Oxytocic Agents Research Articles

Sweeping Membrane at 40 Weeks Initiation of Normal Labour Induction: A Randomized Controlled Trial

One hundred twenty women at 40 weeks pregnancy with singleton foetus in cephalic presentation and intact membrane were randomly assigned to receive membrane sweeping or no membrane sweeping. The aim of this study was to determine the benefit of membrane sweeping at initiation of labour induction in conjunction with other methods of labour induction. After sweeping Bishop Score was done and in sweeping group, oxytocin infusion or misoprostol was administered 6 hours later. In control group, oxytocic agent was administered after vaginal examination. Among one hundred twenty women (60 sweep and 60 non-sweep) show that swept women had higher spontaneous vaginal delivery rate (83% compared with 60%). Shorter induction to delivery interval (12 hours compared with 19 hours), fewer that required oxytocin use (15% compared with 50%), shorter duration of oxytocin infusion (2 hours compared with 4 hours). Membrane sweeping at initiation of lab our induction increased the spontaneous vaginal delivery rate, reduced oxytotic drug use, shortened induction to delivery interval.TAJ 2009; 22(1): 204-206

Anaesthesiological considerations on tocolytic and uterotonic therapy in obstetrics

Significant side effects of tocolytic and uterotonic substances may be of concern to the anaesthesiologist. Recently, new drugs have been introduced having less side effects for both the mother and the neonate. A literature search was undertaken mainly focusing on meta-analyses, to review the possible side effects that might affect the course of anaesthesia and to suggest which precautions should be considered to prevent the occurrence of significant interactions with anaesthetic manipulations and drugs. Magnesium sulphate has a proven benefit in lowering systolic blood pressure and preventing the occurrence of eclampsia, but not as a tocolytic. beta-adrenergic agonists are being abandoned due to the availability of tocolytic agents causing less side effects. Calcium channel blockers (CCB) are frequently used but can cause major maternal cardiovascular complications. Nitroglycerin seems to be appreciated as an acute tocolytic rather than a routine substance during pre-term labour. Cyclo-oxygenase-2 inhibitors are still under investigation but their tocolytic benefit is questionable mainly due to foetal side effects. Atosiban is considered the first-choice tocolytic. With respect to oxytocic drugs, oxytocine, prostaglandines and methylergometrine may all cause serious side effects especially when combined. The cardiovascular side effects of prostaglandins and methylergometrine can be life-threatening. Both oxytocin and carbetocin have a rather low risk for maternal complications. Atosiban and CCB are at least as effective tocolytic agents as beta-mimetics but have significantly less side effects. Magnesium sulphate can cause neuromuscular blockade, especially when combined with CCB. Concerning oxytocic agents, short-acting oxyctocin and long-acting carbetocin have the least side effects as compared with prostaglandins and methylergometrine.

Carbetocin versus syntometrine in prevention of post‐partum hemorrhage following vaginal delivery

To compare the efficacy of a single dose of 100 microg intramuscular carbetocin to a single dose of intramuscular syntometrine (0.5 mg ergometrine and 5IU oxytocin), in preventing post-partum hemorrhage (PPH) in high risk patients following vaginal delivery. A prospective, randomized controlled study was conducted in a tertiary hospital where 120 pregnant women with risk factors for PPH who delivered vaginally were randomized into two groups: the study group where 100 microg intramuscular carbetocin was administered and the control group, who received intramuscular syntometrine. Outcome measures compared included changes in vital signs, amount of intrapartum blood loss, uterine fundal position, addition of another oxytocic agent, side-effects of the drugs, amount of lochia and hemoglobin drop after 24 hours post-partum. Incidence of PPH or other adverse events were also compared. There were no significant differences in terms of requirement for additional oxytocic agents, time interval to well contracted uterus, blood transfusion requirements, adverse effects or complications. There was a significantly lower mean estimated blood loss in the carbetocin group compared to the syntometrine group (244 +/- 114 mL vs 343 +/- 143 mL, 95% CI 52-146 mL). There was also a significantly reduced drop in hemoglobin in the carbetocin group compared to the syntometrine group (0.3 +/- 0.2 g/dL vs 0.4 +/- 0.2 g/dL, 95% CI 0.1-0.2 g/dL). Intramuscular carbetocin may be more effective than intramuscular syntometrine in reducing post-partum blood loss and the drop in hemoglobin level.

Use of oxytocin to prevent haemorrhage at caesarean section—A survey of practice in the United Kingdom

Objective To establish the views and current practice of obstetricians and anaesthetists with regard to the use of oxytocin to prevent haemorrhage at caesarean section. Study design A national survey of all lead consultant obstetricians and anaesthetists for the labour ward in the United Kingdom. A postal questionnaire was sent to all clinicians with one subsequent reminder to non-responders. The use of oxytocin bolus and infusion, perceived side effects of intravenous oxytocin, estimated blood loss at caesarean section, and willingness to participate in a future clinical trial were explored. Results The response rate was 84% (365 respondents). A slow bolus of 5 IU oxytocin was the preferred approach of obstetricians and anaesthetists (153, 86% and 171, 92%, respectively). Oxytocin infusions were used routinely by 72 clinicians (20%) with selective use for particular clinical circumstances by 289 (80%). Most clinicians used either 30 IU (158, 43%) or 40 IU (192, 53%) infusions over 4 h, with a total of 38 different regimens. The perceived risk of side effects with an oxytocin infusion was low. Estimated “average” blood loss varied (150–1500 ml) with 56 clinicians (17%) and 93 (28%) reporting a >20% risk of postpartum haemorrhage for elective and emergency caesarean sections, respectively. Conclusion There is wide variation in the use of oxytocin at caesarean section reflecting limited research in this area. Excess haemorrhage is considered to occur frequently and the perceived risk of oxytocin bolus and infusion is low. Further research is required addressing the optimal use of oxytocic agents at caesarean section.

Cytological effects of oxytocic agents on mitotic chromosomes of <i>Allium cepa </i>

Two synthetic (oxytocin and ergometrin) and one crude (Xylopia aethiopica extract) oxytocic agents, in two formulations were tested on root tip mitosis of Allium cepa. Both synthetic and crude oxytocic agents had depressive effect on the mitotic index and percentage of mitotic phases. There was an accumulation of prophase at the expense of the other phases. Diverse kinds of abnormalities were observed in different mitotic phases. These include disturbed prophase, spindle inhibition, star metaphase, chromatid bridge, precocious chromosome and even nuclear disintegration. The percentage of abnormal cells increased with increase in concentration of treatment drugs and duration of treatment. The possible reasons for the low mitotic index, prophase accumulation and low percentage of mitotic phases as well as increased abnormities at high concentrations have been discussed. Keywords :Oxytocic agents, Cytology, Chromosomes, Mitotic index, Allium cepa . Agro-Science Vol. 5 (2) 2006: pp. 1-6

Uterotrophic, Fetotoxic and Abortifacient Effect of a Malaysian Variety of Plumbago rosea L. on Isolated Rat Uterus and Pregnant Mice

Traditionally Plumbago rosea L. is used as an abortifacient in the Southeast Asian region. Methanolic root extract of a local species of Plumbago rosea L. was studied to evaluate its traditional antifertility claim. Interestingly, it was found to possess dose related inhibitory effect on uterine contractile responses elicited by oxytocic agents on isolated uteri of pregnant and pseudo-pregnant rats. Furthermore, it was found to possess significant (p < 0.05) fetotoxic activity along with mild abortive potential in pregnant mice when given orally at high doses (400 and 800 mg kg(-1)) once daily for ten days starting from day 10 of gestation. The results derived indicated possible presence of utero-active compound (s) in this plant that inhibited oxytocic agents induced uterine motility. Moreover, pronounced fetotoxic and mild abortifacient potentials observed at higher doses in pregnant mice might support its accredited traditional use to avoid unwanted pregnancy.

Effect of oxytocics on the blood pressure of normotensive Nigerian parturients

Background. The single most common direct obstetric disorder accounting for 25% of all maternal deaths globally is severe hemorrhage, generally occurring postpartum. Nearly all these deaths occur in the developing world. The role of oxytocic drugs in the management of the third stage of labor as a strategy to reduce maternal mortality has been emphasized. However, the adverse effects of these oxytocic agents, in particular ergometrine, have not been properly evaluated in our environment.Objectives. To evaluate the effect of ergometrine and oxytocin on the cardiovascular system when used for active management of the third stage of labor.Study design. A double-blind, randomized controlled study was carried out at the Federal Medical Centre, Makurdi over 24 months. Five hundred and ten patients were randomized to treatment with either 0.5 mg of intramuscular ergometrine or 10 IU of intravenous oxytocin, respectively, as single injections. Their effects on the cardiovascular system were observed using blood pressure as a marker.Results. Ergometrine unlike oxytocin was observed to cause a significant rise in blood pressure, and this effect was most marked in the first 24 hours of the puerperium.Conclusions. These results suggest that ergometrine may be safe in normotensive parturients but hazardous in hypertensive parturients in whom oxytocin would be a safer option.

Pro-ejaculatory effect of the aqueous crude extract of cihuapatli ( Montanoa tomentosa) in spinal male rats

In the present study, the pro-sexual effect of the cihuapatli ( Montanoa tomentosa) and its possible pro-ejaculatory properties in spinal male rats were examined. Systemic administration of the aqueous crude extracts of Montanoa tomentosa exerted a pro-ejaculatory effect and produced an increase in the number of discharges in the ejaculatory motor patterns in the spinal rats. The cihuapatli-induced ejaculatory responses included the expression of penile erections and penile movements and the potent expulsion of urethral contents and in some cases the expulsion of seminal plugs. The cihuapatli-induced ejaculatory motor patterns were similar to that obtained after systemic oxytocin. Cihuapatli- and oxytocin-induced ejaculatory motor responses and the penile erections and movements were abolished by the pre-treatment with hexamethonium, a selective oxytocin antagonist. Present data show that the cihuapatli extract acts directly at the spinal system in charge of the expression of the ejaculatory motor patterns and suggest that the aqueous crude extract exerts its aphrodisiacs properties by increasing sexual potency acting as an oxytocic agent.

Infants' Blood Volume in a Controlled Trial of Placental Transfusion at Preterm Delivery

To investigate whether it was possible to promote placental blood transfer to infants at preterm delivery by (1) delaying cord clamping, (2) holding the infant below the placenta, and (3) administering an oxytocic agent to the mother, we measured the infants' blood volumes. Randomized study. Forty-six preterm infants (gestational age: 24[0/7] to 32[6/7] weeks) were assigned randomly to either placental blood transfer promotion (delayed cord clamping [DCC] group, ie, > or =30 seconds from moment of delivery) or early cord clamping (ECC) with conventional management (ECC group). Eleven of 23 and 9 of 23 infants assigned randomly to DCC and ECC, respectively, were delivered through the vaginal route. The study was conducted at a tertiary perinatal center, the Queen Mother's Hospital (Glasgow, United Kingdom). The infants' mean blood volume in the DCC group (74.4 mL/kg) was significantly greater than that in the ECC group (62.7 mL/kg; 95% confidence interval for advantage: 5.8-17.5). The blood volume was significantly increased by DCC for infants delivered vaginally. The infants in the DCC group delivered through cesarean section had greater blood volumes (mean: 70.4 mL/kg; range: 45-83 mL/kg), compared with the ECC group (mean: 64.0 mL/kg; range: 48-77 mL/kg), but this was not significant. Additional analyses confirmed the effect of DCC (at least 30 seconds) to increase average blood volumes across the full range of gestational ages studied. The blood volume was, on average, increased in the DCC group after at least a 30-second delay for both vaginal and cesarean deliveries. However, on average, euvolemia was not attained with the third stage management methods outlined above.

Oral misoprostol in the third stage of labor

Objective: To compare the efficacy of intravenous ergometrine, intramuscular oxytocin, and oral misoprostol in the control of postpartum hemorrhage. Methods: Mean blood loss, rates of blood loss between 500 and 1000 ml, hematocrit fall greater than 10%, and need for additional oxytocic agentsand nature and rates of adverse effects were assessed in this prospective, randomized, controlled study. Results: All outcomes were similar in the 3 groups. The main adverse effects in the misoprostol group were temperatures higher than 99 °F, which normalized within 2 h and shivering, which was mild and self-limiting. Conclusions: Oral misoprostol is as effective as conventional oxytocic agents in preventing postpartum hemorrhage and can be recommended for use in low-resource settings.

Myomectomies : prévention de l'hémorragie

Myomectomy is a surgical procedure that allows preservation of the uterus in case of myomatous disease. Various surgical approaches may be considered. However, abundant peroperative haemorrhage may occur, resulting in complications such as incomplete surgery, modification of the surgical access, hypovolaemic shock, blood transfusion, and severe postoperative anaemia, necessitating aggressive treatment and transfusion, and delaying activity recovery. Such observations justify in seeking for means able to prevent peroperative haemorrhage. Several medical preoperative means have been strictly evaluated. The preoperative usage of gonadotrophin releasing hormone (Gn-RH) agonists seems to result, after a reduction of the uterine volume by myometrium vascular re-arrangements, in a reduction of peroperative haemorrhage; the results are still debated. Administrations of Gn-RH, misoprostol or antiprogesterone seem promising but further studies are necessary to confirmation. Preoperative embolization of the myoma could reduce peroperative blood loss but the use of this procedure in childbearing women is under evaluation. Peroperative means are available: chemical means such as vasoconstrictive or oxytocic agents, and mechanical means which temporarily interrupt the myometrial blood flow. Some have shown efficacy. As alternatives to surgery, techniques such myolysis – which induces in situ myoma destruction – necessitate further research, particularly regarding young childbearing women.

Safe techniques in surgery for hysteroscopic myomectomy

Hysteroscopic myomectomy is regarded as the best treatment for patients with submucous myomata. However, this procedure has a number of associated complications, including uterine perforation, cervical laceration, hyponatremia and hemorrhage, especially in cases of sessile submucous myomata. To avoid these problems, it is important to make well-advised preparations and manipulations both pre- and intraoperatively. The main surgical considerations for safe hysteroscopic myomectomy are shortening the operating time and avoiding cutting too deeply into the myometrium. With these requirements in mind, a combination of techniques using vaporization and a powerful oxytocic agent, such as prostaglandin F-2alpha, appears to be the safest method of carrying out hysteroresectoscopy for unpedunculated sessile submucous myomata.

Epidural anesthesia and uterine contractions

It has been our anecdotal experience that midwives and doctors sometimes perceive uterine contractions to diminish in strength and frequency following the administration of epidural anesthesia. This is probably an incorrect perception, as there is no physiological reason for this phenomenon [1]. Nevertheless, this probable misconception is of some importance, as a perceived reduction in uterine activity could lead to inappropriate use of oxytocic agents. The hypothesis of this study was that the clinical assessment of uterine activity is reduced following the administration of epidural anesthesia. Primiparous women with singleton pregnancies in spontaneous labor who had epidural anesthesia, were selected for this retrospective study. They were identified within a maternity unit of 3500 deliveries/year, between June and December 2003.

Surgical Management of Severe Obstetric Hemorrhage: Experience with an Obstetric Hemorrhage Equipment Tray

Background: Hemorrhage remains a leading cause of severe maternal morbidity and death. In addition to the appropriate use of oxytocic agents for uterine atony, surgical techniques, including uterine tamponade, major vessel ligation, compression sutures, and hysterectomy, may be required. On the rare occasions they are needed, the instruments and equipment required for these surgical techniques may not be readily available.Objective: To record our experience with an obstetric hemorrhage equipment tray for surgical management of severe obstetric hemorrhage.Methods: A severe obstetric hemorrhage equipment tray was established and included packing (5-yard roll) and balloon device for uterine tamponade, straight (10 cm) eyed-needles and large curved eyed-needles for use with No. 1 suture, 3 Heaney vaginal retractors, 4 sponge forceps, and diagrams and instructions for the various types of compression sutures and tamponade techniques.Results: Of the 4400 deliveries that occurred at 1 tertiary maternity hospital during 2002, the obstetric hemorrhage tray was used on 9 occasions: 3 Caesarean sections with placenta previa (uterine tamponade used in 2 cases, compression sutures in 1); 2 Caesarean sections with uterine atony (compression sutures); 1 Caesarean section with placenta previa accreta (major vessel ligation and compression sutures); and 3 vaginal deliveries (suturing of cervical and vaginal lacerations in 2 of the cases, uterine tamponade used in the third case). In all cases, hysterectomy was avoided.Conclusion: The ready availability of an obstetric hemorrhage equipment tray on the labour ward facilitates prompt surgical management of severe obstetric hemorrhage, and may reduce the need for blood transfusion and hysterectomy.

Uterine Compression Sutures as an Alternative to Hysterectomy for Severe Postpartum Hemorrhage

Objective: To assess the use of B-Lynch type uterine compression sutures as an alternative to hysterectomy for severe postpartum hemorrhage (PPH) due to uterine atony.Methods: The use of uterine compression sutures for severe postpartum hemorrhage was reviewed over a 30-month period (January 2000-June 2002) in a tertiary obstetric unit.Results: In 7 cases of uterine atony at the time of Caesarean section, which were unresponsive to all oxytocic agents, a B-Lynch type compression suture was used before resorting to hysterectomy. In 6 of the 7 women, the bleeding was controlled with the suture, while the other required hysterectomy.Conclusion: At the time of writing there were 6 reports in the literature involving a total of 20 women who were successfully treated with this type of compression suture for severe atonic PPH. Our review adds 7 cases and found that the B-Lynch compression suture is easy to apply and should be considered in cases of severe atonic PPH when oxytocic agents fail, and before resorting to hysterectomy.

Sildenafil inhibits agonist-evoked rat uterine contractility: influence of guanylyl cyclase inhibition

Sildenafil shows a potent relaxant effect on corpus cavernosum smooth muscles by prolonging cyclic guanosine monophosphate (cGMP) actions. We investigated whether this inhibitory effect of sildenafil was also displayed on the uterine musculature. Isolated uteri of non-pregnant rats were used to measure the possible sildenafil-induced inhibition of contractions evoked by various oxytocic agents, viz., prostaglandin E 2, oxytocin and acetylcholine. The relation of these effects to sildenafil action on cGMP was also examined, using methylene blue as a guanylyl cyclase inhibitor. Sildenafil (30 and 100 nM) was found to shift to the right the non-cumulative concentration–response curves of the test agonists in a concentration-dependent manner. The shift was accompanied by a reduction in the maximal response of the tissue to all uterine stimulants selected. Sildenafil also elicited a marked concentration-dependent increase in EC 25 of prostaglandin E 2, oxytocin and acetylcholine, as compared to their respective control values. Preincubation of the uterine strip with methylene blue (10 μM) reduced the inhibitory effects of sildenafil on oxytocin- and acetylcholine-evoked contractions, at submaximal concentrations of each agonist. The results suggest that sildenafil inhibits the uterotonic potentials of various oxytocic agents and that this effect could be probably related to the drug's action on cGMP.

The effects of herbal oxytocics on the isolated “stripped” myometrium model

Decoctions of Agapanthus africanus and Clivia miniata are used as oxytocic agents in South African traditional herbal medicine. Aqueous extracts of A. africanus and C. miniata leaves have been shown to possess similar uterotonic activities in the isolated whole uterus preparation. The uterus however, comprises a myometrial and an endometrial layer and the activity of both oxytocin and the prostaglandins differs in these layers. The aim of this study was to determine the uterotonic activity of the herbal remedies in an endometrium-free preparation (i.e. “stripped” myometrium) and, if active, whether this effect could be related to prostaglandin synthesis or to interaction with specific receptors. The effects of the herbal extracts were tested on the isolated “stripped” rat myometrium preparation. Both herbal extracts caused a direct contractile response by the isolated tissue. Pretreatment of the myometrium with either plant extract augmented the initial response to acetylcholine. Preincubation with atropine inhibited the response to cumulative dosage of Agapanthus extract but had no effect on the response to Clivia. Indomethacin administration did not affect the response of the myometrium to cumulative dosage of acetylcholine, oxytocin or Clivia extract but inhibited the response to Agapanthus extract. These results clearly indicate that the Agapanthus and Clivia herbal extracts exhibited uterotonic activity in this model. The study illustrates that the “stripped” myometrium model has successfully differentiated between the mechanisms of action of two herbal oxytocics compared to the whole uterus preparation where their uterotonic activity was thought to be similar.

Pharmacological basis for the use of the antivenene water soluble extract of Diodia scandens as a laxative, oxytocic agent and a possible aphrodisiac in traditional medicine practice in eastern Nigeria.

The effects of the antivenene fraction of an ethanol extract of Diodia scandens on some mammalian smooth muscles were investigated. On the guinea-pig ileum, the extract was shown to be a partial agonist acting via muscarinic receptors. Acetylcholine (ACh) was 2.5 x 10(5) times more potent. On the pregnant guinea-pig uterus, the extract induced concentration-dependent increases in the force of contraction and tonus. Oxytocin and ergometrine were respectively 10(6) and 10(3) times more potent. The extract, at subliminal concentrations, potentiated ACh and adrenaline-induced contractions in the guinea-pig was deferens. It also induced dose-related vasodilatation in the rat hindquarters and depressed the blood pressure in the anaesthetized cat. It was concluded that these pharmacological actions offer some scientific explanation for the use of Diodia scandens in traditional medicine as a laxative and as an oxytocic agent. It is suggested that the extract could enhance erection and ejaculatory processes in the male, thus accounting for its regular use by some elderly males.

Physiological third stage of labour

Active management of the third stage of labour is common practice, and many midwives do not have the opportunity to become practised in caring for a woman having a physiological third stage of labour (Inch, 1988; Levy, 1992; Enkin et al, 1995). Changing Childbirth recommends the provision of choice (Department of Health, 1993), and this choice extends to declining the use of oxytocic agents for third stage of labour. Where a woman chooses a physiological third stage it is important that the midwife attending her understands how to perform this option safely. This article describes research undertaken to find out to what extent midwives understand the conduct of a physiological third stage. According to Inch (1988), adaptive practice, i.e. where care appropriate for the woman who has had syntometrine is used for the woman having a physiological third stage, can predispose the mother to postpartum haemorrhage, retained placenta or inversion of the uterus.

Rectal misoprostol in the prevention of postpartum hemorrhage: A placebo-controlled trial

Objective: This study investigated the effectiveness of rectal misoprostol in preventing postpartum hemorrhage. Study Design: In a randomized, placebo-controlled study, 550 women were randomly allocated to rectally receive 400 μg misoprostol or nonidentical placebo after normal vaginal delivery. Any excessive bleeding was actively managed with conventional oxytocic agents. Blood loss was measured directly. Results: The baseline variables were similar. Blood loss of ≥1000 mL occurred in 4.8% (13/270) of the misoprostol group and 7% (19/272) of the placebo group. Additional oxytocic therapy was required by 3.3% and 4.7%, respectively. No predominance of side effects, particularly shivering, was noted in the misoprostol group. Conclusions: Postpartum use of 400 μg rectal misoprostol was well tolerated and associated with a statistically nonsignificant trend toward less postpartum hemorrhage. The early active management of excessive bleeding with conventional oxytocic agents may have reduced the potential of the study to detect differences between the groups (Am J Obstet Gynecol 1998;179:1043-6.)