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The effects of routine oxytocic administration in the management of the third stage of labour: An overview of the evidence from controlled trials
Abstract
Recent claims that routine active management of the third stage of labour increases rather than decreases maternal and neonatal morbidity have prompted us to conduct a systematic review of the relevant controlled trials. In this paper we have analysed data derived from a total of nine published reports of controlled trials in which an oxytocic drug was compared with either a placebo or no routine prophylactic. Oxytocic drugs used routinely appear to reduce the risk of postpartum haemorrhage by about 40% (typical odds ratio 0.57, 95% confidence interval 0.44-0.73) implying that for every 22 women given such an oxytocic, one postpartum haemorrhage could be prevented. The available data are insufficient to assess the possible effects of this policy on the incidence of retained placenta, hypertension and other possible adverse effects.
... Prevention of PPH is mainly achieved by active management of the third stage of labour which is widely practiced in high resource countries (WHO 2012). Third stage of labour begins immediately with the delivery of the foetus or foetuses and it involves separation and expulsion of placenta with its attached membranes [8] . Although it occupies a very short period of time compared to labour, which last several hours, this crucial phase poses dangers to the life and health of the mother, it can be managed actively or conservatively [9] . ...
... For prevention and treatment PPH drugs such as oxytocin, metheglin and carboprost are used, which reduce incidence by 40% [11] . In rural areas, the availability of such drugs and facilities are limited [8] . Hence, this study was designed to evaluate and compare the efficacy of placental cord drainage after vaginal delivery, which reduces the bulkiness of the placenta, allowing the uterus to contract and retract effectively, resulting in placental detachment and reducing the duration of third stage of labour [12] and the study aims at the following: • Postpartum hemorrhage is the most common cause of maternal mortality and it complicates about 4% of vaginal and 6% of caesarean. ...
... P Value was 0.0662 which is not significant. 8.5% of control group and 2% of study group had blood loss >500 ml. None of both groups had >1000 ml of blood loss. ...
... ± 4.07 ml). The majority of participants were aged [18][19][20][21][22][23][24][25][26][27][28][29][30]. No statistically significant differences were observed in blood loss based on age, gestational age, or parity. ...
... Additionally, the study's findings did not reveal statistically significant differences in efficacy based on maternal age, gestational age, or parity, indicating that both uterotonic agents are equally effective across these variables. This finding aligns with research by Prendiville et al., which found no significant differences in the efficacy of uterotonics based on maternal characteristics (18). One of the strengths of this study was its randomized controlled design, which minimized selection bias and ensured a balanced distribution of participants between the two groups. ...
Background: The active management of the third stage of labor is crucial for preventing postpartum hemorrhage (PPH), a leading cause of maternal mortality. Syntocinon (oxytocin) and Misoprostol are prominent pharmacological agents used to manage this stage by inducing uterine contractions and minimizing blood loss. Objective: This study aimed to compare the efficacy of 10 IU intravenous Syntocinon and 800 µg sublingual Misoprostol in the active management of the third stage of labor, focusing on maternal outcomes, blood loss, side effects, and the need for additional interventions. Methods: A randomized controlled trial was conducted in the Department of Obstetrics and Gynaecology at Hayatabad Medical Complex from August 1, 2021, to February 1, 2022. A total of 284 women aged 18-40 years with singleton pregnancies were enrolled and randomized into two groups of 142 each. Group A received 800 µg of sublingual Misoprostol, while Group B received 10 IU intravenous Syntocinon at the delivery of the anterior shoulder of the baby. The third stage of labor was managed with early cord clamping and controlled cord traction. Blood loss was meticulously recorded, and patients were monitored for 24 hours postpartum. Data were analyzed using IBM SPSS Statistics version 25, with continuous variables expressed as mean ± standard deviation and categorical variables as frequencies and percentages. Post-stratification analysis utilized an independent sample t-test, with a p-value of ≤ 0.05 considered statistically significant. Results: The mean age of participants was 29.507±3.24 years in the Misoprostol group and 28.352±3.77 years in the Syntocinon group. Blood loss was slightly lower in the Misoprostol group (242.4 ± 3.72 ml) compared to the Syntocinon group (249.176 ± 4.07 ml). The majority of participants were aged 18-30 years (69.7% in Group A and 71.1% in Group B). No statistically significant differences were observed in blood loss based on age, gestational age, or parity. Conclusion: Misoprostol offers practical advantages in terms of ease of administration and stability at room temperature, making it a viable alternative, especially in low-resource settings. Both Misoprostol and Syntocinon are effective in managing the third stage of labor, with comparable efficacy in reducing blood loss.
... They are used because of their ability to produce tonic uterine contractions capable of promoting placental separation. However, in some cases, both physiologic and pharmacologic approaches fail leading to retention of an adherent placenta 13 . If a retained placenta is left untreated there is high risk of maternal death. ...
... The volume of oxytocin ranged from 10 to 100 iu in 10-30 ml saline solution. In most studies a dose of 10 iu oxytocin was used 13 All trials used 20 ml saline solution except kristiansen, et al. 19 and Chestnut and Wilox 2 who used 10 ml and Reddy and Carey 17 who used 30 ml. In the majority of the studies, the timing of injection ranged from 20-30 min after delivery 3 . ...
Postpartum haemorrhage & retained placenta are the most common serious abnormalities encountered during the third stage of labour, the aim of this study was to compare three different management protocols for retained placenta. This prospective study was carried out in Basrah Maternity & Children hospital during the period from march 2001 till march 2002. A total of 75 women with retained placenta after active management of third stage of labour were included, they were divided into three groups , the first group received oxytocin and normal saline injected in the umbilical vein, the second received normal saline and the third was the expectant group. In 56% of women in the oxytocin group, placental expulsion occurred within 45 minutes compared to 16% in the expectant group and 24% in the saline group respectively. Also 44% of women in the oxytocin group needed manual removal of the placenta compared to 84% in the expectant and 76% in the saline group. We conclude that intraumbilical vein injection in cases with retained placenta seems simple and promising technique to reduce the incidence of potentially morbid procedures.
... One of the commonest causes of maternal mortality in the developing world is obstetric haemorrhage, particularly postpartum hemorrhage(1-3). The incidence of fatal PPH has been reduced in the Western world, largely because of active management of the third stage, which involves controlled cord traction, uterine fundal massage, and administrationof a pharmacologic uterotonic (4).The standard pharmacologic uterotonic agent has traditionally been oxytocin or a combination of oxytocin and ergometrine maleate (Syntometrine). Use of these agents routinely during the third stage of labour has demonstrated a 40% average decrease in PPH (4). ...
... The incidence of fatal PPH has been reduced in the Western world, largely because of active management of the third stage, which involves controlled cord traction, uterine fundal massage, and administrationof a pharmacologic uterotonic (4).The standard pharmacologic uterotonic agent has traditionally been oxytocin or a combination of oxytocin and ergometrine maleate (Syntometrine). Use of these agents routinely during the third stage of labour has demonstrated a 40% average decrease in PPH (4). These drugs, however, must be refrigerated to remain effective. ...
... One of the commonest causes of maternal mortality in the developing world is obstetric haemorrhage, particularly postpartum hemorrhage (1)(2)(3). The incidence of fatal PPH has been reduced in the Western world, largely because of active management of the third stage, which involves controlled cord traction, uterine fundal massage, and administration of a pharmacologic uterotonic (4). The standard pharmacologic uterotonic agent has traditionally been oxytocin or a combination of oxytocin and ergometrine maleate (Syntometrine). ...
... The standard pharmacologic uterotonic agent has traditionally been oxytocin or a combination of oxytocin and ergometrine maleate (Syntometrine). Use of these agents routinely during the third stage of labour has demonstrated a 40% average decrease in PPH (4). These drugs, however, must be refrigerated to remain effective. ...
... Postpartum haemorrhage (PPH) represents a leading cause of maternal morbidity and mortality [30] and the administration of oxytocin immediately after birth has been shown to reduce the risk for PPH [4,20]. ...
... Postpartum administration of oxytocin is known to decrease the risk of PPH (by at least 50 %) [4,18,20,29]. Historically it was common to use an intravenous or intramuscular bolus of 5-10 IU oxytocin for the prevention of PPH. Several regimens of postpartum oxytocin for preventing PPH have been studied under varying conditions [1,7,17,24,26,31]. ...
Purpose
Postpartum haemorrhage (PPH) represents a leading cause of maternal morbidity and mortality. Giving oxytocin after birth reduces the risk for PPH. It has never been tested whether different methods of oxytocin administration affect the maternal outcome. This study aims to compare the infusion versus the bolus application of oxytocin after singleton vaginal delivery.
Methods
This retrospective monocentre study compares the incidence of clinically relevant postpartum complications in women receiving 5 IE of oxytocin as a bolus or as a 100 ml-infusion over 5 min, given immediately after birth. Included were women delivering singletons vaginally at term. We used propensity score weighting to compare outcomes between women receiving bolus and infusion and to minimize the selection bias in this retrospective cohort.
Results
1765 patients were included. Patient characteristics were balanced. We found no significant differences for the combined overall postpartum adverse outcome (the incidence of PPH, manual removal of the placenta and/or curettage). For the single outcomes, we observed a significantly higher frequency of manual removal of the placenta (Odds ratio 1.47, 95 % CI 1.02–2.13) and a slightly higher but clinically not relevant estimated blood loss (Relative effect 1.05, 95 % CI 1.01–1.10) in the infusion group.
Conclusion
The data show a tendency towards more complications in the infusion group. It is related to a more frequent need for manual removal of the placenta.
... Postpartum haemorrhage (PPH) represents a leading cause of maternal morbidity and mortality [30] and the administration of oxytocin immediately after birth has been shown to reduce the risk for PPH [4,20]. ...
... Postpartum administration of oxytocin is known to decrease the risk of PPH (by at least 50 %) [4,18,20,29]. Historically it was common to use an intravenous or intramuscular bolus of 5-10 IU oxytocin for the prevention of PPH. Several regimens of postpartum oxytocin for preventing PPH have been studied under varying conditions [1,7,17,24,26,31]. ...
Purpose:
Postpartum haemorrhage (PPH) represents a leading cause of maternal morbidity and mortality. Giving oxytocin after birth reduces the risk for PPH. It has never been tested whether different methods of oxytocin administration affect the maternal outcome. This study aims to compare the infusion versus the bolus application of oxytocin after singleton vaginal delivery.
Methods:
This retrospective monocentre study compares the incidence of clinically relevant postpartum complications in women receiving 5 IE of oxytocin as a bolus or as a 100 ml-infusion over 5 min, given immediately after birth. Included were women delivering singletons vaginally at term. We used propensity score weighting to compare outcomes between women receiving bolus and infusion and to minimize the selection bias in this retrospective cohort.
Results:
1765 patients were included. Patient characteristics were balanced. We found no significant differences for the combined overall postpartum adverse outcome (the incidence of PPH, manual removal of the placenta and/or curettage). For the single outcomes, we observed a significantly higher frequency of manual removal of the placenta (Odds ratio 1.47, 95 % CI 1.02-2.13) and a slightly higher but clinically not relevant estimated blood loss (Relative effect 1.05, 95 % CI 1.01-1.10) in the infusion group.
Conclusion:
The data show a tendency towards more complications in the infusion group. It is related to a more frequent need for manual removal of the placenta.
... Therefore, the WHO recommends administering 10 IU (IM/IV) oxytocin to prevent PPH. Indeed, the prophylactic use of oxytocic agents has been shown to reduce the incidence of PPH by up to 40% [6]. ...
Objective
To study the efficacy of intraoperative IV oxytocin and intramuscular (IM) oxytocin versus conventional intramuscular oxytocin alone for active management of the third stage of labor in lower segment cesarean section (CS). The study was performed to determine the effect of 5 IU (International Unit) oxytocin infusion at the time of skin incision and that of 10 IU IM oxytocin infusion after delivery in reducing blood loss during and after CS, in comparison with the effect of administrating conventional 10 IU IM oxytocin in the same time period. In addition, it assessed the ability of the IV+IM oxytocin group to reduce the need for additional uterotonic as well as its safety determination and postoperative blood transfusion in CS.
Materials and methods
It is a randomized control study. The effect of 5 IU of oxytocin infusion at the time of skin incision and 10 IU of IM oxytocin (IV+IM) in reducing blood loss during and after the CS was compared to conventional 10 IU IM oxytocin.
Results
The study showed that the IV+IM group had a mean blood loss of 316.5 ± 74.36 ml, while the IM group had a mean loss of 403.90 ± 107.2 ml (p-value < 0.001) from placental delivery to the end of CS. A total of 90% of the patients in the IV+IM group had blood loss <50 ml compared to 95% of patients in the IM group who had a blood loss between 50 and 100 ml range from the end of cesarean to two hours postpartum. When total blood loss was compared in both groups, 84% of patients had a blood loss between 300 and 400 ml, compared to 81% of the patients in the IM group who had blood loss of 400-500 ml. Total blood loss in the IM group was 483.20 ± 115.86 ml, which was significantly higher compared to the IV group, 362.60 ± 78.07 ml (p-value=<0.001).
Conclusion
5IU oxytocin infusion at the time of skin incision and 10 IU IM oxytocin after delivery of the baby significantly reduced the amount of blood loss, need for blood transfusion, and additional uterotonics during and after lower segment CS.
... Amongst the other uterotonics, oxytocin (OT) is the agent of choice in the prevention and treatment of postpartum uterine atony and is used worldwide either as a bolus or infusion. Prendiville et al. [2] in their controlled trial concluded that the prophylactic routine use of OT reduces the incidence of PPH by up to 40%, implying that in every 22 women receiving OT, one PPH can be prevented. ...
Background
Oxytocin (OT) is routinely administered during caesarean delivery to prevent and treat postpartum haemorrhage (PPH). The common adverse effects of intravenous OT are tachycardia, hypotension, chest pain, Electrocardiogram (ECG) changes, nausea and vomiting. We aimed to compare the uterine contractility, haemodynamic changes, need for other uterotonics and adverse effects by comparing the intravenous bolus dose versus infusion dose of OT while retaining its benefits.
Methods
Sixty patients undergoing elective caesarean delivery under spinal anaesthesia were randomised to receive OT 3 IU as a bolus (repeat 3 IU at an interval of 3 min) in group B (Bolus) or as an infusion 1 IU per minute in group I (infusion). The uterine tone was assessed by a blinded obstetrician as either adequate or inadequate. The intraoperative heart rate, blood pressure, blood loss and any other adverse events were recorded.
Results
The adequacy of uterine tone was more sustained and the requirement of other uterotonics was less in group I. The heart rate increased to 20–25 beats/min at 3–5 min in group B and 8–10 beats/min at 2–4 mins and reached the baseline at 8–9 min in group B as well as in group I. Also, a significant fall in the mean blood pressure was observed at 3–5 min in group B. The ECG changes (ST-T changes) were more common in group B compared to group I. There was no significant difference in the estimated blood loss between the two groups.
Conclusion
The infusion dose of OT provides more haemodynamic stability, better uterine tone and fewer adverse effects compared to the bolus dose.
... Pregnancy-related health issues affect 40% of expectant mothers, while long-term or life-threatening illnesses affect 15% of all expectant mothers. [1] According to report of the World Health Organisation (WHO), 515,000 women died in 1995 as a result of pregnancy-related and childbirth-related problems. Because women frequently lose access to life-saving care, the majority of these deaths take place in two underdeveloped nations. ...
Objective: The study's objective is to examine the effectiveness of syntometrine and oxytocin in actively managing the third stage of labour in order to lower the risk of PPH and other undesirable third stage outcomes. Study Design: Randomized/Prospective study Place and Duration: Gynae & Obs department of Combined Military Hospital Peshawar for the duration from 1st June 2021 to 30th November 2021. Methods: This study comprised of 140 females of third stage labour. Age of the females was 18-40 years. After getting informed written consent detailed demographics of enrolled cases were recorded. Patients were equally divided in two groups. Group I had 70 patients and received syntometrine (5 IU Synthetic Oxytocin and 0.5 mg ergometrine maleate) and in group II oxytocin was given to 70 females. Outcomes among both groups were recorded in terms of blood loss and postpartum hemorrhage. SPSS 23.0 was used to analyze all data. Results: The mean age of the patients was 28.3±6.18 years and had mean BMI 27.6±11.25 kg/m2. Mean gestational age was 36.11±5.19 weeks. Frequency of primigravida was 80 (57.1%). Frequency of emergency delivery was found in 85 (60.7%) cases while 55 (39.3%) females admitted to OPD. 72 (51.4%) females were from rural areas and 67 (47.8%) cases were educated. We found that mean blood loss in group II was higher 165.1±8.66 ml as compared to group I 118.7±9.39 ml with p value <0.005. There was no any PPH found in group I while in group II PPH found in 3 (4.3%) cases. Frequency of hypertension was higher in group I. We found higher number of adverse outcomes among females of syntometrine group as compared to oxytocin group. Conclusion: In this study we concluded that use of syntometrine in third stage of labour was effective and useful in terms of reduction in blood loss and PPH as compared to oxytocin while frequency of adverse events and hypertension was higher in syntometrine group as compared to oxytocin. Keywords: Pregnant Females, Third Stage Labour, Syntometrine, Oxytocin, Blood Loss
... Drugs used for prophylaxis against PPH include Oxytocin, Ergometrine and Syntometrine. Randomized trials and there meta-analysis confirm that these agents can reduce the incidence of PPH by about 60% to 70% when given parentally following delivery of the baby 3,4 . The WHO has recommended the use of I/M prophylactic administration of oxytocin in third stage of labour, is now routinely used in many countries as well in Bangladesh 5 . ...
Background: PPH is a single largest and leading cause of maternal mortality & severe morbidity in developing countries. A drug is needed which should be effective, cheap, safe, does not need refrigeration and that can be easily administered by untrained person. Misoprostol is the drug that fulfills these requirements. So this study is designed to evaluate the efficacy of Misoprostol in prophylaxis & management of PPH. Materials and methods: This observational study was carried out in the department of Obstetrics and Gynecology of Bangabandhu Memorial Hospital, Chattogram, during the period January to June, 2013. Total 168 pregnant women who were at term and expected to have a vaginal delivery were taken for this study. Results: The median length of the 3rd stage of labour was 8.8 minutes. 11 women (6.54%) required a manual removal of the placenta and 23 patients (13.69%) needed further therapeutic oxytocin to control bleeding. In 145 cases (86.30%) additional oxytocic was not required, about 93.45% cases placenta was expelled out easily by active management of 3rd stage. There was a drop in Hb and haematocrit concentration after delivery, which was statistically significant. An upward trend was (>0.11°F) noticed regarding temperature after delivery. Conclusion: Misoprostol is effective for prevention and management of postpartum haemorrhage, & can consider as a good alternative to other conventional oxytocic drugs. JCMCTA 2019 ; 30 (1) : 47-50
... The WHO has recommended the use of intramuscular prophylactic administration of oxytocin in the third stage of labour 2 , which is now routinely used in many countries as well as in Bangladesh 3 . Ergometrine has also been used as an oxytocic but is associated with side effects and contraindicated in hypertension, cardiac disease, Rh (-ve) mother and pre eclampsia 4 . Potential problems with the use of ergometrine and oxytocin in developing countries especially in rural areas include the need of protection from light and for refrigeration because oxytocic agents are not stable at high ambient temperature, they require special storage condition as well as needles and syringes for administration 5 . ...
Background: Post-partum haemorrhage condition is a serious condition after delivery. Objective: The purpose of the present study was to see the efficacy and safety of misoprostol for the prevention of post-partum haemorrhage. Methodology: This analytic cross-sectional study was carried out in the Department of Gynaecology and Obstetrics at Mymensingh Medical College Hospital (MMCH), Mymensingh, Bangladesh from January 2006 to June 2006 for a period of six months. Pregnant women who were admitted in MMCH during the above period and were expected to have vaginal delivery and women at term with singleton pregnancy were included as study population. Women were divided into 2 groups. Women were in the group A who were treated with misoprostol and women who were treated with oxytocin were in group B. Blood loss during delivery was estimated subjectively by the attending obstetrician. Results: A total number of 100 women were recruited for this study of which 50 women were in the group A and the rest of 50 women were in group B. In this study majority of the patients were belonged to age group 20 to 25 years in both the groups. In oxytocin group 2.0% have developed nausea, 4.0% patients have developed shivering. None have developed vomiting, diarrhoea, temperature. In misoprostol group 10.0% patients have developed nausea, 18.0% patients have developed shivering, 4.0% patients have developed rise of temperature, none have developed diarrhoea, vomiting. The differences were statistically significant. In this study 4.0% patients from oxytocin group and 2.0% patient from misoprostol group required blood transfusion. Conclusion: In conclusion less amount of blood loss is found in misoprostol group than oxytocin group. Journal of National Institute of Neurosciences Bangladesh, July 2021, Vol. 7, No. 2, pp. 152-155
... 4 Prophylactic routine use of oxytocics has been shown to reduce incidence of PPH by up to 40%. 5 The best management of the third stage would be one that effectively minimizes serious problems such as blood loss and retained placenta, while interfering as little as possible with the physiological mechanisms of placental delivery and bonding between mother and baby, and has few side effects. 6 Recent studies show that there are still wide variations in practice around the world in the management of third stage of labour. ...
Background: The incidence of postpartum haemorrhage varies from 2-11%. Postpartum haemorrhage complicates approximately 4% of deliveries in most large obstetric services. Postpartum haemorrhage is the third major cause of maternal mortality next to pregnancy induce hypertension (pre-eclampsia) and infection. Prevention, early recognition and prompt appropriate intervention are keys to minimizing its impact. Conventionally loss of more than 500 ml of blood following vaginal delivery and 1000 ml of blood following caesarean section is defined as postpartum haemorrhage. In this study we compared the efficacy of intravenous oxytocin bolus (2 IU) dose followed by infusion (160 mIU/minute) and only i.v. oxytocin infusion following delivery of fetus in elective and emergency LSCS with regard to uterine tone.Methods: This study was a prospective observational study. 200 low risk patients scheduled to undergo elective and emergency caesarean section under spinal anaesthesia in Department of obstetrics and gynecology, SSMC, Tumkur. Group A included i.v. bolus + i.v. injection, group B: i.v. infusion.Results: There was significant drop in haemoglobin and PCV in both group A and group B. But it was comparable among two groups. At 15th minute MBP was 77.2 mm of Hg and 80.04 mm of Hg in Group B. In group A better uterine tone was achieved earlier compared to group B at 2, 5, 10, 20 minutes.Conclusions: It was concluded from this study that oxytocin i.v. bolus with infusion causes earlier attainment of better uterine tone when compared with only infusion.
... Syntometrin, a first line utrotonic is in use since early 19th century. Routine use of oxytocin for active management of third stage of labour can decrease the risk of PPH in more than 40% 16 delivering mothers, but if uterus fail to contract even after use of first line utrotonic agent then uterine massage by bimanual compression should be done. ...
Objective: To determine the better route of prostaglandin F2α either intramyometrial or intramuscular for the management of uterine atony and to prevent surgical intervention. Study Design: Randomized Controlled Trial. Settings: Bahawal Victoria Hospital. Period: Feb 2018 to July 2018. Material & Method: A total of 266 patients with primary PPH due to uterine atony of 20 to 39 years of age were enrolled in the study. Patients of primary PPH due to bleeding disorders, ruptured uterus, on anticoagulant therapy and hypersensitivity to prostaglandin were excluded. Patients were divided randomly into two groups i.e. Group A (for intramyometrial injection) & Group B (for intramuscular injection). Outcome variables like arrest of bleeding within 30 minutes after start of treatment (efficacy) were noted for successful or unsuccessful outcome. Results: The mean age of women in group A was 26.94 ± 4.43 and in group B was 26.21 ± 4.09 years (p=0.005). The mean parity in group A was 2.92 ± 0.87 and in group B was 2.93 ± 0.98 (p=0.8579). Efficacy was 82.71% in group A (Intramyometrial group) and 91.73% in group B (Intramuscular group) with p-value of 0.0276. Conclusion: This study concluded that intramuscular prostaglandin F2α has better efficacy i.e. 91.73% in a patient of uterine atony for management of primary PPH as compared to intramyometrial rout of administration for prostaglandin F2α.
... One of the earliest mechanisms for haemostasis following delivery is mechanical, in which case the contraction of the myometrium compresses the blood vessels supplying the placental bed with resultant haemostasis. Other mechanisms include local decidual haemostatic factors which cause clotting like tissue factor [5] , type-1 plasminogen activator inhibitor [6] and systemic coagulation factors. [1] Perturbation in any or a combination of these mechanisms and/or loss of intact vasculature (as seen in trauma) results in postpartum haemorrhage. ...
Background: Postpartum haemorrhage may cause maternal mortality. Uterine atony is a major cause of primary Objective: partum haemorrhage (PPH). Calcium plays a role in uterine contraction and may contribute to the causation of uterine atony. To determine the seru primary PPH. Subject and Method: m calcium levels in parturient women and its relationship to A cohort study of 140 consecutive parturient women at Nnamdi Azikiwe University Teaching Hospital, Nigeria, involving intrapertum estimation of serum calcium leve primary PPH. Data analysis was done using SPSS version 21.0. Comparison of variables employed student’s t with pvalues of <0.05 at 95% confidence interval considered to be statistically significant. parturie Conclusion: ls and relating it to Results: test, of the 140 nt, 97 (69.3%) had Spontaneous Vertex Delivery (SVD); 25 (17.9%), assisted delivery, and 18 (12.9%), caesarean section. Sixteen (11.4%) women (all with SVD) had primary PPH, 10 (62.5%) of which were due to uterine atony. The mean serum ionized calcium leve l of participants without primary PPH was higher (1.11±0.25 mmol/L) than that of participants who had primary PPH from uterine atony (1.0±0.35 mmol/L), (P = 0.037). This study shows that hypocalcaemia occurred in parturient women with primary P PH from uterine atony. Suggesting the role of adequate calcium in preventing obstetrics haemorrhage. The relationship between serum calcium and primary PPH could be explored in the development of predictive, preventive and therapeutic strategies for primar y PPH and ultimate reduction of maternal morbidity and mortality from PPH. KEYWORDS: S erum calcium, uterine atony, primary postpartum haemorrhage, parturient women.
... Use of uterotonic agents decreases the incidence of PPH by approximately 40% when compared with placebo. 1 Oxytocin, a naturally occurring peptide hormone produced by the posterior pituitary gland, is the most frequently and routinely administered drug after delivery by bolus and/ or infusion in both spontaneous or operative to initiate and maintain adequate uterine contractility, to minimise blood loss and prevent Postpartum Haemorrhage (PPH). Doses ranging from 0.3 to 20 units have been proposed for oxytocin administration during Caesarean Delivery (CD) by various authors. ...
... Several controlled trials suggested that the prophylactic use of oxytocics in the third stage of labor has been successful in reducing blood loss and the incidence of severe postpartum hemorrhage (6). El-Refaey, et. ...
Objective: To compare the effect oral misoprostol with and without oxygen inhalation on the amount of blood loss per vagina after normal delivery. .
Methods: In a controlled trial, 772 women were random¬ized into two groups, group 1(n==388) received oral misoprostol 400µg after clamping the umbilical cord while group 2 (n==384) patients had oxygen inhalation for one hour starting from calmping the cord in addition to the same oral dose of misoprostol. The outcome measures were the amount of blood loss within one hour after delivery, incidence of post partum hemorrhage and the change in hemoglobin level 24 hours after delivery.
Results: The incidence of post¬partum hemorrhage either if it is more than 500 ml or 1000ml w was not statisticaly different in both groups. The mean blood loss was 328 in group1 and 312 in group 2 while women who needed additional oxytocin were 23 and 26 in group 1 and 2 respectively. There was no statistical difference in the incidence of postpartum blood transfusion in both groups or in the change of hemoglobin concentrations.There was no difference in the length of the third stage of labor ( 9.2 ± 3 in group 1 and 8.7 ± 1.7 in group 2).
Conclusion: The effect of oral misoprostol on the third stage of labor was not enhanced by oxygen inhalation for one hour
... CONTACT Marzieh Zamaniyan marziehzamaniyan@gmail.com Infertility Center, Department of Obstetrics and Gynecology, Mazandaran University of Medical Sciences, Sari, Iran Some side effects of ergotamine consist of coronary artery spam and muscle contraction, so its use is contra-indicated in asthmatic patients [10], and also in preeclamptic women due to adverse effects on blood pressure [11,12]. ...
Objective: To compare the use of carbetocin and oxytocin in prevention of postpartum hemorrhage after cesarean section.
Methods: The present study was a prospective double-blind randomized controlled clinical trial performed in two university based hospitals in Tehran, Iran. Two hundred twenty women with the gestational age of more than 37 weeks, who needed cesarean operation, participated in the study. Patients were assigned to receive either a single 100 µg IV dose of carbetocin or a standard 30-international unit IV infusion of oxytocin during 2 hours after delivery of placenta. The primary outcome measures were postpartum hemorrhage requiring additional uterotonic drugs, bleeding volume and the hemoglobin drops.
Results: There were meaningful differences in carbetocin versus oxytocin group regarding the hemoglobin drops (1.01 vs. 2.05, p=0.01), bleeding volume (430.68 CC vs. 552.6 CC, p<0.001), uterine massages frequency (3.7 vs. 4.26, p<0.001) and uterine height at 2, 4 and 24 hrs (p<0.001). Oxytocin side effects were significantly higher in comparison to the carbetocin except pruritus which was observed in 27% of patients in the carbetocin versus no cases in the oxytocin group.
Conclusions: It may be concluded that carbetocin is a good alternative modality to conventional uterotonic agents such as oxytocin for prevention of postpartum hemorrhage after cesarean sections.
Registration ID in IRCT:NCT02079558
... In evaluating systems concerned with RCTs, the authors reviewed 20 scales, 18, 24-42 11 checklists, 12-14, 43-50 one component evaluation, 51 and seven guidancedocuments. 1,11,[52][53][54][55][56][57] In addition, they reviewed 10 rating systems used by AHRQ's EPCs. [58][59][60][61][62][63][64][65][66][67][68] The authors designated a set of high-performing scales or checklists pertaining to RCTs by assessing their coverage of the following seven domains (see Box A): study population, randomization, blinding, interventions, outcomes, statistical analysis, and funding or sponsorship. ...
Purpose:
To investigate the trends and regional variations in uterotonics dispensed around birth between 2003 and 2018 in Belgium.
Methods:
Data, including outpatient and inpatient prescriptions were extracted from a nationally representative prescription database. The prevalence of uterotonics dispensed during a period including the 7 days before birth, the delivery day and the 7 days after birth was computed over three 4-year-long study periods from 2003 to 2018. The trends between periods and associations between the use of at least one uterotonic and maternal age, region of residence, delivery type and social status were assessed using logistic regression.
Results:
In total, 31,675 pregnancies were included in the study. The proportion of pregnancies exposed to at least one uterotonic decreased significantly from 92.9% (95%CI, 92.3-93.4) in 2003-2006 to 91.4% (95%CI, 90.7-92.0) in 2015-2018 for vaginal births and from 95.5% (95%CI, 94.5-96.4) to 93.7% (95%CI, 92.6-94.7) for caesarean sections. However, for vaginal births, the proportion of oxytocin increased from 84.5% (95%CI, 83.7-85.2) to 89% (95%CI 88.3-89.7). A significant association was found between uterotonic agent use and maternal age, region of residence, and delivery type. The dispensation of some uterotonic agents differed significantly between the regions.
Conclusions:
The proportion of pregnancies exposed to at least one uterotonic was high across the study period but decreased slightly between 2003 and 2018. Important variations in uterotonic use between regions highlight the need for improved national guidance. This article is protected by copyright. All rights reserved.
Introduction: One of the leading causes of maternal mortality with uterine atony is Postpartum haemorrhage (PPH) and can be reduced by proper use of uterotonic agents like oxytocin which is most commonly used. Approximately 80% of the patients suffers Spinal-induced hypotension (SIH) for cesarean delivery (CD) and is a frequently encountered problem. Postpartum haemorrhage (PPH) is one of the leading causes of maternal mortality with uterine atony in about 50% cases. There are many approaches to prevent hypotension but no single approach has been shown as the gold standard, and each prophylactic treatment comes with accompanying risks. Crystalloid preload can prevent hypotension has a poor efficacy in preventing hypotension, due to rapid redistribution into the extracellular space. Phenylephrine is a short-acting alpha agonist, can be administered by bolus as well as by infusion to treat oxytocin induced hypotension. Phenylephrine obtunds oxytocin-induced decrease in systemic vascular resistance (SVR) and increase in heart rate and cardiac output Material and Methods: Patients were randomized to be in the colloid or crystalloid infusion groups. Normal singleton pregnancy, beyond 36 weeks gestation, between 19and 35 years of age, weight between 50 and 100 kg, and height ranging from 150-180 cm. Pre-anaesthetic evaluation of all the patients was done. Intravenous administration of preload was delivered for 30 min, prior to spinal anaesthesia and when the fluid load was complete, IV patency was maintained at a rate of 5 ml/hour and medications were flushed with LR. Standard monitoring for all patients was done through use of non-invasive blood pressure (NIBP) measurement, electrocardiography, and pulse oximetry. Oxygen (2 l/min) was administered via nasal cannula. The average Systolic BP and accompanying heart rate (HR) of these 3 measurements were recorded as mean baseline values. Patients feeling about nausea was recorded from start of anaesthesia at every 5 minutes interval. Results: Mean age in lacteted ringer solution group was 25.27±5.11 years while in hydroxyethyl starch group it was 26.19±4.67. Mean Spinal uterine incision time was 15.88±4.27 and 17.18±3.35 in lacteted ringer solution group and hydroxyethyl starch group respectively. Estimated blood loss in ml(mean±SD) was 443±59.44 and 479±61.32 in lacteted ringer solution group and hydroxyethyl starch group respectively. Systolic blood pressure baseline (mean±SD) 126.45±11.33 and 129.12±9.24 in lacteted ringer solution group and hydroxyethyl starch group respectively. Heart rate (mean±SD) was 88.87±9.45 and 88.21±10.55 in lacteted ringer solution group and hydroxyethyl starch group respectively. Significantly less phenylephrine was used in the colloid group (1058 ± 558 mcg) compared to the crystalloid group (1400 ± 513 mcg) (P = 0.0019) . There was no significant difference in the incidence of maternal nausea and vomiting, as well as APGAR scores at 1 and 5 min. Conclusion: In prevention of SIH and treatment, Phenylephrine with collids are found to be superior than crystelloids because of the sparing effect of phenylephrine associated with preloading colloids. Keywords: crystelloids, collids, lactated, cesarean delivery
Background: The objective of the present study was to determine the maternal outcome of complications of third stage of labour and to determine the risk factors and evaluate the management protocols for these complications.Methods: This is retrospective study of maternal outcome with complications of third stage of labour carried out at tertiary care centre from June 2016 to December 2019. Patients who developed any complications of third stage of labour after vaginal delivery or caesarean section were included.Results: Complications observed during third stage of labour were atonic PPH 0.82% (74 cases), traumatic PPH 0.55% (50 cases), retained placenta (including placenta accreta spectrum) 0.21% (19 cases), secondary PPH 0.03% (3 cases), uterine inversion 0.03% (3 cases) and amniotic fluid embolism 0.01% (1 case). Maximum cases were seen in 18-24 years of age group. Only 36% patients having atonic PPH responded to medical treatment, 46% patients having atonic PPH responded to conservative surgery, 18% of patients required radical surgery.Conclusions: Third stage complications are potentially life threatening. Associated conditions for third stage complication are high parity, anemia, hydramnios, multiple pregnancy, malpresentation, placenta previa, and adherent placenta. Early anticipation and early intervention with proper planning is required to reduce the maternal morbidity and mortality in third stage complication.
Background:
Active management of the third stage of labour reduces the risk of postpartum blood loss (postpartum haemorrhage (PPH)), and is defined as administration of a prophylactic uterotonic, early umbilical cord clamping and controlled cord traction to facilitate placental delivery. The choice of uterotonic varies across the globe and may have an impact on maternal outcomes. This is an update of a review first published in 2001 and last updated in 2013.
Objectives:
To determine the effectiveness of prophylactic oxytocin to prevent PPH and other adverse maternal outcomes in the third stage of labour.
Search methods:
For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP) (6 March 2019) and reference lists of retrieved studies.
Selection criteria:
Randomised, quasi- or cluster-randomised trials including women undergoing vaginal delivery who received prophylactic oxytocin during management of the third stage of labour. Primary outcomes were blood loss 500 mL or more after delivery, need for additional uterotonics, and maternal all-cause mortality.
Data collection and analysis:
Two review authors independently assessed trials for inclusion, extracted data, and assessed trial quality. Data were checked for accuracy. We assessed the quality of the evidence using the GRADE approach.
Main results:
This review includes 24 trials, with 23 trials involving 10,018 women contributing data. Due to many trials assessed at high risk of bias, evidence grade ranged from very low to moderate quality.Prophylactic oxytocin versus no uterotonics or placebo (nine trials)Prophylactic oxytocin compared with no uterotonics or placebo may reduce the risk of blood loss of 500 mL after delivery (average risk ratio (RR) 0.51, 95% confidence interval (C) 0.37 to 0.72; 4162 women; 6 studies; Tau² = 0.10, I² = 75%; low-quality evidence), and blood loss 1000 mL after delivery (RR 0.59, 95% CI 0.42 to 0.83; 4123 women; 5 studies; low-quality evidence). Prophylactic oxytocin probably reduces the need for additional uterotonics (average RR 0.54, 95% CI 0.36 to 0.80; 3135 women; 4 studies; Tau² = 0.07, I² = 44%; moderate-quality evidence). There may be no difference in the risk of needing a blood transfusion in women receiving oxytocin compared to no uterotonics or placebo (RR 0.88, 95% CI 0.44 to 1.78; 3081 women; 3 studies; low-quality evidence). Oxytocin may be associated with an increased risk of a third stage greater than 30 minutes (RR 2.55, 95% CI 0.88 to 7.44; 1947 women; 1 study; moderate-quality evidence), however the confidence interval is wide and includes 1.0, indicating that there may be little or no difference.Prophylactic oxytocin versus ergot alkaloids (15 trials)It is uncertain whether oxytocin reduces the likelihood of blood loss 500 mL (average RR 0.84, 95% CI 0.56 to 1.25; 3082 women; 10 studies; Tau² = 0.14, I² = 49%; very low-quality evidence) or the need for additional uterotonics compared to ergot alkaloids (average RR 0.89, 95% CI 0.43 to 1.81; 2178 women; 8 studies; Tau² = 0.76, I² = 79%; very low-quality evidence), because the quality of this evidence is very low. The quality of evidence was very low for blood loss of 1000 mL (RR 1.13, 95% CI 0.63 to 2.01; 1577 women; 3 studies; very low-quality evidence), and need for blood transfusion (average RR 1.37, 95% CI 0.34 to 5.51; 1578 women; 7 studies; Tau² = 1.34, I² = 45%; very low-quality evidence), making benefit of oxytocin over ergot alkaloids uncertain. Oxytocin probably increases the risk of a prolonged third stage greater than 30 minutes (RR 4.69, 95% CI 1.63 to 13.45; 450 women; 2 studies; moderate-quality evidence), although it is uncertain if this translates into increased risk of manual placental removal (average RR 1.10, 95% CI 0.39 to 3.10; 3127 women; 8 studies; Tau² = 1.07, I² = 76%; very low-quality evidence). Oxytocin may make little or no difference to risk of diastolic blood pressure > 100 mm Hg (average RR 0.28, 95% CI 0.04 to 2.05; 960 women; 3 studies; Tau² = 1.23, I² = 50%; low-quality evidence), and is probably associated with a lower risk of vomiting (RR 0.09, 95% CI 0.05 to 0.14; 1991 women; 7 studies; moderate-quality evidence), although the impact of oxytocin on headaches is uncertain (average RR 0.19, 95% CI 0.03 to 1.02; 1543 women; 5 studies; Tau² = 2.54, I² = 72%; very low-quality evidence).Prophylactic oxytocin-ergometrine versus ergot alkaloids (four trials)Oxytocin-ergometrine may slightly reduce the risk of blood loss greater than 500 mL after delivery compared to ergot alkaloids (RR 0.44, 95% CI 0.20 to 0.94; 1168 women; 3 studies; low-quality evidence), based on outcomes from quasi-randomised trials with a high risk of bias. There were no maternal deaths reported in either treatment group in the one trial that reported this outcome (RR not estimable; 1 trial, 807 women; moderate-quality evidence). Need for additional uterotonics was not reported.No subgroup differences were observed between active or expectant management, or different routes or doses of oxytocin for any of our comparisons.
Authors' conclusions:
Prophylactic oxytocin compared with no uterotonics may reduce blood loss and the need for additional uterotonics. The effect of oxytocin compared to ergot alkaloids is uncertain with regards to blood loss, need for additional uterotonics, and blood transfusion. Oxytocin may increase the risk of a prolonged third stage compared to ergot alkaloids, although whether this translates into increased risk of manual placental removal is uncertain. This potential risk must be weighed against the possible increased risk of side effects associated with ergot alkaloids. Oxytocin-ergometrine may reduce blood loss compared to ergot alkaloids, however the certainty of this conclusion is low. More high-quality trials are needed to assess optimal dosing and route of oxytocin administration, with inclusion of important outcomes such as maternal mortality, shock, and transfer to a higher level of care. A network meta-analysis of uterotonics for PPH prevention plans to address issues around optimal dosing and routes of oxytocin and other uterotonics.
Objective : To compare oral misoprostol with conventional oxytocics in the management of the third stage of labor.
Methods : In a controlled trial 1574 women were randomized into four groups, as follows: Group 1 received intravenous infusion of oxytocin 10 U plus oral misoprostol 400µg, followed by two doses of oral misoprostol l00 µg 4 hours apart; group 2 received oral misoprostol 400µg, followed by two doses of oral misoprostol 400µg 4 hours apart; group 3 received intra¬venous infusion of oxytocin 10 IU; and group 4 received intravenous Infu¬sion of oxytocin 10 IU plus intramuscular administration of methylergonovine maleate (Methergine) 0.2 mg. The incidence of postpartum hemorrhage and decrease in hemoglobin concentration from before delivery to 24 hours postpartum were the main outcome measures.
Results : The primary outcome measures were similar in groups 2 and 3. The incidence of postpartum hemorrhage was 9% In group 2, compared with 3.2% In group1and 3.5% in group 4 (P < .01, and P=.01, re¬spectively). There were no significant differences among the four groups re¬garding hemoglobin concentrations. Significantly more women needed additional oxytocin in group 2, when compared with group 4 (5.9%, versus 2.2%; P = .01). The proportion of women requiring addition¬al methylergonovine maleate was 4.8% in group 2, compared with 0.7% in group 1 and 1% in group 4 (P < .01 and P = .01, respectively).
Conclusion : Oral misoprostol alone is as effective as oxytocin alone for the prevention of postpartum hemorrhage; it is less effective than oxytocin plus methylergonovine maleate and oral misoprostol plus oxytocin.
Background:
Systemic therapies for metastatic cutaneous melanoma, the most aggressive of all skin cancers, remain disappointing. Few lasting remissions are achieved and the therapeutic aim remains one of palliation.Many agents are used alone or in combination with varying degrees of toxicity and cost. It is unclear whether evidence exists to support these complex regimens over best supportive care / placebo.
Objectives:
To review the benefits from the use of systemic therapies in metastatic cutaneous melanoma compared to best supportive care/placebo, and to establish whether a 'standard' therapy exists which is superior to other treatments.
Search methods:
Randomised controlled trials were identified from the MEDLINE, EMBASE and CCTR/CENTRAL databases. References, conference proceedings, and Science Citation Index/Scisearch were also used to locate trials. Cancer registries and trialists were also contacted.
Selection criteria:
Randomised controlled trials of adults with histologically proven metastatic cutaneous melanoma in which systemic anti-cancer therapy was compared with placebo or supportive care.
Data collection and analysis:
Study selection was performed by two independent reviewers. Data extraction forms were used for studies which appeared to meet the selection criteria and, where appropriate, full text articles were retrieved and reviewed independently.
Main results:
No randomised controlled trials were found comparing a systemic therapy with placebo or best supportive care in metastatic cutaneous melanoma.
Authors' conclusions:
There is no evidence from randomised controlled clinical trials to show superiority of systemic therapy over best supportive care / placebo in the treatment of malignant cutaneous melanoma.Given that patients with metastatic melanoma frequently receive systemic therapy, it is our pragmatic view that a future systematic review could compare any systemic treatment, or combination of treatments, to single agent dacarbazine.
Introduction
Co-administration of phenylephrine prevents oxytocin-induced hypotension during caesarean section under spinal anaesthesia (SA), but higher doses cause reflex bradycardia. This study compares the effects of co-administration of two different doses of phenylephrine on oxytocin-induced hypotension during caesarean section under SA.
Methods
In this prospective, double-blind study, 90 parturients belonging to the American Society of Anesthesiologists' physical status 1 or 2, undergoing caesarean section under SA were randomised into Group A: oxytocin 3U and phenylephrine 50 μg, Group B: oxytocin 3U and phenylephrine 75 μg, Group C: oxytocin 3U and normal saline, administered intravenously over 5 min after baby extraction. The incidence of hypotension (the primary outcome), rescue vasopressor requirement and side effects were recorded. Statistical analyses were with analysis of variance, Kruskal-Wallis, chi-square and Fisher's exact tests.
Results
Demographic parameters such as age, height, weight, level of sensory block at 20 min and duration of surgery were comparable in all the groups. The incidence of hypotension (Group A – 90%, Group B – 10%, Group C – 98%, P = 0.001), magnitude of fall in mean arterial pressure (Group A-15.03 ± 6.12 mm of Hg, Group B – 6.63 ± 4.49 mm of Hg and Group C-13.03 ± 3.39 mm of Hg, P < 0.001) and rescue vasopressor requirement (Group A-45 ± 15.25 mg, Group B-5 ± 15.25, Group C-91.66 ± 26.53, P < 0.001) were significantly lower in Group B compared to A and C.
Conclusion
Co-administration of phenylephrine 75 μg with oxytocin 3U reduces the incidence of oxytocin-induced hypotension compared to phenylephrine 50 μg with oxytocin 3U during caesarean section under spinal anaesthesia.
Objective: To describe our cases of postpartum hemorrhage (PPH) with pelvic arterial embolization (PAE).
Material and methods: All patients with PPH who underwent PAE in our center in the interval 2011–1016 were retrospectively studied, evaluating the technical procedure, clinical results and subsequent fertility.
Results: There were 33 cases of PPH with PAE. The majority occurred in primiparous women (N = 22, 66.6%) who delivered vaginally (N = 20, 61%). In addition, most PPH with PAE cases had an early onset (N = 26, 79%) and were caused by uterine atony (N = 14, 42.4%). Success of PAE occurred in 27 (81.8%) cases and a satisfactory clinical follow-up was the rule, with 21 (64%) women recovering their normal menstruation, and 6 (18.2%) becoming pregnant in the following years.
Conclusion: PAE is a safe and efficacious technique with minor complications. Moreover, it allows conservation of the uterus with preservation of fertility.
De discussie over het al dan niet actief leiden van het derde tijdperk is nog niet gesloten. Er zijn inmiddels al wel studies verschenen over dit onderwerp. In 1988 verscheen een overview waarin 9 studies werden geanalyseerd (1).
Background:
The debate about how, where and by whom young children should be looked after is one which has occupied much social policy and media attention in recent years. Mothers undertake most of the care of young children. Internationally, out-of-home day-care provision ranges widely. These different levels of provision are not simply a response to different levels of demand for day-care, but reflect cultural and economic interests concerning the welfare of children, the need to promote mothers' participation in paid work, and the importance of socialising children into society's values. At a time when a decline in family values is held responsible for a range of social problems, the day-care debate has a special prominence.
Objectives:
To quantify the effects of out-of-home day-care for preschool children on educational, health and welfare outcomes for children and their families.
Search methods:
Randomised controlled trials of day-care for pre-school children were identified using electronic databases, hand searches of relevant literature, and contact with authors.
Selection criteria:
Studies were included in the review if the intervention involved the provision of non-parental day care for children under 5 years of age, and the evaluation design was that of a randomised or quasi-randomised controlled trial.
Data collection and analysis:
A total of eight trials were identified after examining 920 abstracts and 19 books. The trials were assessed for methodological quality.
Main results:
Day-care increases children's IQ, and has beneficial effects on behavioural development and school achievement. Long-term follow up demonstrates increased employment, lower teenage pregnancy rates, higher socio-economic status and decreased criminal behaviour. There are positive effects on mothers' education, employment and interaction with children. Effects on fathers have not been examined. Few studies look at a range of outcomes spanning the health, education and welfare domains. Most of the trials combined non-parental day-care with some element of parent training or education (mostly targeted at mothers); they did not disentangle the possible effects of these two interventions. The trials had other significant methodological weaknesses, pointing to the importance of improving on study design in this field. All the trials were carried out in the USA.
Authors' conclusions:
Day care has beneficial effect on children's development, school success and adult life patterns. To date, all randomised trials have been conducted among disadvantaged populations in the USA. The extent to which the results are generaliseable to other cultures and socioeconomic groups has yet to be evaluated.
( Anesthesiology . 2015;123:92–100)
Oxytocin is commonly used to improve uterine tone during cesarean delivery. However, if administered too quickly or in high doses it can lead to such adverse effects as hemodynamic instability, cardiovascular collapse, and even death. There are also currently no established recommended doses, timing, or rates of administration.
Although hemorrhage remains one of the two major complications in the field of obstetrics, new approaches to its control are continuously being developed and explored. This chapter summarizes the current management approach for the in-house obstetrician and anesthesiologist who are the first line of the management team.
The third stage of labour begins with the birth of the baby and ends with the delivery of the placenta and membranes, a process which, for most women, is rapidly accomplished without complication. However, history testifies to the drama which can arise where problems, notably postpartum haemorrhage (PPH) occur, and contemporary midwifery textbooks still carry warnings similar to that published in 1718 by the apothecary, Nicholas Culpeper:
A Woman cannot be said to be safely delivered, tho’ the Child be born, till the After-burden be also taken from her… Women have an After-labour which sometimes proves more difficult than the first.
This chapter concerns the midwife’s management of the third stage of labour. Optimum management of the third stage implies the following.
Die Geburt ist ein natürlicher Vorgang, und es ist die Aufgabe des Geburtshelfers, unter Berücksichtigung der individuellen geburtsmechanischen, physiologischen und auch psychischen Gegebenheiten eine Begleitung und risikoadaptierte Überwachung der Schwangeren und des Kindes zu gewährleisten.
Eine Häufigkeitsberechnung der, „normalen Geburt“ ist aufgrund der Dehnbarkeit der Definition und somit unterschiedlichen Auslesekriterien nicht möglich. Starke Verteilungsschwankungen ergeben sich zudem zwischen den einzelnen Kliniken als Folge einer risikoorientierten Selektion und Betreuung in Abteilungen mit unterschiedlichem Behandlungspotential.
Die Aufnahmeuntersuchung in den Kreißsaal erlaubt eine prognostische Beurteilung des Geburtsverlaufs. Nach Ergänzung der anamnestischen Daten erfolgt routinemäßig eine allgemeine und geburtshilfliche Begutachtung der Gebärenden sowie eine CTG-Kontrolle. Zusätzliche diagnostische Maßnahmen (Ultraschall, Labor) werden fakultativ je nach erhobenem Risiko angeordnet. Während der Entbindung wird analog vorgegangen, wobei die Untersuchungsfrequenz auf ein notwendiges Minimum beschränkt bleiben sollte.
Eine intermittierende kardiotokographische Überwachung des Feten während der Eröffnungsperiode und ein kontinuierliches Monitoring in der Austreibungsphase der Geburt sind zu empfehlen.
Eine aktive Geburtsleitung mit routinemäßigem Einsatz von hochdosiertem Oxytocin und der Durchführung einer Amniotomie werden als unnötige, „Technisierung“ der Geburt angesehen. Eine lange Geburtsdauer kann zur fetalen Hypoxämie und Acidämie führen; diese Veränderungen können jedoch rechtzeitig durch Auffälligkeiten des Kardiogramms und durch Mikroblutgasanalyse erkannt werden. Ein sich schon während der frühen Geburtsphase abzeichnender potentiell pathologischer Verlauf sollte durch großzügige Sectioindikation vermieden werden.
In der modernen Geburtshilfe sollte die überlange Geburtsdauer auch als ein maternales Problem angesehen werden. Der Abbau von Angst und Streß, die Optimierung der Analgesie und der gezielte Einsatz von wehenfördernden Mitteln sind bevorzugte Maßnahmen zur aktiven Beeinflussung der Geburtsdauer.
Die Inzidenz der Episiotomie variiert stark; verschiedene Studien weisen darauf hin, daß ihre routinemäßige Durchführung abzulehnen ist. Zweckmäßig ist sie dagegen zur Verkürzung der Austreibungsperiode bei fetaler Gefährdung und/oder zur Erleichterung einer vaginal-operativen Entbindung.
Der posthämorrhagische Schock in der Plazentarpenode gehört immer noch zu den häufigsten maternalen Todesursachen, jedoch bedeutet die routinemäßige Prophylaxe eine unnötige Medikalisierung der geburtshilflichen Abläufe und wirkt sich negativ auf die Sorgfalt der postpartalen Kontrolle aus. Die Verabreichung von Uterotonika ist indikationsgebunden, während die routinemößige Applikation Risikopatientinnen (z. B. belastete Anamnese, Hydramnion, Makrosomie, Mehrlingsschwangerschaften, prolongierter Geburtsverlauf) vorbehalten bleibt.
Die Erstversorgung des Neugeborenen soll vor allem durch entsprechende Lagerung und die Wahl des Abnabelungszeitpunkts einen unnötigen Blutverlust des Kindes verhindern.
Das Freimachen der Atemwege durch Absaugen ist erst in Rahmen der primären Reanimation angebracht. Der kindliche Zustand, der aligemein nach dem Apgar-Score beurteilt wird, erlaubt keinen Rückschluß auf die Ursache einer Anpassungsstörung und darf nicht als prognostischer Faktor für die spätere Entwicklung des Kindes verwendet werden. Nur eine anhaltende Depression des Neugeborenen als Ausdruck eines schweren Sauerstoffmangels, der durch eine ausgeprägte metabolische Azidose charakterisiert ist, kann zu hypoxischen Gewebsschäden führen. Deswegen ist die Bestimmung des Nabelarterien-pH-Werts ein wichtiger Teil der Erstversorgung. Dieser Wert dient als objektiver Indikator für den kindlichen Zustand.
Objective: To investigate whether orally administered misoprostol during the third stage of labor is efficient in reducing postpartum blood loss. Methods: In a double-masked trial, during vaginal delivery women were randomly assigned to receive a single oral dose of misoprostol (600 μg) or placebo in third stage of labor, immediately after cord clamping. The third stage of labor was managed routinely by early cord clamping and controlled cord traction; oxytocin was administered only if blood loss seemed more than usual. Blood loss was estimated by the delivering physician and differences in hematocrit were measured before and after delivery. Results: Mean (± standard error of the mean) estimated blood loss (345 ± 19.5 mL versus 417 ± 25.9 mL, P = .031) and hematocrit difference (4.5 ± 0.9% versus 7.9 ± 1.2%, P = .014) were significantly lower in women who received misoprostol than those who received placebo. Fewer women in the misoprostol group had postpartum hemorrhage (blood loss of at least 500 mL), but that difference was not statistically significant (7% versus 15%, P = .43). Additional oxytocin before or after placental separation was used less often in the misoprostol group (16% versus 38%, P = .047). There were no differences in the length of third stage of labor (8 ± 0.9 minutes versus 9 ± 1 minutes, P = .947). There were no differences in pain during third stage of labor, postpartum fever, or diarrhea, but shivering was more frequent in the misoprostol group. Conclusion: Oral misoprostol administered in the third stage of labor reduced postpartum blood loss and might be effective in reducing incidence of postpartum hemorrhage. Postpartum hemorrhage is a major cause of maternal morbidity and death. Hemorrhage might lead to severe postpartum anemia and hemorrhagic shock requiring blood transfusions or major surgical interventions to stop uncontrollable uterine bleeding. In industrialized countries, 1 and particularly in the developing world, 2 postpartum hemorrhage is an important cause of maternal death. Several strategies have reduced postpartum blood loss and the incidence of severe postpartum hemorrhage. Active management of third-stage labor, 3 including early cord clamping and controlled cord traction 4 and administration of oxytocic drugs such as oxytocin, 5 with or without ergometrine, have been beneficial. Risk of postpartum hemorrhage by routine use of oxytocic drugs has been estimated to be reduced by approximately 40%. 6 Timing and combination of prophylactic measures vary widely between countries and institutions, and remain controversial. Current oxytocic drugs are far from ideal, particularly for routine use in developing countries, where simple routes of administration and stable, inexpensive drugs are needed because many deliveries take place far from hospitals or medical facilities and are supervised solely by birth attendants. Oxytocin must be injected and lacks stability in tropical conditions, and ergometrine has been ineffective when administered orally. 7 Prostaglandin E2 derivatives such as sulprostone are effective oxytocic drugs, but they are expensive and not storable at room temperature. Misoprostol, a synthetic prostaglandin E1 analogue, is used widely for prophylaxis and treatment of peptic ulcer disease. 8 It is rapidly absorbed after oral administration, 9 has few side effects, is stable at room temperature, and is inexpensive. It stimulates uterine contractions, and has been used for first- and second-trimester termination of pregnancy, and labor induction at term. 10 Its use in the third stage of labor was suggested in a recent letter (El-Refaey H, O'Brien P, Morafa W, Walder J, Rodeck C. Misoprostol for third stage of labour [letter]. Lancet 1996;347:1257). The aim of our study was to assess the effect of misoprostol on postpartum blood loss.
OBJECTIVE: To compare oral misoprostol with conventional oxytocics in the management of the third stage of labor. METHODS: In a controlled trial, 1574 women were randomized into four groups, as follows: Group 1 received intravenous infusion of oxytocin 10 IU plus oral misoprostol 400 μg, followed by two doses of oral misoprostol 100 μg 4 hours apart; group 2 received oral misoprostol 400 μg, followed by two doses of oral misoprostol 100 μg 4 hours apart; group 3 received intravenous infusion of oxytocin 10 IU; and group 4 received intravenous infusion of oxytocin 10 IU plus intramuscular administration of methylergonovine maleate (Methergine) 0.2 mg. The incidence of postpartum hemorrhage and decrease in hemoglobin concentration from before delivery to 24 hours postpartum were the main outcome measures. RESULTS: The primary outcome measures were similar in groups 2 and 3. The incidence of postpartum hemorrhage was 9% in group 2, compared with 3.2% in group 1 and 3.5% in group 4 (P < .01, and P = .01, respectively). There were no significant differences among the four groups regarding hemoglobin concentrations. Significantly more women needed additional oxytocin in group 2, when compared with group 4 (5.9% versus 2.2%; P = .01). The proportion of women requiring additional methylergonovine maleate was 4.8% in group 2, compared with 0.7% in group 1 and 1% in group 4 (P < .01 and P = .01, respectively). CONCLUSION: Oral misoprostol alone is as effective as oxytocin alone for the prevention of postpartum hemorrhage; it is less effective than oxytocin plus methylergonovine maleate and oral misoprostol plus oxytocin.
Ergot alkaloids are well known preparations. Ergot alkaloids used in obstetrics and gynaecology are egometrine (ergonovine; EM), methylergometrine (methergine; ME) and bromocriptine. The pharmaceutical properties of MEEM) are critical. To guarantee stability, ME and EM ampoules should be stored in a cool, dark place. ME and EM tablets are unstable in all conditions and they show an unpredictable bioavailability, which prevents oral use of the drugs for any purpose. ME and EM are known for their strong uterotonic effect and, compared with other ergot alkaloids, for their relatively slight vasoconstrictive abilities. ME and EM do have a place in the management of the third stage of labour as they are strong uterotonics. They act differently from oxytocin and prostaglandins, and have different adverse effects. Oxytocin should be used as prophylaxis or a the drug of first choice; next, ME or EM should be used, and if none of these drugs produce the desired effects, prostaglandins should be used to control bleeding. Ergot alkaloid use in gynaecology has been limited and today is discouraged even in essential menorrhagia. It is suggested that EM and ME be used (parenterally) only in first trimester abortion curettage, to reduce blood loss. Bromocriptine has been used for lactation suppression. However, alternatives such as cabergoline, which possess fewer adverse effects, are now available and therefore preferred for this indication. In sum, there is no place for the prophylactic use of ME and EM in obstetrics or gynaecology. They can be used for therapeutic purposes in the third stage of labour. During use, the practitioner must be alert for adverse effects.
This chapter discusses my involvement in research concerning care in the third stage of labour, leading up to the Bristol third-stage trial (Prendiville et al., 1988), and its aftermath. Although the perspective is personal, I hope my experience of how decisions about research priorities were arrived at, about which research methods were used, and about the interface between research and policy and practice, has wider relevance for researchers with different backgrounds, and for areas other than the third stage of labour.
Postpartum hemorrhage remains one of the leading causes of maternal death, in both industrialized and nonindustrialized nations. Approximately 140,000 women die annually from postpartum hemorrhage worldwide, and more than 50% of these mortalities occur within the first 24 h post partum. In the USA, 12% of all maternal mortality is due to obstetric hemorrhage.
Introduction Although childbirth is a wonderful and enjoyable experience by most, it still is an anatomically traumatic event, associated with tissue injury, vascular disruption and the potential for blood loss. All deliveries are accompanied by physiologic hemorrhage from the genital tract, and the abdominal soft tissue in cesarean section (Table 12.1). Post partum hemorrhage (PPH) is an obstetrical complication, which can transform a normal physiologic process of labor and delivery into a life-threatening emergency within minutes. A routine cesarean section can be complicated by massive hemorrhage. The healthy mother may quickly become a patient in the critical care unit, requiring all of the available skill and resources of physicians, nurses, the medical laboratory and the blood bank for survival. A thorough knowledge of the risk factors, preventive strategies, approach to diagnosis and management of PPH are required to properly care for women presenting for delivery. Once PPH is diagnosed, hospital facilities and/or referral centers, laboratories and blood banks must be readily available to provide the optimal chance for a successful outcome. The availability of blood replacement and modern critical care are major determinants of survival in women who develop post partum hemorrhagic shock. Mortality from PPH is strongly correlated with substandard care. Clearly, it is the problem of PPH that most vividly illustrates the difference, worldwide, between management of the puerperium in developed countries from that in underdeveloped countries.
Ergot alkaloids are well known preparations. Ergot alkaloids used in obstetrics and gynaecology are ergometrine (ergonovine; EM), methylergometrine (methergine; ME) and bromocriptine. The pharmaceutical properties of ME EM) are critical. To guarantee stability, ME and EM ampoules should be stored in a cool, dark place. ME and EM tablets are unstable in all conditions and they show an unpredictable bioavailability, which prevents oral use of the drugs for any purpose.
ME and EM are known for their strong uterotonic effect and, compared with other ergot alkaloids, for their relatively slight vasoconstrictive abilities. ME and EM do have a place in the management of the third stage of labour as they are strong uterotonics. They act differently from oxytocin and prostaglandins, and have different adverse effects. Oxytocin should be used as prophylaxis or a the drug of first choice; next, ME or EM should be used, and if none of these drugs produce the desired effects, prostaglandins should be used to control bleeding.
Ergot alkaloid use in gynaecology has been limited and today is discouraged even in essential menorrhagia. It is suggested that EM and ME be used (parenterally) only in first trimester abortion curettage, to reduce blood loss. Bromocriptine has been used for lactation suppression. However, alternatives such as cabergoline, which possess fewer adverse effects, are now available and therefore preferred for this indication.
In sum, there is no place for the prophylactic use of ME and EM in obstetrics or gynaecology. They can be used for therapeutic purposes in the third stage of labour. During use, the practitioner must be alert for adverse effects.
Objective:
To compare the effectiveness of 400 microg rectal misoprostol in 5 cm(3) of saline with oxytocin 10 IU, i.m., in reducing bleeding during the third stage of labor.
Design:
A double blind, randomized, clinical trial including 663 women with uncomplicated vaginal delivery who received misoprostol (n=324) or oxytocin (n=339).
Main outcome measures:
Changes in hemoglobin and hematocrit from before to 72 h postpartum; blood loss during the third stage; duration of the third stage of labor; need for additional oxytocic drug; frequency of requisition and of administration of blood; changes in blood pressure; and occurrence of side effects.
Results:
No significant differences were observed between groups, before and 72 h postpartum, in mean hemoglobin and hematocrit, on volume of blood loss and duration of third stage of labor. The incidence of shivering and mean temperature (P<0.01) was significantly greater among women receiving misoprostol than oxytocin.
Conclusions:
Misoprostol administered as a micro-enema, 400 microg in 5 ml of saline during the third stage of labor, appears to be as effective as oxytocin 10 IU, i.m., but misoprostol produced more side effects than oxytocin.
The administration of uterotonic agents during cesarean delivery is highly variable. The authors hypothesized a "rule of threes" algorithm, featuring oxytocin 3 IU, timed uterine tone evaluations, and a systematic approach to alternative uterotonic agents, would reduce the oxytocin dose required to obtain adequate uterine tone.
Sixty women undergoing elective cesarean delivery were randomized to receive a low-dose bolus or continuous infusion of oxytocin. To blind participants, the rule group simultaneously received intravenous oxytocin (3 IU/3 ml) and a "wide-open" infusion of 0.9% normal saline (500 ml); the standard care group received intravenous 0.9% normal saline (3 ml) and a "wide-open" infusion of oxytocin (30 IU in 0.9% normal saline/500 ml). Uterine tone was assessed at 3, 6, 9, and 12 min, and if inadequate, additional uterotonic agents were administered. Uterine tone, total dose and timing of uterotonic agent use, maternal hemodynamics, side effects, and blood loss were recorded.
Adequate uterine tone was achieved with lower oxytocin doses in the rule versus standard care group (mean, 4.0 vs. 8.4 IU; point estimate of the difference, 4.4 ± 1.0 IU; 95% CI, 2.60 to 6.15; P < 0.0001). No additional oxytocin or alternative uterotonic agents were needed in either group after 6 min. No differences in the uterine tone, maternal hemodynamics, side effects, or blood loss were observed.
A "rule of threes" algorithm using oxytocin 3 IU results in lower oxytocin doses when compared with continuous-infusion oxytocin in women undergoing elective cesarean delivery.
The existence of a Register of Controlled Trials in Perinatal Medicine (National Perinatal Epidemiology Unit, Oxford, England) has offered an opportunity to assess the efficacy of online searching of MEDLINE, an example of a broad bibliographic database. Retrieval of all relevant randomized control trials (RCTs) in a given field is important in analyses in which results are pooled (meta-analyses). Reports of RCTs of prevention and treatment of neonatal hyperbilirubinemia and prevention of intraventricular hemorrhage (IVH) for the years 1966-1983 were sought in both the Register and MEDLINE files. Comparison of subject searches revealed a number of unlisted papers in each file that were then found to be present by an author search. In the MEDLINE searching an amateur was clearly less efficient than an expert, but the expert recovered only 29% of the relevant hyperbilirubinemia papers available in MEDLINE, and only 56% of the identified IVH RCTs. Some of the deficiencies in recovery have been corrected by indexing improvements, such as the capability of identifying text words in abstracts, and the addition of new medical subject heading terms (MeSH) such as RANDOM ALLOCATION. Efficiency will be best facilitated by authors and editors keeping the MeSH terms used by MEDLINE indexers in mind when they compose titles and abstracts.
The Medical Research Council has for some years encouraged collaborative clinical trials in leukaemia and other cancers, reporting the results in the medical literature. One unreported result which deserves such publication is the development of the expertise to design and analyse such trials. This report was prepared by a group of British and American statisticians, but it is intended for people without any statistical expertise. Part I, which appears in this issue, discusses the design of such trials; Part II, which will appear separately in the January 1977 issue of the Journal, gives full instructions for the statistical analysis of such trials by means of life tables and the logrank test, including a worked example, and discusses the interpretation of trial results, including brief reports of 2 particular trials. Both parts of this report are relevant to all clinical trials which study time to death, and wound be equally relevant to clinical trials which study time to other particular classes of untoward event: first stroke, perhaps, or first relapse, metastasis, disease recurrence, thrombosis, transplant rejection, or death from a particular cause. Part I, in this issue, collects together ideas that have mostly already appeared in the medical literature, but Part II, next month, is the first simple account yet published for non-statistical physicians of how to analyse efficiently data from clinical trials of survival duration. Such trials include the majority of all clinical trials of cancer therapy; in cancer trials,however, it may be preferable to use these statistical methods to study time to local recurrence of tumour, or to study time to detectable metastatic spread, in addition to studying total survival. Solid tumours can be staged at diagnosis; if this, or any other available information in some other disease is an important determinant of outcome, it can be used to make the overall logrank test for the whole heterogeneous trial population more sensitive, and more intuitively satisfactory, for it will then only be necessary to compare like with like, and not, by chance, Stage I with Stage III.
Obstetrics and the newborn gives as a textbook a short and concise survey of the whole area of obstetrics from the time of conception to childbirth. It deals with the physiological facets as well as the pathological events. A separate chapter is devoted to each subject. The neonate is dealt with separately, the routine, immediate post partum a well as the pathological aspects. The whole work is clarified by photographs and schematic drawings. The separate chapter on family planning as well as the chapter on examination questions with answers are notable.
The modern western management of the third stage consists of a series of interlocking interventions which are applied so routinely that many obstetricians now regard them as ‘normal’. This management had its roots only 300 years ago when the dorsal position for delivery and cord traction were first introduced in France1. Now, once the baby has been delivered, the cord is divided with scissors between double clamps. Often triple clamps are used in order to ensure the availability of umbilical arterial and venous blood samples for acid-base and blood gas analysis. This division of the cord frees the infant for transfer to the resuscitation area, where all too often he or she is placed in the disadvantageous head-down position2,3. Meanwhile, in most developed countries, the third stage is usually managed actively4. An oxytocic agent, usually syntometrine, is given as the anterior shoulder delivers and, once the uterus is contracting, steady traction is exerted on the umbilical cord, while the free hand holds the uterus out of the pelvis. The aim of all these interventions is to reduce the risk of postpartum haemorrhage and retained placenta. Yet the fact remains that significant postpartum haemorrhage (> 500 ml) is commonly reported in 2–8% of hospital deliveries5 and manual removal of the placenta in at least 1–2% of all cases.
Evidence is reviewed that points to sleep as a time during which synthetic processes for growth and repair are enhanced. REM (paradoxical) sleep seems especially related to increased synthetic processes in the brain.
The effects of ergometrine 0.5 mg i.v. and of synthetic oxytocin 5 units i.v. on the alpha and the beta adrenoceptive blood
vessels of the forearm have been studied by means of volume-pulse plethysmography in 40 gynaecological patients. Ergometrine
constricted the alpha and the beta blood vessels. It is thought that the widespread vasoconstriction may precipitate post-partum
hypertension or pulmonary oedema in obstetric patients whin other alpha vasoconstrictive factors are present. Synthetic oxytocin
caused transient dilatation of the alpha and the beta adrenoceptive blood vessels and predisposed to severe postural hypotension.
The hypotensive effect of the oxytocin was much less when the drug was given to patients who were in the lithotomy position.
It was concluded that oxytocin is preferable to ergometrine in obstetric patients in whom an alpha vasoconstrictive tendency
has been induced by one or other of the several factors described.
The factors responsible for postpartum haemorrhage (PPH) in singleton vaginal deliveries, not complicated by a retained placenta, were identified by comparing labour characteristics in 86 women who had a PPH (blood loss > 500 ml) with 351 women whose blood loss at delivery was < 350 ml. Primiparity, induction of labour by amniotomy/ oxytocin, forceps delivery, long first and second stages, oxytocin compared with syntometrine (oxytocin plus ergometrine maleate), as a prophylactic oxytocic, were identified as significant risk factors. Epidural analgesia contributed indirectly to an increase in the risk of postpartum haemorrhage. The changes in labour ward practice over the last 20 years have resulted in the re-emergence of PPH as a significant problem.
Syntometrine, a combination of ergometrine and oxytocin, is used almost universally in Great Britain at the end of the second stage of labour to reduce blood loss and prevent postpartum haemorrhage. In the United States of America, ergometrine has rarely if ever been used in recent years for this purpose as it is considered to be neither the safest nor the most effective drug for third stage management. A review of the literature suggests that the danger of ergometrine compared with oxytocin has been exaggerated.
In a series of 2102 cases, Syntometrine has been compared with oxytocin. Intramuscular oxytocin is less effective in reducing postpartum blood loss than intramuscular Syntometrine. The treatment of choice is intravenous oxytocin, but there are practical difficulties in routinely giving an intravenous injection during the second stage of labour, unless the patient already has an intravenous dextrose drip. So, patients who have a drip running should be given intravenous oxytocin: those who have not, should be given intramuscular Syntometrine
In a study of 8,000 deliveries performed under continuous caudal block analgesia, the records of 741 women indicated that the combined effect of a vasoconstrictor and an oxytocic drug, given three to six hours apart, led to severe hypertension in 34 (4.6% of 741) patients. These findings suggest that the patient's need for prophylactic administration of vasoconstrictor drugs in conjunction with caudal block analgesia in obstetrics should be evaluated before giving them. Treatment with chlorpromazine hydrochloride, to prevent the severe and disabling complications of postpartum hypertension, is essential.
The effect of ergonovine maleate on prolactin secretion and lactation was determined in 10 puerperal women. Serum prolactin concentration measured by radioimmunoassay resulted in 537.2=45.9 ng/ml (M +/- SE) before the oral administration of 0.6 mg ergonovine maleate, and 89.7 +/- 25.6 ng/ml after 7 days of therapy. The scrum prolactin concentration seen in the control group of nonlactating women (562.0 +/- 36.1 and 218.0 +/- 27.3 ng/ml) was significantly greater than (P < 0.01) that seen in the treated group. In 2 additional patients it was also demonstrated that the simultaneous administration of ergonovine by oral and intravenous routes potentiates the suppressive effect on prolactin secretion. Three of the 10 treated women showed progressive inhibition of lactation^ This study shows that ergonovine maleate interferes with prolactin secretion, and may decrease milk production.
(C) 1976 The American College of Obstetricians and Gynecologists
Prophylactic use of oxytocics reduces the risk of postpartum haemorrhage by about 40%. The analysis presented in this paper assesses which oxytocic preparation is associated with the least risk of postpartum haemorrhage and examines the relative effects of different preparations on the length of the third stage, the risk of manual removal of the placenta, blood pressure and other side-effects. A mixture of oxytocin and ergometrine (Syntometrine) appears to be the safest and most effective prophylactic of the alternatives which have been compared, but the quality of the evidence is not satisfactory. There is scope for a randomized comparison of Syntometrine with oxytocin to obtain unbiased and more precise estimates of their relative effects on postpartum haemorrhage, blood pressure and unpleasant side-effects.
The existence of a Register of Controlled Trials in Perinatal Medicine (National Perinatal Epidemology Unit, Oxford, England) has offered an opportunity to assess the efficacy of online searching of MEDLINE, an example of a broad bibliographic database. Retrieval of all relevant randomized control trials (RCTs) in a given field is important in analyses in which results are pooled (meta-analyses). Reports of RCTs of prevention and treatment of neonatal hyperbilirubinemia and prevention of intraventricular hemorrhage (IVH) for the years 1966–1983 were sought in both the Register and MEDLINE files. Comparison of subject searches revealed a number of unlisted papers in each file that were then found to be present by an author search. In the MEDLINE searching an amateur was clearly less efficient than an expert, but the expert recovered only 29% of the relevant hyperbilirubinemia papers available in MEDLINE, and only 56% of the identified IVH RCTs. Some of the deficiencies in recovery have been corrected by indexing improvements, such as the capability of identifying text words in abstracts, and the addition of new medical subject heading terms (MeSH) such as RANDOM ALLOCATION. Efficiency will be best facilitated by authors and editors keeping the MeSH terms used by MEDLINE indexers in mind when they compose titles and abstracts.
Postpartum hemorrhage is a common and serious complication of the third stage of labor resulting in anemia and increased morbidity in the puerperium. Administration of uterotonic drugs and suitable mechanical assistance in delivery of the placenta may significantly reduce this hazard. Ergometrine and oxytocin have been used for a long time in markedly different doses and by various routes of administration with varying success. In order to compare these two oxytocics with regard to their hemostatic effects as well as their possible interference with the physiologic placental separation mechanism, three groups (ergometrine, oxytocin, and control) of women have been studied during a 2-year period. Ergometrine (0.2 mg) and oxytocin (10 IU) administered in the stated doses and as single intravenous injections are comparable with regard to hemostatic efficiency, but oxytocin seems to promote placental separation and expulsion better and thereby reduces the risk of partial retention and trapping with bleeding reguiring further emergency measures as a frequent consequence.
Blood loss and the frequency of vomiting were assessed at 88 spontaneous vertex deliveries. An i. v. injection of oxytocin
10 u was as effective as ergometrine 0.5 mg in controlling bleeding from the uterus after delivery. The continuous infusion
of a dilute solution of oxytocin in the first stage of labour was not followed by an increased blood loss at delivery. Oxytocin
infusions were maintained for 1 h after delivery. Vomiting or retching occurred in 13% of the mothers who received i. v. ergometrine.
None of the women who received oxytocin suffered emetic sequelae.
The effects of intramyometrially injected PGF2 alpha intravenous Ergometrin and no treatment were compared during 3rd stage labor in 140 patients. In comparison with Ergometrin or no treatment, PGF2 alpha significantly reduced the duration of 3rd stage labor, blood loss, incidence of subinvolution and subfebrility.
Use of an automatic sphygmomanometer showed that intravenous ergometrine given immediately after delivery caused significant elevation of diastolic blood pressure in all 10 normotensive women studied. Blood pressure was also raised in some patients following the use of intramuscular oxytocin and ergometrine (Syntometrine). Uterine stimulants for use after delivery must be chosen with care.
Peripheral pulses became impalpable following the administration of ergometrine during Caesarean section. The subsequent clinical
course suggested sensitivity to ergometrine in a patient with Raynaud's disease.
An 18-year-old primipara developed acute hypertension leading to cerebral edema and convulsions following the IV injection of a bolus of 10 units of oxytocin with 0.2 mg methylergonovine maleate. Oxytocin in a dose of more than 2 units should not be administered IV in a single injection, as severe hypotension may result. If oxytocin is required, it can be injected either IM, or by IV pump or drip. The use of ergot in obstetrics should be limited to the treatment of life-threatening postpartum hemorrhage and be given only by the IM route. Ergot should not be administered to patients with cardiac, renal, or hypertensive disease, or in association with a vasoconstrictor.
Serum prolactin concentration was measured by radioimmunoassay in 29 women, in the first 1 1/2 hours postpartum. Fourteen women received 0.2 mg methylergonovine maleate (Methergine) intramuscularly after the delivery of the placenta. Fifteen women who served as controls received only saline. The rise in serum prolactin concentration seen in the control women (266.4 ng/ml +/- 40.8 SE) was significantly greater than that seen in methylergonovine-treated patients (141.0 ng/ml +/- 29.0. SE).
Long-term beta blockade for perhaps a year or so following discharge after an MI is now of proven value, and for many such patients mortality reductions of about 25% can be achieved. No important differences are clearly apparent among the benefits of different beta blockers, although some are more convenient than others (or have slightly fewer side effects), and it appears that those with appreciable intrinsic sympathomimetic activity may confer less benefit. If monitored, the side effects of long-term therapy are not a major problem, as when they occur they are easily reversible by changing the beta blocker or by discontinuation of treatment. By contrast, although very early IV short-term beta blockade can definitely limit infarct size, more reliable information about the effects of such treatment on mortality will not be available until a large trial (ISIS) reports later this year, with data on some thousands of patients entered within less than 4 hours of the onset of pain. Our aim has been not only to review the 65-odd randomized beta blocker trials but also to demonstrate that when many randomized trials have all applied one general approach to treatment, it is often not appropriate to base inference on individual trial results. Although there will usually be important differences from one trial to another (in eligibility, treatment, end-point assessment, and so on), physicians who wish to decide whether to adopt a particular treatment policy should try to make their decision in the light of an overview of all these related randomized trials and not just a few particular trial results. Although most trials are too small to be individually reliable, this defect of size may be rectified by an overview of many trials, as long as appropriate statistical methods are used. Fortunately, robust statistical methods exist--based on direct, unweighted summation of one O-E value from each trial--that are simple for physicians to use and understand yet provide full statistical sensitivity. These methods allow combination of information from different trials while avoiding the unjustified direct comparison of patients in one trial with patients in another. (Moreover, they can be extended of such data that there is no real need for the introduction of any more complex statistical methods that might be more difficult for physicians to trust.) Their robustness, sensitivity, and avoidance of unnecessary complexity make these particular methods an important tool in trial overviews.
Prophylactic use of oxytocics reduces the risk of postpartum haemorrhage by about 40%. The analysis presented in this paper assesses which oxytocic preparation is associated with the least risk of postpartum haemorrhage and examines the relative effects of different preparations on the length of the third stage, the risk of manual removal of the placenta, blood pressure and other side-effects. A mixture of oxytocin and ergometrine (Syntometrine) appears to be the safest and most effective prophylactic of the alternatives which have been compared, but the quality of the evidence is not satisfactory. There is scope for a randomized comparison of Syntometrine with oxytocin to obtain unbiased and more precise estimates of their relative effects on postpartum haemorrhage, blood pressure and unpleasant side-effects.
A database of perinatal trials is currently being established to provide a resource for reviews of the safety and efficacy of interventions used in perinatal care and to foster cooperative and coordinated research efforts in the perinatal field. The database will ultimately comprise four main elements: a register of published reports of trials; a register of unpublished trials; a register of ongoing and planned trials; and data derived from pooled overviews (meta-analyses) of trials. This article describes the development of the first of these four elements.
This is the first paper in a series of articles which will report the main results of a national study mounted in England in 1984 to survey midwifery policies for the care of childbearing women in maternity hospitals and to explore the links between policy and practice. This first paper sets out the reasons for carrying out the study, describes the methodology and outlines the plans for reporting the results in subsequent articles.
Reported is the first known case of postpartum myocardial infarction probably induced by ergonovine maleate, a drug known to provoke coronary artery spasm in susceptible patients.
Over the past 20 years at least 11 randomised trials of the prevention with diuretics of pre-eclampsia and its sequelae have been undertaken. Nine of these were reviewed. Reliable data from the remaining two were not available. The nine reviewed had investigated a total of nearly 7000 people. Significant evidence of prevention of "pre-eclampsia" was overwhelming, even when oedema was not included as a diagnostic criterion. But as the definitions of pre-eclampsia that had been used depended heavily on increases in blood pressure this evidence may simply have reflected the well known ability of diuretics to reduce blood pressure. When the data on perinatal death were reviewed a little difference was seen in postnatal survival. The incidence of stillbirths was reduced by about one third with treatment, but, perhaps owing to small numbers (only 37 stillbirths), the difference was not significant. Thus these randomised trials failed to provide reliable evidence of either the presence or the absence of any worthwhile effects of treatment with diuretics on perinatal mortality. The implications of this for current and future trials of beta blockers and other agents in the prevention of pre-eclampsia and its sequelae are that extremely large, ultra simple randomised trials are needed, of a size sufficient to permit direct assessment of the effects of treatment not on pre-eclampsia but on perinatal mortality itself. This may require the study of tens of thousands of pregnancies.
The published literature contains numerous reports of clinical studies. A problem in their interpretation is that studies in which the observed efficacy of the treatment is high are much more likely to be reported than those in which the observed efficacy is average or poor. This phenomenon has had the consequence of generally discrediting the reliability of the literature, especially that of non-randomized studies.
In this paper a model is developed which permits estimation of the potential magnitude by which the reported efficacy of a treatment might be inflated. This quantity is termed the publication bias. The magnitude of the bias depends on the sample size of the study and the number of similar studies conducted concurrently. Tabulated values of the bias are presented, permitting easy computation.
The new measure may have potential use for physicians in clinical decision making in that it characterizes the reliability of results from a specific published study, especially when there are no definitive randomized studies. However, correction of publication bias in this manner is not a substitute for a well controlled or a randomized study. The technique merely assists in the interpretation of available evidence from the literature. Moreover, it must be used with due caution in recognition of the assumptions and approximations involved in the calculation.
The postpartum administration of ergometrine in 4 patients resulted in hypertension in 3 (with eclampsia in 1) and in cardiac arrest in the fourth. The routine use of ergometrine in obstetrics is questioned and its abandonment is suggested.