Changing hemostatic management in post-partum hemorrhage.

Early and fast assessment of hemostasis during postpartum hemorrhage (PPH) is essential to allow early characterization of coagulopathy, estimate bleeding severity and improve outcome. During PPH, fibrinogen decrease occurs earlier than other coagulation factors deficiency and hypofibrinogenemia is an early marker of PPH severity of progression. With good evidence in the context of PPH, point-of-care viscoelastic (VET) hemostatic assays have been shown to provide rapid assessment of hemostatic disorders, low fibrinogen levels, and allow VET-guided fibrinogen replacement. Further studies are needed to define the thresholds for the other coagulation parameters.

Tranexamic acid dose-response relationship for antifibrinolysis in postpartum haemorrhage during Caesarean delivery: TRACES, a double-blind, placebo-controlled, multicentre, dose-ranging biomarker study.

BACKGROUND: The 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. METHODS: Women 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. RESULTS: In 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. CONCLUSIONS: Fibrinolytic 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. CLINICAL TRIAL REGISTRATION: NCT02797119.

Maternal mortality in women with pre-viable premature rupture of membranes: An analysis from the French confidential enquiry into maternal deaths.

INTRODUCTION: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Understanding maternal mortality in women with obesity and the role of care they receive: a national case-control study.

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 (<18.5 kg/m2) had an adjusted OR of death of 0.75 (95% CI, 0.42-1.33), overweight women (25-29.9 kg/m2) 1.65 (95% CI, 1.24-2.19), women with class 1 obesity (30-34.9 kg/m2) 2.22 (95% CI, 1.55-3.19) and those with class 2-3 obesity (≥35 kg/m2) 3.40 (95% CI, 2.17-5.33). Analysis by cause showed significant excess risk of maternal death due to cardiovascular diseases, venous thromboembolism, hypertensive complications and stroke in women with obesity. Suboptimal care was as frequent among women with (35/62, 57%) as without obesity (136/244, 56%), but this inadequate management was directly related to obesity among 14/35 (40%) obese women with suboptimal care. Several opportunities for improvement were identified. CONCLUSIONS: The risk of maternal death increases with BMI; it multiplied by 1.6 in overweight women and more than tripled in pregnant women with severe obesity. Training clinicians in the specificities of care for pregnant women with obesity could improve their outcomes.

Effect of Different Concentrations of Propofol Used as a Sole Anesthetic on Pupillary Diameter: A Randomized Trial.

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.

Assessment of Coagulation by Thromboelastography During Ongoing Postpartum Hemorrhage: A Retrospective Cohort Analysis.

BACKGROUND: 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. METHODS: Women with ongoing PPH >500 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. RESULTS: 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 PPH >2500 mL. CONCLUSIONS: 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.

EEG profiles during general anesthesia in children: A comparative study between sevoflurane and propofol.

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.

Pupillometry-guided Intraoperative Remifentanil Administration versus Standard Practice Influences Opioid Use: A Randomized Study.

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 · 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]; 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.

Renal Cortical Necrosis in Postpartum Hemorrhage: A Case Series.

BACKGROUND: Pregnancy-related renal cortical necrosis may lead to end-stage renal disease. Although this obstetric complication had virtually disappeared in high-income countries, we have noted new cases in France over the past few years, all following postpartum hemorrhage. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: We retrospectively identified 18 patients from 5 French nephrology departments who developed renal cortical necrosis following postpartum hemorrhage in 2009 to 2013. OUTCOMES: Obstetric and renal features, therapeutic measures, and kidney disease outcome were studied. RESULTS: All patients had a severe postpartum hemorrhage (mean blood loss, 2.6±1.1 [SD] L). Hemodynamic instability and disseminated intravascular coagulation were reported in 5 and 11 patients, respectively. All developed rapid onset of acute kidney injury and required hemodialysis. Diagnosis of renal cortical necrosis was performed 4 to 33 days following delivery. At 6 months postpartum, 8 patients remained dialysis dependent and none recovered normal kidney function. The length of exposure to tranexamic acid treatment was significantly more prolonged in women whose estimated glomerular filtration rate remained <15mL/min/1.73m(2) (7.1±4.8 vs 2.9±2.4 hours; P=0.03). LIMITATIONS: Retrospective study; small sample size. CONCLUSIONS: In the setting of gravid endothelium, the conjunction of disseminated intravascular coagulation with the life-saving use of procoagulant and antifibrinolytic agents (recently implemented in France in a postpartum hemorrhage treatment algorithm) may give rise to a risk for uncontrolled clotting in the renal cortex and hence irreversible partial or diffuse cortical necrosis.

Bispectral index under propofol anesthesia in children: a comparative randomized study between TIVA and TCI.

BACKGROUND: 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.

[Maternal mortality due to hypertensive disorders in France, 2016-2018]. / Mortalité maternelle par complications hypertensives en France, 2016­2018.

Between 2016 and 2018, 13 maternal deaths were due to hypertensive disorders. During this period, the maternal mortality ratio was 0.6/100 000 live births. Hypertensive disorders were responsible for 4.8% of maternal deaths during the first year, 5.1% up to 42 days postpartum and for 13.5% of direct maternal mortality. Maternal deaths due to hypertensive disorders increased close to signification (p=0.09) compared to the last triennium (MMR=0.2/100.000). Classification of the hypertensive disorders was: 5 severe preeclampsia, 3 eclampsia, 4 HELLP syndromes et 1 undefined hypertension. In five cases, a stroke was associated. Mode of delivery was a cesarean section when the hypertensive disorder started before the labour (8/13, 62%). Six women were older than 35years old and 5/12 were nulliparous. Among the 12 cases where place of birth was known, 5 were born foreigners. BMI was over 30 for 46%. Medical care were estimated non optimal in 11/13 of the cases. Among these deaths, 66% (8/12) seemed to be preventable versus 82% for the last period 2013-2015. The main causal factor of suboptimal management was inappropriate management by the obstetrical or anesthetist/intensive care squads, respectively: 3 lack of diagnosis, 8 delays for diagnosis and 5 underestimated severity. Four cases corresponded to inappropriate health care organization. This study offers the opportunity to stress major points to optimize medical management and health care organization facing hypertensive disorders during pregnancy.

[Maternal mortality due to genital tract infection in France, 2016-2018]. / Mortalité maternelle par infection à porte d'entrée génitale en France 2016­2018.

Over the 2016-2018 period, maternal mortality due to direct infectious causes accounted for 13% of maternal deaths by direct causes. The increasing trend in genital-tract infections related-deaths noted in the 2013-2015 report continues for the 2016-2018 period, but this 2010-2018 increase remains at the limit of statistical significance given the low number of cases (p 0.08). The 13 deaths from direct infectious causes for the 2016-2018 period were due to 4 cases of puerperal toxic shock syndrome (Streptococcus A beta hemolyticus or Clostridium group bacilli), 6 sepsis caused by intrauterine infection due to E. Coli and 3 cases of septic shock from intrauterine origin and no documented bacteria. In this 2016-2018 triennium, the quality of care concerning women who died of direct infections was considered non-optimal in 85% (11/13). Death was considered possibly or probably avoidable in 9/13 cases (69%), which made it one of the most avoidable causes of maternal mortality. Preventable factors related to the medical management were the most frequent (9/13), with in particular a diagnostic failure or delayed diagnosis leading to a delay in the introduction of medical treatment. The others contributory factors to these deaths were related to the organization of healthcare (delayed transfer, lack of communication between practitioners) as well as factors related to patient social and/or mental vulnerability.

Diabetic acidosis with severe fetal hypoxia in pregnancy: Narrative review and case study.

Diabetic ketoacidosis (DKA) in pregnancy could be a disastrous event with increased maternal and perinatal morbidity and mortality. DKA can occur with a normal blood glucose level, known as euglycemic DKA. It particularly affects pregnant women with type I diabetes. Here, we report the case of a 28 year-old primigravid patient, with a diagnosis of type 1 diabetes for 8 years. This patient consulted our department at 29 weeks of gestation with a previous history of headaches, vomiting and diarrhea for 9 h. Blood glucose level was 8.8 mmol/L with a ketone test positive (>15 mg/dL). Blood test showed high anion gap (17.9 mmol/L) with low serum bicarbonate rate (21 mmol/L). Systemic examination and fetal heart rate (FHR) was reassuring. The patient was subsequently discharged. She returned to the clinic 19 h later with further symptoms of nausea, polyuria-polydipsia, asthenia and a weight loss of 4 kg since the day before. Blood sugar was 14.3 mmol/L and a ketone test was strongly positive. Cardiotocography showed fetal tachycardia and repeated late decelerations. A diagnosis of DKA was made and emergency cesarean was performed for fetal distress. At delivery, pH was acidosis (pH: 7.02, lactates: 6.2). The patient was successfully treated with intravenous hydration and insulin. Neonatal evolution was favorable. Pregnant women with type I diabetes can develop euglycemic DKA. Early recognition and prompt treatment could help prevent severe maternal and fetal adverse outcomes. DKA in pregnant women can induce fetal acidosis with abnormal FHR. In this situation, a cesarean can be performed to improve neonatal outcome even inducing a premature delivery. Prolonged pregnancy can lead to irreversible neonatal brain abnormalities.

Epileptogenic effect of sevoflurane: determination of the minimal alveolar concentration of sevoflurane associated with major epileptoid signs in children.

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.

Open fetal surgery for myelomeningocele repair in France.

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.

Guidelines 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.

Pharmacokinetic-pharmacodynamic modeling of propofol in children.

BACKGROUND: The aim of this study was to identify the best model to describe pharmacokinetics and pharmacodynamics in prepubertal children and therefore to calculate the corresponding pharmacodynamic parameters. In addition, and to confirm our method, a group of postpubertal subjects was also studied. METHODS: Sixteen children (9.5 yr, range 6-12) and 13 adults (22 yr, range 13-35) were included. Induction was performed by plasma target-controlled infusion of propofol (6 microg/ml) based on the Kataria model in children and on the Schnider model in adults. The relationship of bispectral index to predicted concentrations was studied during induction using the Kataria, pediatric Marsh, Schüttler, and Schnider models in children. Because the best performance was obtained, strangely enough, with the Schnider model, the two groups were pooled to investigate influence of puberty on pharmacodynamic parameters (kE0 [plasma effect-site equilibration rate constant] and Ce50 [effect-site concentration corresponding with 50% of the maximal effect]). The time-to-peak effect was calculated, and the kE0 was determined for the Kataria model (nonlinear mixed-effects modeling; pkpdtools). RESULTS: In children, the predicted concentration/effect relationship was best described using the Schnider model. When the whole population was considered, a significant improvement in this model was obtained using puberty as a covariate for kE0 and Ce50. The time to peak effect, Tpeak (median, 0.71 [range, 0.37-1.64] and 1.73 [1.4-2.68] min), and the Ce50 (3.71 [1.88-4.4] and 3.07 [2.95-5.21] microg/ml) were shorter and higher, respectively, in children than in adults. The kE0 linked to the Kataria model was 4.6 [1.4-11] min. CONCLUSIONS: In children, the predicted concentration/effect relationships were best described using the Schnider model described for adults compared with classic pediatric models. The study suggests that the Schnider model might be useful for propofol target-control infusion in children.

Which model for propofol TCI in children.

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.

The relationship between bispectral index and propofol during target-controlled infusion anesthesia: a comparative study between children and young adults.

BACKGROUND: 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. METHODS: 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. RESULTS: 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)], P < 0.001; 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) P < 0.05, 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). CONCLUSIONS: 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.