Efficacy and Safety Analyses of Recombinant Factor VIIa in Severe Post-Partum Hemorrhage.

Background: Despite a range of available treatments, it is still sometimes challenging to treat patients with severe post-partum hemorrhage (sPPH). Objective: This study evaluated the efficacy and safety of recombinant activated factor VIIa (rFVIIa) in sPPH management. Methods: An open-label, multi-center, randomized controlled trial (RCT; NCT00370877) and four observational studies (OS; OS-1 (NCT04723979), OS-2, OS-3, and OS-4) were analyzed regarding efficacy (need for subsequent invasive procedures, including uterine compression sutures, uterine or iliac artery ligations, arterial embolization, or hysterectomy) and safety (incidence of thromboembolic events (TE) and maternal mortality) of rFVIIa for sPPH. The RCT, and OS-1 and OS-2, included a control group of women who did not receive rFVIIa (with propensity score-matching used in OS-1 and OS-2), whereas OS-3 and OS-4 provided descriptive data for rFVIIa-exposed women only. Results: A total of 446 women exposed to rFVIIa and 1717 non-exposed controls were included. In the RCT, fewer rFVIIa-exposed women (50% [21/42]) had an invasive procedure versus non-exposed women (91% [38/42]; odds ratio: 0.11; 95% confidence interval: 0.03-0.35). In OS-1, more rFVIIa-exposed women (58% [22/38]) had an invasive procedure versus non-exposed women (35% [13.3/38]; odds ratio: 2.46; 95% confidence interval: 1.06-5.99). In OS-2, 17% (3/18) of rFVIIa-exposed women and 32% (5.6/17.8) of non-exposed women had an invasive procedure (odds ratio: 0.33; 95% confidence interval: 0.03-1.75). Across all included women, TEs occurred in 1.5% (0.2% arterial and 1.2% venous) of rFVIIa-exposed women and 1.6% (0.2% arterial and 1.4% venous) of non-exposed women with available data. Conclusions: The positive treatment effect of rFVIIa on the RCT was not confirmed in the OS. However, the safety analysis did not show any increased incidence of TEs with rFVIIa treatment.

Preparedness for severe maternal morbidity in European hospitals: The MaCriCare study.

PURPOSE: To evaluate obstetric units (OUs) and intensive care units (ICUs) preparedness for severe maternal morbidity (SMM). METHODS: From September 2021 to January 2022, an international multicentre cross-sectional study surveyed OUs in 26 WHO Europe Region countries. We assessed modified early obstetric warning score usage (MEOWS), approaches to four SMM clinical scenarios, invasive monitoring availability in OUs, and access to high-dependency units (HDUs) and onsite ICUs. Within ICUs, we examined the availability of trained staff, response to obstetric emergencies, leadership, and data collection. RESULTS: 1133 responses were evaluated. MEOWS use was 34.5%. Non-obstetric early warning scores were being used. 21.4% (242) of OUs provided invasive monitoring in the OU. A quarter lacked access to onsite HDU beds. In cases of SMM, up to 13.8% of all OUs indicated the need for transfer to another hospital. The transfer rate was highest (74.0%) in small units. 81.9% of centers provided onsite ICU facilities to obstetric patients. Over 90% of the onsite ICUs provided daily specialist obstetric reviews but lacked immediate access to key resources: 3.4% - uterotonic drugs, 7.5% - neonatal resuscitation equipment, 9.2% - neonatal resuscitation team, 11.4% - perimortem cesarean section equipment. 41.2% reported obstetric data to a national database. CONCLUSION: Gaps in provision exist for obstetric patients with SMM in Europe, potentially compromising patient safety and experience. MEOWS use in OUs was low, while access to invasive monitoring and onsite HDU and ICU facilities was variable. ICUs frequently lacked resources and did not universally collect obstetric data for quality control.

An observational study of gastric content in women scheduled for cesarean section or operative hysteroscopy.

BACKGROUND: The estimation of gastric content in third trimester pregnant women has already been studied, conclusions remain contradictory. The aim of this study was to compare gastric content in pregnant and non-pregnant women using gastric ultrasound. We performed an observational two-center study of women scheduled for a cesarean section (CS group) and of non-pregnant women scheduled for hysteroscopy (HS group). METHODS: Ultrasound evaluation was performed before surgery with measurement of antral cross-sectional area (CSA) in the semi-recumbent position (SRP), primary outcome, and in the right lateral position (RLD). Gastric fluid volume (GFV) was calculated. Results are expressed as medians (25th and 75th percentiles). Perlas Score was evaluated and expressed as number (percentage). RESULTS: Sixty patients in the CS group and 64 in the HS group were analyzed. Antral CSA (SRP) was greater in the CS group (350 mm2 [236-415] vs. 247 mm2 [180-318]; P=0.001). Antral CSA (RLD) was also significantly greater in the CS group (P=0.027). GFV was not different between groups whether expressed in absolute value (P=0.516) or relative to weight (P=0.946) mL.kg-1. Perlas Score repartition was similar in both groups (P=0.860). Kappa coefficients of concordance between CSA, GFV and Perlas Score were slight or at best fair. CONCLUSIONS: Our study confirmed that antral CSA is increased among pregnant women and outlined that antral CSA should not be used alone in the decision-making process especially when the results of indicators (antral CSA, GFV, and Perlas Grading Score) are discordant.

Factors associated with failed epidural blood patch after accidental dural puncture in obstetrics: a prospective, multicentre, international cohort study.

BACKGROUND: Epidural blood patch is commonly used for management of post-dural puncture headache after accidental dural puncture. The primary aim was to determine factors associated with failed epidural blood patch. METHODS: In this prospective, multicentre, international cohort study, parturients ≥18 yr receiving an epidural blood patch for treatment of post-dural puncture headache were included. Failed epidural blood patch was defined as headache intensity numeric rating scale (NRS) score ≥7 in the upright position at 4, 24, or 48 h, or the need for a second epidural blood patch, and complete success by NRS=0 at 0-48 h after epidural blood patch. All others were considered partial success. Multinominal logistic regression was used for statistical analyses with P<0.01 considered statistically significant. RESULTS: In all, 643 women received an epidural blood patch. Complete data to classify failure were available in 591 (91.9%) women. Failed epidural blood patch occurred in 167 (28.3%) patients; 195 (33.0%) were completely successful and 229 (38.7%) partially successful. A total of 126 women (19.8%) received a second epidural blood patch. A statistically significant association with failure was observed in patients with a history of migraine, when the accidental dural puncture occurred between lumbar levels L1/L3 compared with L3/L5 and when epidural blood patch was performed <48 h compared with ≥48 h after accidental dural puncture. In patients having radiological investigations, three intracranial bleeds were diagnosed. CONCLUSIONS: Failed epidural blood patch occurred in 28.3% of women. Independent modifiable factors associated with failure were higher lumbar level of accidental dural puncture and short interval between accidental dural puncture and epidural blood patch. A history of migraine was associated with a higher risk of second epidural blood patch. CLINICAL TRIAL REGISTRATION: NCT02362828.

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

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

Outcomes following medical termination versus prolonged pregnancy in women with severe preeclampsia before 26 weeks.

OBJECTIVE: To compare maternal complications and describe neonatal outcomes in women with severe preeclampsia at ≤ 26+0 weeks in two countries with different management policies: expectant management (Brazil) versus termination of pregnancy (France). METHODS: We conducted a retrospective comparative study by reviewing the medical records of women with severe preeclampsia at ≤ 26+0 weeks, from January 2010 to June 2018, in two centers: Hospital das Clínicas da Faculdade de Medicina, in Sao Paulo, Brazil (where medical abortion is forbidden in this indication) and Hôpital Antoine-Béclère, Clamart, France (where medical termination is accepted). We collected information on maternal characteristics, laboratory tests, maternal complications and fetal and newborn characteristics. We used Student's t-test and the Mann-Whitney U nonparametric test to compare quantitative variables, and Chi-square test or Fisher's exact test to evaluate the associations between the qualitative variables. RESULTS: There was no between-group difference in maternal complications during hospitalization (p = 0.846). In Brazil, the rate of cesarean section was 66.7%, and 20% of patients had vertical incision. The rate of spontaneous fetal death was 35.6% and among the live-born infants 26.6% were discharged from hospital. In France, one patient had a cesarean section with vertical incision. CONCLUSION: When comparing termination of pregnancy to expectant management in severe preeclampsia before 26 weeks, maternal complications were equivalent but maternal reproductive future might have been compromised in 20% of cases due to a higher risk of uterine rupture in subsequent pregnancies for patients having classic cesarean (vertical incision). 26.6% of children survived the neonatal period when pregnancy was pursued, however we lack information on their long-term follow-up.

Efficacy of Intra-Uterine Tamponade Balloon in Post-Partum Hemorrhage after Cesarean Delivery: An Impact Study.

Invasive therapies (surgery or radiological embolization) are used to control severe post-partum hemorrhage. The intra-uterine tamponade balloon is a potential alternative, well documented after vaginal delivery. However, available data on its use after cesarean delivery remain scarce. This study assessed the efficacy of the intra-uterine tamponade balloon during post-partum hemorrhage in a cesarean delivery setting. Using a retrospective impact design, post-partum hemorrhage-related outcomes before ("pre-balloon" period) versus after implementation of intra-uterine tamponade balloon ("post-balloon" period) were compared. All women with post-partum hemorrhage requiring potent uterotonic treatment with prostaglandins after cesarean delivery over a 9-year period were eligible. The primary outcome was the rate of invasive procedure (conservative surgery, radiological embolization and/or hysterectomy). p < 0.05 was considered statistically significant. A total of 279 patients were included (140 vs. 139). Most baseline characteristics were comparable between the two studied periods. The success rate of the intra-uterine tamponade balloon was 82%, and no related complications occurred. Rates of invasive procedures and transfusion were significantly reduced (28.6% vs. 11.5%, p < 0.001 and 44.3% vs. 28.1%, p = 0.006 respectively) during the "post-balloon" period, and length of hospital stay was shorter (p < 0.001). Implementation of intra-uterine tamponade balloon during post-partum hemorrhage after cesarean delivery appears to be safe and effective, with a decrease in both invasive procedures and transfusion rates.

European minimum standards for obstetric analgesia and anaesthesia departments: An experts' consensus.

: An important variability of anaesthetic standards of care was discovered in the obstetric departments of many European Union countries. After discussing this issue in various meetings of the European Society of Anaesthesiology (ESA) board and its obstetric subcommittee, European Board of Anaesthesiology of the European Union of Medical Specialists (EBA-UEMS) executive members, ESA obstetric subcommittee members and European experts in obstetric anaesthesiology have participated in the elaboration of this document. This experts' opinion is focused mainly on obstetric patients and safety concerns in terms of minimum standards of practice. An initial bibliographical search was performed in medical databases and general literature, searching for obstetric anaesthesiology standards to select the most important safety issues. After the initial presentation of the project during EBA-UEMS and ESA obstetric subcommittee meetings, participants were asked to review the document; several rounds of revisions were performed by the experts, to reach a common opinion concerning the topics considered central to patient safety in the obstetric setting. After three rounds of revision, a consensus was reached and is presented in this document, which includes the list of topics considered relevant by the involved areas, and the respective recommendations. These recommendations covered some EBA-UEMS strategic key areas, in addition to several clinical aspects of common obstetric practice.

Management practices for postdural puncture headache in obstetrics: a prospective, international, cohort study.

BACKGROUND: Accidental dural puncture is an uncommon complication of epidural analgesia and can cause postdural puncture headache (PDPH). We aimed to describe management practices and outcomes after PDPH treated by epidural blood patch (EBP) or no EBP. METHODS: Following ethics committee approval, patients who developed PDPH after accidental dural puncture were recruited from participating countries and divided into two groups, those receiving EBP or no EBP. Data registered included patient and procedure characteristics, headache symptoms and intensity, management practices, and complications. Follow-up was at 3 months. RESULTS: A total of 1001 patients from 24 countries were included, of which 647 (64.6%) received an EBP and 354 (35.4%) did not receive an EBP (no-EBP). Higher initial headache intensity was associated with greater use of EBP, odds ratio 1.29 (95% confidence interval 1.19-1.41) per pain intensity unit increase. Headache intensity declined sharply at 4 h after EBP and 127 (19.3%) patients received a second EBP. On average, no or mild headache (numeric rating score≤3) was observed 7 days after diagnosis. Intracranial bleeding was diagnosed in three patients (0.46%), and backache, headache, and analgesic use were more common at 3 months in the EBP group. CONCLUSIONS: Management practices vary between countries, but EBP was more often used in patients with greater initial headache intensity. EBP reduced headache intensity quickly, but about 20% of patients needed a second EBP. After 7 days, most patients had no or mild headache. Backache, headache, and analgesic use were more common at 3 months in patients receiving an EBP.

Fluid loading therapy to prevent spinal hypotension in women undergoing elective caesarean section: Network meta-analysis, trial sequential analysis and meta-regression.

BACKGROUND: Fluid loading is one of the recognised measures to prevent hypotension due to spinal anaesthesia in women scheduled for a caesarean section. OBJECTIVE: We aimed to evaluate the current evidence on fluid loading in the prevention of spinal anaesthesia-induced hypotension. DESIGN: Systematic review and network meta-analysis with trial sequential analysis and meta-regression. DATA SOURCES: Medline, Epub, Embase.com (Embase and Medline), Cochrane Central, Web of Science and Google Scholar were used. ELIGIBILITY CRITERIA: Only randomised controlled trials were used. Patients included women undergoing elective caesarean section who received either crystalloid or colloid fluid therapy as a preload or coload. The comparator was a combination of either a different fluid or time of infusion. RESULTS: A total of 49 studies (4317 patients) were included. Network meta-analysis concluded that colloid coload and preload offered the highest chance of success (97 and 67%, respectively). Conventional meta-analysis showed that crystalloid preload is associated with a significantly higher incidence of maternal hypotension than colloid preload: risk ratio 1.48 (95% CI 1.29 to 1.69, P < 0.0001, I = 60%). However, this result was not supported by Trial Sequential Analysis. There was a significant dose-response effect for crystalloid volume preload (regression coefficient = -0.073), which was not present in the analysis of only double-blind studies. There was no dose-response effect for the other fluid regimes. CONCLUSION: Unlike previous meta-analysies, we found a lack of data obviating an evidence-based recommendation. In most studies, vasopressors were not given prophylactically as is recommended. Studies on the best fluid regimen in combination with prophylactic vasopressors are needed. Due to official european usage restrictions on the most studied colloid (HES), we recommend crystalloid coload as the most appropriate fluid regimen. TRIAL REGISTRATION: CRD42018099347.

Incidence and risk factors for maternal hypoxaemia during induction of general anaesthesia for non-elective Caesarean section: a prospective multicentre study.

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<0.0001) and BMI >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<0.001). 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.