Anti-depression effects of oxytocin on postpartum depression model rats and its mechanism / 中华行为医学与脑科学杂志

Objective To investigate the expression of oxytocin ( OXT ) and oxytocin receptor (OXTR) in the prefrontal cortex of postpartum depression (PPD) rats induced by restraint stress during pregnancy and to observe the antidepressant effect of oxytocin and its analogue capitoxin and its mechanism. Methods Twenty-four adult female SD rats of SPF grade were randomly divided into control group,PPD +saline group,PPD + oxytocin group and PPD + captopril group with 6 rats in each group. Rats were subjec-ted to restraint stress for 2 hours every day on the 8th to 21st day of pregnancy to establish PPD model. While the rats in control group were not given any treatment. Rats in PPD + saline,PPD + oxytocin and PPD +captopril were injected bilaterally into prefrontal cortex (PFC) at 10 days postpartum (1 μl/side),oxytocin (30 ng/side) and captopril (45 ng/side) respectively once a day for 5 days. The depressive behaviors of rats were detected by sugar-water preference experiment. Rats were sacrificed 18 days after delivery. The ex-pression of OXT was detected by ELISA method,OXTR by Western blot,Iba-1 by immunofluorescence,and IL-1β,IL-6 and TNF-α by qRT-PCR. Results (1) The sucrose consumption of the PPD + saline group ((67. 1±10. 4)%) was significantly lower than that of the control group((92. 6± 3. 9)%,t=-5. 31,P<0. 01). (2) The expression of oxytocin in prefrontal cortex in PPD group was significantly lower than that in control group ((0. 03±0. 01) ng/mg) vs (0. 08 +0. 05) ng/mg,t=-2. 67,P<0. 05). However,there was no significant difference in the expression of oxytocin receptor between PPD group and control group ((0. 90 ±0. 06) vs (0. 90±0. 05),t=0. 709,P=0. 517). (3) The sucrose consumption of PPD+saline group de-creased than that of control group((65. 6±16. 9)% vs (91. 5±3. 5)%,t=3. 35,P<0. 001). Compared with PPD+saline group,the sucrose consumption of PPD+oxytocin group ((81. 8±8. 4)%) and PPD+carbetocin group ((78. 4±9. 4)%) increased(t=1. 98,1. 68,both P<0. 05). (4) The expression of Iba-1 in the pre-frontal lobe of PPD + saline group was higher than that of control group ((1. 15±0. 05) vs (1. 04 +0. 06), t=3. 50,P<0. 01). Compared with PPD + saline group,the expression of Iba-1 in PPD + oxytocin group (1. 03±0. 06) and in PPD + captopril group (1. 00±0. 02) were lower (t=-3. 50,-6. 55,both P<0. 01). (5) The expression of inflammatory factors IL-1β mRNA (1. 0±0. 1),IL-6 mRNA (1. 1±0. 1) and TNF-α mRNA (1. 7±0. 4) in the prefrontal cortex of rats in the PPD group were higher than that in the control group (IL-1β mRNA (0. 7± 0. 3),IL-6 mRNA (0. 9± 0. 1),TNF-α mRNA ( 1. 1± 0. 3),t=1. 92,3. 19, 2. 43 respectively,all P<0. 05). The expression of inflammatory factors IL-1β,IL-6 and TNF-α mRNA of the PPD+oxytocin group(IL-1β mRNA (0. 6±0. 1),IL-6 mRNA (0. 9±0. 1),TNF-α mRNA (1. 2±0. 4) )and the PPD+carbetocin group ( IL-1β mRNA ( 0. 7± 0. 1),IL-6 mRNA ( 0. 9 ± 0. 1),TNF-α mRNA ( 1. 0 ± 0. 2))in the prefrontal cortex were lower than that in the PPD group(t=-3. 17,-2. 78,-1. 84,t=-2. 76,-2. 40,-2. 94 respectively,all P<0. 05). Conclusion Oxytocin and capitoxin injected into prefrontal cortex can effectively improve depression-like behaviors in PPD model rats. Activation of microglia and decrease of inflammatory factors in prefrontal cortex may be the potential antidepressant mechanism.

Cost-effectiveness of carbetocin versus oxytocin for prevention of postpartum hemorrhage resulting from uterine atony in women at high-risk for bleeding in Colombia / Rendimento da carbetocina versus oxitocina para a prevenção da hemorragia pós-parto resultante da atonia uterina em mulheres com alto risco de sangramento na Colômbia

Abstract Objective To assess the cost-effectiveness of carbetocin versus oxytocin for prevention of postpartum hemorrhage (PPH) due to uterine atony after vaginal delivery/ cesarean section in women with risk factors for bleeding. Methods A decision treewas developed for vaginal delivery andanother one for cesarean, in which a sequential analysis of the results was obtained with the use of carbetocin and oxytocin for prevention of PPH and related consequences. A third-party payer perspective was used; only directmedical costs were considered. Incremental costs and effectiveness in terms of quality-adjusted life years (QALYs) were evaluated for a one-year timehorizon. The costs were expressed in 2016 Colombian pesos (1 USD = 3,051 Col$). Results In the vaginal delivery model, the average cost of care for a patient receiving prophylaxis with uterotonic agents was Col$ 347,750 with carbetocin and Col$ 262,491 with oxytocin,while theQALYs were 0.9980 and 0.9979, respectively. The incremental costeffectiveness ratio is above the cost-effectiveness threshold adopted by Colombia. In the model developed for cesarean section, the average cost of a patient receiving prophylaxis with uterotonics was Col$ 461,750 with carbetocin, and Col$ 481,866 with oxytocin, and the QALYs were 0.9959 and 0.9926, respectively. Carbetocin has lower cost and is more effective, with a saving of Col$ 94,887 per avoided hemorrhagic event. Conclusion In case of elective cesarean delivery, carbetocin is a dominant alternative in the prevention of PPH compared with oxytocin; however, it presents higher costs than oxytocin, with similar effectiveness, in cases of vaginal delivery.

Resumo Objetivo Avaliar a relação custo-eficácia da carbetocina versus oxitocina para prevenção de hemorragia pós-parto (HPP) vaginal e cesariana devido à atonia uterina em mulheres com fatores de risco para desenvolver sangramento. Métodos Foram desenvolvidos protocolos de manejo para parto vaginal e outra para parto por cesárea e analisados resultados obtidos com carbetocina e oxitocina na prevenção de HPP, assim como, consequências relacionadas à ocorrência do evento hemorrágico. A perspectiva utilizada foi a do terceiro pagador, portanto, apenas os custos médicos diretos foram levados em consideração. Os custos incrementais e a eficácia em termos de anos de vida ajustados pela qualidade (QALY) foram avaliados para um horizonte de tempo de um ano. Os custos foram expressos em pesos colombianos de 2016 (1 USD = 3.051 Col$). Resultados No modelo de parto vaginal, o customédio de cuidados para um paciente que recebeu profilaxia com agentes uterotônicos foi de Col$ 347.750 com carbetocina e Col$ 262.491 com oxitocina, enquanto os QALYs foram 0,9980 e 0,9979, respectivamente. O índice incremental de custo-efetividade está acima do limite de custoefetividade adotado pela Colômbia. No modelo desenvolvido para parto por cesárea, o custo médio do paciente que recebeu profilaxia com terapia uterotônica foi de Col$ 461.750 com carbetocina e Col$ 481.866 com oxitocina e os QALYs foram 0,9959 e 0,9926, respectivamente. A carbetocina foi a alternativa com menor custo e maior efetividade com uma economia de $94.887 por evento hemorrágico evitado. Conclusão A carbetocina no parto eletivo por cesárea é uma alternativa dominante na prevenção da PPH em relação à oxitocina; porém representa custos mais altos com uma eficácia similar à da oxitocina no caso de parto vaginal.

Uso de carbetocina frente al uso de oxitocina en pacientes intervenidas por cesárea con alto riesgo de atonía uterina / Use of Carbetocin versus Oxytocin in Cesareans with High Risk of Uterine Atony

Introducción: la utilización adecuada de medicamentos uterotónicos es fundamental en el manejo de la hemorragia obstétrica. Objetivo: describir los efectos de la carbetocina y su comparación con la oxitocina como primera elección para prevenir la hemorragia obstétrica en pacientes cesareadas con riesgo de atonía uterina. Métodos: se realizó un estudio prospectivo, comparativo y transversal, en el 2016, donde se incluyeron 165 pacientes embarazadas que ingresaron para interrupción del embarazo por cesárea, las cuales tenían factores de riesgo de atonía uterina. Se formaron dos grupos: el A, con 110 pacientes que recibieron oxitocina a dosis de 10 U por vía intravenosa, y el B, con 55 pacientes a las que se les administraron 100 mg de carbetocina después del nacimiento. Resultados: ambos grupos resultaron similares en la edad. En el grupo A, el promedio de edad fue de 27,5 años, y en el B, de 28,1 años. Se encontró una adecuada contractilidad en 83 pacientes del grupo A (75,45 por ciento) y en 53 del grupo B (96,36 por ciento). El grupo que recibió carbetocina requirió menor cantidad de maniobras o medicamentos adicionales. El sangrado transoperatorio fue, en promedio, de 845 ± 124,8 mL, para el grupo A, y de 709 ± 275,21 mL para el grupo B, en 21 pacientes del grupo A fue mayor de 1 000 mL y en 12 del grupo B. Conclusiones: las pacientes que recibieron carbetocina tuvieron resultados mejores en la contractilidad uterina. La necesidad de maniobras y medicamentos adicionales así como en la magnitud del sangrado y por tanto menor cantidad de transfusiones de hemoderivados(AU)

Introduction: the proper use of uterotonic drugs is fundamental in the management of obstetric hemorrhage. Objective: describe the effects of carbetocin and its comparison with oxytocin as the first choice to prevent obstetric hemorrhage in patients who are at risk for uterine atony. Methods: aprospective, comparative and cross-sectional study was conducted in 2016, which included 165 pregnant patients admitted for cesarean section, who had risk factors for uterine atony. Two groups were formed: A, with 110 patients receiving oxytocin at a dose of 10 U intravenously, and B, with 55 patients given 100 mcg of carbetocin after birth. Results: both groups were similar in age. In group A, the mean age was 27.5 years, and in B, 28.1 years. Adequate contractility was found in 83 patients in group A (75.45 percent) and 53 patients in group B (96.36 percent). The group receiving carbetocin required fewer maneuvers or additional medications. The intraoperative bleeding was, on average, 845 ± 124.8 mL in group A and 709 ± 275.21 mL in group B. It was more than 1,000 mL in 21 patients in group A and 12 patients in group B. Conclusions: patients who received carbetocin had better results in uterine contractility. The need for maneuvers and additional drugs was lesser as well as the magnitude of bleeding and therefore less transfusions of blood products(AU)

Oxitocina frente a Carbetocina para prevenir hemorragias posparto tras cesárea

Antecedentes: La hemorragia posparto (HPP) es la causa aislada más importante de mortalidad materna y su causa más frecuente es la atonía uterina. El mejor tratamiento es su prevención. La oxitocina reduce el riesgo de HPP. Se ha comercializado en España la carbetocina, análogo de la oxitocina humana que tiene inicio de acción rápido y una vida media 4 a 10 veces más larga que la oxitocina, produciendo una contracción tónica que reduce la pérdida hemática posparto. Objetivos: Comparar efectos de carbetocina y oxitocina para prevenir hemorragias posparto tras cesárea. Diseño: Estudio observacional retrospectivo de comparación. Institución: Servicio de Obstetricia y Ginecología, Hospital General Universitario de Elche, Alicante, España. Participantes: Gestantes con factor de riesgo de atonía uterina tras cesárea. Metodología: Se ha incluido 247 mujeres con algún factor de riesgo de atonía uterina tras cesárea, estudiadas desde abril de 2010 hasta marzo de 2012. Se ha comparado los efectos de administrar 100 microgramos de carbetocina y 10 UI de oxitocina tras el alumbramiento. Se ha evaluado las cifras de hemoglobina previas a la cesárea y tras 24 a 48 horas de la misma, y el porcentaje de transfusiones realizadas. Principales medidas de resultados: Anemia, transfusiones sanguíneas, hierro intravenoso. Resultados: En el grupo carbetocina, la hemoglobina tras la cesárea descendió menos (P=0,56) y existió menos casos de anemia tras la misma (P=0,852). Las transfusiones y el hierro intravenoso no aportaron datos concluyentes. Conclusiones: No existieron diferencias estadísticamente significativas entre carbetocina y oxitocina para prevenir HPP tras cesáreas.

Background: Postpartum haemorrhage (PPH) is the single most important cause of maternal mortality, and uterine atony is its most common cause. The best treatment is prevention. Oxytocin reduces the risk of PPH. In Spain carbetocin has been marketed, a human oxytocin analogue that has rapid onset of action and an average life 4-10 times longer than oxytocin, producing tonic contraction that reduces postpartum blood loss. Objectives: To compare effects of carbetocin and oxytocin, in order to prevent postpartum haemorrhage after cesarean section. Design: Observational retrospective comparative study. Setting: Obstetrics and Gynecology Service, Hospital General Universitario de Elche, Alicante, España. Participants: Pregnant women with risk factor of uterine atony following cesarean section. Methods: From April 2010 through March 2012 247 women with a risk factor for uterine atony after cesarean section The effects of administering 100 micrograms of carbetocin and 10 UI of oxytocin following delivery were compared. Hemoglobin levels prior and 24-48 hours after cesarean section and the percentage of transfusions given were assessed. Main outcome measures: Anemia, blood transfusions, intravenous iron. Results: In the group of carbetocin, hemoglobin decreased less than in the oxytocin group (P=0.56), and there was less anaemia after cesarean section (P=0,852). Transfusions and intravenous iron did not provide conclusive data. Conclusions: There were no significant differences between carbetocin and oxytocin to prevent PPH after cesarean sections.

Effects of carbetocin infusion on hemodynamics during cesarean delivery under spinal anesthesia

BACKGROUND: Carbetocin is a long-acting synthetic analogue of oxytocin that is used to prevent postpartum hemorrhage. Cardiovascular effects of oxytocin include tachycardia and hypotension. We investigated hemodynamic changes induced by carbetocin during spinal anesthesia. METHODS: Carbetocin 100 microg was infused over 5 min in 40 women undergoing cesarean delivery. Hemodynamic parameters were measured noninvasively using the Finometer(R) device. The hemodynamic values were analyzed using multivariate analysis of variance followed by Bonferroni test for multiple comparisons. RESULTS: Statistically significant hemodynamic effects were seen with a maximal effect at about 75 seconds after infusion start compared with those of baseline: Mean arterial pressure (MAP) decreased 21.6 +/- 8.8 mmHg, systemic vascular resistance (SVR) decreased 28.6 +/- 11.1% and heart rate (HR) increased 15.3 +/- 7.9 beats/min. Following the maximal effect, MAP and SVR remained almost constant at this decreased level until the end of study period. However, HR was slowly recovered after the peak, approaching the baseline value. CONCLUSIONS: We observed that the maximal hemodynamic changes were occurred at about 75 seconds after administration of carbetocin. Therefore, careful observation is required during this early period.

Contacto madre-hijo en cesáreas: estudio controlado y randomizado con carbetocina / Contact mother-son in cesarean: ramdomized and controlled study with carbetacin

Objetivo. Comparar dos esquemas de manejo postoperatorio en cesáreas programadas. Métodos. Investigación clínica controlada y randomizada. Se comparó un esquema de manejo de cesárea con ocitocina y dextropropoxifeno más dipirona endovenosos más ayuno de 12 h (grupo control) con un nuevo esquema en que se utiliza carbetocina y dextroporpoxifeno más dipirona endovenosa intraoperatoria con dieta líquida y medicación oral (grupo estudio). Resultados. Se randomizaron mediante sobres cerrados 25 embarazadas al grupo de estudio y 25 al de control. Las características iniciales de ambos grupos no presentaron diferencias evidentes. Las madres del grupo estudio tomaron contacto con su hijo dentro de las primeras 6 h en mayor proporción que las del grupo control (RR=0,33, IC 95 por ciento 0,13-0,84); a las 12 h el RR fue de 0,26 (0,13-0,53). Conclusiones. El nuevo esquema de manejo postoperatorio acortó la demora en el contacto madre-hijo, sin diferencias en la hemorragia posparto y otras complicaciones mayores.