Intramuscular Oxytocin Research Articles

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The LENTE Study: The Effectiveness of Prophylactic Intramuscular Oxytocin in the Third Stage of Labor Among Low-Risk Women in Primary Care Midwifery Practice: A Randomized Controlled Trial

PURPOSE:To test third stage management of labor for low-risk women comparing routine prophylactic intramuscular oxytocin management versus modified expectant management.STUDY DESIGN:Randomized controlled multicenter trial in primary care midwifery practice.MAJOR FINDINGS:32.4% of women in the prophylactic intramuscular oxytocin management group had blood loss of 500 mL or more versus 44.2% in the modified expectant management group, relative risk (RR) 0.61, 95% confidence interval (CI) [0.50, 0.74]. The percentage of women experiencing postpartum hemorrhage (PPH) defined as more than 1,000 mL blood loss was 6.3% in the prophylactic intramuscular oxytocin management group versus 11.9% in the modified expectant management group (RR 0.50, 95% CI [0.36, 0.71]). The type of management showed no significant differences between the two groups in clinically relevant indicators of women’s short-term health such as the number of referrals, treatment given, hemoglobin level 36 hours postpartum, and breastfeeding rates after 1 week. Medium-term health such as hemoglobin level at 6 weeks postpartum, women’s perceptions of tiredness, and breastfeeding rates at 3 months after birth also showed no differences between the two groups.CONCLUSION:Third stage management by means of routine prophylactic intramuscular oxytocin reduced the risk of postpartum hemorrhage in a group of childbearing women at low risk of complications in primary midwifery care compared to modified expectant third stage management, but there was no evidence this was associated with a reduction in clinically relevant adverse health outcomes.

Prevention of Postpartum Hemorrhage: Our Options.

In many deprived areas of the world, motherhood is associated with high morbidity and mortality. Lack of skilled birth attendance, unavailability of appropriate equipment and inadequate caregivers training have important roles in decreasing maternal safety in some middle-income countries (1). Postpartum hemorrhage (PPH) as a preventable cause of maternal mortality and morbidity is responsible for approximately 25% of maternal mortality worldwide and up to 60% in some countries (2). Each year, postpartum hemorrhage is diagnosed in 14 million women, of them 140,000 die and 1.6 million will become anemic (3). The prevalence of PPH is 18% of all deliveries (4). Approximately, no risk factors for PPH exist in two-thirds of women, therefore, all women are at risk and prevention of PPH must be considered in all deliveries. Active management of the third stage of labor (AMTSL) is recommended by the world health organization (WHO), international federation of gynecologists and obstetricians (FIGO), and the international confederation of midwives (ICM) for reducing the risk of PPH in all vaginal deliveries. AMTSL is consisted of prophylactic administration of uterotonic drugs (intramuscular oxytocin 10 IU), controlled cord traction, and fundal massage after placental delivery (5).

Comparison of Oral Misoprostol with Intramuscular Oxytocin in the Active Management of Third Stage of Labour

Aims: This study aimed at comparing the efficacy of oral misoprostol 600 mcg with intramuscular oxytocin 10 IU in the active management of third stage of labour. Methods: This prospective comparative study was performed in Tribhuvan University Teaching Hospital to compare the efficacy of oral misoprostol with intramuscular oxytocin in the third stage of labour for the prevention of postpartum hemorrhage. One hundred and twenty women without risk of PPH were randomly allocated to receive either 600 mcg misoprostol orally (Group A) or 10 unit of oxytocin intramuscularly (Group B) within 1 minute of delivery. The efficacy and the safety of these two drugs were analyzed on the basis of percentages fall in hemoglobin (Hb) and hematocrit (Hct) level from before delivery to 8 completed hours after delivery, need for additional uterotonic agents, need for exploration and uterine evacuation, need for blood transfusion, duration of third stage of labour and the numbers of retained placenta and need for MRP. Results: Oral misoprostol was observed to be equally effective as intramuscular oxytocin in prevention of post-partum hemorrhage (PPH). There was no statistical difference in the duration of third stage of labour, need for additional uterotonics, need for uterine exploration/evacuation and need for blood transfusion in the two groups. Conclusions: Routine use of oral misoprostol 600 mcg appears to be as effective as 10 IU intramuscular oxytocin in minimizing blood loss during the third stage of labour.

A randomized controlled trial of sublingual misoprostol and intramuscular oxytocin for prevention of postpartum hemorrhage.

In India, two third of maternal deaths occur in rural areas where there is lack of transportation facilities, lack of refrigeration to store the injectable uterotonic drug such as oxytocin, lack of skilled personnel to administer them and lack of sterile syringes and needles. Hence, this study was conceived to evaluate misoprostol as a safe, effective, easily administered non-parenteral drug in the prevention of postpartum hemorrhage. This study was conducted during the period from August 2012 to July 2014. Low risk women with singleton pregnancy at term admitted for vaginal delivery were eligible for the study. A total of 500 women were randomized to two groups, 250 in each group, either to receive 400 mcg misoprostol sublingually or 10 units oxytocin intramuscularly at the delivery of anterior shoulder. Patient factors, labor parameters, blood loss and side effects were noted. The women in both the groups were well matched with respect to age, parity, gestational age and labor parameters. There was statistical significance in the blood loss (p = 0.04) between the two groups. The average blood loss was 70 ml in misoprostol group and 75 ml in oxytocin group. Shivering was the statistically significant side effect (p = 0.004) in the misoprostol group and nausea was the statistically significant side effect (p = 0.003) in the oxytocin group. Sublingual misoprostol is as effective as intramuscular oxytocin as a prophylactic oxytocic in the active management of third stage of labor for prevention of postpartum hemorrhage.

Double-blind randomized controlled trial comparing misoprostol and oxytocin for management of the third stage of labor in a Nigerian hospital

ObjectiveTo compare the efficacy of oral misoprostol with that of oxytocin for active management of the third stage of labor (AMTSL). MethodsA double-blind randomized control trial was undertaken at a center in Ilorin, Nigeria, between January and June 2013. Every other eligible patient (in the first stage of labor at term, to have a spontaneous vaginal delivery, and no/low risk of postpartum hemorrhage [PPH]) were randomly assigned with computer-generated random numbers to receive oral misoprostol (600μg) plus placebo injection or oral placebo plus oxytocin injection (1mL of 10IU) in the third stage of labor. The primary outcome was amount of blood loss during delivery. ResultsMean postpartum blood loss was 325.85±164.72mL in the 100 patients given misoprostol and 303.95±163.33mL in the 100 patients given oxytocin (P=0.391). PPH (≥500mL blood loss) was recorded in 15 (15.0%) patients given misoprostol and 14 (14.0%) given oxytocin (P=0.841). Shivering, pyrexia, and diarrhea were all significantly more common in the misoprostol group (P<0.01 for all). ConclusionThe efficacy of oral misoprostol was similar to that of intramuscular oxytocin. Adverse effects associated with misoprostol were transient and self-limiting. Thus, oral misoprostol is efficacious and a good alternative to oxytocin for AMTSL.Pan African Clinical Trials Registry: PACTR201407000825227.

Role of Oral Misoprostol 600 mcg versus Inj. Syntometrinein the Active Management of Third Stage of Labour

Postpartum haemorrhage is the leading cause of direct maternal death in developing countries. The incidence of PPH may vary from less than 5% to more than 10%. About 30% of maternal deaths in India occur due to massive haemorrhage. Normal blood loss in a vaginal delivery may exceed 500 ml and can range from 500 to 1000 ml. A decline in hematocrit is a more reliable estimation of blood loss. Active management had definitely reduced third stage blood loss. World Health Organisation (WHO) recommends Intra muscular oxytocin in the third stage oflabour. Misoprostol PGE1 is a potent uterotonic agent. Ergometrine is also an effective oxytocic. This study has been conducted to compare the efficacy and safety of oral misoprostol 600 mcg with parenteral syntometrine in the active management of third stage of labour in 100 pregnant women of low risk pregnancies by objective assessment of the difference in pre- and post-delivery haemoglobin values. This study concludes that misoprostol has the potential of an effective, stable oral oxytocic with rapid onset of action. Though this study was limited to low risk patients, misoprostol has scope for use even in high risk patients of bronchial asthma, gestational hypertension, pre-eclampsia and Rhesus (Rh) negative groups where syntometrine is contraindicated. Thus, misoprostol may be used as an alternative to IM syntometrine in the active treatment of third stage of labour.

Nicolau syndrome following intramuscular injection of oxytocin in pregnant women: report of two cases

Nicolau syndrome, also known as embolia cutis medicamentosa, is a well known but very rare complication occuring after intramuscular drug injections and presenting with local intense pain. Immediately after injection the skin blanches and within minutes to hours an erythematous macule develops, which evolves into a livedoid violaceous patch with dendrites. This condition is initially hemorrhagic, then it ulcerates, and eventually heals with an atrophic scar. Many different drugs have been reported to cause Nicolau syndrome . To date there have been no reports of Nicolau syndrome caused by intramuscular oxytocin injection. We would like to report two cases that occured after intramuscular injection of oxytocin.

584: The effect of intramuscular oxytocin versus intravenous oxytocin on the rate of postpartum hemorrhage during 0.9% NaCl shortage

584: The effect of intramuscular oxytocin versus intravenous oxytocin on the rate of postpartum hemorrhage during 0.9% NaCl shortage

A Comparison of Prophylactic Intramuscular Ergometrine and Oxytocin for Women in the Third Stage of Labor

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Prospective randomized trial of oxytocin administration for active management of the third stage of labor

ObjectiveTo determine the most efficient route and timing of oxytocin administration for active management of the third stage of labor. MethodsA prospective randomized study was done at one center in Ankara, Turkey, between January and October 2010. Women with a singleton pregnancy (>37weeks) who had a live vaginal birth were randomly allocated to four groups: iv-A (intravenous oxytocin after delivery of the fetus), iv-B (when anterior shoulder seen), im-A (intramuscular oxytocin after delivery), and im-B (when anterior shoulder seen). Postpartum blood loss within the first hour, hemoglobin, hematocrit, and duration of the third stage were compared. ResultsA total of 600 eligible women were recruited; 150 were assigned to each group. Postpartum blood loss, prepartum and postpartum hemoglobin and hematocrit, and need for additional uterotonics were similar among groups (P>0.05). The duration of the third stage of labor and changes in hemoglobin and hematocrit were significantly reduced in group iv-B (P<0.05). Among women not exposed to oxytocin before delivery, postpartum blood loss was significantly lower in group iv-B (P=0.019). Labor augmentation was related to significantly increased postpartum blood loss in all groups except iv-A. ConclusionAlthough postpartum blood loss was similar in all groups, early intravenous administration seemed to have beneficial effects.ClinicalTrials.gov: NCT01954186.

Effect of oxytocin treatment on explant size, plasma and peritoneal levels of MCP-1, VEGF, TNF-α and histopathological parameters in a rat endometriosis model

ObjectiveTo determine the effects of oxytocin (OT) on surgically induced endometriosis in a rat model. Study designTwelve female Sprague-Dawley rats were included. After the implantation and establishment of autologous endometrium onto the abdominal wall peritoneum, the rats were randomly divided into two groups, treated with intramuscular oxytocin (OT group, 160μgkg/day, n=6) or isotonic NaCl solution (control group, 1mLkg/day, n=6) for 28 days. To evaluate the therapeutic effects of OT, the explant volumes were calculated and the levels of vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1, and TNF-α were measured in plasma and peritoneal fluid. Endometriotic explants were examined histologically by semiquantitative analysis. ResultsAfter treatment, the mean endometriotic explant volume was decreased in the OT group (p=0.016). The histopathological score and VEGF immunoexpression of endometriotic explants were significantly lower in the OT group (p=0.007) than in controls (p=0.000). Inflammatory cytokine levels in plasma and peritoneal fluid were considerably decreased in the OT group. Moreover, TUNEL immunohistochemistry clearly demonstrated more apoptotic changes in the mononuclear cells of the OT group compared with controls. ConclusionWe suggest that oxytocin might be considered as a potential candidate therapeutic agent for endometriosis.

The Effect of the Timing of Intramuscular Oxytocin Injection on Maternal Bleeding during the Third Stage of Labour

Background and aim: The third stage of labour is one of the most troublesome stages of child delivery. The basic principle of the third stage management is administrating prophylactic uterotonics. However, the time of its administration varies in different hospitals. This study aimed to determine the effect of intramuscular oxytocin injection after emergence of the fetal anterior shoulder or placental expulsion on bleeding in the third stage of labour. Methodology: This clinical trial was conducted on 100 pregnant women with gestational age of 38-42 weeks, and singleton pregnancies. Subjects were selected using convenience sampling and were then randomly assigned to intervention (injection of 10 IU intramuscular oxytocin after emergence of the fetal anterior shoulder) and control (injection of 10 IU intramuscular oxytocin after placental expulsion) groups. Blood was collected in containers and weighed with a weighing scale. A checklist was used to record labor and delivery related data. Data were analyzed by SPSS version 11.5, using Chi-square and t-test. Findings: The mean amount of bleeding during the third stage of labour was 183.4 ± 145.8 and 202.2 ±208.8 ml in intervention and control group, respectively. No significant difference was found between two groups in terms of maternal bleeding. Conclusion: Injection of intramuscular oxytocin either after emergence of the fetal anterior shoulder or placental expulsion does not affect the amount of maternal bleeding during the third stage of labour.

Active Management of Third Stage of Labor: A Comparison of Various Uterotonic

ABSTRACT Aims and objectives This study was aimed at comparing the various uterotonics in active management of third stage of labor and reducing blood loss. Materials and methods A prospective study was conducted in the Department of Obstetrics and Gynecology of SRMSIMS, Bareilly, in 100 women. Patients were randomized into four groups of 25 each and were given oxytocic within 1 minute of delivery of the baby. Oxytocics used were 10 IU intramuscular oxytocin, 0.2 mg intravenous methylergometrine, 125 μg intramuscular 15-methyl PGF2-alpha and 600 μg tablet misoprostol per rectally in groups A, B, C and D respectively. Results Duration of third stage of labor recorded was minimum with methergine with mean duration of 3.84 ± 0.99 minutes and was maximum with prostodin with mean duration of 5.04 ± 1.02 minutes. Amount of blood loss observed was minimum with methergine (mean 131 ± 72.037 ml) and maximum with Prostodin (mean 435 ± 147.578 ml). Hemoglobin drop was also seen maximally with prostodin with mean drop of 0.872 ± 0.458 gm% and minimally with methergine with mean drop of 0.236 ± 0.221 gm%. Change in the general condition of the patients in the form of tachycardia, fall in systolic and diastolic blood pressure was observed maximum with prostodin group whereas, in other groups, there was no significant change. Conclusion It is concluded from this study that methergine is the uterotonic of choice followed by oxytocin for active management of third stage of labor. How to cite this article Modi V, Goel JK, Kashyap A, Arya SB, Kar J, Goel R. Active Management of Third Stage of Labor: A Comparison of Various Uterotonic. J South Asian Feder Obst Gynae 2014;6(3):151-155.

Comparison Between Intramuscular and Intravenous Administration of Oxytocin in Captive-Bred Red-Eared Sliders (Trachemys scripta elegans) with Nonobstructive Egg Retention

Nonobstructive egg retention is quite common in captive-bred turtles and may result from several different factors, including poor husbandry and poor physical condition. Oxytocin, 1 to 40IU/kg, can be used to stimulate oviductal contraction and induce egg deposition. The purpose of this study was to investigate the efficacy of low-dose intravenous (IV) and intramuscular (IM) oxytocin for managing turtles with nonobstructive egg retention. Physical examination and radiographic and computed tomographic evaluations were performed in 39 female red-eared sliders (Trachemys scripta elegans) that were showing overt clinical signs of egg retention. After being placed for 7 days in a suitable environment without laying their eggs, a diagnosis of nonobstructive egg retention was made in 30 of the turtles. These 30 turtles were then randomly divided in 2 groups. Group OXY-IM (n = 15) received 2IU/kg of oxytocin IM, whereas group OXY-IV (n = 15) received the same dose IV. If animals did not lay all of their eggs within 60 minutes, a second dose (2IU/kg) was administered. Follow-up doses were given every 120 minutes until all eggs were laid. The mean time for animals on OXY-IM to start laying and complete egg deposition was 97 ± 22.4 minutes and 246.1± 27.37 minutes, respectively. All animals required a second dose, 10 turtles (66.6%) required a third dose, and 5 turtles (33.3%) required a fourth dose. The animals in OXY-IV started laying eggs on average of 61.26 ± 13.9 minutes after treatment and completed laying eggs 147.2 ± 25.5 minutes after treatment. Six animals (40%) required a second dose of oxytocin, and 4 (26.6%) required a third dose. There were significant differences (p < 0.001) in the elapsed time between the first injection and the start of egg deposition and total egg deposition between the 2 treatment groups. In conclusion, oxytocin administered IV provided faster results than IM dosing for the treatment of nonobstructive egg retention in red-eared sliders. No side effects were observed in either treatment group.

Use of Oral Misoprostol, Intramuscular Oxytocin and Intravenous Methergin in Prevention of Postpartum Haemorrhage

Aims: The purpose of the study was to compare the efficacy of misoporstol 600mg orally (Group A), injection oxytocin 10 IU intramuscularly (Group B) and injection methylergometrine 0.2 mg intravenously (Group C) on reducing blood loss in third stage of labour, duration of third stage of labour, effect on haemoglobin of the patient, need of additional oxytocics or blood transfusion and associated side effects and complications. Methods: A prospective study enrolling 510 women and randomising them into three groups was done in S P Medical College, Bikaner, Rajasthan, India. Active management of third stage of labour was done using one of the three uterotonics as per the group of the patient. Results: Methylergometrine was superior to rest of the drugs with lowest duration of third stage of labour (p = 0.02), lowest amount of blood loss (p = 0.0001) and lowest rate of post partum hemorrhage (p = 0.08). The need of additional oxytocics and blood transfusion was highest with oral misoprostol as compared to all other drugs used in the study with p value of 0.08 and 0.009 respectively. Conclusions: Methylergometrine has the best uterotonic drug profile amongst the drugs used, strongly favouring its routine use as oxytocic for active management of third stage of labour. Oral misoprostol resulted in a higher blood loss compared to other drugs and hence it should be used only in low-resource settings where other drugs are not available. However, a large multi-centre study is needed for the confirmation of the finding. Nepal Journal of Obstetrics and Gynaecology / Vol 8 / No. 1 / Issue 15 / Jan- June, 2013 / 34-36 DOI: http://dx.doi.org/10.3126/njog.v8i1.8859

A comparison of prophylactic intramuscular ergometrine and oxytocin for women in the third stage of labor

ObjectiveTo compare the efficacy and adverse effects of ergometrine and oxytocin given intramuscularly for the prevention of postpartum hemorrhage during the third stage of labor. MethodsThe study included women with a singleton pregnancy of at least 28weeks’ gestation who had a vaginal delivery. High-risk pregnancies were excluded. Oxytocin (10IU) or ergometrine (0.5mg) were administered intramuscularly in a blinded pattern immediately after delivery of the infant. An intention-to-treat analysis was performed. ResultsPostpartum blood loss (301.8±109.2mL versus 287.1±84.4mL, P=0.011) and packed cell volume (30.7±1.7% versus 31.6±2.0%; Z=0.00; P=0.008) were considerably reduced among parturients who received intramuscular ergometrine. The rates of therapeutic oxytocics use, blood transfusion, placental retention, and manual removal of the placenta were significantly higher in the oxytocin group. No significant differences between the groups were observed in terms of adverse effects, with the exception of diastolic hypertension, which was more common in the ergometrine group (odds ratio, 0.00; 95% confidence interval, 0.00–0.75; P=0.007). ConclusionIntramuscular ergometrine is superior to intramuscular oxytocin in averting postpartum hemorrhage during the third stage of labor. There are no significant risks of adverse effects except for diastolic hypertension.Pan African Clinical Trial Registry (www.pactr.org): 201105000292708.

A randomised controlled trial of sublingual misoprostol and intramuscular oxytocin for prevention of postpartum haemorrhage

This study aims to evaluate the efficacy and side-effects of 200 μg sublingual misoprostol vs 5 IU i.m. oxytocin, administered immediately following cord clamping in normal non-augmented vaginal delivery, in prevention of postpartum haemorrhage (PPH). A total of 104 women were randomised into three groups: misoprostol group (28 patients); oxytocin group (37 patients) and control group (39 patients). Misoprostol and oxytocin significantly minimised the blood loss during the third stage of labour and reduced the need for additional treatments for PPH as compared with the control group. Oxytocin was more effective than misoprostol in minimising blood loss and the need for additional uterotonic treatments. However, a significant decrease in systolic and diastolic blood pressure, associated with tachycardia was observed in the oxytocin group. In conclusion, sublingual misoprostol appears to be less effective than i.m. oxytocin in the prevention of PPH; however, it has the potential advantages of being easily used, cost-effective and stable at room temperature. Therefore, sublingual misoprostol is still a feasible drug for routine management of third stage, especially in areas with limited medical facilities.

Criticism of misguided Chu et al. article

Chu, Brhlikova and Pollock's article suggests the WHO rethink its decision to include misoprostol on the Essential Medicines List. Their paper is a sad example of workers in an elite setting advocating policies with the potential to endanger the lives of thousands of vulnerable women in low-resource settings. The self-administration of misoprostol, or use by traditional birth attendants, is the most immediate and practical solution to help the least developed countries move towards achieving Millennium Development Goal 5.1 It is true that in some studies oxytocin performs marginally better than misoprostol,2 but as mentioned by Chu et al., oxytocin administration is not currently feasible in most low-resource settings. Misoprostol presents an opportunity to achieve some semblance of health equity.3 The paper is also methodologically and ethically flawed. It reviews the 172 published papers on the use of misoprostol to control postpartum haemorrhage (PPH) in the framework of high-quality obstetric services and it explicitly omits studies that are not randomized controlled trials (RCTs). However, RCTs are often impossible to conduct in most low-resource settings where maternal death rates are highest. The paper by Prata et al4. included in the review, in fact, was not an RCT. In the case of misoprostol, an undisputed powerful uterotonic, the most practical RCT would compare misoprostol to a placebo, since the reality in low-resource settings leaves only these two options. Consequently, a RCT would randomly allocate the risk of death to women in the control arm when we know that misoprostol might have the potential to save their lives. Since Chu et al. conducted their review; a RCT in Belgaum India found 400 μg sublingual misoprostol to be more effective than 10 IU intramuscular oxytocin, as measured by blood loss (mean blood loss 192 ± 124 mL with misoprostol and 366 ± 136 mL blood loss with oxytocin).5 These data, together with compelling literature from non-RCTs in low-resource settings, strongly endorse the WHO's decision, which weighed all of the evidence, with considerations of the larger context and implications. A reversal of their decision would only hurt the very women that Chu et al. purport to be helping.

Reduced postpartum hemorrhage after implementation of active management of the third stage of labor in rural Honduras

ObjectiveTo assess outcomes after auxiliary nurses were trained and given resources to use active management of the third stage of labor (AMTSL) for all women giving birth in a low-resource, low-risk, rural, public birth center setting in northern rural Honduras. MethodsAuxiliary nurses received training on estimation of blood loss before the preintervention phase of the study (July 2004 through April 2005) and AMTSL, including use of intramuscular oxytocin, and estimation of blood loss prior to the intervention phase (July 2007 through June 2008). Preintervention and intervention data on use of oxytocin, blood loss postpartum, hemorrhage rates, and management interventions were collected and compared. ResultsAfter nurses received training on AMTSL using intramuscular oxytocin, the use of intramuscular oxytocin during the third stage of labor increased from 63.8% to 96.5%. Postpartum hemorrhage rates decreased from 14.8% to 5.9% (P=0.001). Use of intrapartum oxytocin, which can have adverse effects, also increased: from 6.1% to 22.7% (P<0.001). ConclusionTraining auxiliary nurses to perform AMTSL using oxytocin in this birth center setting was effective in reducing the rate of postpartum hemorrhage; however, increased use of intrapartum oxytocin may be an unintended outcome of the increased accessibility of oxytocin.