Informe rápido: carbetocina para la prevención de la atonía uterina y la hemorragia post-parto tras parto por cesárea / Quick report: carbetocin for the prevention of uterine atony and postpartum hemorrhage after cesarean delivery

TECNOLOGÍA: carbetocina inyectable ampollas de 100 mcg/ml. INDICACIONES: prevención de la hemorragia post-parto (HPP) y la atonía uterina luego del parto por cesárea. CARACTERÍSTICAS DE LA TECNOLOGÍA: Carbetocina es un agonista de oxitocina de acción prolongada. Como la oxitocina, la carbetocina se une selectivamente a receptores de oxitocina en el músculo liso del útero, estimula las contracciones rítmicas del útero, aumenta la frecuencia de contracciones existentes y el tono de la musculatura del útero. En el útero postparto, la carbetocina es capaz de incrementar el índice y la fuerza de las contracciones espontáneas uterinas. PREGUNTAS: En mujeres que fueron sometidas a cesárea, el uso de carbetocina ¿es más efectiva y segura que la oxitocina para la prevención de la atonía uterina y la hemorragia post parto? ¿Cuál es el costo del tratamiento con la carbetocina comparado con la oxitocina? BÚSQUEDA Y ANÁLISIS DE LA EVIDENCIA CIENTÍFICA: en fuentes primarias se encontraron 4 ensayos controlados aleatórios (1233 mujeres) que compararon carbetocina con oxitocina para la prevención de la HPP y la atonía uterina luego de una cesárea. En fuentes secundarias se encontraron un metaanálisis y una revisión sistemática. También se consultaron guías de práctica clínica. RESUMEN DE LOS RESULTADOS DE LOS ESTUDIOS SELECCIONADOS: En comparación con la oxitocina, la evidencia recopilada demuestra que la utilización de carbetocina reduce significativamente el uso de dosis adicionales de útero-tónicos em mujeres sometidas a cesáreas electivas, así como la necesidad de masaje uterino. Si bien es cierto que la carbetocina puede ser un oxitócico más potente que la oxitocina, la evidencia demuestra que la utilización de carbetocina no reduce las tasas de HPP ni de HPP severa. No hay evidencias sobre impacto en la mortalidad materna, que junto a las hemorragias, son las medidas de resultado clínicamente relevantes. No habría diferencias importantes en cuanto a la seguridad de ambos fármacos. El tratamiento con carbetocina es 13 veces más costoso que el tratamiento com oxitocina. Los británicos, en sus guías NICE y SOCG no recomiendan el uso de carbetocina. RECOMENDACIONES: Intervención no recomendada-evidencia encontrada concluyente en relación a ausencia de beneficios.(AU)

[Clinical value of adjuvant therapy with estrogen for postpartum hemorrhage].

OBJECTIVE: To investigate the clinical efficacy of estrogen in management of postpartum hemorrhage due to uterine atony. METHODS: Totalling 112 puerperants with postpartum hemorrhage due to uterine atony were randomly assigned into 2 groups and received routine managements for uterine atony such as uterine massage and uterotonics administration. The puerperants in one group (n=52) was treated with 4 mg estradiol benzoate injected intramuscularly, and the amount of blood loss 2 h after delivery and between 2 and 24 h after delivery was recorded. RESULTS: There were significant differences in vaginal blood loss at 2 h after delivery between the 2 groups (P<0.05). The puerperants with estrodiol benzoate treatment had blood loss of 589.6-/+226.4 ml at 2 h and 110.8-/+76.2 ml within 2-24 h after delivery, which were both less than those in the control group (864.5-/+359.5 ml and 161.5-/+98.3 ml, respectively). Postpartum hysterectomy was performed in 3 cases of the control group while none in estradiol benzoate-treated group. In the mothers and neonates, no major adverse effects were observed. CONCLUSION: Estrogen shows cooperative efficacy with uterotonics in stimulating uterine contraction for managements of postpartum hemorrhage due to uterine atony, and can be of value in clinical application.

Potentiation of uterine effects of prostaglandin F2{alpha} by adenosine 5'-triphosphate.

OBJECTIVE: To investigate the interaction of exogenous adenosine 5'-triphosphate (ATP), a P2 receptor agonist, with prostaglandin F(2alpha) (PGF(2alpha)) on pregnant women in labor as well as on isolated human pregnant uterus preparations. METHODS: For an in vitro study, myometrial samples were obtained from 27 women undergoing elective cesarean delivery at term. Concentration-response relationships for ATP (10(-8) -3 x 10(-4) mol/L), PGF(2alpha) (10(-9) -10(-5) mol/L), and their combination were obtained by using routine pharmacological organ bath technique. An in vivo study was performed with 34 pregnant women with dysfunctional abnormalities of the active stage of labor who were randomly allocated into 2 study groups. The women in the control group (18 patients) received intravenous prostaglandin F(2alpha) at an initial rate of 7.5 mug/min, whereas the women in the ATP group (16 patients) received prostaglandin F(2alpha) concomitantly with ATP (0.45 nmol/min, intravenously). RESULTS: Adenosine 5'-triphosphate at concentrations of 10(-6) -3 x 10(-4) mol/L and PGF(2alpha) at concentrations of 10(-8) -10(-5) mol/L caused concentration-dependent contractions of isolated smooth muscle preparations of the human pregnant uterus. At concentrations of 10(-6) mol/L and below, ATP had no effects on mechanical activity of the isolated uterus, but at concentrations of 10(-7) mol/L and 10(-6) mol/L, it significantly potentiated the contractile responses of the uterus induced by PGF(2alpha) (P < .05, 2-way analysis of variance). Patients receiving intravenous infusion of ATP as a supplement to PGF(2alpha) treatment, compared with those without ATP, had a significantly shorter interval from the start of the treatment to full cervical dilatation (3.31 +/- 1.49 hours and 4.67 +/- 1.11 hours in ATP and control groups, respectively; P = .014, Wilcoxon Mann-Whitney test). The total dose of prostaglandin received was significantly lower in the ATP group than that of controls (1,489.8 +/- 699.9 mug and 3,394.2 +/- 1,951.9 mug, respectively; P = .003, Wilcoxon Mann-Whitney test). No side effects of ATP treatment were observed during or after infusion. CONCLUSION: Adenosine 5'-triphosphate potentiates effects of PGF(2alpha) on pregnant human uterus in vitro and in vivo and thus could be a useful supplemental drug to increase uterine contractility at labor.

A clinical trial of active management of labor.

BACKGROUND: Active management of labor is a multifaceted program that, as implemented at the National Maternity Hospital in Dublin, is associated with a lower rate of cesarean delivery than the rate usually found in the United States. We conducted a randomized trial to evaluate the efficacy of this approach in lowering the rate of cesarean section among women delivering their first babies. METHODS: We randomly assigned 1934 nulliparous women at low risk of complications of pregnancy, before 30 weeks' gestation, to active management of labor or to a usual-care group. The components of active management were customized childbirth classes; strict criteria for the diagnosis of labor; standardized management of labor, including early amniotomy and treatment with high-dose oxytocin; and one-to-one nursing. A low-risk subgroup was defined as including women with full-term, uncomplicated pregnancies who spontaneously went into labor (the protocol-eligible subgroup). Women meeting these criteria who had been randomly assigned to the active-management group were admitted to a separate unit where their labor was managed by trained, certified nurse-midwives. RESULTS: There was no difference between groups in the rate of cesarean section either among all women (active management, 19.5 percent; usual care, 19.4 percent) or in the protocol-eligible subgroup (active management, 10.9 percent; usual care, 11.5 percent). In the protocol-eligible subgroup, the median duration of labor was shortened by 2.7 hours by active management (from 8.9 to 6.2 hours), and the rate of maternal fever was lower (7 percent vs. 11 percent, P = 0.007). The percentage of women in whom labor lasted longer than 12 hours was three times higher in the usual-care group than in the active-management group (26 percent vs. 9 percent, P < 0.001). CONCLUSIONS: Active management of labor did not reduce the rate of cesarean section in nulliparous women but was associated with a somewhat shorter duration of labor and less maternal fever.