire was completed by each patient to assess shoulder pain (Numeric Rating Scale [NRS], from 0 to 10) at H4, H8, H24, and consumption of morphinics was notified. During each procedure, anesthesia parameters were collected (peak airway pressure, systolic blood pressure, end tidal CO2). Results Laparoscopy was performed on 30 patients in AirSeal®-LP group without need to increase pressure above 7 mmHg, and no complication was reported. Incidence of shoulder pain was significantly lower in the AirSeal®-LP group (23.3% vs. 73.3%, P Conclusion LP (7 mmHg) laparoscopy with AirSeal® platform allows laparoscopic surgery with less postoperative shoulder pain. These results could facilitate the development of ambulatory laparoscopy.

MYH9-related disease (MYH9-RD) is an inherited rare autosomal dominant macrothrombocytopenia. Patients with MYH9-RD have giant platelets and leukocyte inclusion bodies caused by mutations in the MYH9 gene encoding the non-muscle myosin heavy chain II-A. Before identification of the causative gene, patients were diagnosed as Epstein or Fechtner or Sebastian syndromes or May-Hegglin anomaly. As with other inherited thrombocytopenias, the risk of increased bleeding during perioperative period or delivery is a major concern. We report here the first successful cesarean delivery of a woman with MYH9-RD treated with eltrombopag during the last month of pregnancy.

Performing a feticide as part of termination of late pregnancy is recommended in many countries. Feticide avoids a live birth of a severely affected premature newborn and prevents fetal pain. There are limited data on feticide procedures since only a few countries in the world authorize late termination of pregnancy. The objective of this review was to assess the most appropriate feticide procedure based on published data during the last thirty years. Administration of an initial fetal analgesia followed by a lethal lidocaine injection through the umbilical cord, under ultrasound guidance, appears to be the most effective, safe and ethical way to perform feticide. According to the current knowledge regarding the risk of fetal pain and survival of extremely preterm infants, a feticide should be discussed as early as 20-22 weeks of gestation.

BACKGROUND Pupillometry monitoring under general anesthesia is based on the assumption that pupillary diameter variations reflect the adequacy of the provided analgesia to the intensity of the nociceptive surgical stimulus. The accurate interpretation of pupillometric data requires establishing clearly what the expected baseline unstimulated pupillary diameter at each specific level of hypnosis is. Opioids decrease pupillary diameter in a dose-dependent fashion. In contrast, the effects of hypnotic drugs on pupillary diameter are not well known. Our aim was to describe the potential relationship between propofol predicted effect-site concentrations (Cets) ranging from 1 to 3 µg/mL and pupillary diameter. METHODS Patients were randomized to receive propofol by target-controlled infusion at a predicted Cet of 1, 2, or 3 µg/mL (groups P1, P2, and P3, respectively). Pupillary diameter measurements were performed after 10 minutes of steady-state propofol infusion at the randomized Cet. No stimulation was performed during the study. Heart rate and bispectral index (BIS) were continuously recorded. RESULTS Forty patients were included: (13, 14, and 13 in groups P1, P2, and P3, respectively). Mean pupillary diameter was 5.7 mm (1 mm) in group P1, 4.8 mm (1.3 mm) in group P2, and 3.3 mm (0.8 mm) in group P3. Propofol had a dose-dependent effect on pupillary diameter (linear regression R = 0.45, P < .001). Pupillary diameter was positively correlated with the BIS (Spearman r = 0.75 [95% confidence interval (CI), 0.54 to -0.87] P < .001). CONCLUSIONS From 1 to 3 µg/mL of predicted Cet, propofol has a dose-dependent effect on pupillary diameter. Within this concentrations range, there is a positive correlation between BIS and pupillary diameter. The subcortical effect of propofol on pupillary diameter is correlated to its effect on the cortex. Studies assessing pupillary diameter as a marker of the nociception-antinociception balance should be performed in patients with a standardized depth of hypnosis.

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 45 - N° 7 - p. 738-744

The optimal management of pain is crucial to facilitate perioperative rehabilitation. These well-known principles apply to patients after a cesarean section or a vaginal delivery. Indeed, if the cesarean has been considered as a reproducible model of acute pain, acute pain have been largely underestimated or ignored after vaginal delivery, andhas been taken into account only recently. Perineal pain is indeed very common: duration and intensity are correlated with the severity of tissue damage. They may be an obstacle to postpartum rehabilitation. For the physician, post-partum rehabilitation focused on appropriate analgesic strategies should also take into account the specificities of the post-partum period which are motherchild relationship, breastfeeding facilitation and newborn care. Beyond the immediate postpartum rehabilitation, consideration and treatment of acute pain also prevent the emergence of persistent pain and post-partum depressions. Indeed, severity of acute post-partum pain but not mode of delivery is related to the risk of persistent pain and postpartum depressions.

Over the period 2010-2012, maternal mortality from infectious causes accounted for 5% of maternal deaths by direct causes and 16% of maternal deaths by indirect causes. Among the 22 deaths caused by infection occurred during this period, 6 deaths were attributed to direct causes from genital tract origin, confirming thus the decrease in direct maternal deaths by infection during the last ten years. On the contrary, indirect maternal deaths by infection, from extragenital origin, doubled during the same period, with 16 deaths in the last triennium, dominated by winter respiratory infections, particularly influenza: the 2009-2010 influenza A (H1N1) virus pandemic was the leading cause of indirect maternal mortality by infection during the studied period. The main infectious agents involved in maternal deaths from direct causes were Streptococcus A, Escherichia Coli and Clostridium perfringens: these bacterias were responsible for toxic shock syndrome, severe sepsis, secondary in some cases to cellulitis or necrotizing fasciitis. Of the 6 deaths due to direct infection, 4 were considered avoidable because of inadequate management: delayed or missed diagnosis, delayed or inadequate initiation of a specific medical and/or surgical treatment. Of the 16 indirect maternal deaths due to infection causes, the most often involved infectious agents were influenza A (H1N1) virus and Streptococcus pneumonia with induced purpura fulminans: the absence of influenza vaccination during pregnancy, delayed diagnosis and emergency initiation of a specific treatment, were the main contributory factors to these deaths and their avoidability in 70% of the cases analyzed.

Pupillometry has shown promising results for assessing nociception in anesthetized patients. However, its benefits in clinical practice are not demonstrated. The aim of this prospective randomized study was to evaluate the impact of intraoperative pupillometry monitoring on perioperative opioid consumption in major gynecologic surgery.After receiving ethics committee approval and written consent of patients, American Society of Anesthesiologists status I to II women undergoing gynecologic surgery were included in this single-blinded, prospective, parallel-arm randomized study. General anesthesia was standardized with propofol-remifentanil target-controlled infusion. Patients were randomly assigned into two groups. In the pupillometry group, remifentanil administration was guided by pupillary diameter changes. In the standard group, remifentanil administration was left to the discretion of the anesthesiologist. The primary outcome was intraoperative remifentanil consumption.Fifty-five patients were analyzed. Remifentanil consumption was markedly decreased in the pupillometry group (3.8 [3.4 to 4.8 µg · kg · h] vs. 7.9 µg · kg · h [6.5 to 9.0 µg · kg · h] in the standard group; difference = 4.2 µg · kg · h [95% CI, 3.0 to 5.3 µg · kg · h]; P0.001). Cumulative 0- to 12-h morphine consumption was reduced in the pupillometry group (two-way repeated measures ANOVA 0.3 ± 0.1 vs. 0.4 ± 0.2 mg/kg; P = 0.048). A telephone survey 3 months after surgery revealed that 15 of 29 patients in the standard group still experienced procedure-related pain versus 3 of 23 in the pupillometry group (chi-square P = 0.037). No adverse events associated with pupillometry were observed during the study.The use of pupillometry to guide intraoperative analgesia reduced intraoperative remifentanil consumption and postoperative morphine requirements. The possible consequences of decreasing intraoperative remifentanil in terms of chronic pain require further investigation.

© 2017 Royal College of Obstetricians and Gynaecologists Objective: Develop a core outcome set of international consensus definitions for severe maternal morbidities. Design: Electronic Delphi study. Setting: International. Population: Eight expert panels. Methods: All 13 high-income countries represented in the International Network of Obstetric Surveillance Systems (INOSS) nominated five experts per condition of morbidity, who submitted possible definitions. From these suggestions, a steering committee distilled critical components: eclampsia: 23, amniotic fluid embolism: 15, pregnancy-related hysterectomy: 11, severe primary postpartum haemorrhage: 19, uterine rupture: 20, abnormally invasive placentation: 12, spontaneous haemoperitoneum in pregnancy: 16, and cardiac arrest in pregnancy: 10. These components were assessed by the expert panel using a 5-point Likert scale, following which a framework for an encompassing definition was constructed. Possible definitions were evaluated in rounds until a rate of agreement of more than 70% was reached. Expert commentaries were used in each round to improve definitions. Main outcome measures: Definitions with a rate of agreement of more than 70%. Results: The invitation to participate in one or more of eight Delphi processes was accepted by 103 experts from 13 high-income countries. Consensus definitions were developed for all of the conditions. Conclusion: Consensus definitions for eight morbidity conditions were successfully developed using the Delphi process. These should be used in national registrations and international studies, and should be taken up by the Core Outcomes in Women's and Newborn Health initiative. Tweetable abstract: Consensus definitions for eight morbidity conditions were successfully developed using the Delphi process.

The risk of difficult upper airway access is increased during pregnancy, especially in labor. Changes in upper airway calibre have been poorly studied during pregnancy. The acoustic reflection method is a non-invasive technique that allows a longitudinal assessment of the cross-sectional area of the upper airway from the mouth to carina. We used this technique to evaluate upper airway calibre during normal pregnancy.We conducted a prospective, single centre, observational study with a clinical and upper airway acoustic reflection method evaluation of healthy women during the first, second and third trimesters of pregnancy, and up to two days and one month after delivery.Fifty women participated to the study. The mean pharyngeal cross-sectional area decreased between the first and third trimesters (P0.001) with no significant change of the minimal and mean tracheal cross-sectional areas. The Mallampati score increased during pregnancy between the first and third trimesters (P0.001).Using measurements with the acoustic reflection method, normal pregnancy is associated with a significant reduction in the cross-sectional area of the pharynx and a concomitant increase in the Mallampati score. No change was observed in the minimal and mean tracheal cross-sectional areas.

Face aux considerables opportunites d’investissement offertes par ses mutations demographiques, urbaines et economiques, l’AfSS est devenu un veritable terrain d’action pour les acteurs du capital-investissement. Les grands bailleurs de fonds sont en train d'etre remplaces par des investisseurs de plus en plus diversifies. Cet interet grandissant des investisseurs montre que l’image de la region s’ameliore. Il existe toutefois aujourd’hui un risque de « surchauffe ». Les acteurs doivent s’adapter aux specificites de l’AfSS, caracterisee par des operations de petite taille dans des contextes d’entrepreneurs familiaux qui ne souhaitent pas ceder la majorite. Ainsi, les fonds de private equity investissant en Afrique ont une triple utilite : mobiliser l’epargne longue disponible et l’investir dans des projets de qualite, fournir les fonds propres necessaires aux entreprises en forte croissance, et reduire l’ecart entre les industriels des pays developpes et des pays emergents.Classification JEL : F21, G11, G24, O16, O55.

Dans la periode perinatale, patients et soignants sont confrontes a des peurs de types differents. La crainte de survenue d’evenements indesirables graves (EIG) pour les patientes et leurs enfants domine les peurs des soignants. Differentes strategies d’anticipation et de prevention des EIG ont ete developpees : elles passent par leur reconnaissance, leur analyse et en particulier la recherche de leur evitabilite en se placant dans une demarche continue d’amelioration des pratiques professionnelles. Les patientes peuvent etre, quant a elles, confrontees a des peurs « a priori », liees aux nombreuses incertitudes et inconnues de la periode perinatale pour elle et leur enfant, mais aussi a des peurs « a posteriori », pouvant aller jusqu’a un etat de stress post-traumatique (ESPT), qui peut perturber l’etablissement du lien mere-enfant, et conditionner le vecu des grossesses ulterieures. Permettre aux patientes d’acceder pendant toute la periode perinatale, a des informations claires et detaillees, de beneficier d’une communication et d’une attention humaine adaptee, ainsi que depister precocement des symptomes d’ESPT en post-natal, constituent les principaux moyens a mettre en oeuvre pour minimiser l’anxiete, prevenir la survenue d’un ESPT et favoriser la relation mere-enfant.

Gestational diabetes insipidus is an uncommon clinical disease whose prevalence is approximately two to three pregnancies per 100,000. It may be isolated or associated with preeclampsia. We report a case of gestational diabetes insipidus in a twin pregnancy, originally isolated during two months, and secondarily complicated by HELLP-syndrome. We recall the specific pathophysiology of polyuric-polydipsic syndrome during pregnancy and summarize its various causes. Finally, we discuss the indications, in case of isolated gestational diabetes insipidus, of treatment by dDAVP.

For several years, total intravenous anaesthesia (TIVA) has demonstrated many advantages that allow considering propofol anaesthesia as an interesting alternative in pediatric anaesthesia. TCI in children requires calculation and validation of pharmacokinetic (PK) models specifically adapted to the paediatric population. Several PK models based on a 3-compartement approach have been proposed in children: all these models, which integrate only weight as covariable, show increased distribution volumes with a wide interindividual variability. The particular importance to include physiological covariables, as age and lean body mass, to describe metabolic processes during growth and maturation in pediatric PKPD models is in agreement with recent allometric scaling works in children. However, as pharmacodynamic (PD) parameters are still debated in children, there is up to now, no PKPD model currently available for paediatric anaesthesia. Schnider et al.'s model, a model described in adults that includes numerous covariables, may be adapted and more efficient than the classical paediatric models to describe propofol-PKPD relationship in children over 5years. Whatever the model, a pharmacodynamic feedback such as the bispectral index may be useful to counteract interindividual variability in the paediatric population.

Background Sevoflurane has become the gold standard for inhalation induction in children. However in children as in adults, epileptiform electroencephalographic signs have been described under high concentrations of sevoflurane. The aim of this study was to determine the minimal alveolar concentration (MAC) of sevoflurane associated with the occurrence of major epileptiform signs (MES) in 50% children under steady-state conditions. The MAC of MES (MAC MES) was determined in 100% oxygen and with the addition of 50% nitrous oxide or after the injection of alfentanil (ALFENTA). Methods Seventy-nine children (3-11 yr), undergoing elective surgery and premedicated with hydroxyzine were included. After induction by inhalation and tracheal intubation, a 10-min period with a stable expired fraction of sevoflurane was obtained. The MES were defined as rhythmic polyspikes or epileptiform discharges. Electroencephalographic recordings were blindly analyzed by two independent experts. The MAC MES were determined by the Dixon method: the concentration of sevoflurane was determined by the result from the previous patient: increase of 0.2% if MES were absent or decrease of 0.2% if MES were present. Three consecutive series were performed: (1) in 100% oxygen (MAC MESO2); (2) in 50% oxygen and 50% nitrous oxide (MAC MESN2O); and (3) in 100% oxygen with a bolus of alfentanil (MAC MESALFENTA). Results The MAC MESO2 was 4.3±0.1% (mean±SD), the MAC MESN2O and the MAC MESALFENTA were higher, respectively: 4.6±0.2% (P=0.01) and 4.6±0.2% (P=0.02). Conclusions In children premedicated with hydroxyzine, the MAC MES of sevoflurane calculated in 100% O2 corresponded to 1.75 surgical MAC. In addition, our results have demonstrated a moderate effect of nitrous oxide and alfentanil in raising the threshold of MES.

To evaluate feasibility of performing benign gynecologic pathology low pressure (7mmHg) laparoscopy (LPL) with AirSealIn this prospective randomized pilot study, 60 patients had laparoscopy for gynecologic benign pathology: 30 with 7mmHg and AirSeal system, and 30 with 15mmHg standard insufflator. The primary endpoint was incidence of shoulder pain. A postoperative questionnaire was completed by each patient to assess shoulder pain (Numeric Rating Scale [NRS], from 0 to 10) at H4, H8, H24, and consumption of morphinics was notified. During each procedure, anesthesia parameters were collected (peak airway pressure, systolic blood pressure, end tidal COLaparoscopy was performed on 30 patients in AirSealLP (7mmHg) laparoscopy with AirSeal

SummaryBackground In children, only a few studies have compared different modes of propofol infusion during a total intravenous anesthesia (TIVA) with propofol and remifentanil. The aim of this study was to compare Bispectral Index (BIS) profiles (percentage of time spent at adequate BIS values) between four modes of propofol infusion: titration of the infusion rate on clinical signs (TIVA0), titration of the infusion rate on the BIS (TIVABIS), target controlled infusion (TCI) guided by the BIS either with the Kataria model (TCI KBIS) or the Schnider model (TCI SBIS). Methods Sixty-six children (aged from 4 to 14 years) were prospectively randomized into one of the four groups. In the TIVA0 group, the anesthesiologist was blinded to the BIS. In each group, the percentage of time with adequate BIS values (45–55), the bias, and imprecision were calculated. Results The propofol consumption was similar in the four groups. During the maintenance phase, the percentage of time spent in the targeted BIS range was significantly lower in the TIVA0 group compared to the three other groups (TIVA0: 31% ± 22, TIVABIS: 59% ± 17, TCI KBIS: 53% ± 12, TCI SBIS: 56% ± 17). The bias was not statistically different between the four groups, but the imprecision was larger for the TIVA0 group. Compared to the Kataria model, the Schnider model was associated with shorter time delay to reach the desired BIS, to eyes opening, and to tracheal extubation. Conclusions Propofol administration using manual infusion guided by clinical signs was associated with higher risks of over- or underdosage when compared to BIS-guided administrations. When propofol infusion was guided by the BIS, no major difference was found between TIVA and TCI (either with the Kataria or the Schnider model). This study highlights the need of a pharmacodynamic feedback during propofol anesthesia in children.

Pregnancy in women with inherited thrombocytopenias is a major matter of concern as both the mothers and the newborns are potentially at risk of bleeding. However, medical management of this condition cannot be based on evidence because of the lack of consistent information in the literature. To advance knowledge on this matter, we performed a multicentric, retrospective study evaluating 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia. Neither the degree of thrombocytopenia nor the severity of bleeding tendency worsened during pregnancy and the course of pregnancy did not differ from that of healthy subjects in terms of miscarriages, fetal bleeding and pre-term births. The degree of thrombocytopenia in the babies was similar to that in the mother. Only 7 of 156 affected newborns had delivery-related bleeding, but 2 of them died of cerebral hemorrhage. The frequency of delivery-related maternal bleeding ranged from 6.8% to 14.2% depending on the definition of abnormal blood loss, suggesting that the risk of abnormal blood loss was increased with respect to the general population. However, no mother died or had to undergo hysterectomy to arrest bleeding. The search for parameters predicting delivery-related bleeding in the mother suggested that hemorrhages requiring blood transfusion were more frequent in women with history of severe bleedings before pregnancy and with platelet count at delivery below 50 × 10(9)/L. Fil: Noris, Patrizia. Istituti di Ricovero e Cura a Carattere Scientifico. Policlinico San Matteo di Pavia; Italia. Università degli Studi di Pavia; Italia Fil: Schlegel, Nicole. Université Paris Diderot - Paris 7; Francia Fil: Klersy, Catherine. Istituti di Ricovero e Cura a Carattere Scientifico. Policlinico San Matteo di Pavia; Italia Fil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Civaschi, Elisa. Università degli Studi di Pavia; Italia Fil: Pujol Moix, Nuria. Universitat Autònoma de Barcelona; España Fil: Fabris, Fabrizio. Università di Padova; Italia Fil: Favier, Remi. Inserm; Francia. Armand Trousseau Children’s Hospital; Francia. French Reference Center for Inherited Platelet disorders; Francia Fil: Gresele, Paolo. Università di Perugia; Italia Fil: Latger Cannard, Véronique. Centre Hospitalo-Universitaire. Service d’Hématologie Biologique; Francia. Reference French Centre. Centre de Compétence Nord-Est des Pathologies Plaquettaires; Francia Fil: Cuker, Adam. University of Pennsylvania; Estados Unidos Fil: Nurden, Paquita. Hôpital Xavier Arnozan; Francia Fil: Greinacher, Andreas. Institut für Immunologie und Transfusionsmedizin; Alemania Fil: Cattaneo, Marco. Università degli Studi di Milano; Italia Fil: De Candia, Erica. Università Cattolica del Sacro Cuore; Italia Fil: Pecci, Alessandro. Università degli Studi di Pavia; Italia Fil: Hurtaud Roux, Marie Françoise. Université Paris Diderot - Paris 7; Francia Fil: Glembotsky, Ana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Muñiz Diaz, Eduardo. Banc de Sang i Teixits de Catalunya. Immunohematology Department; España Fil: Randi, Maria Luigia. Università di Padova; Italia Fil: Trillot, Nathalie. Centre Hospitalier Régional Universitaire de Lille. Pôle Biologie Pathologie Génétique. Institut d’Hématologie-Transfusion; Francia Fil: Bury, Loredana. Università di Perugia; Italia Fil: Lecompte, Thomas. Hôpitaux Universitaires de Genève; Suiza. Université de Genève. Faculté de Médecine; Suiza Fil: Marconi, Caterina. Università di Bologna; Italia Fil: Savoia, Anna. Università degli Studi di Trieste; Italia Fil: Balduini, Carlo L.. Istituti di Ricovero e Cura a Carattere Scientifico Burlo Garofolo. Institute for Maternal and Child Health; Italia. Università degli Studi di Pavia; Italia Fil: European Hematology Association Scientific Working Group on Thrombocytopenias and Platelet Function Disorders. No especifica

For several years, total intravenous anesthesia (TIVA) has demonstrated many advantages that allow consideration of propofol anesthesia as an interesting alternative in pediatric anesthesia. TIVA in children requires calculation and validation of pharmacokinetic (PK) models specifically adapted to the pediatric population. Several PK models based on a 3-compartment approach have been proposed in children: all these models, which integrate only weight as covariable, show increased distribution volumes with a wide interindividual variability. However, as pharmacodynamic (PD) parameters are still debated in children, there is up to now, no PKPD model currently available for pediatric anesthesia. The particular importance to include physiological covariables, as size and age, to describe metabolic processes during growth and maturation in pediatric PKPD models is in agreement with recent allometric scaling works in children. The Schnider's model, a model described in adults that includes numerous covariables, may be adapted and more efficient than the classical pediatric model to describe propofol-PKPD relationship in children over 5 years. Whatever is the model, a pharmacodynamic feed back such as the bispectral index may be useful to counteract the interindividual variability in the pediatric population.

In this prospective study, we compared the relationship between propofol concentrations and bispectral index (BIS) in children versus young adults anesthetized with target-controlled infusion (TCI) of propofol.Forty-five prepubertal subjects (children) and 45 postpubertal subjects (adults) were studied. All patients were anesthetized with TCI of propofol, based on the Kataria et al.'s model for children and on the Schnider et al.'s model for adults. All data from the BIS and the TCI system were continuously recorded using Rugloop software. Remifentanil was continuously administered throughout the study (0.25 microg x kg(-1) x min(-1)). In all patients, after the end of surgery, a 12-min period with a stable target plasma concentration (Ct) of propofol, randomly assigned at 2, 3, 4, 5, and 6 microg/mL, was performed. In addition, in most of the patients, another 12-min period was performed during which the BIS was targeted at 50 +/- 5. After each 12-min steady-state period, the Ct and BIS were noted and the plasma concentration of propofol was measured (Cm). The Ct and Cm corresponding to half maximal effect (BIS(50)) was determined by the Hill equation, and by targeting BIS at 50.In children, as in adults, BIS values were highly correlated with the corresponding Ct or Cm of propofol following classical E(max) dose-response curves. The ECt(50) and the ECm(50), derived from the dose-response curves, were higher in children than in adults: ECm(50): 4.0 (3.6-4.5) microg/mL vs 3.3 (3.0-3.7) microg/mL [mean (95% CI)], P0.001; as well were the Ct and Cm clinically obtained when BIS was targeted at 50 (Cm(50): 4.3 +/- 1.1 microg/mL vs 3.4 +/- 1.2 microg/mL, (mean +/- SD) P0.05, children versus adults). Cm was generally under-estimated by the Ct, and the bias was higher in children than in adults: 2.6 +/- 2.6 microg/mL vs 1.7 +/- 1.6 microg/mL (P = 0.05).The good relationship between propofol and BIS demonstrated in children as in adults suggested a slightly lower sensitivity to propofol in children. As the predictability of plasma propofol concentrations with the classical pharmacokinetic/pharmacodynamic models is limited in children, a cerebral pharmacodynamic feedback, such as BIS, may be useful in this population.

To present the preliminary results of the PRIUM study, a French pilot study of prenatal repair for myelomeningoceles (MMC).The fetal surgery for MMC is offered in cases of patients that did not opt for termination of pregnancy.Thirty-six patients were referred in an 18-month period. Eight patients were not eligible for prenatal repair. Another type of dysraphism was made in 6 cases (one spina-lipoma, 5 cases of limited dorsal myeloschisis). Twenty-two patients were eligible to fetal surgery. A prenatal repair was performed in three cases (14%). Four patients opted for a conventional postnatal treatment. Fifteen patients opted for termination of the pregnancy.The establishment of a prenatal repair of MMC protocol in France was justified. The experience of the first 18months of this study however suggests that only a limited number of couples will choose this procedure after specialized counseling in a reference center.