Use of misoprostol in the treatment of postpartum hemorrhage: a pharmacoepidemiological approach / Uso do misoprostol no tratamento da hemorragia pós-parto: uma abordagem farmacoepidemiológica

ABSTRACT Objective To characterize the use of the drug misoprostol for treatment of postpartum hemorrhage in pregnant women. Methods A descriptive observational study was carried out with secondary data from pregnant women who used misoprostol to treat postpartum hemorrhage in a reference public maternity, from July 2015 to June 2017. Clinical and sociodemographic profiles of pregnant women, how misoprostol was used and success rate in controling postpartum hemorrhage were characterized. Results A total of 717 prescriptions of misoprostol were identified. Of these, 10% were for treatment of postpartum hemorrhage. The majority of pregnant women were young adults, married, with complete high school education, white, residing in urban areas, multiparous (68.1%) and 25% had previous cesarean sections. The mean gestational age was 39 weeks and 51.4% had a cesarean section. There was prophylactic use of oxytocin in 47.2% of women. Treatment of postpartum hemorrhage was successful in 84.7% of women. Of these, 79.2% also used oxytocin and 54.2% methylergonovine. Only 13.5% of pregnant women had less than five prenatal visits, and the main cause of postpartum hemorrhage was uterine atony. There were 13 complications after hemorrhage, 15.3% required blood transfusion and there was one case of maternal death. Conclusion Misoprostol showed to be effective and safe for treating postpartum hemorrhage.

RESUMO Objetivo Caracterizar o uso do medicamento misoprostol para o tratamento da hemorragia pós-parto em gestantes. Métodos Estudo observacional descritivo realizado por meio de dados secundários de gestantes que fizeram uso do misoprostol para tratamento da hemorragia pós-parto em maternidade pública de referência, no período de julho de 2015 a junho de 2017. Caracterizaram-se os perfis clínico e sociodemográfico das gestantes, o padrão de utilização do misoprostol e sua taxa de sucesso no controle da hemorragia pós-parto. Resultados Foram identificadas 717 prescrições do misoprostol. Destas, 10% foram para tratamento da hemorragia pós-parto. Predominaram gestantes adultas jovens, casadas, com Ensino Médio completo, raça branca, da região urbana, multíparas (68,1%) e 25% apresentavam cesáreas prévias. A idade gestacional média foi 39 semanas e 51,4% das gestantes tiveram parto cesárea. Houve uso profilático de ocitocina em 47,2% das mulheres. O tratamento da hemorragia pós-parto eve sucesso em 84,7% das gestantes que usaram misoprostol. Destas, 79,2% também usaram ocitocina e 54,2% metilergometrina. Apenas 13,5% das gestantes tiveram menos de cinco consultas de pré-natal, e a principal causa da hemorragia pós-parto foi atonia uterina. Foram registrados 13 casos de complicações após a hemorragia, 15,3% necessitaram de hemotransfusão e houve um caso de óbito materno. Conclusão O misoprostol demonstrou ser efetivo e seguro para o tratamento da hemorragia pós-parto.

A meta-analysis on the efficacy of carboprost versus methylergometrine maleate in the active management of third stage of labor for the prevention of postpartum haemorrhage / Philippine Journal of Obstetrics and Gynecology

OBJECTIVE: To determine the efficacy of Carboprost versus methylergometrine maleate in the active management of third stage of labor for the prevention of postpartum hemorrhage. METHODS: Entries in electronic databases with references cited in original studies and review articles were used to identify randomized clinical trials of carboprost versus methergin in the active management of third stage of labor. The quality of published clinical trials were evaluated and assessed based on the efficacy of Carboprost versus methylergometrine maleate for the prevention of postpartum hemorrhage. RESULTS: Six (6) clinical trials were analyzed comprising a total sample pool of 525 women randomized to carboprost group and another 525 women to methergin. The risk ratio for dichotomous outcomes were calculated using a random-effects model while continuous outcomes were pooled using the standard mean difference. Results showed that both carboprost and methergin are both effective in preventing postpartum hemorrhage. But carboprost was found to be more efficacious in reducing the duration and decreasing the amount of blood loss in the third stage of labor and there was less need for an additional drug dose. Risks of side effects were higher in carboprost. Vomiting is the most frequent adverse event followed by diarrhea but are usually self-limiting. CONCLUSION: Carboprost is well known for its therapeutic role in the management of postpartum hemorrhage, well-tolerated and with minimal adverse effects. It is therefore recommended to be used in hypertensive patients where methylergometrine maleate is contraindicated and in cases refractory to other uterotonic agents.

A comparative study of methylergonovine and 15-methyl prostaglandin F2alpha in active management of third stage of labor

OBJECTIVE: Postpartum hemorrhage is most common cause of maternal mortality. Active management of third stage of labor minimizes the risk of postpartum hemorrhage. To compare the effect of methylergonovine and 15-methyl prostaglandin F2alpha (15-methyl PGF2alpha) in active management of third stage of labor. METHODS: A randomized open labelled parallel study with 50 women in normal labor, 25 in each group were included. The drugs methylergonovine (0.2 mg) intravenous and 15-methyl PGF2alpha (250 microg) intramuscular were administered at the time of delivery of anterior shoulder. Main outcomes measured were amount of blood loss during the first four hours of delivery and objective measurement of hemoglobin and hematocrit levels before delivery and third day postpartum. RESULTS: There was no statistically significant difference in the blood loss between the two groups at delivery (P = 0.130), at 1 hour of delivery (P = 0.453). The blood loss with 15-methyl PGF2alpha was significantly less as compared to that of blood loss with methylergonovine at four hours of delivery (P = 0.014) and the total, i.e., during first four hours, amount of blood loss was significantly less with 15-methyl PGF2alpha (P = 0.026). There was no statistically significant difference in the hemoglobin and hematocrit levels measured predelivery and postpartum third day between both the drugs. CONCLUSION: Both the drugs were effective in controlling the amount of blood loss during the third stage of labor, 15-methyl PGF2alpha being more efficacious.

Diagnosis and management of postpartum hemorrhage

Postpartum hemorrhage (PPH) is an important cause of maternal mortality. There is currently no single, satisfactory definition of PPH. The various definitions of PPH may result in delayed diagnosis. Underestimated blood loss concerning PPH is considered one of the biggest problems. The diagnosis of PPH should include proper estimation of blood loss before vital signs and clinical symptoms change. Management of PPH involves early recognition, assessment and resuscitation. Careful monitoring of vital signs, laboratory tests, coagulation testing in particular, and timely diagnosis of the cause of PPH are important. The first priority in the management of PPH is the rapid correction of hypovolemia with fluid infusion and packed red blood cells transfusion, followed by blood component therapy as indicated by the hematocrit, coagulation tests, platelet count and clinical features. Pharmacological management of PPH is to contract uterus (e.g., oxytocin, methylergonovine, 15-methylprostaglandin F2alpha, misoprostol) and to aid hemostasis (e.g., tranexamic acid, recombinant factor VIIa). Surgical management (e.g., balloon tamponade, uterine compression suture, iliac artery ligation) should be considered if hemorrhage persists or vital signs is unstable.

Diagnosis and management of postpartum hemorrhage

Postpartum hemorrhage (PPH) is an important cause of maternal mortality. There is currently no single, satisfactory definition of PPH. The various definitions of PPH may result in delayed diagnosis. Underestimated blood loss concerning PPH is considered one of the biggest problems. The diagnosis of PPH should include proper estimation of blood loss before vital signs and clinical symptoms change. Management of PPH involves early recognition, assessment and resuscitation. Careful monitoring of vital signs, laboratory tests, coagulation testing in particular, and timely diagnosis of the cause of PPH are important. The first priority in the management of PPH is the rapid correction of hypovolemia with fluid infusion and packed red blood cells transfusion, followed by blood component therapy as indicated by the hematocrit, coagulation tests, platelet count and clinical features. Pharmacological management of PPH is to contract uterus (e.g., oxytocin, methylergonovine, 15-methylprostaglandin F2alpha, misoprostol) and to aid hemostasis (e.g., tranexamic acid, recombinant factor VIIa). Surgical management (e.g., balloon tamponade, uterine compression suture, iliac artery ligation) should be considered if hemorrhage persists or vital signs is unstable.

Severe vaginal bleeding secondary to cesarean scar dehiscence following incomplete abortion management

Severe uterine bleeding is not a common presentation of cesarean section scar dehiscence in the first trimester. We present a 41-year-old lady with uterine scar dehiscence that was probably secondary to uterotonic medication used for the management of first trimester incomplete abortion. The use of uterotonic medications [Methergine] may be a contributing factor in this case. It should be used with caution in patients with previous uterine scar

A study of prophylactic use of 15-methyl prostalglandin F2alpha in the active management of third stage of labour.

To compare active management of third stage of labour with 15-methyl prostaglandin F2alpha (PGF2alpha) and conventional management with methylergometrine as prophylaxis for postpartum hemorrhage, a randomised comparative study was carried out at Calcutta National Medical College and Hospital, Kolkata on 100 women. They were randomly allotted to one of the two groups. Group A included 50 women who received 15-methyl PGF2alpha (125 microg) intramusculary at the time of delivery of the anterior shoulder and group B included 50 women who underwent conventional management of the third stage of labour where methylergometrine 0.2 mg was given after delivery of placenta. Main outcome measured were duration of third stage, amount of bleeding and side-effects. The present study showed that there were significent reduction of the duration of third stage as well as reduction of amount of bleeding particularly when 125 microg of 15-methyl PGF2alpha was given intramuscularly at the time of delivery of the anterior shoulder in comparison to coventional method of management of third stage of labour with methylergometrine. Placental expulsion occurred within 4 minutes in group A and 16.5 minutes in group B. The amount of bleeding following delivery was 95.6 ml in average in group A and 249.6 ml in average in group B. 15-methyl PGF2alpha (125 microg) is certainly effective in prevention of postpartum haemorrhage particularly in developing country like India where this complication contributes a major factor for maternal mortality.

Sublingual administration of misoprostol for treatment of postpartum hemorrhage

To examine the effectiveness and safety of high-dose sublingual misoprostol for treatment of postpartum hemorrhage compared to methylergometrine by means of a double blind randomized clinical trial. After active management of third stage of labor, 94 women with atonic postpartum hemorrhage were randomized between misoprostol treatment [4 x 200 ug sublingual and IV saline] or four placebo tablets and IV 0.25 mg methylergometrine injection. The primary outcome variable was the measured blood loss >/= 500 ml in one hour after enrolment. The significance level was chosen at P < .05. The measured blood loss > 500 ml in one hour after enrollment was not significantly different between misoprostol and ergometrine groups [p = 0.77]. Other estimations of blood loss showed no significant differences between the groups, though, more patients in misoprostol group needed additional uterotonics to stop their bleeding [27 [57.45%] vs. 16 [34.04%], p = .04]. With misoprostol side-effects were increased, namely shivering and pyrexia > 38.5°C [p = .01]. compared with methylergometrine, misoprostol provides nearly equal effect against postpartum hemorrhage but associated with more side effects and more demands of additional uterotonics

Different doses of sublingual misoprostol versus methylergometrine for the prevention of atonic postpartum haemorrhage

In the poor underdeveloped countries, anaemia is very common in pregnant women. Maternal mortality is four times higher in severely anaemic women than non-anaemic ones and postpartum haemorrhage [PPH] is the most common cause of death Its main cause is uterine atony, which accounts for more than 70%. The objective of this study is to evaluate the use of sublingual misoprostol in different doses of 600, 800 and 1000 micro g in management of the third stage of labor, with regards to blood loss and incidence of atonic postpartum haemorrhag [APPH]. Double blind randomized controlled study. One thousand and two hundred parturient were studied in a control and three study groups, each composed of 300 women. Methylergometrine 0.2 mg IM injection and sublingual misoprostol 600, 800 and 1000 micro g tablets were given to women in control and the three study groups respectively, immediately after delivery. Outcome Measures: Duration of the third stage of labour, Blood loss in the third stage of labour, Outcomes in anaemic compared to non-anaemic women, Incidance of atonic postpartum haemorrhage in different groups, Haemoglobin deficit after 24 hrs of delivery, Changes in the women's blood pressure during the study, Side effects of the drug, and, Women's acceptability of sublingual misoprostol administration. Only significant reduction in blood loss and haemoglobin deficits were seen in the third stage of labour and after delivery in women used misoprostol doses of 800 M9 and 1000 micro g. The incidences of PPH in studied women and controls were almost similar, ranging between 2 and 3%. Similar results were seen in anaemic and non-anaemic women with a higher incidence of APPH in the non-misoprostol user anaemic women. Side effects of the drug were dose related. Misoprostol in high dose may be used for managing third stage of labour to reduce maternal morbidity and mortality due to APPH particularly, in the poor underdeveloped countries where, facilities to deliver in health centers, purchase and store the oxytocic ampoules or medically trained persons are not readily available in all places. Benefits of large dose misoprostol outweigh its side effects

Clinical use of a Sengstaken-Blakemore tube in the management of postpartum hemorrhage / 대한산부인과학회지

OBJECTIVE: To evaluate the efficacy of clinical use of a intrauterine Sengstaken-Blakemore tube (S-B tube) in postpartum hemorrhage not controlled with medication and conservative treatment. METHODS: Retrospective review was done in 18 women with insertion of S-B tube into intrauterine cavity who did not controlled with medication and conservative treatment for postpartum hemorrhage. After third stage of labor, women were treated with prophylactic intramuscular Methylergonovine 0.2 mg and intravenous infusions of oxytocin routinely. If the postpartum bleeding continued, Misoprostol 800 microgram (per rectal) and intravenous infusions of Dinoprost 2 mg mixed with 5% D/S 500 cc were employed. And then women were examined for retained placenta and laceration of birth canal. Where necessary, retained placenta was removed and lacerations were sutured. If the postpartum bleeding did not controlled despite all of procedures, we decided use of intrauterine S-B tube. RESULTS: The mean age of the patients was 30.9+/-4.4 (27-39) years, their mean body weights and parities were 67.8+/-8.2 (56.2-85.7) kg, 1.8+/-0.8 (1-4) and mean gestational age was 38.5+/-2.9 (37-42) weeks respectively. The mean time from delivery to insertion of S-B tube was 107.6+/-94.0 (24-360) minutes. The mean filled normal saline amount was 190.5+/-35.2 (120-230) cc. Of 18 who was inserted of S B tube, 15 cases needed not additional surgical therapy. So success rate was 83.3%. CONCLUSION: Insertion of intrauterine S-B tube appears as a simple and effective means of treating postpartum hemorrhage not controlled with medication and conservative treatment.

Is treatment with oral or rectal misoprostol effective to prevent postpartum hemorrhage?

To compare the efficacy of 400 mg of oral or rectal misoprostol with 0.2 mg intramuscular methylergometrine to prevent postpartum hemorrhage [PPH]. 672 women were randomized into three groups: Group 1 received 400 mg misoprostol orally [n =240], Group 2 received 400 mg misoprostol rectally [n = 222], and Group 3 received 0.2 mg methylergometrine IM [n =210]. The mean blood loss, PPH >/= 500 ml, needs for additional oxytocic drugs, and decrease in hemoglobin concentration were the main outcomes measured. The demographic characteristics were comparable. There were no significant differences among the three groups in mean blood loss [P = 0.112], incidence of PPH >/= 500 ml [P=0.334], need for additional oxytocic agents [P=0.574], and decrease in mean hemoglobin concentration [P=0.613]. Significant differences detected with the use of misoprostol whether given orally or rectally, were elevated temperature >/= 38°C [P= 0.002] and shivering [P=0.001]. Oral or rectal misoprostol is as effective as conventional, intramuscular methylergometrine in preventing postpartum hemorrhage, and the drug has the advantages of stability at room temperature and ease of administration. It can be recommended for routine use anywhere for prevention of PPH

Does Methergine Aggravate Chest Symptom and/or Electrocardiographic Changes during Cesarean Delivery under Spinal Anesthesia? / 대한마취과학회지

BACKGROUND: Complaints of chest symptoms including pressure, tightness, or pain frequently occur during cesarean delivery under regional anesthesia. The aim of this study was to test whether methergine (methylergonovine maleate) aggravates chest symptoms and/or ECG changes during cesarean section under spinal anesthesia, and to determine if these changes are associated with any discernable intraoperative event. METHODS: After delivery, patients were given intravenous methergine 0.2 mg and diluted oxytocin 10 i.u. in 1000 ml Ringer's lactate solution (Methergine group, n = 30) or diluted oxytocin 20 i.u. (Control group, n = 29). ECG and hemodynamic responses were monitored continuously on 12 leads perioperatively. RESULTS: Methergine significantly increased the incidence of chest symptoms compared to the control group (30% vs. 3.4%, P 0.05). CONCLUSIONS: Methergine-induced chest symptoms per se do not signify evident myocardial ischemia during cesarean delivery. However, anesthesiologists must not overlook the possibility of a small coronary arteriolar spasm, especially in high-risk patients.

Uterine arteriovenous malformations associated with pregnancy: An uncommon cause of severe uterine bleeding / 대한산부인과학회지

Uterine arteriovenous malformations are considered very rare conditions, potentially life-threatening lesions combined with various degrees of menorrhagia, postpartum bleeding, postmenopausal bleeding, an asymptomatic mass, and congestive heart failure. Clinical suspicion is essential for a prompt diagnosis and treatment. They may be diagnosed by gray-scale ultrasonography and Color Doppler imaging. Additionally, they can be detected using contrast material-enhanced computed tomography (CT), conventional angiography, hysteroscopy and hysterosalpingogram. More recently, diagnosis of uterine AVM with magnetic resonance imaging (MRI) has been reported. In the past, laparotomy with uterine artery ligation or hysterectomy was the only treatment available. However, successful conservative management with embolization of the affected vessels or methylergonovine maleate has been reported recently. A 37-year-old woman, gravida 3, para 1, presented with massive uterine bleeding that started abruptly four weeks after D and C. We promptly performed non-invasive diagnositic evaluations including color Doppler, MRI and MRA, with a clinical impression of uterine AVM. In this case, we describe the appropriate diagnosis and management of uterine AVMs with literatures.

Comparison between rectal misoprostol and intramuscular oxytocin/methergine for the management of the third stage of labor

Two groups of parturient women, each one hundred, were given either 400 ug misopristol rectally or combination of 5 IU oxytocin and 0.2 mg methergine IM for the management of the third stage of labor. Misoprostol group had shorter third stage of labor, less blood loss and post partum hemorrhage, less incidence of manual removal of the placenta and less side effects. Rectal misoprostol is safe, effective, and cheep drug for the management of the third stage of labor as a primary line of treatment or in cases in which oxytocin / methergine fail to control post partum hemorrhage

The Effectiveness of Resectoscopy in Gynecology / 대한산부인과학회잡지

OBJECTIVE: The purpose of our study is to find out the therapeutic effectiveness, reproductive outcome, and the diagnostic pathologic findings of the patients treated with resectoscopy. METHODS: We examined 110 patients who complained infertility, abnormal uterine bleeding and menorrhagia from May. 1995 to Dec. 2000 via office. Among the infertility and abnormal uterine bleeding patients with abnormal endometrial lesion, resectoscopy was performed and then the resected tissues was sended for pathologic examination, except IUA, uterine septum, and double uterus. After resectoscopy, we inserted Lippes loop and medicated premarin 2.5 mg, 54 days and medroxyprogesterone acetate 10 mg, 10 days to the IUA patients. In AUB patients, we only injected methergin for bleeding control. They visited office after 1 month, and the follow up for endometrial state was done through TVS, HSG, or hysteroscopy. RESULTS: Among the 44 infertility, 41 (93%) had normal endometrium findings. Of twenty pregnancy (48.8%), seven (35%) ended in a second trimester abortion, thirteen (65%) in a full-term infant. Among the 66 with abnormal uterine bleeding, the 62 (93%) had normal endometrial finding and normal menstruation pattern. But 2 patients recurred their symptom, then hysterectomy was done 3, 5 years later respectively. Most of the patients who performed histopathologic study were diagnosed as leiomyoma (59.4%), and then endometrial or endocervical polyp (25.3%) and residual placenta tissue (3.8%) respectively. CONCLUSION: The 101 patients (91.8%) improved their symptoms and intrauterine lesion. we suggest this technique which of diagnostic accuracy, cost safety, convenience, operation time, and patient's satisfaction.

Manejo activo del alumbramiento con Misoprostol sublingual: un estudio clínico controlado en el hospital de Maternidad Rafael Calvo de Cartagena / Active management of the childbirth with sublingual Misoprostol: a clinical controlled trial in the Hospital de Maternidad Rafael Calvo

Objetivos: El objetivo del presente estudio es establecer la seguridad, eficacia y costos del Misoprostol sublingual, en el manejo activo del tercer periódo del parto. Material y métodos: Se hace un estudio prospectivo, randomizado, controlado, donde se distribuyen 75 pacientes en tres grupos de 25 pacientes: A. Misoprostol sublingual, B. Oxitocina endovenosa, C. Metil-ergonovina postalumbramiento. Se cuantificó el sangrado durante la primera hora posparto y tiempo de alumbramiento. Se valoró el costo de los insumos utilizados en cada grupo, el comportamiento de los signos vitales antes y después del alumbramiento y los efectos colaterales de la droga en cada uno de los grupos. Resultados: El sangrado en la primera hora posparto fue de 389cc ñ 271.7 en el grupo de Misoprostol Vs 467cc ñ 427.5 en el grupo de oxitocina; Vs 546.8 ñ 338.5 para el grupo de Metil-ergonovina postalumbramiento, Siendo estos resultados estadísticamente significativos p<0.01. El tiempo de alumbramiento fue menor en el grupo de Misoprostol 308 seg ñ 57 Vs 362 seg ñ 162.3 con oxitocina, Vs 557 seg ñ 256.2 (p<0.05). Los costos con Misoprostol fueron de $500 Vs $8.000 con oxitocina y $2.000 con Metil-ergonovina. No se presentaron efectos colaterales en ninguno de los grupos. Conclusión: El uso de 50 mcgr de Misoprostol sublingual demostró ser seguro, eficaz y económico en el manejo del tercer periodo del parto.

Intravenous Nitroglycerin Administration for Manual Removal of Retained Placenta: A Case Report / 대한마취과학회지

Retained placenta around which the uterus firmly contracted occurs in about 1% of all vaginal deliveries and may require uterine muscle relaxation to facilitate manual extraction. It is associated with profuse hemorrhage and life threatening shock. Therefore anesthesiologist may face the difficulty to provide analgesia and rapid uterine relaxation. A 32-yr-old multigravida was transferred to the emergency room in hypovolemic shock state at 1 hour after vaginal delivery. Ketamine 30 mg, fentanyl 50 mcg were given intravenously for analgesia and sedation. Oxygen 6 L/min was supplied via face mask. With ongoing fluid resuscitation, nitroglycerin 500 mcg was injected as an intravenous bolus. Within 80 seconds, the uterus relaxed enough to extract the retained placenta. The recovery of uterine muscle tone occurred approximately 1 minute after manual removal with administration of intravenous methylergonovine. In summary, the use of intravenous nitroglycerin may be a useful and safe alternative to general anesthesia in cases of manual removal of retained placenta.

Alumbramiento dirigido con oxitocina o metilergobasina / Delivery guided with oxytocin or methylergonovine

Se realizó un estudio prospectivo evaluando el uso de oxitocina o metilergobasina al ocurrir la salida del hombro anterior del feto, para determinar si disminuye el sangrado el tercer período del parto. Se evaluaron 150 pacientes que ingresaron a la sala de parto de la Maternidad Concepción Palacios entre agosto de 1997, con embarazos a término. Se distribuyeron en tres grupos: oxitocina, metilergobasina y sin medicamentos. Ambas drogas redujeron el sangrado durante el tercer período del parto, con respecto al grupo control, con un mínimo de complicacions durante el procedimiento. Recomendamos el uso de oxitocina o metilergobasina durante el alumbramiento por ende la morbimortalidad materna

Umbilical vein oxytocin in the management of third stage of labour.

The aim of the study was to evaluate the efficacy of intra-umbilical oxytocin in minimizing the blood loss during 3rd and 4th stage of labour. Seventy-five pregnant multigravidas without any obstetric or medical complications were studied. It was found that the expulsion of the placenta was rapid as compared to the group treated with normal saline but not with methylergometrine. The drop in hemoglobin and hematocrit was comparable in patients receiving intra-umbilical oxytocin and those with active management of 3rd stage with methylergometrine.