Recombinant human FVIIa for reducing the need for invasive second-line therapies in severe refractory postpartum hemorrhage: a multicenter, randomized, open controlled trial.

BACKGROUND: Case reports on recombinant human factor VIIa (rhuFVIIa) use in women with severe postpartum hemorrhage (PPH) showed encouraging results, but no randomized controlled trial (RCT) is available. PATIENTS AND METHODS: Eighty-four women with severe PPH unresponsive to uterotonics were randomized to receive one early single rhuFVIIa infusion (n = 42) or standard care (no rhuFVIIa; n = 42). The primary efficacy outcome measure was the reduction of the need for specific second-line therapies, such as interventional hemostatic procedures, for blood loss and transfusions. The primary safety outcome measure was the number of deaths and thrombotic events during the 5 days following rhuFVIIa infusion. RESULTS: rhuFVIIa was associated with a reduction in the number of patients who needed second-line therapies compared with controls (standard care). Specifically, 39/42 (93%) patients in the standard care arm received second-line therapies and 22/42 (52%) patients in the rhuFVIIa arm (absolute difference, 41%; range, 18-63%; relative risk RR, 0.56 [0.42-0.76]). The delivery mode (vaginal or Cesarean section) did not affect the primary outcome. No death occurred. Two venous thrombotic events were recorded in the rhuFVIIa arm: one ovarian vein thrombosis and one deep vein thrombosis with a non-severe pulmonary embolism. CONCLUSION: This open RCT in women with severe PPH refractory to uterotonics shows that rhuFVIIa reduces the need for specific second-line therapies in about one in three patients, with the occurrence of non-fatal venous thrombotic events in one in 20 patients.

[Spinal anaesthesia for caesarean section: fluid loading, vasopressors and hypotension]. / Rachianesthésie pour césarienne: remplissage, vasopresseurs et hypotension.

OBJECTIVE: To analyze the different preventive and curative strategies for the management of hypotension during spinal anaesthesia for caesarean section. DATA SOURCES: Data related to hypotension during spinal anesthesia for caesarean section were searched in the Medline database. Trials published in English or French were reviewed. DATA SYNTHESIS: Hypotension during caesarean section under spinal anaesthesia is very frequent (55 to 90%) if not prevented. It can induce complications for the mother and/or the fetus. Crystalloid preload alone is ineffective. Colloid preload is effective but might be better used as a second line treatment. Ephedrine has been the vasopressor of choice for long, but has a weak prophylactic efficacy. In addition, it can induce maternal cardiovascular adverse effects and fetal acidosis. Prophylactic phenylephrine, with or without ephedrine according to maternal heart rate, is at least as effective as ephedrine, with less adverse effects. Crystalloid loading at the time of spinal injection ("co-/post-loading") enhances the haemodynamic control provided by vasopressors. CONCLUSION: Hypotension during spinal anesthesia for caesarean section must be systematically detected, prevented and treated without delay. The association of vasopressor(s) (phenylephrine with or without ephedrine) with a rapid crystalloid loading at the time of spinal injection represents the most interesting strategy nowadays.

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.

[Recombinant activated factor VII as a life-saving therapy for severe postpartum haemorrhage unresponsive to conservative traditional management]. / Intérêt du facteur VII activé recombinant dans l'hémorragie de la délivrance sévère réfractaire à la prise en charge conservatrice conventionnelle.

Postpartum haemorrhage remains the main cause of maternal morbidity and mortality. Treatment aims at maintaining hemodynamic circulation and preventing shock by stopping blood loss both medically and surgically. We report two cases of major postpartum haemorrhage due to uterine atony. Patients developed haemorrhagic shock and severe coagulation disorders (nadir values of PTT were <10% and fibrinogen was <0.1 g/l). Well-codified medical (ocytocin, sulprostone) and surgical management (ligation of both hypogastic arteries in the two cases completed by staged uterine ligation in one case) failed to stop bleeding. Recently, several case reports described successful use of recombinant activated factor VII (rFVIIa) in scheduled surgery, trauma and major postpartum haemorrhage. Thus, after transfusion of more than one blood mass and failure of surgical haemostasis to stop bleeding, rFVIIa (60 microg/kg) was given. A single iv bolus injection stopped ongoing diffuse haemorrhage in the two cases. No further transfusion was required afterwards in both patients. RFVIIa might thus be a strong complementary agent in the management of major postpartum haemorrhage. Optimal dose, timing and safety characteristics of rVIIa administration remain to be determined. One patient developed four weeks later thrombosis of both ovarian veins, a complication that can be related to either rFVIIa or to the staged uterine ligations performed during surgery.

[Management of delivery in patients with Marfan's syndrome presenting aortic dilatation]. / Prise en charge d'un accouchement chez une patiente porteuse d'une maladie de Marfan avec dilatation aortique.

OBJECTIVE: We report the anesthesic and obstetrical management of two pregnant patients with Marfan's syndrome. An important dilatation of the root of aorta was established at the beginning of the pregnancy. Based on a review of the literature and our experience, we searched for clues to identify the ideal term and the best mode of delivery, and which type of anesthesia may be the more appropriate in patients with aortic dilatation. RESULTS: No consensus can be found in the literature as far as anesthesia and obstetric management of these patients is concerned. Pregnancy must be continued as long as possible to ensure adequate fetal growth but fetal extraction should not be delayed if the diameter of the aorta enlarges too much. A diameter of 40 mm is probably the higher limit to accept for vaginal delivery. Beyond, cautious cesarean section would be advisable. In the absence of dural ectasia or a technical problem, neuraxial anesthesia is a good option. CONCLUSION: According to the severity of the aortic dilatation and its evolution, specific management, based on good cooperation between obstetricians and anesthesiologists, is the key of a successful and safe childbirth.

Phenylephrine added to prophylactic ephedrine infusion during spinal anesthesia for elective cesarean section.

BACKGROUND: Because ephedrine infusion (2 mg/min) does not adequately prevent spinal hypotension during cesarean delivery, the authors investigated whether adding phenylephrine would improve its efficacy. METHODS: Thirty-nine parturients with American Society of Anesthesiologists physical status I-II who were scheduled for cesarean delivery received a crystalloid preload of 15 ml/kg. Spinal anesthesia was performed using 11 mg hyperbaric bupivacaine, 2.5 microg sufentanil, and 0.1 mg morphine. Maternal heart rate and systolic blood pressure were measured at frequent intervals. A vasopressor infusion was started immediately after spinal injection of either 2 mg/min ephedrine plus 10 microg/min phenylephrine or 2 mg/min ephedrine alone. Treatments were assigned randomly in a double-blind fashion. The infusion rate was adjusted according to systolic blood pressure using a predefined algorithm. Hypotension, defined as systolic blood pressure less than 100 mmHg and less than 80% of baseline, was treated with 6 mg ephedrine bolus doses. RESULTS: Hypotension occurred less frequently in the ephedrine-phenylephrine group than in the ephedrine-alone group: 37% versus 75% (P = 0.02). Ephedrine (36+/-16 mg, mean +/- SD) plus 178+/-81 microg phenylephrine was infused in former group, whereas 54+/-18 mg ephedrine was infused in the latter. Median supplemental ephedrine requirements and nausea scores (0-3) were less in the ephedrine-phenylephrine group (0 vs. 12 mg, P = 0.02; and 0 vs. 1.5, P = 0.01, respectively). Umbilical artery pH values were significantly higher in the ephedrine-phenylephrine group than in the group that received ephedrine alone (7.24 vs. 7.19). Apgar scores were similarly good in both groups. CONCLUSION: Phenylephrine added to an infusion of ephedrine halved the incidence of hypotension and increased umbilical cord pH.