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

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

A systematic review of phenylephrine vs. noradrenaline for the management of hypotension associated with neuraxial anaesthesia in women undergoing caesarean section.

Phenylephrine is recommended for the management of hypotension after spinal anaesthesia in women undergoing caesarean section. Noradrenaline, an adrenergic agonist with weak ß-adrenergic activity, has been reported to have a more favourable haemodynamic profile than phenylephrine. However, there are concerns that noradrenaline may be associated with a higher risk of fetal acidosis, defined as an umbilical artery pH < 7.20. We performed a systematic review of trials comparing noradrenaline with phenylephrine, concentrating on primary outcomes of fetal acidosis and maternal hypotension. We identified 13 randomised controlled trials including 2002 patients. Heterogeneity among the studies was high, and there were too few data to calculate a pooled effect estimate. Fetal acidosis was assessed in four studies that had a low risk of bias and a low risk of confounding, that is, studies which used a prophylactic vasopressor and where women received the allocated vasopressor only. There were no significant differences between these studies. No significant differences were observed for hypotension. Two trials found a significantly lower incidence of bradycardia when using noradrenaline. Cardiac output was significantly higher after noradrenaline in two of three studies. For other secondary outcomes including nausea, vomiting and Apgar scores at 1 and 5 min, no studies found significant differences. The evidence so far is too limited to support an advantage of noradrenaline over phenylephrine. Concerns of a deleterious effect of noradrenaline on fetal blood gas status cannot currently be assuaged by the available data from randomised controlled studies.

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

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

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

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

Education in obstetric anesthesiology: an international approach.

Competency-based training and active teaching methods are increasingly becoming accepted and utilized in medical schools and hospitals, and obstetric anesthesiology training is expected to follow this process. This article summarizes current modalities of obstetric anesthesiology training in five countries from various parts of the world. Analysis of these curricula shows that implementation of new educational methods is variable, incomplete, and lacking in data related to patient outcomes. Research in assessments and practical applications are required to avoid wide ranges of educational strategies.

Increase in optic nerve sheath diameter induced by epidural blood patch: a preliminary report.

BACKGROUND: Post-dural puncture headache (PDPH) might be related to cerebrospinal fluid hypotension. Studies in brain-injured patients have shown a good relationship between optic nerve sheath diameter (ONSD) measured by ocular sonography and invasively measured intracranial pressure (ICP). The aim of this study was to evaluate changes in ONSD after lumbar epidural blood patch (EBP). METHODS: Consecutive subjects receiving an EBP for PDPH were included. ONSD and pain measurements were performed before (T(0)), 10 min (M(10)), 2 h (H(2)), and 20 h (H(20)) after the EBP. RESULTS: Ten subjects were included. ONSD [median (inter-quartile range)] increased with time after EBP, from 4.8 mm (4.5-5.1) at T(0) to 5.2 mm (4.9-5.7) at M(10) (P=0.005 vs T(0)), 5.5 mm (5.1-6.0) at H(2) (P=0.007 vs T(0)), and 5.8 mm (5.2-6.3) at H(20) (P=0.02 vs T(0)). EBP was clinically successful in nine of 10 subjects. In subjects in whom EBP was successful, ONSD significantly increased at M(10) and T(2) compared with T(0) (P=0.004 and 0.008, respectively) but did not reach statistical significance at H(20) (P=0.06). In the subject in whom EBP failed, a small increase in ONSD was observed over time. CONCLUSIONS: In this preliminary report, EBP was followed by ONSD enlargement in subjects with successful EBP, but not in the subject with EBP failure. Since ONSD is a surrogate marker of ICP, this suggests that a sustained increase in ICP is associated with successful EBP.

Noncardiothoracic nonobstetric surgery in mild-to-moderate pulmonary hypertension.

The anaesthetic management and follow-up of well-characterised patients with pulmonary arterial hypertension presenting for noncardiothoracic nonobstetric surgery has rarely been described. The details of consecutive patients and perioperative complications during the period January 2000 to December 2007 were reviewed. Repeat procedures in duplicate patients were excluded. Longer term outcomes included New York Heart Association (NYHA) functional class, 6-min walking distance and invasive haemodynamics. A total of 28 patients were identified as having undergone major (57%) or minor surgery under general (50%) and regional anaesthesia. At the time of surgery, 75% of patients were in NYHA functional class I-II. Perioperative deaths occurred in 7%. Perioperative complications, all related to pulmonary hypertension, occurred in 29% of all patients and in 17% of those with no deaths during scheduled procedures. Most (n = 11, 92%) of the complications occurred in the first 48 h following surgery. In emergencies (n = 4), perioperative complication and death rates were higher (100 and 50%, respectively; p<0.005). Risk factors for complications were greater for emergency surgery (p<0.001), major surgery (p = 0.008) and a long operative time (193 versus 112 min; p = 0.003). No significant clinical or haemodynamic deterioration was seen in survivors at 3-6 or 12 months of post-operative follow-up. Despite optimal management in this mostly nonsevere pulmonary hypertension population, perioperative complications were common, although survivors remained stable. Emergency procedures, major surgery and long operations were associated with increased risk.

Effect of prophylactic 5-HT3 receptor antagonists on pruritus induced by neuraxial opioids: a quantitative systematic review.

Pruritus is a frequent adverse event observed after neuraxial administration of opioids. Central 5-hydroxytryptamine subtype 3 (5-HT3) receptors may be activated in this process. This systematic review aimed to evaluate the efficacy of prophylactic 5-HT3 receptor antagonists on neuraxial opioid-induced pruritus. We searched Medline, Embase, and Cochrane Collaboration Library databases. Studies were evaluated with the Oxford Validity Scale. Studies with a score of 3 or more and reporting prophylactic administration of 5-HT3 receptor antagonists vs placebo were included. Fifteen randomized double-blind controlled trials (n=1337) were selected. 5-HT3 antagonists (n=775) significantly reduced pruritus [odds ratio (OR) 0.44 (95% confidence interval, 95% CI, 0.29-0.68), P=0.0002, number-needed-to-treat (NNT) 6 (95% CI, 4-14)], the treatment request for pruritus [OR 0.58 (95% CI, 0.43-0.78), P=0.0003, NNT 10 (95% CI, 7-20)], the intensity of pruritus [weighted mean difference (WMD) -0.35 (95% CI, -0.59 to -0.10), P=0.007], the incidence and the intensity of postoperative nausea and vomiting (PONV), and the need of rescue treatment [respectively, Peto odds ratio (Peto OR) 0.43 (95% CI, 0.31-0.58), P<0.00001, NNT 7 (95% CI, 6-10); WMD -0.12 (95% CI, -0.24 to 0.00), P=0.05 and OR 0.42 (95% CI, 0.20-0.86), P=0.02, NNT 8 (95% CI, 5-35)]. However, the funnel plot was asymmetric, suggesting a risk of publication bias. 5-HT3 receptor antagonists may be an effective strategy in preventing neuraxial opioid-induced pruritus and PONV. Further large randomized controlled trials are required to confirm these findings.

[Obstetric anaesthesia for instrumental vaginal delivery]. / Anesthésie obstétricale pour extractions instrumentales.

The aim of the anaesthesia for instrumental delivery is to provide optimal operation conditions for the obstetrician, appropriate maternal comfort, altogether with safety for the mother and her foetus. The type and location for this intervention are chosen individually for each case according to the indication, the risk of caesarean section and the local specificities. The general safety recommendations for obstetric anaesthesia apply in every case. Since an epidural analgesia is often already working, this type of anaesthesia is the most frequently used for the extractions. A spinal anaesthesia is a logical choice where an epidural in sot yet working. The pudendal block is a second line choice and the general anaesthesia remains as the last alternative in acute emergencies, in cases of failed regional anaesthesia or when the mother refuses any other anaesthesia despite proper information or proves unable to cooperate.

Epidural analgesia for parturients with type 1 von Willebrand disease.

BACKGROUND: Epidural analgesia is usually contraindicated in von Willebrand disease. However, in type 1, the increased synthesis of von Willebrand factor (vWF) and factor VIII (FVIII:C) during pregnancy can lead to a correction of biological abnormalities and may allow epidural analgesia to be performed for delivery. METHODS: The clinical files of pregnant patients with type 1 von Willebrand disease who delivered in our tertiary perinatal unit were reviewed. The time profile of hemostasis abnormalities during pregnancy, technical features and complication of epidural analgesia when performed were recorded. RESULTS: Sixteen pregnancies (13 patients) were included. Mean (+/- SD) concentrations of FVIII:C, vWAg, and vWRCo before pregnancy (42+/-12, 46+/-8, 42+/-10 units/dL, respectively) increased to normal values in all cases at term (142+/-42, 142+/-61, 142+/-79 units/dL, respectively). Nine epidurals (6 patients) were performed without complication. Three parturients did not receive epidural analgesia despite normal biological hemostasis because the anesthesiologist was still reluctant to provide it. Four other parturients had PFA-100 closure times (n=3) or a bleeding time that remained prolonged; epidural analgesia was not performed for these cases. CONCLUSIONS: vWF and FVIII:C increased to normal values in all cases at term in these parturients with type 1 von Willebrand disease. Epidural analgesia, when performed for labor, was uncomplicated. However, platelet aggregation tests with PFA-100 unmasked unexpected, persistent abnormalities. The value of this test for clinical decision making remains to be determined by further prospective studies.

[Epidural anaesthesia and lumbar tattoo: what to do?]. / Analgésie par voie péridurale et tatouage lombaire: que faire?

More and more often, the anaesthesiologist may have to perform lumbar epidural anaesthesia in a patient with a central lumbar tattoo, and this can occur in an urgent obstetric setting. Before managing two uneventful cases of epidural analgesia for labour, we have performed a literature review and noted that no serious complication has been reported. Nonetheless, a needle passed through a tattoo can entrap pigmented tissue fragments (cores) into the epidural or subarachnoid space. This could theoretically induce risk of late neurological complications, related to an inflammatory or granulomatous response to the pigmented cores introduced in these spaces. To avoid this theoretical risk, the anesthesiologist should try to avoid puncturing through the tattoo, either by selecting a different vertebral interspace, or by using a paramedian approach or by finding a pigment free skin spot within the area of the tattoo. When these options cannot be implemented, a superficial skin incision prior to needle insertion should prevent from coring tattoo pigment when entering the skin. Whatever the final choice, the technique to be implemented should be determined as early as the antenatal visit, after informed consent.

[Study of the 21 cases of thromboembolism from the 4th report of national confidential enquiry into maternal death in France in 2007-2009]. / Analyse des 21 cas de thromboembolie du 4(e) rapport de l'enquête nationale confidentielle sur la mortalité maternelle en France en 2007-2009.

OBJECTIVES: The Confidential National Enquiry on Maternal Mortality identified 254 deaths in France from 2007 to 2009. Thromboembolism venous disease led to 31 deaths, becoming the 3rd cause of maternal mortality. This study analyses the 21 enquiry files obtained by the National Expert Committee on Maternal Mortality (CNEMM). MATERIALS AND METHODS: Clinical characteristics, arising circumstances and imaging exams were collected in the 20 patients deceased by pulmonary embolism (PE). After excluding two incomplete files, we looked for the PE Risk Factors (RF) in order to sort patients out according to 4 levels of risk (low, moderate, high and major). RESULTS: The main RF were: non-Caucasian ethnic origin (n=8), age over 35years (n=7), diabetes (n=6) and emergency or unplanned caesarean section (n=6). The average number of RF was 3.7: 73% were low, 18% moderate. Among 7 autopsies performed, 6 resulted in PE diagnostic. Only 67% of eligible patients had an imaging exam. CONCLUSION: The search for the RF of thromboembolism accidents, in particular the low RF, should be improved to establish an adapted prophylactic therapy. Autopsy or even post-mortem imaging should be implemented when diagnosis is uncertain in order to avoid over-/under-estimating death incidence caused by PE.

Major obstetric hemorrhage.

Major obstetric hemorrhage is a challenge for anesthesiologists because it remains responsible for over 10% of maternal deaths in high-income countries. A standardized multidisciplinary management, described in locally validated protocols and based on international guidelines is mandatory to prevent these deaths. The first difficulty relies on the systematic underestimation of the bleeding. Collection bags must be used to facilitate the diagnosis and therefore rapid management. The etiologies in antenatal or postpartum must be well-known in order to be treated adequately. A rapid recourse to prostaglandins (sulprostone in France) may reverse uterine atony. Invasive approach with surgery or radiology should be promptly implemented (uterine artery or internal iliac artery ligations±uterus plication) and hysterectomy should then be timely considered. Simultaneously, early and aggressive resuscitation with large-bore venous accesses should be implemented for rapid and massive transfusion (4:4:1 RBC:FFP:platelets ratio), along with an early use of fibrinogen concentrates and tranexamic acid. This transfusion strategy may be then guided by thromboelastography or thromboelastometry and bedside hemoglobin measurements. Activated factor VII remains indicated only before or after hysterectomy in case of uncontrolled bleeding. Management of placentation abnormalities (placenta previa, accreta, increta, percreta) must be well mastered as these etiologies may generate cataclysmic hemorrhages that can be and have to be anticipated.

[Epidural analgesia and fever during labor]. / Analgésie péridurale et fièvre lors du travail.

Fever during labor is quite frequent and may be an etiologic and therapeutic challenge for obstetric and anesthesia teams. Although an infectious cause should be suspected first, intrapartum fever can also be non-infectious, most frequently in association with epidural analgesia. In this article, we review what is presently known about the association between epidural analgesia and intrapartum fever. Neonatal consequences of intrapartum fever are also discussed.

[Alternative techniques to labour epidural analgesia]. / Alternatives à l'analgésie péridurale au cours du travail.

Many systemic techniques, so-called "alternatives" to labor epidural analgesia, have been described: they are all poorly effective and some are associated with significant maternal and neonatal side effects. Nonetheless, these techniques can provide good maternal satisfaction. Accordingly, they are indicated when epidural analgesia is contraindicated or unavailable. Administration of systemic opioids mandates maternal respiratory supervision, oxygen supplementation and/or pulse oxymetry. Systemic opioids may also decrease fetal heart rate variability and produce neonatal respiratory depression; naloxone administration to the neonate is therefore widely indicated. Pethidine should be abandoned because it can produce prolonged neonatal respiratory depression. Nalbuphine produces less nausea/vomiting and less long lasting neonatal respiratory depression. Intravenous PCA fentanyl or sufentanil is presently the method of choice during early labor. Alfentanil seems less effective and may produce more neonatal side effects. Intravenous PCA remifentanil is the most effective technique, but safe administration may be problematic during intermittent supervision usually implemented in labour ward. Nitrous oxide 50% provides little pain relief. Nonetheless, it is associated with few side effects, quite good maternal satisfaction and can be quickly implemented during advanced painful labor. It is not recommended to add it to systemic opioid (except under continuous supervision by the anaesthetic team), because of an increased incidence of maternal desaturation. The use of a subanaesthetic concentration of sevoflurane has been described recently; it is more effective than nitrous oxide. However, guidelines for safe implementation in labor ward remain to be determined.