oxytocin and Fever

Oxytocin (OT) is a critical molecule for social recognition that mediates social and emotional behaviors. OT is released during stress and acts as an anxiolytic factor. To know the precise molecular mechanisms underlying OT release into the brain during stress is important. It has been reported that intracellular concentrations of free calcium in the hypothalamic neurons are elevated by simultaneous stimulation of cyclic ADP-ribose (cADPR) and heat. We have reported in vitro and in vivo data that supports the idea that release of OT in the brain of male mice is regulated by cADPR and fever in relation to stress conditions. 1) Significantly higher levels of OT release were observed in hypothalamus cultures isolated from subordinate mice in group-housed males compared to dominant males after cage-switch stress; 2) OT concentrations in micro-perfusates at the paraventricular nucleus upon perfusion stimulation with cADPR were enhanced in subordinate mice compared to dominant mice; 3) The OT concentration in the cerebrospinal fluid (CSF) was higher in endotoxin-shock mice with fever compared to controls with no body temperature increase; and 4) In mice exposed to new environmental stress, the CSF OT level transiently increased 5 min after exposure, while the rectal temperature increased from 36.6 °C to 37.8 °C from 5 to 15 min after exposure. In this review, we examine whether or not cADPR and hyperthermia co-regulate hypothalamic OT secretion during social stress through the elevation of intracellular free Ca

Topics: ADP-ribosyl Cyclase 1; Animals; Fever; Humans; Hypothalamus; Oxytocin; TRPM Cation Channels

Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Prophylactic uterotonic drugs can prevent PPH, and are routinely recommended. There are several uterotonic drugs for preventing PPH but it is still debatable which drug is best.. To identify the most effective uterotonic drug(s) to prevent PPH, and generate a ranking according to their effectiveness and side-effect profile.. We searched Cochrane Pregnancy and Childbirth's Trials Register (1 June 2015), ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) for unpublished trial reports (30 June 2015) and reference lists of retrieved studies.. All randomised controlled comparisons or cluster trials of effectiveness or side-effects of uterotonic drugs for preventing PPH.Quasi-randomised trials and cross-over trials are not eligible for inclusion in this review.. At least three review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We estimated the relative effects and rankings for preventing PPH ≥ 500 mL and PPH ≥ 1000 mL as primary outcomes. We performed pairwise meta-analyses and network meta-analysis to determine the relative effects and rankings of all available drugs. We stratified our primary outcomes according to mode of birth, prior risk of PPH, healthcare setting, dosage, regimen and route of drug administration, to detect subgroup effects.The absolute risks in the oxytocin are based on meta-analyses of proportions from the studies included in this review and the risks in the intervention groups were based on the assumed risk in the oxytocin group and the relative effects of the interventions.. This network meta-analysis included 140 randomised trials with data from 88,947 women. There are two large ongoing studies. The trials were mostly carried out in hospital settings and recruited women who were predominantly more than 37 weeks of gestation having a vaginal birth. The majority of trials were assessed to have uncertain risk of bias due to poor reporting of study design. This primarily impacted on our confidence in comparisons involving carbetocin trials more than other uterotonics.The three most effective drugs for prevention of PPH ≥ 500 mL were ergometrine plus oxytocin combination, carbetocin, and misoprostol plus oxytocin combination. These three options were more effective at preventing PPH ≥ 500 mL compared with oxytocin, the drug currently recommended by the WHO (ergometrine plus oxytocin risk ratio (RR) 0.69 (95% confidence interval (CI) 0.57 to 0.83), moderate-quality evidence; carbetocin RR 0.72 (95% CI 0.52 to 1.00), very low-quality evidence; misoprostol plus oxytocin RR 0.73 (95% CI 0.60 to 0.90), moderate-quality evidence). Based on these results, about 10.5% women given oxytocin would experience a PPH of ≥ 500 mL compared with 7.2% given ergometrine plus oxytocin combination, 7.6% given carbetocin, and 7.7% given misoprostol plus oxytocin. Oxytocin was ranked fourth with close to 0% cumulative probability of being ranked in the top three for PPH ≥ 500 mL.The outcomes and rankings for the outcome of PPH ≥ 1000 mL were similar to those of PPH ≥ 500 mL. with the evidence for ergometrine plus oxytocin combination being more effective than oxytocin (RR 0.77 (95% CI 0.61 to 0.95), high-quality evidence) being more certain than that for carbetocin (RR 0.70 (95% CI 0.38 to 1.28), low-quality evidence), or misoprostol plus oxytocin combination (RR 0.90 (95% CI 0.72 to 1.14), moderate-quality evidence)There were no meaningful differences between all drugs for maternal deaths or severe morbidity as these outcomes were so rare in the included randomised trials.Two combination regimens had the poorest rankings for side-effects. Specifically, the ergometrine plus oxytocin combination had the higher risk for vomiting (RR 3.10 (95% CI 2.11 to 4.56), high-quality evidence; 1.9% versus 0.6%) and hypertension [RR 1.77 (95% CI 0.55 to 5.66), low-quality evidence; 1.2% versus 0.7%), while the misoprostol plus oxytocin combination had the higher risk for fever (RR 3.18 (95% CI 2.22 to 4.55), moderate-quality evidence; 11.4% versus 3.6%) when compare. Ergometrine plus oxytocin combination, carbetocin, and misoprostol plus oxytocin combination were more effective for preventing PPH ≥ 500 mL than the current standard oxytocin. Ergometrine plus oxytocin combination was more effective for preventing PPH ≥ 1000 mL than oxytocin. Misoprostol plus oxytocin combination evidence is less consistent and may relate to different routes and doses of misoprostol used in the studies. Carbetocin had the most favourable side-effect profile amongst the top three options; however, most carbetocin trials were small and at high risk of bias.Amongst the 11 ongoing studies listed in this review there are two key studies that will inform a future update of this review. The first is a WHO-led multi-centre study comparing the effectiveness of a room temperature stable carbetocin versus oxytocin (administered intramuscularly) for preventing PPH in women having a vaginal birth. The trial includes around 30,000 women from 10 countries. The other is a UK-based trial recruiting more than 6000 women to a three-arm trial comparing carbetocin, oxytocin and ergometrine plus oxytocin combination. Both trials are expected to report in 2018.Consultation with our consumer group demonstrated the need for more research into PPH outcomes identified as priorities for women and their families, such as women's views regarding the drugs used, clinical signs of excessive blood loss, neonatal unit admissions and breastfeeding at discharge. To date, trials have rarely investigated these outcomes. Consumers also considered the side-effects of uterotonic drugs to be important but these were often not reported. A forthcoming set of core outcomes relating to PPH will identify outcomes to prioritise in trial reporting and will inform futures updates of this review. We urge all trialists to consider measuring these outcomes for each drug in all future randomised trials. Lastly, future evidence synthesis research could compare the effects of different dosages and routes of administration for the most effective drugs.

Topics: Drug Therapy, Combination; Ergonovine; Female; Fever; Humans; Hypertension; Misoprostol; Network Meta-Analysis; Oxytocics; Oxytocin; Postpartum Hemorrhage; Vomiting

Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Prophylactic uterotonic agents can prevent PPH, and are routinely recommended. The current World Health Organization (WHO) recommendation for preventing PPH is 10 IU (international units) of intramuscular or intravenous oxytocin. There are several uterotonic agents for preventing PPH but there is still uncertainty about which agent is most effective with the least side effects. This is an update of a Cochrane Review which was first published in April 2018 and was updated to incorporate results from a recent large WHO trial.. To identify the most effective uterotonic agent(s) to prevent PPH with the least side effects, and generate a ranking according to their effectiveness and side-effect profile.. We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (24 May 2018), and reference lists of retrieved studies.. All randomised controlled trials or cluster-randomised trials comparing the effectiveness and side effects of uterotonic agents with other uterotonic agents, placebo or no treatment for preventing PPH were eligible for inclusion. Quasi-randomised trials were excluded. Randomised trials published only as abstracts were eligible if sufficient information could be retrieved.. At least three review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We estimated the relative effects and rankings for preventing PPH ≥ 500 mL and PPH ≥ 1000 mL as primary outcomes. Secondary outcomes included blood loss and related outcomes, morbidity outcomes, maternal well-being and satisfaction and side effects. Primary outcomes were also reported for pre-specified subgroups, stratifying by mode of birth, prior risk of PPH, healthcare setting, dosage, regimen and route of administration. We performed pairwise meta-analyses and network meta-analysis to determine the relative effects and rankings of all available agents.. The network meta-analysis included 196 trials (135,559 women) involving seven uterotonic agents and placebo or no treatment, conducted across 53 countries (including high-, middle- and low-income countries). Most trials were performed in a hospital setting (187/196, 95.4%) with women undergoing a vaginal birth (71.5%, 140/196).Relative effects from the network meta-analysis suggested that all agents were effective for preventing PPH ≥ 500 mL when compared with placebo or no treatment. The three highest ranked uterotonic agents for prevention of PPH ≥ 500 mL were ergometrine plus oxytocin combination, misoprostol plus oxytocin combination and carbetocin. There is evidence that ergometrine plus oxytocin (RR 0.70, 95% CI 0.59 to 0.84, moderate certainty), carbetocin (RR 0.72, 95% CI 0.56 to 0.93, moderate certainty) and misoprostol plus oxytocin (RR 0.70, 95% CI 0.58 to 0.86, low certainty) may reduce PPH ≥ 500 mL compared with oxytocin. Low-certainty evidence suggests that misoprostol, injectable prostaglandins, and ergometrine may make little or no difference to this outcome compared with oxytocin.All agents except ergometrine and injectable prostaglandins were effective for preventing PPH ≥ 1000 mL when compared with placebo or no treatment. High-certainty evidence suggests that ergometrine plus oxytocin (RR 0.83, 95% CI 0.66 to 1.03) and misoprostol plus oxytocin (RR 0.88, 95% CI 0.70 to 1.11) make little or no difference in the outcome of PPH ≥ 1000 mL compared with oxytocin. Low-certainty evidence suggests that ergometrine may make little or no difference to this outcome compared with oxytocin meanwhile the evidence on carbetocin was of very low certainty. High-certainty evidence suggests that misoprostol is less effective in preventing PPH ≥ 1000 mL when compared with oxytocin (RR 1.19, 95% CI 1.01 to 1.42). Despite the comparable relative treatment effects between all uterotonics (except misoprostol) and oxytocin, ergometrine plus oxytocin, misoprostol plus oxytocin combinations and carbetocin were the highest ranked agents for PPH ≥ 1000 mL.Misoprostol plus oxytocin reduces the use of additional uterotonics (RR 0.56, 95% CI 0.42 to 0.73, high certainty) and probably also reduces the risk of blood transfusion (RR 0.51, 95% CI 0.37 to 0.70, moderate certainty) when compared with oxytocin. Carbetocin, injectable prostaglandins and ergometrine plus oxytocin may also reduce the use of additional uterotonics but the certainty of the evidence is low. No me. All agents were generally effective for preventing PPH when compared with placebo or no treatment. Ergometrine plus oxytocin combination, carbetocin, and misoprostol plus oxytocin combination may have some additional desirable effects compared with the current standard oxytocin. The two combination regimens, however, are associated with significant side effects. Carbetocin may be more effective than oxytocin for some outcomes without an increase in side effects.

Topics: Drug Therapy, Combination; Ergonovine; Female; Fever; Humans; Hypertension; Misoprostol; Network Meta-Analysis; Oxytocics; Oxytocin; Postpartum Hemorrhage; Prostaglandins; Randomized Controlled Trials as Topic; Vomiting

While inferior to oxytocin injection in both efficacy and safety, orally administered misoprostol has been included in the World Health Organization Model List of Essential Medicines for use in the prevention of postpartum haemorrhage (PPH) in low-resource settings. This study evaluates the costs and health outcomes of use of oral misoprostol to prevent PPH in settings where injectable uterotonics are not available.. A cost-consequences analysis was conducted from the international health system perspective, using data from a recent Cochrane systematic review and WHO's Mother-Baby Package Costing Spreadsheet in a hypothetical cohort of 1000 births in a mixed hospital (40% births)/community setting (60% births). Costs were estimated based on 2012 US dollars.. Using oxytocin in the hospital setting and misoprostol in the community setting in a cohort of 1000 births, instead of oxytocin (hospital setting) and no treatment (community setting), 22 cases of PPH could be prevented. Six fewer women would require additional uterotonics and four fewer women a blood transfusion. An additional 130 women would experience shivering and an extra 42 women fever. Oxytocin/misoprostol was found to be cost saving (US$320) compared to oxytocin/no treatment. If misoprostol is used in both the hospital and community setting compared with no treatment (i.e. oxytocin not available in the hospital setting), 37 cases of PPH could be prevented; ten fewer women would require additional uterotonics; and six fewer women a blood transfusion. An additional 217 women would experience shivering and 70 fever. The cost savings would be US$533. Sensitivity analyses indicate that the results are sensitive to the incidence of PPH-related outcomes, drug costs and the proportion of hospital births.. Our findings confirm that, even though misoprostol is not the optimum choice in the prevention of PPH, misoprostol could be an effective and cost-saving choice where oxytocin is not or cannot be used due to a lack of skilled birth attendants, inadequate transport and storage facilities or where a quality assured oxytocin product is not available. These benefits need to be weighed against the large number of additional side effects such as shivering and fever, which have been described as tolerable and of short duration.

Topics: Administration, Oral; Cost-Benefit Analysis; Female; Fever; Humans; Labor Stage, Third; Misoprostol; Oxytocics; Oxytocin; Parturition; Postpartum Hemorrhage; Pregnancy; Shivering

The effects of endotoxin (LPS) on the cortisol, glucose, NEFA (non-esterified fatty acids), STH (somatotropin) and oxytocin levels in plasma of goats are described. The changes in plasma cortisol, STH and NEFA, as well as in RT (rectal temperature) were compared after i.v. and i.mam. administration of endotoxin. The other parameters, glucose and oxytocin, were followed only after i.v. endotoxin administration. The observed metabolic and hormonal alterations in plasma were also studied after pretreating the goats with the non-steroidal anti-inflammatory and antipyretic drug flurbiprofen in order to evaluate the possible involvement of prostaglandin in these phenomena. After i.v. administration of LPS a biphasic temperature curve for the highest dose of LPS with peak maxima at 1h and 4h after LPS challenge, was observed. Intramammary administration of endotoxin induces a monophasic fever response, with a latency time of approximately 3h, and peak values after 6h. The onset of the fever response in the i.v. experiments coincided with the oxytocin maximum and with early hyperglycemia. Intravenous endotoxin in goats also induces an increase in plasma NEFA, cortisol and STH. The early increase in NEFA, with a maximum after 2h and occurring before the fever peak, is followed by a significant rise in cortisol with peak effects after 3 h. The increase in plasma STH coincided with the decrease in plasma NEFA returning to control levels again. Peak concentrations in plasma STH occurred after 4 h. All the changes observed after the i.v. administration of endotoxin are dose-dependent. Pretreating goats with flurbiprofen completely abolished fever response, as well as the early hyperglycemia and the oxytocin release to i.v. LPS, indicating that these changes were prostaglandin-mediated and might be a reflexion of an activation of the sympathetic adrenomedullary system. The LPS-induced changes in plasma cortisol, NEFA and STH are only partly depressed and delayed by flurbiprofen. The residual hormonal responses to high doses of endotoxin suggest that an additional direct action of circulating endotoxins on the hypothalamus cannot be excluded. Intramammary LPS administration in goats only induced a very weak increase in plasma cortisol. The complex interplay of hormones and metabolic substances in the homeostasis of the inflammation reaction is discussed.

Topics: Animals; Blood Glucose; Dose-Response Relationship, Drug; Endotoxins; Escherichia coli; Fatty Acids, Nonesterified; Female; Fever; Goats; Growth Hormone; Hydrocortisone; Lactation; Oxytocin; Prostaglandins; Toxemia

To compare efficacy and adverse effects of 200μg and 400μg misoprostol for prevention of postpartum hemorrhage (PPH).. In a randomized control trial, women with term singleton pregnancies in active labor attending University College Hospital, Ibadan, Nigeria, were enrolled between July 2011 and February 2012. Participants were randomly assigned using random numbers (block size four) to receive 200μg or 400μg sublingual misoprostol after delivery of the anterior shoulder, alongside intravenous oxytocin. Investigators were masked to group assignment, but participants were not. The primary outcomes were blood loss up to 1h after delivery, PPH (blood loss ≥500mL), and adverse effects.. Overall, 62 patients were assigned to each group. No significant differences between the 200-μg and 400-μg groups were recorded in mean peripartum blood loss (307±145mL vs 296±151mL; P=0.679) and PPH occurrence (5 [8.1%] vs 6 [9.7%] women; P=0.752). Noticeable adverse effects were reported by 16 (25.8%) women in the 200-μg group and 42 (67.7%) in the 400-μg group (P<0.001). Risk of shivering was significantly lower with 200μg than 400μg (relative risk 0.33, 95% confidence interval 0.19-0.58).. Blood loss and PPH occurrence did not differ by misoprostol dose, but a 200-μg dose was associated with a reduction in adverse effects. Pan Africa Clinical Trials Registry: PACTR201505001107182.

Topics: Administration, Sublingual; Adult; Female; Fever; Humans; Misoprostol; Nigeria; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy; Shivering; Tertiary Care Centers; Treatment Outcome

To evaluate whether a combination of misoprostol and oxytocin more effectively reduces blood loss during and after cesarean delivery than does oxytocin alone among women with known risk factors for postpartum hemorrhage (PPH).. A prospective, randomized, double-blind, placebo-controlled trial was performed at a tertiary care center in Kolkata, India, between October 2012 and December 2013. Women were eligible if they were undergoing emergency cesarean under spinal anesthesia and were at high risk for PPH. Participants were randomly assigned (1:1) to receive 400 μg misoprostol or matched placebo sublingually after delivery of the newborn using a computer-generated random number sequence (block size eight). Participants and providers were masked to assignment. All participants received 20 IU oxytocin. The primary outcomes were intraoperative and postoperative blood loss.. Both groups contained 198 women. Mean intraoperative blood loss was significantly lower in the misoprostol group (505.4±215.5 mL) than in the placebo group (587.3±201.5 mL; P<0.001). Mean postoperative blood loss was slightly lower in the misoprostol group (96.9±57.3 mL) than in the placebo group (103.4±58.4 mL; P=0.07). Shivering and pyrexia were more frequently associated with misoprostol (P<0.05 for both).. Misoprostol as an adjunct to oxytocin seemed to more effectively reduce blood loss than did oxytocin alone. Clinical Trial Registry India:CTRI/2013/05/003645.

Topics: Abortifacient Agents, Nonsteroidal; Administration, Sublingual; Adult; Blood Loss, Surgical; Blood Volume; Cesarean Section; Double-Blind Method; Drug Therapy, Combination; Emergencies; Female; Fever; Humans; Misoprostol; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy; Prospective Studies; Risk Factors; Shivering; Young Adult

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

Topics: Administration, Oral; Adult; Blood Volume; Diarrhea; Double-Blind Method; Female; Fever; Hospitals; Humans; Injections, Intramuscular; Labor Stage, Third; Misoprostol; Nigeria; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy; Shivering; Young Adult

Post-partum hemorrhage (PPH) is the most common direct cause of maternal mortality and timely intervention can save many lives.. To compare the effectiveness of sublingual misoprostol to intravenous oxytocin in preventing post-partum hemorrhage in low risk vaginal birth.. One hundred patients with no risk factor for PPH were randomly allocated to receive 600 μg misoprostol administered sublingually or 10 IU of intravenous oxytocin immediately after the delivery of baby. Main outcome measures were post-partum blood loss, drop in hemoglobin in 24 h, duration of third stage of labor, and drug-related adverse effects.. Mean age, parity and gestational age were similar in both groups. Mean blood loss was significantly lower in oxytocin group (114.28 ± 26.75 versus 149.50 ± 30.78 ml; p = 0.00). Drop in hemoglobin was 0.31 ± 0.16 versus 0.49 ± 0.21 g% (p = 0.01) in oxytocin and misoprostol group, respectively. Duration of third stage labor was shorter in oxytocin group (median 5 min, IQR: 4.5-5.5 versus 5.5 min, IQR: 5-6 min, p < 0.01). Although fever and shivering were common adverse effects with misoprostol but were not clinically significant.. Intravenous oxytocin is more efficacious than sublingual misoprostol in preventing PPH in institutional deliveries.

Topics: Administration, Sublingual; Adult; Delivery, Obstetric; Female; Fever; Hemoglobins; Humans; Infusions, Intravenous; Labor Stage, Third; Misoprostol; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy; Prospective Studies; Shivering; Time Factors

The aim of the study was to compare the efficacy of sublingual misoprostol in addition to intravenous oxytocin, with oxytocin alone, in reducing blood loss during and following caesarean section. A total of 120 women undergoing caesarean delivery at the University College Hospital, Ibadan, were randomised into two equal groups. In Group A, 20 IU of intravenous oxytocin was given after umbilical cord clamping, while in Group B, the women received 400 μg misoprostol sublingually and 20 IU oxytocin intravenously. The outcome measures were blood loss, additional uterotonics, change in packed cell volume and side-effect profile. Associations between variables were determined by the χ(2) and Student's t-test. Relative risks were calculated for side-effects; the level of significance was p < 0.05. Intraoperative and postoperative blood loss were significantly lower in Group B (451.3 ml vs 551.2 ml, p = 0.007; 22.7 vs 42.2 ml, p < 0.001, respectively). In Group B, women were 7.4 (p < 0.001) and 9.0 (p = 0.008) times more likely to experience shivering and fever, respectively. The need for additional uterotonics was greater in the oxytocin group (66.7% vs 27.6%, p < 0.001). The addition of sublingual misoprostol to intravenous oxytocin reduces postpartum blood loss and the need for additional uterotonics. There is however, an increased risk of shivering and fever with this combination.

Topics: Administration, Sublingual; Adult; Cesarean Section; Drug Therapy, Combination; Female; Fever; Humans; Misoprostol; Oxytocics; Oxytocin; Postoperative Hemorrhage; Pregnancy; Shivering; Young Adult

To compare sublingual misoprostol with intramuscular oxytocin for prevention of postpartum hemorrhage (PPH) in low-risk vaginal birth.. In a prospective, randomized, double-blind trial, 530 women without risk of PPH were randomly allocated to receive either 400 μg of misoprostol sublingually or 10 units of oxytocin intramuscularly within 1minute of delivery. The outcome measures were incidence of PPH, postpartum blood loss, drop in hemoglobin level in 24 hours, need for additional uterotonic drug, incidence of adverse effects, and need for blood transfusion. Student t, χ(2), Mann-Whitney U, and Fisher exact tests were used for comparison.. Incidence of postpartum hemorrhage (≥ 500 mL) and postpartum blood loss in the misoprostol group were similar to those in the oxytocin group (6% versus 5.7%, P=0.85; 153 mL versus 146 mL, P=0.36). Shivering and pyrexia were encountered more often in the misoprostol than in the oxytocin group (shivering: 19% versus 0.8%, P<0.001, relative risk [RR] 0.86, 95% confidence interval [CI] 0.82-0.90; pyrexia: 2.3% versus 0%, P=0.03, RR 0.97, 95% CI 0.95-0.99).. The efficacy of 400 μg of misoprostol administered sublingually was equivalent to that of 10 units of oxytocin given intramuscularly for prevention of PPH in low-risk vaginal delivery.

Topics: Administration, Sublingual; Adolescent; Adult; Double-Blind Method; Female; Fever; Follow-Up Studies; Humans; Injections, Intramuscular; Misoprostol; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy; Prospective Studies; Shivering; Statistics, Nonparametric; Treatment Outcome; Young Adult

To compare the impact of a dinoprostone vaginal insert and intravenous oxytocin in reducing blood loss of women undergoing vaginal or cesarean delivery.. This study was conducted among term singleton pregnancies delivered vaginally or by elective cesarean section. In the vaginally delivered cases, active management of the third stage of labor was conducted. During cesarean delivery, 20 IU of intravenous oxytocin was administered. Women, who either delivered via the vaginal or abdominal route, were then randomly allocated to receive 10 mg vaginal dinoprostone insert for 12 hours (group I, n: 100) or intravenous oxytocin (group II, n: 100), respectively.. Mean blood loss and need for additional uterotonics and postpartum hemoglobin and hematocrit levels at 24 and 36 hours after delivery did not differ between the two groups. Women allocated to the dinoprostone vaginal insert arm experienced more nausea and vomiting.. Dinoprostone vaginal insert was as effective as intravenous oxytocin in the prevention of postpartum blood loss.

Topics: Administration, Intravaginal; Adult; Delayed-Action Preparations; Delivery, Obstetric; Diarrhea; Dinoprostone; Female; Fever; Humans; Infusions, Intravenous; Nausea; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy; Prospective Studies; Shivering; Vomiting

To compare the efficacy and adverse effects of sublingual misoprostol, intravenous oxytocin, and intravenous methylergometrine in active management of the third stage of labor (AMTSL).. A double-blind randomized trial of 300 women with a healthy singleton pregnancy allocated into 4 groups to receive either: 400 microg or 600 microg of sublingual misoprostol, 5 IU of intravenous oxytocin, or 200 microg of intravenous methylergometrine. The primary outcome measure was blood loss in the third and fourth stage of labor; secondary measures were duration of the third stage of labor, changes in hemoglobin levels, and adverse effects.. Patients who received 600 microg of misoprostol had the lowest blood loss (96.05+/-21.1 mL), followed by 400 microg of misoprostol (126.24+/-49.3 mL), oxytocin (154.7+/-45.7 mL), and methylergometrine (223.4+/-73.7 mL) (P<0.01). Shortest mean duration of the third stage of labor (5.74 minutes) was with 600 microg of misoprostol, while methylergometrine had the longest (6.83 minutes) (P<0.05). Pyrexia was observed in the misoprostol groups, and raised blood pressure in the methylergometrine group (P<0.001). The 24-hour postpartum hemoglobin level was similar among the groups (P>0.05).. Administration of 600 microg of sublingual misoprostol was more effective than 400 microg of misoprostol, intravenous oxytocin, and intravenous methylergometrine for AMTSL.

Topics: Administration, Sublingual; Adult; Blood Pressure; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fever; Hemoglobins; Humans; Infusions, Intravenous; Labor Stage, Third; Methylergonovine; Misoprostol; Oxytocics; Oxytocin; Postpartum Hemorrhage; Postpartum Period; Pregnancy; Time Factors; Young Adult

Oxytocin is a hormone and neurotransmitter found to have anti-inflammatory functions in rodents. Here we used experimental bacterial endotoxinemia to examine the role of exogenous oxytocin administration on innate immune responses in humans. Ten healthy men received, in a randomized, placebo-controlled, crossover design, placebo, oxytocin, LPS, and LPS + oxytocin. Oxytocin treatment resulted in a transient or prolonged reduction of endotoxin-induced increases in plasma ACTH, cortisol, procalcitonin, TNF-alpha, IL-1 receptor antagonist, IL-4, IL-6, macrophage inflammatory protein-1alpha, macrophage inflammatory protein-1beta, monocyte chemoattractant protein-1 (MCP-1), interferon-inducible protein 10, and VEGF. In vitro, oxytocin had no impact on LPS effects in releasing TNF-alpha, IL-6, and MCP-1 in monocytes and peripheral blood mononuclear cells from healthy human donors. In summary, oxytocin decreases the neuroendocrine and cytokine activation caused by bacterial endotoxin in men, possibly due to the pharmacological modulation of the cholinergic anti-inflammatory pathway. Oxytocin might be a candidate for the therapy of inflammatory diseases and conditions associated with high cytokine and VEGF levels.

Topics: Adult; Body Temperature; Cell Separation; Chemokines; Cross-Over Studies; Cytokines; Double-Blind Method; Endotoxins; Fever; Hormones; Humans; In Vitro Techniques; Lipopolysaccharides; Male; Monocytes; Neurosecretory Systems; Oxytocin; Vascular Endothelial Growth Factor A

To compare the effects of oral misoprostol 800 mug with intramuscular oxytocin 10 IU in routine management of the third stage of labour.. This randomized controlled trial was performed in a rural district hospital in Ghana, West Africa, and enrolled women in labour with anticipated vaginal delivery and no known medical contraindication to prostaglandin administration. Women were randomized to receive oral misoprostol 800 mug or intramuscular oxytocin 10 IU. Blood samples were taken to determine hemoglobin concentration before delivery and at 12 hours post partum. Treatment was administered at delivery of the anterior shoulder. The primary outcome was the change in hemoglobin concentration from before to after delivery. Secondary outcomes included other measures of blood loss and presumed medication side effects.. In total, 450 women were enrolled in the study. Their baseline characteristics were similar. There was no significant difference between the groups in the change in hemoglobin concentration (misoprostol 1.07 g/dL and oxytocin 1.00 g/dL). The only significant secondary outcomes were shivering (80.7% with misoprostol vs. 3.6% with oxytocin) and pyrexia (11.4% with misoprostol, none with oxytocin).. Routine use of oral misoprostol 800 microg appears to be as effective as 10 IU parenteral oxytocin in minimizing blood loss during the third stage of labour, as determined by change in hemoglobin concentration. Misoprostol appears to be a safe, inexpensive, and effective uterotonic for use in rural and remote areas, where intravenous oxytocin may be unavailable.

Topics: Administration, Oral; Adult; Developing Countries; Double-Blind Method; Female; Fever; Ghana; Hemoglobins; Humans; Injections, Intramuscular; Labor Stage, Third; Misoprostol; Oxytocics; Oxytocin; Pregnancy; Shivering; Treatment Outcome

The purpose of this study was to compare misoprostol 600 microg intrarectally with conventional oxytocics in the treatment of third stage of labor.. In a controlled trial, 1606 women were randomly grouped to receive (1) oxytocin 10 IU plus rectal misoprostol, (2) rectal misoprostol, (3) oxytocin 10 IU, and (4) oxytocin 10 IU plus methylergometrine. The main outcome measures were the incidence of postpartum hemorrhage and a drop in hemoglobin concentration from before delivery to 24 hours after delivery.. The incidence of postpartum hemorrhage was 9.8% in the group that received only rectal misoprostol therapy compared with 3.5% in the group that received oxytocin and methylergometrine therapy (P =.001). There were no significant differences among the 4 groups with regard to a drop in hemoglobin concentrations. Significantly more women needed additional oxytocin in the group that received only rectal misoprostol therapy, when compared with the group that received oxytocin and methylergometrine therapy (8.3% vs 2.2%; P <.001). The primary outcome measures were similar in the group that received only rectal misoprostol therapy and the group that received only oxytocin therapy.. Rectal misoprostol is significantly less effective than oxytocin plus methylergometrine for the prevention of postpartum hemorrhage.

Topics: Administration, Rectal; Adult; Drug Therapy, Combination; Female; Fever; Humans; Labor Stage, Third; Methylergonovine; Misoprostol; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy

To select the misoprostol dose to be used in a large multicentre randomised trial comparing misoprostol with oxytocin in the routine management of the third stage of labour.. Randomised pilot trial, double-blinded with the use of double placebos.. Two of the nine hospitals that will participate in the main multicentre trial. The hospitals were located in Johannesburg, South Africa and Khon Kaen, Thailand.. Women during second stage of labour about to be delivered vaginally.. The trial had three arms: misoprostol 400 microg versus misoprostol 600 microg versus intramuscular oxytocin 10 IU. Each group received an injection and three tablets immediately after the birth of the baby.. Shivering and pyrexia rates were the main outcome measures. Data on other side effects and characteristics of the third stage of labour were also collected. Side effects were noted as none, mild, moderate or severe.. Both shivering and pyrexia (temperature > 38 degrees C) were most common in the 600 microg misoprostol group (28% and 7.5% for shivering and pyrexia, respectively) compared with 400 microg misoprostol (19% and 2%), and the oxytocin group (12.5% and 3%). The increase in shivering in the misoprostol 600 microg group was due primarily to a higher rate of moderate shivering. None of the women had a temperature > 40 degrees C. There were no increases in severe side effects and other adverse events in the misoprostol 600 microg group.. When used in the management of the third stage of labour oral misoprostol is associated with an increase in the rate of moderate shivering and pyrexia which seems to be dose-related. Based on the results of this pilot trial, the Steering Committee has decided to use 600 microg misoprostol in the main trial, comparing it with oxytocin, in order to achieve higher effectiveness.

Topics: Adult; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fever; Humans; Misoprostol; Obstetric Labor Complications; Oxytocics; Oxytocin; Pilot Projects; Pregnancy; Shivering

In order to evaluate a dose-related response of cervical ripening and labor induction to a prostaglandin E2 (PGE2) gel, 110 women with uncomplicated postdate pregnancies and unripe cervices received intracervically 0.5 mg PGE2 (n = 40), 1.5 mg PGE2 (n = 35) or 2.5 mg PGE2 (n = 35). The failure rate in terms of cervical ripening was similar in all groups. Labor characteristics such as the duration of the latent phase as well as the total length of labor, the cesarean-section rate, instrumental deliveries and neonatal outcome were similar in all groups. The number of women who required oxytocin for labor augmentation was negatively correlated to the dose of PGE2 (p < 0.05). In addition, 3 out of 35 women in the 2.5-mg group presented hypertonic uterine activity. The increase in the dose of PGE2 gel did not increase the possibility for a vaginal delivery, but reduced the requirement for oxytocin while increasing hypertonic uterine action.

Topics: Administration, Intravaginal; Adult; Cervix Uteri; Dinoprostone; Dose-Response Relationship, Drug; Female; Fetal Distress; Fever; Humans; Labor, Induced; Oxytocin; Parity; Pregnancy; Pregnancy Outcome; Pregnancy, Prolonged; Uterine Contraction; Vaginal Creams, Foams, and Jellies

To compare conservative versus prostaglandin management of prelabour rupture of the membranes (PROM) in healthy primigravid women at term.. A prospective randomized study.. Labour Ward, Aberdeen Maternity Hospital.. 230 primigravidae at terms with PROM, 115 allocated to be treated conservatively and 115 to be managed with prostaglandin treatment.. In the conservatively managed group the women were observed for up to 24 h after hospital admission with PROM. The actively managed group had PGE2 gel (2 mg) instilled into the posterior fornix and if contractions had not commenced, a further dose of PGE2 gel (1 mg) was instilled 6 h later. In both groups, if labour had not established 24 h after admission, intravenous oxytocin was given in escalating doses.. PROM to delivery interval, oxytocin augmentation, mode of delivery, maternal and neonatal infective morbidity.. There was a significant reduction in the PROM to delivery interval in the women managed actively with PGE2 gel and fewer women in the PGE2 group required oxytocin augmentation (31% vs 51%). The two managements groups were comparable for intrapartum analgesia, antibiotic treatment, babies requiring admission to the special care nursery unit and delivery by caesarean section.. The early use of prostaglandin is associated with a significant reduction in PROM to delivery interval without a significant increase in infective morbidity or caesarean section rate. However, the advantages of the conservative approach should not be overlooked. More work is still needed in the management of those women where uterine activity fails to establish within 24 h after PROM.

Topics: Administration, Intravaginal; Adult; Apgar Score; Bacterial Infections; Cesarean Section; Dinoprostone; Female; Fetal Membranes, Premature Rupture; Fever; Humans; Infant, Newborn; Injections, Intravenous; Labor Stage, Second; Oxytocin; Pregnancy; Prospective Studies; Uterine Contraction

Topics: Abortion, Induced; Adult; Female; Fetus; Fever; Humans; Misoprostol; Oxytocin; Pregnancy; Pregnancy Trimester, Second; Retrospective Studies

Oxytocin (OT) has been reported to have a protective effect in lipopolysaccharide-induced experimental acute lung injury (ALI). However, its role in heat stroke-related ALI has never been investigated. Herein, we aimed to explore the therapeutic effects and potential mechanism of action of OT on heat-induced ALI. Rats were treated with OT 60 min before the start of heat stress (42 °C for 80 min). Twenty minutes after the termination of heat stress, the effects of OT on lung histopathological changes, edema, acute pleurisy and the bronchoalveolar fluid levels of inflammatory cytokines and indicators of ischemia, cellular damage, and oxidative damage were assessed. We also evaluated the influence of OT pretreatment on heat-induced hypotension, hyperthermia, ALI score, and death in a rat model of heat stroke. The results showed that OT significantly reduced heat-induced lung edema, neutrophil infiltration, hemorrhage score, myeloperoxidase activity, ischemia, and the levels of inflammatory and oxidative damage markers in bronchoalveolar lavage fluid. The survival assessment confirmed the pathophysiological and biochemical results. An OT receptor antagonist (L-368,899) was administered 10 min before the OT injection to further demonstrate the role of OT in heat-induced ALI. The results showed that OT could not protect against the aforementioned heat stroke responses in rats treated with L-368,899. Interestingly, OT treatment 80 min after the start of heat shock did not affect survival. In conclusion, our data indicate that OT pretreatment can reduce the ischemic, inflammatory and oxidative responses related to heat-induced ALI in rats.

Topics: Acute Lung Injury; Animals; Bronchoalveolar Lavage Fluid; Camphanes; Cytokines; Disease Models, Animal; Fever; Heat Stroke; Heat-Shock Response; Hypotension; Lung; Male; Neutrophil Infiltration; Oxytocin; Peroxidase; Piperazines; Protective Agents; Pulmonary Edema; Rats; Rats, Sprague-Dawley; Receptors, Oxytocin; Survival Analysis

The objective of this study is to study the fetal scalp temperature (FST) and maternal axillary temperature (MAT) during vaginal delivery relative to progression of labor, uterine contractions (UC) and epidural analgesia (EDA), and to construct normal temperature reference ranges related to stage of labor.. Temperatures were recorded continuously in labor of 132 women with a bi-metal temperature sensor attached to the axilla (MAT) and a similar sensor mounted in a scalp electrode (FST). The temperature data were stored electronically and analyzed offline at cervical dilatations of 2-3, 5, 7-8, and 10 cm, and at full retraction. The FST was read before, at increasing, at peak, at decreasing, and after UC. The MAT and FST curves were compared with mixed-effect models statistics for repeated measurements. A two-tailed p <.05 was considered significant.. The FST did not vary during UC (p = .24). Both FST and MAT increased linearly by progression of labor (both p < .001). The increases in temperatures were greater with EDA than without (p < .001).. During UC, the FST showed no alteration. Both FST and MAT increased significantly by progression of labor, and significantly more in the presence of EDA. The presented normal temperature reference ranges can be used for future research.

Topics: Adolescent; Adult; Anesthesia, Epidural; Body Temperature; Female; Fetal Monitoring; Fever; Humans; Labor, Obstetric; Oxytocin; Pregnancy; Prospective Studies; Uterine Contraction; Young Adult

To determine factors associated with intrapartum fever and to examine associated maternal and neonatal outcomes.. Retrospective study of patients between 360/7 and 420/7 gestational weeks who entered spontaneous or induced active labor and developed temperature ≥38°C; a similar group that did not develop fever were controls. Univariate and multivariate analyses were performed with p < 0.05 as significant.. Fifty-four febrile patients and 306 nonfebrile controls met inclusion criteria. Nulligravidity (45.8 vs. 77.8%, p < 0.001), length of first stage ≥720 min (OR 3.59, 95% CI 1.97-6.55, p < 0.001), length of second stage ≥120 min (OR 4.76, 95% CI 2.29-9.89, p < 0.001), membrane rupture ≥240 min (46.4 vs. 79.6%, p < 0.001), increasing number of vaginal exams (4 vs. 6, p < 0.001), oxytocin (44.8 vs. 63.0%, p = 0.014), and meperidine (14.7 vs. 35.2%, p < 0.001) were all associated with intrapartum fever. Associated morbidity included cesarean delivery (22.5 vs. 44.4%, p = 0.001), Apgar score <7 at 5 min (0.7 vs. 5.6%, p = 0.011), and neonatal intensive care unit admission (9.5 vs. 51.9%, p < 0.001).. We have identified several noninfectious factors that are associated with intrapartum fever. Modification of risk factors may improve both maternal and neonatal outcomes.

Topics: Adult; Analgesics, Opioid; Apgar Score; Cesarean Section; Female; Fever; Gestational Age; Humans; Infant, Newborn; Intensive Care, Neonatal; Labor, Induced; Meperidine; Obstetric Labor Complications; Oxytocin; Pregnancy; Pregnancy Outcome; Retrospective Studies; Risk Factors

Uterine atony is the most frequent cause of post-partum haemorrhage. In France, the management is based on early administration of oxytocic agents and prostaglandin analogues (sulprostone-Nalador®). We report the case of a 30-year-old woman who presented soon after administration of sulprostone, a severe hyperthermia with neurological disorders. A complete reversibility was observed a few hours after discontinuation of sulprostone administration. Other causes were eliminated by biological and radiological findings.

Topics: Adult; Anesthesia, Obstetrical; C-Reactive Protein; Cesarean Section; Dinoprostone; Female; Fever; Hemodynamics; Humans; Infant, Newborn; Nervous System Diseases; Oxytocin; Postoperative Complications; Postpartum Hemorrhage; Pregnancy; Uterine Inertia

To analyze outcomes after second-stage labor beyond 3 hours and determine if prolonged second stages were intentional.. Retrospective cohort analysis of maternal and neonatal outcomes in nulliparous women based on second-stage duration. Medical records were reviewed for management decisions in women with second stages ≥4 hours; all other outcomes were accessed via computerized obstetric database.. Second stage exceeding 3 hours occurred in 1489 (7%) of 21,991 pregnancies analyzed. Of the 427 (2%) with second stages ≥4 hours, 315 (74%) reached 4 hours unintentionally, after a decision for operative delivery had been made. Only 34 (8%) women were intentionally allowed to continue second-stage labor beyond 4 hours, and half of these ultimately required cesarean. Indices of maternal and neonatal morbidity were significantly increased when second stages exceeded 3 hours.. Most second stages reaching 4 hours are unintentional, occurring while awaiting an previously decided upon operative delivery. Maternal and neonatal morbidities are significantly increased with second stages beyond 3 hours.

Topics: Adolescent; Adult; Analgesia, Epidural; Analgesia, Obstetrical; Blood Transfusion; Cesarean Section; Chorioamnionitis; Cohort Studies; Female; Fetal Monitoring; Fever; Heart Rate, Fetal; Humans; Hypovolemia; Hysterectomy; Labor Stage, Second; Lacerations; Oxytocics; Oxytocin; Parity; Perineum; Pregnancy; Retrospective Studies; Time Factors; Young Adult

In recent years, several reports have indicated that maternal temperature elevations during labor may also be observed in the absence of an infection. Presumed noninfectious causes of maternal temperature elevations include epidural analgesia, endogenous heat production generated by the contracting uterus, and delivery in an overheated room. To investigate the potential causes of noninfectious maternal temperature changes during labor, we conducted a prospective cohort study in women scheduled for labor induction.. We recorded hourly oral temperatures from admission to delivery. We calculated whether temperature changed during labor in 81 women. We then determined if body mass index, and duration of labor, or time from rupture of amniotic sac to delivery, or oxytocin dose, would affect maternal temperature. To evaluate the possible role of epidural analgesia, we compared the temperature slope before and after starting epidural analgesia.. We observed an overall significant linear trend of temperature over time with an estimated temperature slope of +0.017°C/h (P = 0.0093). Patients with a positive temperature trend had also a significantly longer time from rupture of membranes to delivery (P = 0.0077) and a higher body mass index (P = 0.0067). Epidural analgesia had no effect on the temperature trend.. In our cohort of patients, there was an overall significant linear trend of temperature over time after correcting for heterogeneity among patients. Temperature increase was associated with higher body mass index values and longer time from rupture of membranes to delivery. Epidural analgesia had no effect on maternal temperature.

Topics: Amnion; Analgesia, Epidural; Analgesia, Obstetrical; Analgesics; Body Mass Index; Body Temperature; Cohort Studies; Female; Fever; Humans; Labor, Obstetric; Mothers; Obstetric Labor Complications; Oxytocics; Oxytocin; Pregnancy; Prospective Studies; Time Factors

Maternal intrapartum fever has been associated with an increased incidence of neonatal morbidity. In this retrospective cohort study, we evaluated whether intravenous oxytocin has a fever-inducing effect. Oxytocin augments secretion of prostaglandins E(2) and F(2α) which are inflammatory mediators known to elevate body temperature.. Between January 2005 and June 2008, 279 patients were admitted with mid-trimester fetal demise. Patients meeting inclusion criteria included 34 women who received a high-dose intravenous oxytocin regimen and 29 patients who delivered after spontaneous labor without the need for augmentation. Oral temperatures were measured on admission and at delivery.. The median length of oxytocin infusion was 5.3h. The calculated temperature change was -0.14°C in the oxytocin group and +0.12°C in the control group. These findings were confirmed in a model adjusted for patients' white blood cell count and duration of labor. We did not observe an effect of analgesia type, epidural versus intravenous analgesia, on duration of labor.. Based on this comparative analysis of pregnant women who received high-doses of oxytocin, we found insufficient evidence to support that high-dose intravenous oxytocin elevates intrapartum maternal temperature.

Topics: Adult; Body Temperature; Cohort Studies; Female; Fetal Death; Fever; Humans; Infusions, Intravenous; Leukocyte Count; Linear Models; Oxytocics; Oxytocin; Pregnancy; Pregnancy Trimester, Second; Retrospective Studies

The widely reported effects of oxytocin (OT) on CNS function has generated considerable interest in the therapeutic potential for targeting this system for a variety of human psychiatric diseases, including anxiety disorders, autism, schizophrenia, and depression. The utility of synthetic OT, as both a research tool and neurotherapeutic, is limited by the physiochemical properties inherent in most neuropeptides, notably its short half-life and poor blood brain barrier penetration. Subsequently, the discovery and development of non-peptide molecules that act as selective agonists of the oxytocin receptor (OTR) has been an important goal of the field. In this study, we report the receptor and behavioral pharmacology of WAY-267464, a first generation small-molecule OTR agonist. WAY-267464 is a high-affinity, potent, and selective (vs. V1a, V2, V1b) agonist of the OTR. In assays measuring both behavioral (four-plate test, elevated zero maze) and autonomic (stress-induced hyperthermia) parameters of the anxiety response, WAY-267464 exhibits an anxiolytic-like profile similar to OT. We have demonstrated that the anxiolytic-like profile of WAY-267464 is mediated through central sites of action. WAY-267464 also significantly reverses disruption in prepulse inhibition of the acoustic startle reflex induced by either MK-801 or amphetamine, similar to the antipsychotic-like effects previously reported for OT. Interestingly, in the mouse tail suspension test, WAY-267464 failed to produce changes in immobility that are seen with OT, raising the question of whether the antidepressant-like activity of OT may be working independently of the OTR. A selective OTR antagonist also failed to block the effects of OT on immobility in the TST. The significance of these findings for shaping the clinical development of OTR agonists is discussed.

Topics: Acoustic Stimulation; Animals; Anti-Anxiety Agents; Avoidance Learning; Behavior, Animal; Benzodiazepines; CHO Cells; Cricetinae; Cricetulus; Fever; Hindlimb Suspension; Humans; Male; Maze Learning; Mice; Mice, Inbred C57BL; Neural Inhibition; Oxytocin; Protein Binding; Pyrazoles; Rats; Rats, Sprague-Dawley; Receptors, Oxytocin; Reflex, Startle; Stress, Psychological

Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. BTBR T+tf/J (BTBR) is an inbred mouse strain that displays robust behavioral phenotypes with analogies to all three of the diagnostic symptoms of autism, including low social interactions, reduced vocalizations in social settings, and high levels of repetitive self-grooming. Autism-relevant phenotypes in BTBR offer translational tools to discover neurochemical mechanisms underlying unusual mouse behaviors relevant to symptoms of autism. Because repetitive self-grooming in mice may be a displacement behavior elevated by stressors, we investigated neuroendocrine markers of stress and behavioral reactivity to stressors in BTBR mice, as compared to C57BL/6J (B6), a standard inbred strain with high sociability. Radioimmunoassays replicated previous findings that circulating corticosterone is higher in BTBR than in B6. Higher basal glucocorticoid receptor mRNA and higher oxytocin peptide levels were detected in the brains of BTBR as compared to B6. No significant differences were detected in corticotrophin releasing factor (CRF) peptide or CRF mRNA. In response to behavioral stressors, BTBR and B6 were generally similar on behavioral tasks including stress-induced hyperthermia, elevated plus-maze, light ↔ dark exploration, tail flick, acoustic startle and prepulse inhibition. BTBR displayed less reactivity than B6 to a noxious thermal stimulus in the hot plate, and less immobility than B6 in both the forced swim and tail suspension depression-related tasks. BTBR, therefore, exhibited lower depression-like scores than B6 on two standard tests sensitive to antidepressants, did not differ from B6 on two well-validated anxiety-like behaviors, and did not exhibit unusual stress reactivity to sensory stimuli. Our findings support the interpretation that autism-relevant social deficits, vocalizations, and repetitive behaviors are not the result of abnormal stress reactivity in the BTBR mouse model of autism.

Topics: Adaptation, Ocular; Animals; Autistic Disorder; Corticosterone; Corticotropin-Releasing Hormone; Disease Models, Animal; Fever; Hindlimb Suspension; Interpersonal Relations; Maze Learning; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Oxytocin; Pain Threshold; Radioimmunoassay; Receptors, Glucocorticoid; Reflex, Acoustic; RNA, Messenger; Stress, Psychological

Oxytocin (OXT) that is released centrally is believed to be anxiolytic and have stress-attenuating effects. Oxytocin knockout (OXTKO) mice, a genetic model of OXT deficiency, have heightened corticosterone release after acute stress and greater anxiety-related behaviour in an elevated plus maze compared to wild-type (WT) mice. In the present set of experiments, we recorded the rise in body temperature, referred to as stress-induced hyperthermia (SIH), following transfer to a metabolic cage, which triggers both anxiety and corticosterone release in mice. SIH is a marker of activation of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system. Because corticosterone release after acute stress is typically greater in OXTKO than in WT mice, we measured SIH as a surrogate marker of corticosterone release. Following transfer to a metabolic cage, both OXTKO and WT mice increased body temperature, but to the same degree. Pregnant mice, which are known to have blunted corticosterone release to acute stress, had attenuated SIH after transfer to a metabolic cage compared to cycling mice, but both genotypes manifested the same degree of attenuation. In addition, we tested the effects of the cannabinoid receptor 1 (CBR1) antagonist/inverse agonist (AM251) upon feeding and SIH in OXTKO versus WT mice. CBR1 antagonists are known to diminish food intake and to enhance corticosterone both basally and following acute stress. Although AM251 blunted food intake, the effect was equivalent in both genotypes. The agent did not affect the SIH response compared to mice treated with vehicle. SIH is excellent for defining anxiolytic or blunted corticosterone responses (such as the stress hyporesponsiveness of pregnancy), but is limited in its ability to detect the heightened corticosterone responses that have been reported in OXTKO mice following exposure to psychogenic stress.

Topics: Animals; Body Temperature; Corticosterone; Crosses, Genetic; Environment; Feeding Behavior; Female; Fever; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Oxytocin; Piperidines; Pregnancy; Pyrazoles; Receptor, Cannabinoid, CB1; Stress, Psychological

Retrospective study of 744 women at the Virgen del Camino Hospital in Pamplona concerning two variants for the active treatment of premature rupture of the membranes (PROM). The main purpose of the study was to assess the differences between two variants for the active treatment of PROM at term in pregnant women with negative vaginal-rectal culture screening for Group B Streptococci, and a Bishop test of 4 or less on admission.. Retrospective study of 744 patients with single pregnancy at term, PROM, and Bishop test <4. The patients, who were not randomised, were treated with dinoprostone (Propess) or expectant therapy, according to the physician's choice. Induction with oxytocin was started 12 h after PROM. Qualitative data were analysed using the chi(2) test, while quantitative data were analysed using the Student's t-test or the Mann-Whitney U-test according to the distribution of the variables. Regression models were applied to correct the biases caused by confounding variables.. Of the 744 patients, the cervix of 13% was maturated with pericervical dinoprostone, while 87% were subject to expectant management until 12 h after rupture of the membranes. The time of dilation and the time until labour were significantly shorter in the dinoprostone group (p=0.0). The rate of caesarean sections was also lower in the dinoprostone group at 9.3% compared to 17.6% in the expectant management group, reaching statistical significance (p=0.04). There were no differences in the parameters of fetal well being (Apgar and pH).. The use of therapy with dinoprostone in patients with PROM could be a safe method and more effective than expectant management.

Topics: Administration, Intravaginal; Adult; Anti-Bacterial Agents; Cesarean Section; Delayed-Action Preparations; Dinoprostone; Female; Fetal Membranes, Premature Rupture; Fever; Humans; Labor Stage, First; Labor, Induced; Linear Models; Oxytocics; Oxytocin; Parity; Pregnancy; Retrospective Studies; Time Factors

Topics: Animals; Cattle; Cattle Diseases; Estrogens; Female; Fever; Glucose; Lactation; Oxytocin; Postpartum Period; Time Factors

Maternal fever is associated with chorioamnionitis and has been linked to labour epidural analgesia (LEA). The purpose of this study was to determine possible associations between LEA and chorioamnionitis, maternal fever, operative delivery rate, and neonatal outcome.. Data from 14,073 patients were entered into a database over a two-year period. From this database, 62 nulliparous parturients with clinical chorioamnionitis (amnionitis), but without LEA were identified (Group I). Two other groups who received LEA were matched for parity and gestation: Group II - LEA with concomitant amnionitis (n=50) and, Group III - LEA without concomitant amnionitis (n=201). The diagnosis of chorioamnionitis was confirmed by histologic examination. Results are expressed as mean +/- SD and analyzed at P <0.05 using ANOVA or Chi-square.. No differences were noted among the groups in the operative delivery rate or Apgar scores at five minutes. The percentage of patients with maternal fever during labour (38.0 degrees C) with amnionitis was significantly less in Group III compared to the other groups (100% in both Groups I and II vs 1.0% in Group III; P=0.000). Likewise, Group III had a lower percentage of neonates with Apgar scores <7 at one minute (35.5% in Group I, 20.0% in Group II, 17.4% in Group III; P=0.010). The percentage of histologic chorioamnionitis was significantly higher in both amnionitis groups compared to Group III (67.7% in Group I, 56.0% in Group II, 4.0% in Group III; P=0.000).. LEA without chorioamnionitis is not associated with maternal fever (38.0 degrees C), increased operative delivery rates or low Apgar scores.

Topics: Adult; Analgesia, Epidural; Analgesia, Obstetrical; Chorioamnionitis; Databases, Factual; Female; Fever; Humans; Infant, Newborn; Obstetric Labor Complications; Oxytocics; Oxytocin; Pregnancy; Pregnancy Outcome; Retrospective Studies; Streptococcal Infections

Neuropeptide and cyclooxygenase (Cox) gene expression was examined in the brains of catheterized pigs killed 30 or 120 min after intravenous injection of a low (20 microg) dose of lipopolysaccharide endotoxin (LPS), previously demonstrated to induce fever in this species. In the paraventricular hypothalamic nucleus (PVN), corticotrophin releasing hormone (CRH) mRNA was shown to be present in the pars parvocellularis but was not upregulated 30 or 120 min after 20 microg LPS, or 90 min after 60 microg LPS; there was also no change in proopiomelanocortin (POMC) message in the anterior pituitary (AP). Similarly, expression of mRNAs for lysine vasopressin (LVP) or oxytocin (OT) did not change in the PVN after LPS (20 microg), although LVP message was increased (p<0.05) at 30 min in the hypothalamic supraoptic nucleus (SON). Expression of Cox-1 and Cox-2 genes was quantified in the organum vasculosum lamina terminalis (OVLT) and choroid plexus (CP) in an attempt to determine whether altered expression of prostaglandin (PG) synthetic enzymes in brain vasculature is involved in LPS fever. Although vascular endothelial cells in both structures expressed Cox-1 and Cox-2 mRNAs, neither increased in the OVLT following LPS. However, in the CP, Cox-1 mRNA was enhanced (p<0.05) at 30 and 120 min after LPS injection and Cox-2 showed a similar (NS) change. These results provide the first description of CRH and Cox gene expression in the porcine brain. They also suggest that LPS may influence the activity of genes controlling LVP synthesis in the hypothalamus and PG production by the brain vasculature.

Topics: Animals; Autoradiography; Corticotropin-Releasing Hormone; Cyclooxygenase 1; Cyclooxygenase 2; Endothelium, Vascular; Fever; Gene Expression; Hypothalamus, Anterior; Isoenzymes; Lipopolysaccharides; Lypressin; Oxytocin; Paraventricular Hypothalamic Nucleus; Pituitary Gland, Anterior; Pro-Opiomelanocortin; Prosencephalon; Prostaglandin-Endoperoxide Synthases; RNA, Messenger; Supraoptic Nucleus; Swine; Vasopressins

Low intravenous doses of endotoxin [lipopolysaccharide (LPS), 0.7 microgram/kg] induce monophasic fever, increase anterior and posterior pituitary hormone release, and enhance hypothalamic c-Fos expression in pigs, all of which can be prevented by indomethacin (Ind). The present study shows that the synthetic corticosteroid dexamethasone (Dex, 5 mg/kg) has a similar action to Ind and, when given alone, lowers core temperature. In addition, the corticosteroid synthesis inhibitor metyrapone (Met, 3.3 mg/kg, every one-half hour) reduces LPS fever and amplifies the effect of LPS on vasopressin, but not on oxytocin, release. The similar actions of Dex and Ind suggest that phospholipase A2 pathways controlling prostaglandin synthesis mediate the responses of prepubertal pigs to immunological challenge with LPS. The increased vasopressin release induced when animals receiving Met are also given LPS supports findings in other nonrodent species indicating an inverse relationship between cortisol and vasopressin. The attenuation of LPS fever by Met is suggestive of an endogenous antipyretic mechanism associated with enhanced neurohypophysial vasopressin secretion.

Topics: Analgesics, Non-Narcotic; Animals; Body Temperature Regulation; Dexamethasone; Endotoxins; Escherichia coli; Fever; Genes, fos; Hydrocortisone; Indomethacin; Lipopolysaccharides; Lypressin; Male; Metyrapone; Oxytocin; Pituitary-Adrenal System; Proto-Oncogene Proteins c-fos; Swine; Time Factors

Topics: Animals; Endotoxins; Fever; Interleukin-1; Male; Oxytocin; Rabbits

Urethan-anesthetized rats were used to identify effective stimuli for the release of the peptides arginine vasopressin (AVP) and oxytocin into the ventral septal area (VSA) of the brain. Febrile responses to intracerebroventricular injection of prostaglandin E1 (PGE1) were observed in rats whose body temperatures were maintained at 35, 37, or 39 degrees C. Microinjection of the AVP antagonist d(CH2)5Tyr(Me)AVP into the VSA enhanced fever only when PGE1 administration was associated with a significant rise in body temperature. Passive elevation ("artificial fever") or reduction of body temperature in the absence of a PGE1 stimulus was not affected by the antagonist. Push-pull perfusion of the VSA and the dorsal hippocampus, followed by radioimmunoassay of perfusates for AVP and oxytocin, revealed enhanced release into the VSA of AVP only when PGE1 administration was followed by a rise in body temperature. Oxytocin was released whenever body temperature was raised. Peptide concentrations in simultaneous perfusates of dorsal hippocampus did not change in response to PGE1 administration or to passive elevation of body temperature. We conclude that AVP is released into the VSA, but not the dorsal hippocampus, of the rat during a fever induced by PGE1. Oxytocin is released into the VSA, but not the hippocampus, when temperature is elevated.

Topics: Alprostadil; Animals; Arginine Vasopressin; Body Temperature; Dose-Response Relationship, Drug; Fever; Injections, Intraventricular; Male; Oxytocin; Rats; Rats, Inbred Strains; Septum Pellucidum

The infusion of either 30 micrograms/microliters (approx. 100 micrograms/kg/h) of sodium salicylate or 10 ng/microliters (10(-5) M) arginine vasopressin within the ventral septal area of the Brattleboro rat brain reduced a centrally induced prostaglandin E1 (PGE1) hyperthermia when compared with infusions of artificial cerebrospinal fluid. Conversely, the infusion of a related peptide, oxytocin (10 ng/microliters (10(-5) M), or 33 ng/kg/h) failed to alter the rise in core temperature following the PGE1 injection. These results suggest that the vasopressin receptors reported to be present in the Brattleboro rat may respond normally to exogenously administered vasopressin, thus allowing for the antipyretic action. Moreover, the antipyretic effects of sodium salicylate suggest that aspirin-like drugs may induce the release of alpha-melanocyte-stimulating hormone which, in turn, attenuates the PGE1-evoked fever. Given recent evidence, however, which suggests that the Brattleboro rat may contain vasopressin both peripherally and within the brain, the antipyretic action of sodium salicylate may be alternatively explained through the endogenous release of vasopressin.

Topics: Alprostadil; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arginine Vasopressin; Fever; Male; Oxytocin; Rats; Rats, Brattleboro; Septal Nuclei; Sodium Salicylate

Effects of oxytocin on pyrogenal or endogenous pyrogen-induced fever were studied. Intramuscular injection of oxytocin (0.2 micrograms/kg every half an hour) did not significantly affect the pattern of pyrogenal-induced fever. Constant intravenous injection of oxytocin (0.4 and 4 micrograms/kg/h) 2-4.5 h after pyrogenal decreased the rectal temperature, on an average, by 24% and 31%, respectively. Endogenous pyrogen fever was not attenuated by intravenous oxytocin (4 micrograms/kg/h). The antipyrogenic effect of oxytocin is related to inhibition of endogenous pyrogen synthesis rather than to blockade of its action, which is indicated by a decreased second peak of the temperature curve, inhibition of endogenous pyrogen synthesis in vitro, and persistence of the hyperthermic effect of endogenous pyrogen.

Topics: Animals; Cells, Cultured; Fever; Injections, Intramuscular; Leukocytes, Mononuclear; Lipopolysaccharides; Oxytocin; Pyrogens; Rabbits; Time Factors

The antipyretic action of central arginine vasopressin (AVP) was investigated in mongrel cats. Control push-pull perfusions in the ventral septal area (VSA), with the carrier vehicle alone, did not affect the febrile response to Salmonella typhosa administered intracerebroventricularly. When AVP was perfused similarly, the fever was suppressed in a dose-related manner. The lower dose of AVP delayed the onset of fever, whereas the higher concentration of AVP suppressed consistently the fever throughout the period of administration. Another neurohypophyseal peptide, oxytocin, was ineffective in altering the febrile response at the dose tested. The regions of greatest sensitivity to the antipyretic action of AVP are located ventral to the septum, bounded by the diagonal bands of Broca, extending into the posterior septal nucleus. Sites at which AVP was ineffective in producing antipyresis were found more dorsal and lateral to these. Thus, AVP suppresses fever in the cat via an action in the VSA that is dose related, and site specific and peptide specific. These data provide further evidence that AVP may be involved in the central mechanisms which control core temperature.

Topics: Animals; Arginine Vasopressin; Cats; Female; Fever; Injections, Intraventricular; Male; Oxytocin; Septal Nuclei

Vasopressin and oxytocin modulate memory processes which effects are dissociated from the typical peripheral endocrine effects of these neuropeptides. Recently, vasopressin has been implicated in the regulation of body temperature. In view of this, experiments were designed to determine whether the antipyretic effect of vasopressin was related to the action of the neuropeptide on memory processes. Fever was induced in rats by intracerebroventricular (i.c.v.) injection of 10 ng bacterial endotoxin (ET), which resulted in a rapid rise in colonic temperature. A second i.c.v. injection 15 min after ET administration of graded amounts (0.01, 0,1, 1 and 100 ng) or arginine-vasopressin (AVP) suppresses ET-induced fever in a dose-dependent manner, 1 ng being the minimally effective amount. Equivalent amounts of des-9-glycinamide-arginine-vasopressin (DG-AVP) or oxytocin (OXT) were ineffective. Large amounts (1,000 ng) of the latter two peptides, however, transiently mimicked the effect of AVP. On one-trial learning passive avoidance behavior, the neurohypophyseal peptides exerted a completely different pattern of effects. AVP and DG-AVP induced a dose-dependent facilitation, while OXT resulted in a dose-dependent attenuation of passive avoidance behavior. These findings suggest that AVP-induced antipyresis is related to the hormonally active AVP and dissociated from the effects of neurohypophyseal hormones and hormone fragments on other CNS processes-like learning and memory.

Topics: Animals; Arginine Vasopressin; Avoidance Learning; Dose-Response Relationship, Drug; Endotoxins; Escherichia coli; Fever; Male; Oxytocin; Rats; Rats, Inbred Strains

The recent Food and Drug Administration's approval of prostaglandin E2 (PGE2) vaginal suppositories provides the clinician with a technique for the immediate management of missed abortion and intrauterine fetal death (IUFD). During a 4-year period at our institution, 78 of 80 patients with gestations ranging from 13 to 42 weeks had pregnancy successfully terminated with PGE2 suppositories with a dose schedule of 20 mg every 2 hours. The mean interval from induction to delivery of the fetus was 8.9 hours. Fifty percent of the patients spontaneously expelled the placenta; active intervention to remove the placenta within 2 hours of delivery of the fetus is recommended to avoid excessive vaginal bleeding. The most frequently encountered side effect was a temperature elevation, which was managed by less frequent administration of the prostaglandin. Gastrointestinal side effects were minimized by premedication with antidiarrheal and antiemetic agents, which also were administered during the induction period when indicated by the patient's symptoms. A concomitant oxytocin infusion was utilized in 38 patients. In gestations of less than 24 weeks the oxytocin was administered via intravenous drip at a rate of 10 U/hour. In the case of a patient with IUFD and a gestation of 24 weeks or more, oxytocin should be administered only with a constant-rate infusion pump starting at a dose schedule of 1 mU/minute with careful titration of the dose against the monitored uterine activity. The availability of the vaginal PGE2 suppositories for missed abortion and IUFD makes it important for the clinician to fully acquaint himself with the drug, its administration, effects, and side effects.

Topics: Abortion, Therapeutic; Adolescent; Adult; Drug Synergism; Drug Therapy, Combination; Female; Fetal Death; Fever; Gestational Age; Humans; Oxytocin; Pregnancy; Prostaglandins E; Suppositories; Time Factors; Vagina

The combined use of 40 mg of intraamniotic prostaglandin F2alpha, followed immediately by the insertion of one or more laminaria tents, and of a high-dose oxytocin infusion of 166 milliiunits per minute is a safe, effective, and efficient regime for midtrimester abortion. In 100 consecutive patients between 16 and 20 weeks of gestation, no failures occurred. The mean injection-abortion time was 15.7 hours. Six patients required the reinjection of 20 mg of prostaglandin F2alpha at 24 hours. The placenta was removed with instruments after four hours in 19 patients and done electively in seven patients in less than four hours. Physician-patient contacts were minimized, for all the abortion-initiating techniques were accomplished concomitantly, as opposed to regimes with laminaria pretreatment, or deliberately staggered prostaglandin injections were used. Most of the patients were able to be discharged after one day in the hospital. Thus, the patients' inconvenience and expense were minimized, with no sacrifice in safety.. To induce midtrimester abortion, 40 mg prostaglandin F2a (PGF2a) was instilled intraamniotically in 100 patients. Immediately thereafter from 1 to 6 laminaria tents were inserted into the cervix; 6 hours postinjection an iv infusion of oxytocin was begun at a rate of 100 ml/hour. All patients aborted successfully, 86% within 24 hours. 6 who did not abort by 24 hours were reinjected with 20 mg PGF2a. The mean injection-abortion interval was 15.7 hours. The placenta was removed surgically in 26% of the cases. Nausea and vomiting were frequent but were controlled by antiemetics, 11 patients developed fevers between 37.8-38.3 C, which were controlled by parenteral antibiotics. Heavy blood loss occurred in 2 patients. It is concluded that the combined regimen used in this series reduced the injection-abortion interval and frequent need for reinjection that occurs when PGF2a is used alone. The results compare favorably with those of saline-induced abortions and attendant morbidity.

Topics: Abortion, Induced; Adolescent; Adult; Female; Fever; Humans; Oxytocin; Pregnancy; Pregnancy Trimester, Second; Prostaglandins F; Seaweed; Time Factors

The hyperthermic effect of purified lipopolysaccharides (Pyrexal, Wander) was tested and analyzed in pregnant rabbits. The fever produced premature deliveries - probably caused by oxytocin, released from the posterior pituitary - in 50% of 40 tested rabbits on the 31st day of gestation. Injections of Syntocinon had a roughly equally strong effect. In control animals injection of saline did not accelerate delivery. The offspring of several animals, in which hyperthermia had been induced, were born dead. Fever during pregnancy thus can result in premature delivery and in injury to the fetus. Fever and febrile conditions occurring during pregnancy should therefore be treated as promptly and as effectively as possible.

Topics: Animals; Female; Fetal Death; Fever; Lipopolysaccharides; Obstetric Labor, Premature; Oxytocin; Pituitary Gland, Posterior; Pregnancy; Pregnancy Complications; Pyrogens; Rabbits; Sodium Chloride

In a group of 84 women in the second trimester of pregnancy abortion was induced by intramniotic transabdominal instillation of 20 per cent NaCl. In a second group of 91 women the abortion was induced by means of extraamniotic physiological infusion of saline solution. The only complication observed in the first group was an increasing fever. In the second group there were better results. The fetus abortion was complete and in a shorter time. We assume that the new method is the method of choice because it gives no complications and may be easily performed. It may be used also in cases of missed abortion or intrauterine fetal death.. In a group of 84 women in the 2nd trimester of pregnancy, abortion was induced by intraamniotic transabdominal instillation of 20% NaCl. In a 2nd group of 91 women abortion was induced using extraamniotic physiological infusion of saline solution. The only complication observed in the 1st group was an increasing fever. In the 2nd group there were better results: fetus abortion was complete and in a shorter time. It is assumed that the new method is the method of choice because it gives no complications and may be easily performed. It may be used also in cases of missed abortion or intrauterine fetal death.

Topics: Abortion, Induced; Abortion, Missed; Adolescent; Adult; Female; Fetal Death; Fever; Humans; Oxytocin; Pregnancy; Pregnancy Trimester, Second; Saline Solution, Hypertonic; Sodium Chloride

The role of hyperthermia in the absence of infection has been investigated in the pregnant baboon. Twenty-three near term animals were used. Catheters were placed in maternal and fetal arteries and thermocouples implanted in maternal colon and fetal esophagus. Maternal temperature was raised to between 41 and 42 degrees Centigrade (C.), by applying external heat. The temperature gradient between fetus and mother (delta T F-M) was 0.47 degree C. under steady-state conditions with maternal temperature at 38 degrees C. and rose to 0.75 degree C. at 42 degrees C. Hyperthermia caused a twofold increase in uterine activity; a metabolic acidosis developed in the mother and a profound acidosis and hypoxia developed in the fetus. There was also a marked fall in blood pressure and an increase in heart rate in both mother and fetus; late deceleration of the fetal heart rate occurred at a higher oxygen level and pHa than has been observed under normothermic conditions.

Topics: Acidosis; Animals; Arrhythmias, Cardiac; Body Temperature; Female; Fetal Death; Fetal Diseases; Fetal Heart; Fever; Haplorhini; Heart Rate; Hypotension; Hypoxia; Labor, Obstetric; Oxytocin; Papio; Pregnancy; Pregnancy Complications; Vasopressins

One hundred women seeking interruption of pregnancy between 7-20 weeks were given prostaglandin E2 as a 20 mg vaginal suppository every four hours. Abortion was achieved within an arbitrary time limit of 36 hours in 97 patients and was complete in 76. Mean abortion intervals according to gestational length and parity ranged between 7.67 and 14.93 hours. Augmentive intravenous oxytocin, usually for placental expulsion, was given to 31 patients. Side-effects such as vomiting, diarrhea, and drug fever were encountered in the majority of patients but no sepsis was noted and no patient was transfused. The results are discussed with particular reference to other prostaglandin and hypertonic saline regimens for pregnancy interruption.. A series of 100 consecutive patients seeking pregnancy termination in pregnancy weeks 7-20 were treated with a schedule of 20-mg vaginal suppositories containing prostaglandin E2 (PGE2); the schedule was being tested for its efficacy, specifically reduction of total dose and related side effects. 94 of the 100 patients were aborted within an arbitrary time span of 36 hours. Total drug dose ranged from 40-160 mg. 31 patients received augmentative intravenous oxytocin. Induction-abortion interval varied from 6-32.5 hours. Of the 97 successes, 76 were classified as complete abortions. No significant differences were noted in midtrimester groups based on increasing parity, although parous patients in gestation week 13-15 seemed to have the best results, based on average interval time. No sepsis or need for transfusion was encountered. Side effects were emesis (n-75), diarrhea (n=17), and drug fever (n=66); less frequent side effects included headache, breast tenderness, and vasomotor symptoms (n=13, 1, and 1, respectively). The midtrimester patient results compared favorably with results of studies using saline for abortifacient. The number of first trimester patients was too small to yield any conclusion.

Topics: Abortion, Induced; Diarrhea; Female; Fever; Gestational Age; Humans; Oxytocin; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Prostaglandins; Vagina; Vomiting

PGE2 (prostaglandin E2), 20 mgm vaginal suppositories were administered to 2 groups of women seeking termination of pregnancy. 1 group had the suppository inserted inside a contraceptive diaphragm. Statistical comparisons were carried out for instillation to abortion time, side effects, and intrauterine pressure parameters. The usage of the diaphragm significantly reduced side effects, and resulted in an instillation to abortion time of 12.8 + or - 2.3 hours with no failures. The quantitative analysis of the uterine pressure recordings revealed activity significantly different than that seen with intraamniotic or extraovular PGF2alpha. The development of uterine activity simulates that of normal labor in that elevation of resting pressure does not occur and maximum active pressure evolves slowly.

Topics: Abortion, Induced; Adult; Contraceptive Devices; Diarrhea; Female; Fever; Humans; Muscle Contraction; Nausea; Oxytocin; Parity; Placenta; Pregnancy; Pressure; Progesterone; Prostaglandins; Stimulation, Chemical; Suppositories; Time Factors; Uterus; Vomiting

Topics: Abortion, Induced; Adolescent; Adult; Amniotic Fluid; Female; Fever; Gastrointestinal Diseases; Humans; Injections; Oxytocin; Pregnancy; Pregnancy Trimester, Second; Prostaglandins; Suppositories; Time Factors; Vagina

This study evaluates the efficacy of prostaglandin E2 (PGE2) as an oxytocic agent for the augmentation of delay in labor in 40 consecutive patients matched with another group of 40 patients (treated with intravenous oxytocin) as to age, parity, maturity, cervical dilation at time of augmentation, and analgesia. Delay in labor was diagnosed clinically when there was arrest in the descent of the presenting part and/or arrest of dilatation of the cervix. All patients were continuously monitored by means of a presenting part electrode and an intrauterine pressure catheter. Both oxytocin and PGE2 were administered via a constant infusion Palmer pump. Standard dosage increments were used until adequate contractions were achieved and no deleterious effect on the fetus was observed. 0.75 ml of 1 mg/ml ampoule of PGE2 in ethanol was diluted in 500 ml normal saline. Initial rate of infusion was 0.285 mcg/minute for a minimum of 30 minutes; the dose was subsequently doubled at intervals of 1 hour until adequate contractions were achieved. Initial rate for infusion for oxytocin was 2mu/minute; the dose was doubled every hour until adequate contractions were noted. Further cervical dilatation and descent of the presenting part occurred in all cases. Mean Apgar scores at 1 and 5 minutes respectively were 7.53 and 9.50 for the PG group, and 6.93 and 9.18 for the oxytocin group. No perinatal deaths occurred. Mean birthweight was 3.34 kg for the PG group and 3.39 kg for the oxytocin group. The oxytocin group exhibited significantly higher augmentation/delivery interval (7.32 hours vs. 5.2 for the PG group, p 0.001), mean basal uterine tone (13.23 vs. 7.38, p 0.001), mean frequency of contraction (4.39 vs. 3.61, p 0.01), and incidence of side effects (nausea, vomiting, and pyrexia). A fetal heart rate of less than 100 beats/minute was seen in 3 patients in the PG group and 7 in the oxytocin group.

Topics: Adult; Cesarean Section; Female; Fever; Gestational Age; Humans; Injections, Intravenous; Ketosis; Labor, Induced; Nausea; Obstetric Labor Complications; Oxytocin; Parity; Pregnancy; Prostaglandins; Statistics as Topic; Time Factors; Vomiting

Topics: Abortion, Induced; Abortion, Missed; Blood Pressure; Female; Fetal Death; Fever; Gestational Age; Humans; Hydatidiform Mole; Infusions, Parenteral; Oxytocin; Pregnancy; Prostaglandins; Pulse; Ultrasonics

Laminaria tents were used in addition to the technique of saline abortion in an attempt to shorten the injection-abortion interval. 142 second trimester therapeutic abortion patients, aged 13 to 40 years, agreed to participate in the study and were assigned to 1 of 4 groups. 72.2% were single, 27.8% were married, and the gestational age was from 13 to 20 weeks. Group 1 (26 primigravid patients) served as the control group (no oxytocin or laminaria tent used). Group 2 (25 primigravid patients) received an intravenous infusion of 20 units oxytocin/500 ml of 5% dextrose in water (beginning 12 hours after saline injection). Group 3 (50 primigravid patients) likewise received an infusion of 20 units oxytocin/500 ml of 5% dextrose in water (beginning 12 hours after saline injection), and in addition, a single medium, sterile laminaria tent was inserted at the time of the saline injection and removed 12 hours after insertion. Group 4 (41 multigravid patients) received treatment identical to that of Group 3. The mean interval time from injection to delivery in Group 1 was 41.26 hours. The mean injection-abortion time was 30.67 hours for Group 2, 26.84 hours for Group 3, and 22.96 hours for Group 4. The complication rate was significantly higher for both the oxytocin plus saline group (Group 2) as well as the laminaria plus saline groups (Groups 3 and 4). Group 3 experienced a 22% febrile rate, and 18% of patients required uterine curettage, while the figures for Group 4 were 12.2% and 24.4%, respectively. The laminaria tents did result in an 11% to 15% increase in complications in Groups 3 and 4, respectively, as compared with Group 2.

Topics: Abortion, Induced; Abortion, Therapeutic; Adolescent; Adult; Cervix Uteri; Curettage; Dilatation; Female; Fever; Humans; Oxytocin; Pregnancy; Seaweed; Sodium Chloride; Time Factors

Topics: Abortion, Induced; Adolescent; Adult; Amnion; Diarrhea; Female; Fever; Gestational Age; Humans; Hypotension; Injections; Methods; Oxytocin; Pregnancy; Prostaglandins; Time Factors; Vomiting

Topics: Abortion, Induced; Adolescent; Adult; Amniocentesis; Female; Fever; Gestational Age; Humans; Hypertonic Solutions; Infections; Injections, Intravenous; Oxytocin; Parity; Pregnancy; Sodium Chloride; Time Factors; Uterine Hemorrhage

This paper reports on the 1st experiences with extraamniotic administration of prostaglandin F2alpha (PGF2alpha) in induced abortion. It was found that the average dose in 30 primigravidae and 32 multigravidae was approximately equal. The average time of application was 28 hours 30 minutes in the 1st group and 24 hours 40 minutes in the 2nd. In 11 cases, PG application was followed by oxytocin infusion. The method proved successful in 83.5%; partial success was achieved in 15% of the cases. As partial successes, those cases in which the cervical channel was not completely opened, the evacuation of the uterus with instruments was still achievable without difficulty. 1 failure was observed. The highest doses were needed between weeks 13-16 of pregnancy (the small numbers did not allow the computation of statistical significance). Side effects were remarkably low (e.g., nausea, vomiting, profuse perspiration). A temporary rise in temperature above 38 degrees Celsius was noted in 8 women. Compared with reports from the literature, the dose, number, and degree of side effects were lower than those found with intravenous administration. In contrast to other authors, we administered single doses up to 2000 mcg, at which time the application should be diminished. (author's)

Topics: Abortion, Induced; Female; Fever; Gestational Age; Humans; Nausea; Oxytocin; Parity; Pregnancy; Prostaglandins; Sweating; Time Factors; Vomiting

Topics: Abortion, Induced; Adolescent; Adult; Age Factors; Amniocentesis; Blood Transfusion; Curettage; Dilatation; Female; Fever; Follow-Up Studies; Hemorrhage; Humans; Hypertonic Solutions; Infections; Labor, Induced; Outpatient Clinics, Hospital; Oxytocin; Parity; Pregnancy; Pregnancy Complications; Private Practice; Sodium Chloride; Time Factors

Topics: Adolescent; Adult; Amnion; Female; Fever; Humans; Injections, Intravenous; Labor, Induced; Oxytocin; Pregnancy; Prostaglandins; Time Factors

132 physically health patients (aged 12-41 years; 12-21 weeks gestation) were given intraamniotic PGF2alpha (prostaglandin F2alpha) for induction of midtrimester abortion. Analgesic agents and antiemetics were administered intramuscularly as needed. The patients were grouped as follows: 1) Group A (n=48), those who were given an initial dose of 25 mg PGF2a, then as needed; 2) Group B (n=43), initial dose of 30 mg, 25 mg at hour 6-8, and 25 mg at hour 24; 3) Group C (n=17), initial dose of 40 mg, subsequent 40 mg if unaborted at hour 24; and 4) Group D (n=24), initial dose of 40 mg, 10-25 mg at hour 6-8, additional 20 mg if unaborted at hour 24. A 94.7% incidence of abortion was achieved. In Group A, 29 had complete abortion, 16 incomplete, and 3 failures. Group B had 32 complete abortions, 8 incomplete, and 3 failures. Group C had 9 complete, 7 incomplete, and 1 failure. Corresponding figures for Group D were 19, 5 and 0 respectively. Average time to abortion ranged from 13 hours 22 minutes to 25 hours 33 minutes. The primary side effects of PGF2a were gastrointestinal (vomiting, diarrhea). 70% of patients vomited and 13.6% became febrile. Serious complications included sepsis, systemic reaction to prostaglandin, and cervical laceration. Advantages of intraamniotic PGF2a include ease of administration; generally short injection-abortion time; and its ability to induce myometrial contractions regardless of gestational size. However, the safety, convenience, and acceptability of PGF2 are yet to be established. The following guidelines are suggested for minimizing complications: 1) a test dose of 2.5 mg should be administered slowly over at least 1 minute, 2) fever should not be attributed to drug reaction but considered as suggestive evidence of developing infection, 3) patients unaborted at hour 24 should be considered as high risk with respect to potential failure to abort, development of infection, or cervical laceration, and 4) cervical inspection should be performed, especially in the nulliparous patient with a later gestation and a long labor.

Topics: Abortion, Therapeutic; Adolescent; Adult; Amniocentesis; Amnion; Child; Diarrhea; Endometritis; Female; Fever; Humans; Infections; Injections, Intravenous; Oxytocin; Parity; Pregnancy; Prostaglandins; Time Factors; Vomiting

This study determines the efficacy of extraamniotic administration of prostaglandins E2 and F2alpha (PGE2 and PGF2alpha) in abortion induction. The method consists of introducing a Foley catheter (14 gauge) through the cervix with the aid of a speculum so that the inflated balloon lies just within the internal os. The balloon volume varies from 30 ml at 12 weeks to 40 ml at 16 weeks gestation and over. Following an initial test dose, a fully effective dose of 200 mcg PGE2 or 750 mcg PGF2alpha is instilled for diffusion into the extraovular space; this dose is repeated at 2 hourly intervals. An automatic pump may also be used to administer the PG. The pattern of uterine contractility with this method is similar to that seen with intravenous therapy. Of 163 consecutive cases analyzed, 144 (88%) achieved abortions within 36 hours, 72% aborted within 24 hours and 94% within 48 hours. Mean abortion time was 22.2 hours. No significant difference was seen in the success rate or abortion time between 21 patients in their 1st trimester of pregnancy and 142 patients in the 2nd trimester. In primigravidas, abortion (within 36 hours) was successful in 87% of the cases; mean abortion time was 24.0 hours. Multigravidas had higher success rate (90%) and shorter mean abortion time (20.4 hours). Comparison of results obtained separately with PGF2alpha and PGE2 shows the superiority of PGE2. Of 93 patients receiving PGF2alpha, 85% aborted within 36 hours (mean abortion time, 24.9 hours). Of 70 PGE2-treated patients, 93% aborted within 36 hours (p=.01) (mean abortion time, 19.4 hours). When parity was considered, PGE2 came out superior again over PGF2alpha. In primigravidas, only 84% of PGF2alpha-treated patients had abortion within 36 hours compared to 90% for PGE2-treated patients. In multigravidas, the success rates at 36 hours were 86% for PGF2alpha and 95% for PGE2. Side effects were minimal. In another trial, intravenous oxytocin was used in addition to extraamniotic PG, resulting in a very substantial decrease in mean abortion time. This method is a simple, effective abortion technique which can be carried out in most cases on a 24-hour basis.

Topics: Abortion, Induced; Administration, Topical; Diarrhea; Dose-Response Relationship, Drug; Drug Synergism; Female; Fever; Humans; Oxytocin; Pregnancy; Prostaglandins; Prostaglandins E; Prostaglandins F; Time Factors; Uterus; Vomiting

Topics: Abortion, Induced; Administration, Topical; Female; Fever; Humans; Oxytocin; Pregnancy; Prostaglandins F; Time Factors; Uterus; Vomiting

Topics: Amnion; Apgar Score; Delivery, Obstetric; Female; Fetal Death; Fever; Gravitation; Humans; Infant Mortality; Infant, Newborn; Injections; Labor, Induced; Methods; Oxytocin; Postpartum Hemorrhage; Pregnancy; Prospective Studies; Puerperal Disorders; Time Factors

Topics: Abortion, Induced; Abortion, Therapeutic; Adolescent; Adult; Amnion; Child; Evaluation Studies as Topic; Female; Fever; Follow-Up Studies; Humans; Injections; Oxytocics; Oxytocin; Pain; Pregnancy; Prostaglandins; Time Factors; Vomiting

Topics: Abortion, Induced; Afibrinogenemia; Female; Fever; Humans; Hypertonic Solutions; Oxytocin; Postoperative Complications; Postpartum Hemorrhage; Pregnancy; Retrospective Studies; Sodium Chloride; Time Factors

Topics: Amnion; Asphyxia Neonatorum; Cesarean Section; Delivery, Obstetric; Female; Fever; Humans; Infant, Newborn; Labor Presentation; Labor, Induced; Obstetric Labor Complications; Oxytocin; Postpartum Hemorrhage; Pregnancy

Topics: Female; Fever; Humans; Intestinal Obstruction; Lactation; Methylergonovine; Oxytocin; Pregnancy; Puerperal Disorders; Thrombophlebitis; Uterus