oxytocin and Hypotension

Despite advances in health care and ample resources, post-partum hemorrhage (PPH) rates are increasing in high income countries. Although guidelines recommend therapeutic uterotonics, timing of administration is open to judgement and most often based on (inherently inaccurate) visual estimates of blood loss. With severe hemorrhage, every minute of delay can have significant consequences. Our objective was to examine the timing of uterotonic administration and its impact upon maternal outcomes. We hypothesized that increased time to uterotonic administration following the identification of PPH would be associated with a greater decline in hemoglobin (Hb) and higher odds of hypotension and transfusion.. We reviewed all cases of PPH that occurred at an academic centre between June 2015 and September 2017. All cases of primary PPH (i.e., those declared within 24 h of delivery with estimated blood loss [EBL] >500 mL for vaginal and >1000 mL for cesarean deliveries) were analyzed. Patient records were excluded if they were missing information regarding time of PPH declaration, uterotonic administration, and/or Hb measures, or if a pre-existing medical condition could have contributed to PPH.. Of 4397 births, there were 259 (5.9%) cases of primary PPH, of which 128 were included in this analysis. For these patients, each 5-minute delay in uterotonic treatment was associated with 26% higher odds of hypotension following delivery of any type. For vaginal deliveries (n = 86), each 5-minute delay was associated with 31% and 34% higher odds of hypotension and transfusion, respectively.. In this study, delay in administration of therapeutic uterotonics was associated with a higher incidence of hypotension and transfusion in primary PPH patients.

Topics: Ergonovine; Female; Humans; Hypotension; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy; Retrospective Studies

Topics: Anesthesia, Obstetrical; Anti-Bacterial Agents; Cesarean Section; Emergencies; Female; Humans; Hypotension; Intraoperative Complications; Maternal Mortality; Oxytocics; Oxytocin; Pregnancy

For a long time, epidural anaesthesia has been considered the method of choice for Caesarean delivery. The increased incidence of hypotension by the rapid onset of sympathetic blockade under spinal anaesthesia has been associated with a decline in uteroplacental blood flow and significant fetal acidosis, which may compromise neonatal well-being. Nevertheless, a decrease in fetal pH has not been shown to reduce neonatal Apgar or neurobehavioural assessment scores. Maternal blood pressure can be preserved with little side effects with low doses of vasopressors. On the other hand, spinal anaesthesia conveys significant advantages over epidural anaesthesia such as the simplicity of its use and the speed of onset, which allows neuraxial anaesthesia in urgent Caesarean sections and thus reduces the necessity for general anaesthesia. The small doses of local anaesthetics required to perform spinal anaesthesia reduce the risks of systemic toxicity to zero. Spinal anaesthesia is now considered the method of choice for urgent Caesarean section. The use of intrathecal opioids has profoundly changed the quality of spinal anaesthesia, with improved analgesia, a reduction in local anaesthetic requirements and shorter duration of motor blockade. Preliminary studies indicate that spinal anaesthesia may be safely performed in patients with severe pre-eclampsia, in whom spinal anaesthesia was previously considered contraindicated.

Topics: Anesthesia, Obstetrical; Anesthesia, Spinal; Anesthetics, Local; Cesarean Section; Contraindications; Female; Fetus; Humans; Hypotension; Obstetric Labor Complications; Oxytocin; Pre-Eclampsia; Pregnancy; Risk Assessment

The purpose of this article is to profile research findings targeting the intrapartum care implications of the most common side effects and co-interventions that go along with the use of epidural analgesia during labor. Randomized, controlled trials published in English from 1990 to 2000 that addressed each of the targeted side effects and 3 specified co-interventions were evaluated for inclusion in this report. Side effects such as pruritus, nausea, and hypotension during labor are common, but they are usually mild and necessitate treatment infrequently. However, even with the advent of newer low-dose epidurals, the extent of impaired motor ability remains variable across studies. The incidence of "walking" epidurals during labor is likely to be complicated by multiple factors, including individual patient desires, safety considerations, and hospital policies. In response to risks for a decrease in uterine contractions that could prolong labor, oxytocin augmentation is likely to be administered after epidural analgesia. The use of "delayed" pushing may be an effective way to minimize the risk for difficult deliveries. Upright positioning even when confined to bed may be advantageous and desirable to women; however, additional research to determine actual outcome benefits with epidurals is needed. Implications for further research linked to epidural analgesia also include informed consent, modification of caregiving procedures, and staffing/cost issues.

Topics: Analgesia, Epidural; Analgesia, Obstetrical; Female; Humans; Hypotension; Motor Activity; Oxytocin; Pregnancy; Pruritus; Shivering; Urinary Retention

Topics: Animals; Cattle; Endocrine Glands; Humans; Hypotension; Hypothalamus; Neurophysins; Oxytocin; Rats; Shock; Stress, Physiological; Vasopressins

Topics: Acetylcholine; Acute Kidney Injury; Angiotensin II; Animals; Bradykinin; Diuretics; Dogs; Dopamine; Electric Stimulation; Epinephrine; Heart Failure; Hemorrhage; Humans; Hypotension; Isoproterenol; Kidney Cortex; Kidney Transplantation; Liver Cirrhosis; Norepinephrine; Oxytocin; Prostaglandins; Regional Blood Flow; Transplantation, Homologous; Ureter; Vasomotor System; Vasopressins; Vena Cava, Inferior; Water-Electrolyte Balance

Topics: Acid-Base Equilibrium; Anesthesia, Epidural; Asphyxia Neonatorum; Blood Chemical Analysis; Blood Specimen Collection; Delivery, Obstetric; Echocardiography; Electrocardiography; Female; Fetal Death; Fetal Diseases; Fetal Heart; Heart Rate; Humans; Hydrogen-Ion Concentration; Hypotension; Infant Mortality; Infant, Newborn; Injections, Intravenous; Methods; Monitoring, Physiologic; Obstetric Labor Complications; Oxytocin; Phonocardiography; Pregnancy; Pregnancy Complications, Cardiovascular; Scalp; Uterus

Topics: Anesthesia, Conduction; Asphyxia; Blood Specimen Collection; Carbon Dioxide; Electrocardiography; Electronics, Medical; Endoscopy; Female; Fetal Diseases; Fetal Heart; Fetal Hemoglobin; Fetus; Humans; Hydrogen-Ion Concentration; Hypotension; Labor, Obstetric; Oxygen Consumption; Oxytocin; Phonocardiography; Pregnancy; Ultrasonics

Oxytocin is routinely administered after delivery for prophylaxis and treatment of postpartum hemorrhage, but it is associated with considerable cardiovascular side-effects. Carbetocin, a synthetic oxytocin analogue, has a myometrial contraction effect of 60 min when given IV, compared with 16 min for oxytocin.. To investigate whether there are differences in cardiovascular effects between oxytocin and carbetocin up to 1 h after treatment.. Sixty-one healthy pregnant women undergoing elective cesarean section in spinal anesthesia were randomized to receive an IV bolus of either five units (8.3 µg) of oxytocin or 100 µg of carbetocin after delivery of the baby. Heart rate (HR), mean arterial blood pressure, ECG ST index, oxygen saturation (SaO. The drugs had equal vasodilatory and hypotensive effects. Oxytocin, but not carbetocin, caused a decrease in HR at 1 min and a sustained decrease in cardiac left ventricular ejection time. Aggregate vasopressor use was higher in the carbetocin group. Neither drug caused any change in ST index, SaO. Single doses of oxytocin and carbetocin had similar dilatory effects on vascular tonus, where the difference in aggregate vasopressor use can be attributed to a more persistent hypotensive effect of carbetocin. A transient negative chronotropic and sustained negative inotropic effect occurred after oxytocin. Neither drug showed any alarmingly adverse effects. Differences in drug effects may be attributed to differences in oxytocin and vasopressin receptor signaling pathways.

Topics: Cesarean Section; Double-Blind Method; Female; Humans; Hypotension; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy; Prospective Studies; Pulse Wave Analysis

A recent publication investigating intrathecal oxytocin, 100 μg, administered immediately prior to a spinal anesthetic in patients undergoing primary total hip arthroplasty surgery demonstrated a reduction in disability for 3-weeks, increased walking distance at 8-weeks, and earlier opioid cessation. This secondary analysis study was undertaken to assess the acute cardiovascular safety and analgesic efficacy of intrathecal oxytocin in this study population.. 90 patients were included in the analysis (44 randomized to spinal oxytocin and 46 to placebo [saline]). Data collected prospectively during the previously published study were supplemented with additional retrospectively collected data. The primary outcomes were comparisons of the duration of hypotension (minutes with mean arterial pressure < 65 mmHg) and cumulative vasopressor requirements during the initial 60 min following spinal placement. Secondary outcomes included hypotension durations and vasopressor requirements at later time points, perioperative fluid administration, physical therapy metrics, time to first opioid administration, cumulative opioid consumption through 24 h, and verbal pain scores through 24 h.. The duration of hypotension during the first 60 min following spinal placement did not differ between intrathecal oxytocin and placebo groups (12.2 ± 10.7 vs 14.0 ± 13.0 min, respectively; p = 0.476). There was also no difference in cumulative vasopressor requirements (1303 ± 883 vs 1156 ± 818 μg [phenylephrine equivalents]; p = 0.413) during that time period. No group differences were found for any of the investigated secondary outcomes.. The administration of 100 μg of intrathecal oxytocin does not significantly impact the duration of hypotension or the need for vasopressor agents when given as a component of a spinal anesthetic. The oxytocin and placebo groups also did not differ in regards to physical therapy related metrics, time to first opioid administration, cumulative opioids at 24-h, or pain scores through 24-h. What is already known on this topic: Rapid intravenous oxytocin causes hypotension after cesarean delivery, but intrathecal oxytocin does not cause hypotension in healthy volunteers.. Compared to saline control, intrathecal oxytocin, 100 μg did not increase the duration of hypotension or vasopressor requirements in patients during total hip arthroplasty. How this study might affect research, practice, or policy: Lack of hypotension from intrathecal oxytocin in this study supports future investigations to further explore its potential benefits, in terms of both analgesia and functional recovery following surgery.

Topics: Analgesics, Opioid; Anesthesia, Spinal; Anesthetics; Arthroplasty, Replacement, Hip; Double-Blind Method; Female; Humans; Hypotension; Injections, Spinal; Oxytocin; Pain; Pregnancy; Retrospective Studies; Vasoconstrictor Agents

Prior studies have shown that, when administered as an intravenous bolus to prevent uterine atony, prophylactic phenylephrine infusion increased the dose requirement of oxytocin and second-line uterotonics. For the prevention of uterine atony, oxytocin should be delivered by continuous infusion. Here, we aimed to determine the ED50 and ED90 parameters (the effective doses for 50 and 90% patients without uterine atony) of oxytocin for co-infusion with prophylactic phenylephrine during cesarean delivery.. In this prospective randomized double-blinded dose-finding study, one hundred patients were divided into four groups to receive 2.5, 5.0, 7.5, or 10 IU/h oxytocin infusion, after the umbilical cord was clamped during the study period. The uterine tone was evaluated and defined as either adequate or inadequate. Probit regression analysis was applied to calculate the ED50 and ED90 of oxytocin infusion. Uterine tone, the percentage of patients who needed additional oxytocin bolus, second-line uterotonics, side effects, estimated blood loss, and neonatal outcomes were monitored.. The estimated ED50 and ED90 values of the oxytocin infusion doses for the prevention of uterine atony were 1.9 IU/h (95% CI -4.6-3.8) IU/h and 9.3 IU/h (95% CI 7.3-16.2) IU/h, respectively. Across groups, there was a significant linear trend between the infusion dose and the percentage of patients who required additional oxytocin (p-value = 0.002). No differences were observed in the incidence of side effects and neonatal outcomes.. Under the conditions of this study, the ED90 of oxytocin infusion for the prevention of uterine atony was 9.3 IU/h, which is higher than the current recommendation. This finding is helpful for clinical practice, because of the routine use of phenylephrine in cesarean delivery. Further studies are needed to determine the appropriate initial bolus of oxytocin after neonatal delivery.. The study was registered on the Chinese Clinical Trial Register (register no. ChiCTR2200059556 ).

Topics: Double-Blind Method; Female; Humans; Hypotension; Infant, Newborn; Infusions, Intravenous; Oxytocics; Oxytocin; Phenylephrine; Pregnancy; Prospective Studies; Uterine Inertia

Carbetocin, an oxytocin analog, given as a postpartum hemorrhage prophylaxis in elective Cesarean deliveries, frequently causes tachycardia and hypotension. Phenylephrine infusion has been shown to prevent spinal anesthesia-induced hypotension. The goal of this study was to evaluate if a slow infusion of carbetocin would reduce maternal heart rate variation and hemodynamic disturbances compared with a rapid bolus in parturients receiving a prophylactic phenylephrine infusion during elective Cesarean delivery.. In this double-blinded randomized controlled trial, 70 healthy parturients were allocated to either a bolus group or an infusion group. At cord clamping, participants in the bolus group received carbetocin 100 µg as a rapid intravenous bolus, while participants in the infusion group received carbetocin 100 µg over 10 min. The primary outcome was the variation in maternal heart rate from baseline during the 20 min following cord clamping. Secondary outcomes included blood pressure, cardiac output, and stroke volume variations during the study period, measured with the ClearSight™ hemodynamic monitor.. Maximum heart rate variation was not different between the groups: bolus group, mean (standard deviation) 29.8 (25.2)% vs infusion group, 27.2 (23.3)%; P = 0.67. The increase in heart rate occurred significantly earlier in the bolus group than in the infusion group (median [interquartile range] time, 105 [69-570] sec vs 485 [255-762] sec; P = 0.02; group × time interaction: two-way repeated measures ANOVA, P = 0.04). There was no significant difference in maximum variations for the other hemodynamic parameters between the groups.. Carbetocin infused over ten minutes did not reduce the magnitude of maternal heart rate variation but delayed its occurrence. This finding could be relevant to the anesthesiologist caring for parturients in whom a slight increase in maternal heart rate is clinically undesirable.. www.. gov (NCT03404544); registered 19 January 2018.. RéSUMé: OBJECTIF: Lorsque la carbétocine, un analogue de l’ocytocine, est administrée à titre de prophylaxie pour les hémorragies du post-partum dans les accouchements par césarienne programmée, cet agent provoque fréquemment une tachycardie et une hypotension. Il a été démontré qu’une perfusion de phényléphrine prévenait l’hypotension induite par la rachianesthésie. L’objectif de cette étude était d’évaluer si une perfusion lente de carbétocine réduirait la variation de fréquence cardiaque maternelle et les perturbations hémodynamiques par rapport à un bolus rapide chez les parturientes recevant une perfusion prophylactique de phényléphrine pendant un accouchement par césarienne programmée. MéTHODE: Dans cette étude randomisée contrôlée à double insu, 70 parturientes en bonne santé ont été allouées à un groupe bolus ou à un groupe perfusion. Lors du clampage du cordon, les participantes du groupe bolus ont reçu 100 μg de carbétocine sous forme de bolus intraveineux rapide, tandis que les participantes du groupe perfusion ont reçu 100 μg de carbétocine sur dix minutes. Le critère d’évaluation principal était la variation de la fréquence cardiaque maternelle par rapport aux valeurs de base au cours des 20 minutes suivant le clampage du cordon. Les critères secondaires comprenaient la tension artérielle, le débit cardiaque et les variations du volume d’éjection au cours de la période d’étude, tels que mesurés avec le moniteur hémodynamique ClearSight™. RéSULTATS: La variation maximale de fréquence cardiaque n’était pas différente entre les groupes : groupe bolus, moyenne (écart type) 29,8 (25,2) % vs groupe perfusion, 27,2 (23,3) %; P = 0,67. L’augmentation de la fréquence cardiaque s’est produite significativement plus tôt dans le groupe bolus que dans le groupe perfusion (temps médian [écart interquartile], 105 [69-570] sec vs 485 [255-762] sec; P = 0,02;× interaction groupe x temps : ANOVA bidirectionnelle à mesures répétées, P = 0,04). Il n’y avait pas de différence significative dans les variations maximales pour les autres paramètres hémodynamiques entre les groupes. CONCLUSION: La carbétocine perfusée pendant dix minutes n’a pas réduit l’ampleur de la variation de la fréquence cardiaque maternelle, mais a retardé son apparition. Cette découverte pourrait être pertinente pour l’anesthésiologiste qui prend soin de parturientes chez qui une légère augmentation de la fréquence cardiaque maternelle serait cliniquement indésirable. ENREGISTREMENT DE L’éTUD

Topics: Anesthesia, Spinal; Double-Blind Method; Female; Heart Rate; Humans; Hypotension; Infusions, Intravenous; Oxytocin; Phenylephrine; Pregnancy; Vasoconstrictor Agents

Oxytocin causes clinically significant hypotension and tachycardia. This study examined whether prior administration of phenylephrine obtunds these unwanted haemodynamic effects.. Forty pregnant women undergoing elective caesarean section under spinal anaesthesia were randomised to receive either an intravenous 50 μg bolus of phenylephrine (Group P) or saline (Group S) immediately before oxytocin (3U over 15s). Systolic blood pressure, diastolic blood pressure, mean arterial pressure and heart rate were recorded using a continuous non-invasive arterial pressure device. Baseline values were averaged for 20s post-delivery. Between-group comparisons were made of the mean peak changes in blood pressure and heart rate, and the mean percentage changes from baseline, during the 150s after oxytocin administration.. The mean ± SD peak percentage change in systolic blood pressure was -16.9 ± 2% in Group P, and -19.0 ± 1.9% in Group S and the estimated mean difference was 2.1% (95% CI -3.5% to 7.8%; P=0.44); corresponding changes in heart rate were 13.5 ± 2.3% and 14.0±1.5% and the mean estimated difference was 0.5% (95% CI -6.0% to 5%; P=0.87). The mean percentage change from the baseline measurements during the 150s period of measurement was greater for Group S than Group P: systolic blood pressure -5.9% vs -3.4% (P=0.149); diastolic blood pressure -7.2% vs -1.5% (P=0.014); mean arterial pressure -6.8% vs -1.5% (P=0.007); heart rate 2.1% vs -2.4% (P=0.033).. Intravenous phenylephrine 50 μg immediately before 3U oxytocin during elective caesarean section does not prevent maternal hypotension and tachycardia.

Topics: Adult; Anesthesia, Obstetrical; Anesthesia, Spinal; Blood Pressure; Cardiotonic Agents; Cesarean Section; Double-Blind Method; Female; Humans; Hypotension; Oxytocics; Oxytocin; Phenylephrine; Pregnancy; Prospective Studies; Tachycardia; Young Adult

The aim of this study was to determine the intravenous dose of carbetocin required to produce effective uterine contraction in 95% of women (ED95) undergoing elective Cesarean delivery under spinal anesthesia.. One hundred and twenty term pregnant women at low risk for postpartum hemorrhage (PPH) undergoing elective Cesarean delivery under spinal anesthesia were randomly allocated to receive carbetocin in doses of 20, 40, 60, 80, or 100 μg iv upon delivery of the fetus. The obstetrician evaluated the efficacy of uterine tone as satisfactory or unsatisfactory, and in case of unsatisfactory tone, additional uterotonics were administered as per routine institutional practice. The primary outcome measure was satisfactory uterine tone at two minutes after carbetocin administration, and the secondary outcomes were the estimated blood loss, need for additional uterotonic agents within 24 hr, and side effects.. Overall satisfactory uterine tone at two minutes was observed in 94.2% (113/120) of the women, and there was no difference across the different study groups. It was not possible to calculate the ED95 of carbetocin due to the even distribution of women with unsatisfactory uterine tone at two minutes across all dose groups (P = 0.60). Additional uterotonics within 24 hr were required in 13% (16/120) of the women. Side effects were similar across all dose groups, with an overall 42.5% incidence of hypotension following the administration of carbetocin.. In women at low risk for PPH undergoing elective Cesarean delivery under spinal anesthesia, carbetocin is similarly effective in doses of 20-100 μg. There is a high incidence of hypotension associated with carbetocin in these doses. Further dose-finding studies are warranted, including doses lower than 20 μg. This trial was registered at www.clinicaltrials.gov (NCT01428817).

Topics: Adult; Anesthesia, Spinal; Cesarean Section; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Hypotension; Incidence; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy; Treatment Outcome; Uterine Contraction

The primary objective of our study was to determine the minimum intravenous dose of carbetocin required to produce adequate uterine contraction in 95% of women (effective dose [ED](95)) undergoing elective Cesarean delivery (CD).. Eighty term pregnant women with low risk for postpartum hemorrhage (PPH) undergoing elective CD under spinal anesthesia were randomly allocated to receive carbetocin intravenously in doses of 80 μg, 90 μg, 100 μg, 110 μg, or 120 μg upon delivery. The consultant obstetrician evaluated the efficacy of the patient's uterine tone as satisfactory or unsatisfactory. In case of unsatisfactory uterine tone, additional uterotonics were administered as per routine institutional practice. Side effects were monitored during the study period. The main outcome measure was satisfactory uterine tone at two minutes after carbetocin administration.. Satisfactory uterine tone was obtained in 70 subjects (87%) within the dose range of 80-120 μg of carbetocin. It was not possible to calculate the ED(95) of carbetocin due to the even distribution of women with satisfactory uterine tone across all dose groups (P = 0.99). Similarly, the side effects were similar across all dose groups. There was a high overall incidence of hypotension (55%) following the administration of carbetocin.. In women at low risk for PPH undergoing elective CD, carbetocin doses of 80-120 μg are similarly effective. There is a high incidence of hypotension associated with carbetocin in these doses, and further studies with doses lower than 80 μg are warranted to assess the balance of efficacy and side effects. This trial was registered at www.clinicaltrials.gov (NCT01262742).

Topics: Adult; Cesarean Section; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hypotension; Infusions, Intravenous; Oxytocics; Oxytocin; Pregnancy; Treatment Outcome; Uterine Contraction

There are no guidelines for the anaesthetic management of caesarean section in women with long QT syndrome; the description of myocardial ventricular repolarisation in healthy women during caesarean delivery could be a first step. The aim of this study was to describe modification of the QT interval, corrected for heart rate, and the interval between the peak and the end of the T-wave (Tpeak-Tend interval) during caesarean section under spinal anaesthesia. We studied 40 patients scheduled for caesarean section under spinal anaesthesia. Patients were randomly assigned to receive either ephedrine or phenylephrine to prevent hypotension. We injected 5 IU oxytocin after delivery. Corrected QT and Tpeak-Tend intervals were unchanged from pre-operative values after induction of spinal anaesthesia, but increased significantly after oxytocin injection. The choice of vasopressor did not affect the Tpeak-Tend interval. The risk-benefit balance of oxytocin bolus during caesarean delivery should be discussed with women with a history of long QT syndrome.

Topics: Adult; Anesthesia, Obstetrical; Anesthesia, Spinal; Cesarean Section; Electrocardiography; Ephedrine; Female; Humans; Hypotension; Intraoperative Complications; Long QT Syndrome; Oxytocics; Oxytocin; Phenylephrine; Pregnancy; Vasoconstrictor Agents; Young Adult

The aim of this study was to determine the lowest effective bolus dose of oxytocin to produce adequate uterine tone (UT) during elective Caesarean delivery (CD).. Seventy-five pregnant patients undergoing elective CD under spinal anaesthesia were randomized to receive oxytocin (0.5, 1, 3, 5 units) or placebo. UT was assessed by a blinded obstetrician as either adequate or inadequate, and using a verbal numerical scale score (0-10; 0, no UT; 10, optimal UT) at 2, 3, 6, and 9 min after oxytocin administration. Minimum effective doses of oxytocin were analysed (ED(50) and ED(95)) using logistic regression. Oxytocin-related side-effects (including hypotension) were recorded.. There were no significant differences in the prevalence of adequate UT among the study groups at 2 min (73%, 100%, 93%, 100%, and 93% for 0, 0.5, 1, 3, and 5 units oxytocin, respectively). The high prevalence of adequate UT after placebo and low-dose oxytocin precluded determination of the ED(50) and ED(95). UT scores were significantly lower in patients receiving 0 unit oxytocin at 2 and 3 min compared with 3 and 5 units oxytocin (P<0.05, respectively). The prevalence of hypotension was significantly higher after 5 units oxytocin vs 0 unit at 1 min (47% vs 7%; P=0.04).. The routine use of 5 units oxytocin during elective CD can no longer be recommended, as adequate UT can occur with lower doses of oxytocin (0.5-3 units).

Topics: Adult; Algorithms; Anesthesia, Obstetrical; Anesthesia, Spinal; Cesarean Section; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hypotension; Infusions, Intravenous; Oxytocics; Oxytocin; Pregnancy

Rapid intravenous injection of oxytocin is associated with marked hypotension secondary to decreased venous return. Reductions in dose and rate of bolus administration have reduced the incidence of cardiovascular side effects, but no study has yet investigated cardiovascular stability when oxytocin is infused for several hours after delivery. This study compared maternal haemodynamics during a 4-h 30-unit oxytocin infusion and during a placebo infusion following caesarean section.. Women booked for elective caesarean section were randomised to receive either oxytocin 5-unit bolus and placebo infusion or oxytocin 5-unit bolus and oxytocin 30-unit infusion. Before, during and for 4 h after surgery electrocardiogram, oxygen saturation, systolic and diastolic pressure and heart rate were monitored non-invasively and cardiac index (CI), left ventricular work index (LVWi) and systemic vascular resistance index (SVRi) by thoracic bioimpedance.. A total of 74 women agreed to haemodynamic measurements. Heart rate, systolic and diastolic pressure, CI, LCWi and SVRi all fell following the onset of spinal anaesthesia, and, with the exception of SVRi, continued to decrease throughout surgery. After delivery of the baby, slow injection of oxytocin 5 units was associated with a temporary rise in CI, LCWi and heart rate, a decrease in SVRi and no change in systolic or diastolic pressure. Thereafter, haemodynamic measures returned to normal over 60 min with no adverse effects apparent from the additional oxytocin infusion.. An additional oxytocin infusion at elective caesarean section did not adversely affect maternal haemodynamics either during or after surgery.

Topics: Adult; Analysis of Variance; Anesthesia, Spinal; Area Under Curve; Cardiography, Impedance; Cesarean Section; Dose-Response Relationship, Drug; Elective Surgical Procedures; Female; Hemodynamics; Humans; Hypotension; Infusions, Intravenous; Oxygen; Oxytocics; Oxytocin; Time Factors; Treatment Outcome; Young Adult

Ambulation during labor is becoming more popular, although its impact on the progress of labor and on pain intensity remains unclear. We wondered whether prolonged ambulation with epidural analgesia had a possible effect on duration of labor and pain. In this prospective, randomized trial, 61 parturients with uncomplicated term pregnancies were allocated to be recumbent (n = 31) or to ambulate (n = 30). Epidural analgesia was provided with intermittent administrations of 0.08% bupivacaine-epinephrine plus 1 microg/mL of sufentanil. Of the 30 women assigned to the ambulatory group, 25 actually walked. Their ambulating time was 64 +/- 34 min (mean +/- SD), i.e., 29% +/- 16% of the first stage. There were no differences between the two groups in the length of labor and in pain visual analog scale scores. However, the ambulatory group received smaller doses of bupivacaine (6.4 +/- 2.2 mg/h versus 8.4 +/- 3.6 mg/h; P = 0.01) and of oxytocin (6.0 +/- 3.7 mUI/min versus 10.2 +/- 8.8 mUI/min; P < 0.05). A greater ability to void was also found in the ambulatory group (P < 0.01). Although the duration of labor and pain relief was unchanged, these findings support that ambulation during labor may be advantageous.. This study compared the duration of labor and pain relief between parturients receiving epidural analgesia who were ambulated or were recumbent. Whereas walking had no impact on either duration of labor or pain relief, it was associated with a reduction in both bupivacaine and oxytocin requirements.

Topics: Adult; Analgesia, Epidural; Analgesia, Obstetrical; Female; Humans; Hypotension; Labor, Obstetric; Oxytocin; Pain Measurement; Pregnancy; Urination; Walking

To determine the efficacy and safety of intradural-epidural analgesia in comparison with continuous epidural analgesia during labor and childbirth.. Forty-two women whose labor began spontaneously were enrolled and distributed randomly in two groups. The intradural-epidural analgesia group (IEA, n = 21) received 25 microgram of intradural fentanyl with 2.5 mg of isobaric bupivacaine with adrenalin, after which analgesia was maintained with epidural administration of one 8 mL bolus of 0.125% bupivacaine, followed by perfusion of a balanced concentration at a rate of 8 ml/h. Patients in the continuous epidural analgesia group (CEA, n = 21) were given 8 ml of 0.25% bupivacaine with adrenalin; the epidural perfusion of 0.125% bupivacaine and 1 microgram/ml of fentanyl was started at the same rate as in the IEA group. We recorded pain as assessed on a visual analog scale, extension of sensory and motor block, maternal hemodynamic constants, number of boluses of bupivacaine used, total doses of bupivacaine and oxytocin, instruments needed for childbirth, and side effects (pruritus, nausea and vomiting).. Analgesic efficacy during the first 30 minutes was greater in the IEA group. The total dose of bupivacaine, required top-up boluses, and the extension of sensory block at 30 minutes, one hour and two hours were also significantly less in the IEA group. The incidence of pruritus was higher in the IEA group. No significant differences were observed for other variables.. Intradural-epidural analgesia provides effective analgesia for labor, with rapid onset, reduced extension of sensory block, lower total doses of local anesthetics and few side effects.

Topics: Adult; Analgesia, Epidural; Analgesia, Obstetrical; Anesthesia Recovery Period; Bupivacaine; Cesarean Section; Epinephrine; Female; Fentanyl; Humans; Hypotension; Infant, Newborn; Labor, Obstetric; Nausea; Oxytocin; Patient Acceptance of Health Care; Pregnancy; Prospective Studies; Pruritus; Safety; Single-Blind Method; Vomiting

Topics: Acid-Base Equilibrium; Anesthesia, Epidural; Anesthesia, Obstetrical; Apgar Score; Carbon Dioxide; Clinical Trials as Topic; Delivery, Obstetric; Electrocardiography; Female; Fetal Heart; Heart Rate; Humans; Hydrogen-Ion Concentration; Hypotension; Infant, Newborn; Lidocaine; Oxygen; Oxytocin; Pregnancy; Toxemia; Umbilical Arteries; Umbilical Veins

Oxytocin and its analogue carbetocin are uterotonics whose prophylactic use is recommended to prevent postpartum haemorrhage, which is one of the leading causes of maternal deaths worldwide. However, both drugs can cause specific adverse effects and haemodynamic challenges.. The aim of this work was to exploratively examine reports of adverse drug events of both drugs and to establish a comparative haemodynamic profile.. Using data extracted from the World Health Organization's pharmacovigilance database VigiBase, a descriptive analysis was performed of all reports for oxytocin and carbetocin as a suspected or interacting drug followed by a disproportionality analysis for haemodynamic events. Reporting odds ratios (ROR) of carbetocin for hypertension, hypotension, tachycardia, and bradycardia were calculated, with oxytocin-related reports serving as comparators.. Oxytocin and carbetocin were mentioned as suspected or interacting drugs in 11,258 and 374 reports, respectively. Resulting RORs for carbetocin were 3.45 (95%CI: 1.72-6.92) for hypertension, 2.65 (1.64-4.28) for hypotension, 2.84 (1.79-4.49) for tachycardia, and 2.00 (0.87-4.60) for bradycardia, when compared to oxytocin. Of 231 patients for whom oxytocin-related tachycardia was reported, 2.6% died, and of 91 patients for whom bradycardia was reported, 2.2% died. No deaths were reported with carbetocin for any of the haemodynamic adverse events.. Compared to oxytocin, carbetocin showed an elevated reporting for adverse hypertension, hypotension, and tachycardia in pharmacovigilance data. Clinicians should be aware of their patients' individual susceptibility and the possibility of haemodynamic deterioration until causal inferences are possible.

Topics: Bradycardia; Drug-Related Side Effects and Adverse Reactions; Female; Hemodynamics; Humans; Hypertension; Hypotension; Oxytocics; Oxytocin; Pharmacovigilance

The present study was designed to determine the role of centrally acting oxytocin (OT) in the regulation of blood pressure during chronic mild stress (CMS) in spontaneously hypertensive (SHR;

Topics: Animals; Blood Pressure; Heart Rate; Hypotension; Infusion Pumps, Implantable; Infusions, Intraventricular; Male; Oxytocin; Random Allocation; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Oxytocin; Stress, Physiological; Time Factors

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

This study sought to compare postpartum blood loss and maternal outcomes after 3IU and 5IU oxytocin at elective caesarean delivery. In a prospective observational study, 73 women undergoing elective caesarean delivery under spinal anaesthetic received a slow I.V. injection of either 3IU (n = 35) or 5IU (n = 38) oxytocin after delivery. The main outcome was gravimetrically measured 24-hour postpartum blood loss with a non-inferiority margin of 300 mL. Uterine tone, phenylephrine dose, emesis and hypotension after oxytocin administration were secondary outcomes. Gravimetric postpartum blood loss was lower in the 3IU group (-58.8 mL [95% CI: -212.1, 94.3]) after adjusting for BMI, pre-delivery vasopressor dose, parity, and risk of uterine atony, with the upper confidence limit below the 300 mL margin in support of non-inferiority. Patients receiving 3IU had a higher (non-significant) rate of having post-delivery phenylephrine to treat hypotension (RR = 1.59 [95% CI: 0.97, 2.63]), but of those treated, the 3IU group required significantly less (-427 mcg [95% CI: -740, -114]). The 3IU group had a lower prevalence of vomiting compared to those receiving 5IU (6% versus 24%; P = 0.047). Administration of 3IU oxytocin was non-inferior compared to standard 5IU with respect to blood loss in women undergoing elective caesarean delivery.

Topics: Adult; Cesarean Section; Female; Humans; Hypotension; Injections, Intravenous; Oxytocin; Phenylephrine; Postpartum Hemorrhage; Pregnancy; Prospective Studies; Uterus; Vasoconstrictor Agents

Besides their well-established endocrine roles, vasopressin and oxytocin are also important regulators of immune function, participating in a complex neuroendocrine-immune network. In the present study, we investigated whether and how vasopressin and oxytocin could modulate lipopolysaccharide (LPS)-induced nitric oxide (NO) production in a well-established model of experimental endotoxaemia. Male Wistar rats were previously treated i.v. with vasopressin V1 or oxytocin receptor antagonists and then received either an i.v. LPS injection to induce endotoxaemia or a saline imjection as a control. The animals were divided into two groups: in the first group, blood was collected at 2, 4 and 6 h after LPS injection; in the second group, mean arterial blood pressure (MABP) and heart rate (HR) were recorded over 6 h. Plasma vasopressin and oxytocin values were higher in LPS- compared to saline-injected animals at 2 and 4 h but returned to basal levels at 6 h. NO levels exhibited an opposite pattern, showing a progressive increase over the entire period. The previous administration of a vasopressin V1 receptor antagonist significantly reduced NO plasma concentrations at 2 and 4 h but not at 6 h. By contrast, oxytocin receptor agonist pre-treatment had no effect on the NO plasma concentration. In relation to MABP, previous treatment with vasopressin V1 receptor antagonist reversed the LPS-induced hypotension at 4 h, although this was not the case for oxytocin antagonist-treated animals. None of the antagonists affected HR. Our findings indicate that vasopressin (but not oxytocin) has effects on NO production during endotoxaemia in rats, although they do not lend support to the proposed anti-inflammatory actions of vasopressin during endotoxaemia.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Blood Pressure; Endotoxemia; Heart Rate; Hypotension; Lipopolysaccharides; Male; Nitric Oxide; Oxytocin; Pituitary Gland, Posterior; Rats; Receptors, Oxytocin; Time Factors; Vasopressins

Haemodynamic changes that occur during pregnancy are maximal between 28 and 34 weeks. In the pregnant woman with several associated diseases, such as hypertensive myocardiopathy and pre-gestational diabetes, these changes can lead to a difficult control of pulmonary hypertension and acute pulmonary oedema. We report the case of a pregnant woman with long term type 1 diabetes mellitus who suffered pre-eclampsia in a previous pregnancy, and since then developed hypertensive cardiomyopathy. She was admitted at 30 week gestation for metabolic and blood pressure control, and developed congestive cardiac failure after the administration of betamethasone for foetal lung maturity. A transthoracic echocardiogram showed a non-dilated hypertrophic left ventricle with good systolic function, restrictive diastolic dysfunction and moderate pulmonary arterial hypertension. When her general condition improved, we performed a caesarean section under regional anaesthesia to prevent the complications of pulmonary and systemic hypertension. We present the anaesthetic management and resolution of complications after oxytocin administration.

Topics: Adult; Anesthesia, Epidural; Anesthesia, Obstetrical; Betamethasone; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Cesarean Section, Repeat; Diabetes Mellitus, Type 1; Diastole; Female; Heart Failure; Humans; Hypertension, Pulmonary; Hypotension; Infant, Newborn; Intraoperative Complications; Norepinephrine; Oxytocin; Phenylephrine; Pre-Eclampsia; Preanesthetic Medication; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy in Diabetics; Supine Position

Topics: Adult; Cesarean Section; Ductus Arteriosus, Patent; Eisenmenger Complex; Female; Humans; Hypotension; Oxygen; Oxytocics; Oxytocin; Pregnancy

Tachykinin neurokinin 3 receptor (NK3R) signaling has a broad role in vasopressin (VP) and oxytocin (OT) release. Hydralazine (HDZ)-induced hypotension activates NK3R expressed by magnocellular neurons, increases plasma VP and OT levels, and induces c-Fos expression in VP and OT neurons. Intraventricular pretreatment with the specific NK3R antagonist, SB-222200, eliminates the HDZ-stimulated VP and OT release. NK3R are distributed in the central pathways conveying hypotension information to the magnocellular neurons, and the NK3R antagonist could act anywhere in the pathways. Alternatively, the antagonist could act at the NK3R expressed by the magnocellular neurons. To determine whether blockade of NK3R on magnocellular neurons impairs VP and OT release to HDZ, rats were pretreated with a unilateral PVN injection of 0.15 M NaCl or SB-222200 prior to an intravenous injection of 0.15 M NaCl or HDZ. Blood samples were taken, and brains were processed for VP/c-Fos and OT/c-Fos immunohistochemistry. Intravenous injection of 0.15 M NaCl did not alter plasma hormone levels, and little c-Fos immunoreactivity was present in the PVN. Conversely, intravenous injection of HDZ increased plasma VP and OT levels and c-Fos expression in VP and OT magnocellular neurons. Intra-PVN injection of SB-222200 prior to an intravenous injection of HDZ significantly decreased c-Fos expression in both VP and OT neurons by approximately 70% and attenuated plasma VP and OT levels by 33% and 35%, respectively. Therefore, NK3R signaling in magnocellular neurons has a critical role for the release of VP and OT in response to hypotension.

Topics: Animals; Blood Pressure; Cell Nucleus; Hydralazine; Hypotension; Hypothalamus, Anterior; Immunohistochemistry; Male; Neurons; Oxytocin; Paraventricular Hypothalamic Nucleus; Proto-Oncogene Proteins c-fos; Quinolines; Rats; Rats, Inbred Strains; Receptors, Neurokinin-3; Signal Transduction; Vasopressins

Topics: Adrenergic beta-Antagonists; Adult; Anesthesia, Obstetrical; Anesthesia, Spinal; Anesthetics, Local; Blood Pressure; Bupivacaine; Cardiomyopathy, Hypertrophic; Cesarean Section; Ephedrine; Female; Heart Rate; Humans; Hypertension; Hypotension; Metoprolol; Myocardial Infarction; Oxytocics; Oxytocin; Postoperative Complications; Postpartum Period; Tachycardia; Vasoconstrictor Agents

Activation of the neurokinin 3 receptor (NK3R) by a receptor agonist, hypotension, and hyperosmolarity results in the internalization of NK3R expressed by magnocellular neurons and the release of vasopressin (VP) and oxytocin (OT) into the circulation. The contribution of NK3R activation to the release of VP and OT in response to hyperosmolarity and hypotension was evaluated by measuring the release of both hormones following pretreatment with a selective NK3R antagonist, SB-222200. Freely behaving male rats were given an intraventricular injection of either 0.15 M NaCl or 250, 500, or 1,000 pmol SB-222200, and then were administered an intravenous infusion of 2 M NaCl or 0.15 M NaCl (experiment 1), or a bolus intra injection of 0.15 M NaCl or hydralazine (HDZ), a hypotension-inducing drug (experiment 2). Blood samples were taken from indwelling arterial catheters at various time points for 1-2 h, both before and after treatments. Plasma VP and OT levels were determined by ELISA. Blockade of NK3R did not affect the baseline levels of either hormone. In contrast, pretreatment with SB-222200 significantly reduced ( approximately 60%) or abolished the release of VP and OT, respectively, to 2 M NaCl infusion. HDZ-induced VP and OT release was eliminated by pretreatment with 500 pmol SB-222200. Therefore, NK3R activation contributes significantly to the systemic release of both VP and OT in response to osmotic and hypotensive challenges.

Topics: Animals; Hydralazine; Hypotension; Hypothalamus; Infusions, Intravenous; Injections, Intraventricular; Male; Osmotic Pressure; Oxytocin; Quinolines; Rats; Receptors, Neurokinin-3; Sodium Chloride; Vasodilator Agents; Vasopressins; Water-Electrolyte Balance

The present study sought to determine whether chemical destruction of peripheral catecholaminergic fibers with 6-hydroxydopamine (6OHDA) attenuates vasopressin (VP) and oxytocin (OT) secretion stimulated by hemorrhage, hypotension, and hyperosmolality. Rats received 6OHDA (100 mg/kg iv) or vehicle (1 ml/kg iv) on days 1 and 7, and experiments were performed on day 8. Serial hemorrhage (4 samples of 2 ml per 300 g body wt at 10-min intervals) increased plasma VP and OT levels in both groups; however, the increase in plasma VP and OT levels was significantly attenuated in 6OHDA-treated vs. control rats despite a significantly lower mean arterial blood pressure. Similarly, the increase in plasma VP and OT levels in response to hypotension produced by the selective arteriolar vasodilator diazoxide was significantly attenuated in 6OHDA-treated rats. In marked contrast to hemorrhage and hypotension, hyperosmolality produced by an infusion of 1 M NaCl (2 ml/h iv) stimulated increases in plasma VP and OT levels that were not different between 6OHDA-treated and control rats. In a parallel set of experiments, intravenous 6OHDA treatment reduced dopamine--hydroxylase immunoreactivity in the posterior pituitary but had no substantial effect in the hypothalamic paraventricular and supraoptic nuclei. In each experiment, the pressor response to tyramine (250 microg/kg iv) was significantly attenuated in 6OHDA-treated rats, thereby confirming that 6OHDA treatment destroyed sympathetic catecholaminergic fibers. Collectively, these findings suggest that catecholaminergic fibers located outside the blood-brain barrier contribute to VP and OT secretion during hemorrhage and arterial hypotension.

Topics: Animals; Diazoxide; Dopamine beta-Hydroxylase; Hemorrhage; Hypotension; Hypothalamus; Injections, Intravenous; Male; Oxidopamine; Oxytocin; Pituitary Gland, Posterior; Rats; Rats, Sprague-Dawley; Sympatholytics; Tyramine; Vasopressins; Water-Electrolyte Imbalance

Neurokinin 3 receptors (NK3-Rs) are expressed in the supraoptic nucleus (SON), and SON is innervated by substance P (SP)-expressing A1 neurons in the medulla. Because SP stimulates vasopressin (VP) and oxytocin release from explants of the hypothalamo-neurohypophyseal system (HNS), two hypotheses were tested: (1) SP-stimulated VP release is mediated by NK3-Rs, and (2) stimulation of the A1 pathway by hypotension activates SON NK3-Rs. Senktide, an NK3-R agonist, stimulated VP release from HNS explants, but neither a neurokinin 1 receptor antagonist [L732,138 (N-acetyl-L-tryptophan 3,5-bis(tri-fluoromethyl)benzyl ester)] nor two NK3-R antagonists (SB222200 and SB235375) prevented SP-stimulated VP release. Because the affinity of these antagonists for rat NK-Rs may limit their efficacy, NK3-R internalization was used to assess the ability of SP to activate SON NK3-Rs. Senktide, SP, or vehicle was microinjected above SON. The brain was perfused 5 min after injection and stained for NK3-R immunoreactivity. Using confocal microscopy, the number of NK3-R-immunoreactive (-IR) endosomes was counted in a 5.6(2) mu region of cytoplasm in SON neurons. Senktide, but not SP or vehicle, significantly increased the number of NK3-R-IR endosomes in the cytoplasm. When hypotension was induced with hydralazine, NK3-R internalization was observed within 5 min (p < 0.005). A decrease in cytoplasmic NK3-R immunoreactivity was observed within 15 min of hypotension. Unexpectedly, both senktide and hypotension resulted in translocation of NK3-R-IR immunoreactivity to the nucleus. Thus, although these studies do not identify SP as the NK3-R ligand, they do provide evidence for hypotension-induced release of an endogenous tachykinin in SON and evidence suggesting a role for NK3-Rs in transcription regulation.

Topics: Acetates; Animals; Catecholamines; Cell Compartmentation; Cell Nucleus; Cytoplasm; Endosomes; Hydralazine; Hypotension; Hypothalamo-Hypophyseal System; Hypothalamus, Anterior; Male; Microinjections; Microscopy, Confocal; Neurons; Oxytocin; Peptide Fragments; Quinolines; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled; Receptors, Neurokinin-1; Receptors, Neurokinin-3; Substance P; Tachykinins; Transcription, Genetic; Tryptophan; Vasopressins

Medullary catecholamine and hypothalamic neurosecretory oxytocin cells are activated by hypotension, but previous studies have provided uncertain outcomes concerning their ability to respond to a purely hypovolaemic stimulus. In the present study, injections of PEG/water and pentolinium were used to elicit non-hypotensive, isosmotic hypovolaemia and isovolaemic, isosmotic hypotension, respectively, in conscious rats. Animals were sacrificed 2 h after treatment. Immunolabelling for Fos, tyrosine hydroxylase and oxytocin established that these two stimuli activate almost identical populations of catecholamine neurons in the ventrolateral and dorsomedial medulla, and very similar populations of oxytocin cells in the supraoptic and paraventricular nuclei of the hypothalamus.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Catecholamines; Hypotension; Hypovolemia; Medulla Oblongata; Neurons; Oxytocin; Paraventricular Hypothalamic Nucleus; Pentolinium Tartrate; Polyethylene Glycols; Proto-Oncogene Proteins c-fos; Rats; Rats, Wistar; Supraoptic Nucleus; Tyrosine 3-Monooxygenase; Vasopressins

Previous experiments have indicated that arterial hypotension increases plasma oxytocin (OT) levels in rats and that OT infused intravenously causes an increase in plasma renin activity (PRA). The goal of the present study was to determine whether systemic administration of an OT receptor antagonist would attenuate the increase in PRA that is normally evoked by arterial hypotension in rats. In conscious male rats, intravenous injection of hydralazine or diazoxide produced sustained hypotension and evoked a significant increase in PRA, as expected. Intravenous infusion of an OT receptor antagonist did not alter the hypotension induced by hydralazine or diazoxide, but it did markedly blunt the induced increase in PRA. The OT receptor antagonist also blunted the hypotension-evoked increase in heart rate and plasma vasopressin levels, suggesting that the antagonist may have generally disrupted afferent signaling of hypotension. Thus hypotension-evoked OT secretion may contribute to cardiovascular homeostasis by enhancing baroreceptor signals that stimulate increases in renin secretion, vasopressin secretion, and heart rate during arterial hypotension in rats.

Topics: Animals; Diazoxide; Heart Rate; Hormone Antagonists; Hydralazine; Hypotension; Kinetics; Male; Oxytocin; Rats; Rats, Sprague-Dawley; Renin; Vasodilator Agents; Vasopressins; Vasotocin

Fetal cardiovascular responses to an altered intrauterine environment of increased myometrial contractures induced by oxytocin (OT) pulses to the ewe over the final 50 days of gestation were studied in chronically instrumented sheep. Ewes received saline (Cntl) or long-term OT treatment (LTOT, 600 microU x kg(-1) x min(-1) in 5-min pulses every 20 min) from 96 days gestational age. Fetal baroreflex responses to sodium nitroprusside (SNP) and phenylephrine (PE) were studied at 133 days gestation. OT increased contractures in LTOT ewes. Fetal blood pressure (FBP) was higher, and fetal heart rate (FHR) and slope of daily change in FBP and FHR were lower in LTOT fetuses. Fetal SNP-induced hypotension resulted in a narrow R-R interval variation range in LTOT fetuses; Cntl fetuses showed early breakdown in compensation. Baroreflex response slope during PE-induced fetal hypertension was lower in LTOT than in Cntl fetuses. Although the cortisol-to-ACTH ratio was lower in LTOT fetuses, fetal plasma ACTH and cortisol changes were similar in control and LTOT fetuses. We hypothesize that contracture-induced alterations in the intrauterine environment accelerate fetal cardiovascular development through mild hypoxemia, repetitive fetal pituitary-adrenal stimulation, and/or physical stimulation.

Topics: Animals; Antihypertensive Agents; Baroreflex; Blood Pressure; Cardiovascular System; Embryonic and Fetal Development; Female; Fetus; Heart Rate, Fetal; Hypertension; Hypotension; Myocardial Contraction; Nitroprusside; Oxytocin; Phenylephrine; Pregnancy; Sheep; Vasoconstrictor Agents

To determine the maximum tolerated dose (MTD) of carbetocin (a long-acting synthetic analogue of oxytocin), when administered immediately after vaginal delivery at term.. Carbetocin was given as an intramuscular injection immediately after the birth of the infant in 45 healthy women with normal singleton pregnancies who delivered vaginally at term. Dosage groups of 15, 30, 50, 75, 100, 125, 150, 175 or 200 microg carbetocin were assigned to blocks of three women according to the continual reassessment method (CRM).. All dosage groups consisted of three women, except those with 100 microg (n=6) and 200 microg (n=18). Recorded were dose-limiting adverse events: hyper- or hypotension (three), severe abdominal pain (0), vomiting (0) and retained placenta (four). Serious adverse events occurred in seven women: six cases with blood loss > or = 1000 ml, four cases of manual placenta removal, five cases of additional oxytocics administration and five cases of blood transfusion. Maximum blood loss was greatest at the upper and lower dose levels, and lowest in the 70-125 microg dose range. Four out of six cases with blood loss > or = 1000 ml occurred in the 200 microg group. The majority of additional administration of oxytocics (4/5) and blood transfusion (3/5) occurred in the dose groups of 200 microg. All retained placentae were found in the group of 200 microg.. The MTD was calculated to be at 200 microg carbetocin.

Topics: Abdominal Pain; Female; Humans; Hypertension; Hypotension; Injections, Intramuscular; Oxytocics; Oxytocin; Placenta, Retained; Postpartum Hemorrhage; Pregnancy; Vomiting

Topics: Blood Loss, Surgical; Cesarean Section; Elective Surgical Procedures; Ephedrine; Female; Humans; Hypotension; Infusions, Intravenous; Oxytocics; Oxytocin; Postoperative Hemorrhage; Pregnancy; Uterine Contraction; Vasoconstrictor Agents

Hemorrhage and nonhypotensive hypovolemia are known to increase plasma levels of oxytocin (OT) and vasopressin (VP) in rats. The present experiments demonstrated that secretion of OT and VP also are stimulated by acute drug-induced hypotension. Injection of hydralazine abruptly decreased arterial blood pressure in conscious rats and induced Fos expression, a marker of neuronal activation, within OT and VP neurons in the hypothalamus. Hydralazine also elicited substantial increases in plasma levels of both OT and VP. Injection of chlorisondamine similarly elicited acute hypotension and increased plasma levels of OT and VP. Furthermore, when the hypotensive effect of chlorisondamine was blunted by coinfusion of phenylephrine, the induced increases in OT and VP were markedly attenuated. Across all treatments, arterial blood pressure was inversely related to plasma levels of OT and VP. Plasma osmolality was not increased by hydralazine, nor was there evidence of gastric malaise, two known stimuli for OT secretion in rats. These results suggest that arterial hypotension increases neurohypophysial release of OT and VP in conscious rats.

Topics: Animals; Antihypertensive Agents; Avoidance Learning; Blood Pressure; Chlorisondamine; Conditioning, Psychological; Hydralazine; Hypotension; Hypothalamus; Male; Neurons; Oxytocin; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Saccharin; Taste; Vasopressins

Results were kept on 43 spinal anaesthetics performed for caesarean section in the Solomon Islands, a developing tropical country in the Pacific Ocean. A 25-gauge Quincke needle was used and either 2.5 ml of heavy bupivacaine 0.5% or 2.0-2.5 ml of plain bupivacaine 0.5% were injected. Hypotension down to 85 mmHg occurred in four patients and there were no spinal headaches. Five patients had to be given a general anaesthetic. We recommend this technique to other doctors working in the Pacific Islands.

Topics: Anesthesia, General; Anesthesia, Obstetrical; Anesthesia, Spinal; Bupivacaine; Cesarean Section; Female; Headache; Humans; Hypotension; Ketamine; Melanesia; Obstetric Labor Complications; Oxytocin; Pregnancy

We examined the role of arginine vasopressin (AVP) as a mediator of neurohypophysial (NH) blood flow regulation in anesthetized dogs. First, we evaluated the NH hyperemia that occurs during hemorrhagic hypotension in the presence (n = 7) and absence (n = 7) of the selective AVP-V1 receptor antagonist [d(CH2)5Tyr(Me)]AVP. AVP-V1 blockade did not alter NH transient or steady-state flow responses to a standardized decrease to 80 mmHg mean arterial blood pressure. We then determined whether exogenous AVP alters NH and regional cerebral blood flow (CBF) (n = 8). Sequential intracarotid infusions resulted in sagittal sinus blood AVP concentrations ranging from 6.97 +/- 3.3 x 10(3) to 2.45 +/- 0.47 x 10(6) pg/ml. No change in NH blood flow (control 428 +/- 162 vs. 487 +/- 75 ml.min-1.100 g-1) was observed even at the highest blood level. However, CBF at the highest AVP level increased from a control value of 20 +/- 3 to 40 +/- 4 ml.min-1.100 g-1, while cerebral oxygen consumption remained unchanged. Administration of a selective AVP-V1 receptor antagonist, [d(CH2)5Tyr(Me)]AVP, blocked AVP-induced elevation in CBF in a third set of dogs (n = 5). Oxytocin was also given by intracarotid infusion at a constant rate (1-200 micrograms/ml) in a final group (n = 5). NH blood flow was unchanged at all doses, whereas CBF increased from control (24 +/- 2 to 38 +/- 5 ml.min-1.100 g-1) at the highest dose. (ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Dogs; Female; Hypotension; Male; Oxytocin; Pituitary Gland, Posterior; Regional Blood Flow

Topics: Adult; Anaphylaxis; Anesthesia, Obstetrical; Angioedema; Cesarean Section; Chlorobutanol; Female; Humans; Hypotension; Oxytocin; Pregnancy

Immunoreactivity to Fos protein (Fos-IR) was detected in rat hypothalamic neurons within 1 h of onset of hemorrhage by withdrawing 4-5 ml of blood, which lowered the arterial blood pressure to 50-70 mm Hg. About 70% of vasopressin (AVP)-containing neurons in the supraoptic nucleus (SON) and 20% in the paraventricular nucleus (PVN) expressed Fos-IR. In contrast, 5% of oxytocin (OXY)-containing neurons in the SON and < 1% in PVN were Fos-IR. Intravenous infusion of the vasodilating agent, nitroprusside, which lowered the blood pressure to levels comparable to that attained by hemorrhage, induced Fos-IR in greater than 65% of AVP-containing neurons in the SON, while relatively few AVP neurons in the PVN were Fos positive. These results suggest that hemorrhage or hypotension preferentially induces c-fos expression in supraoptic AVP-containing neurons.

Topics: Animals; Arginine Vasopressin; Genes, fos; Hypotension; Male; Neurons; Nitroprusside; Oxytocin; Paraventricular Hypothalamic Nucleus; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Supraoptic Nucleus

Two cases of acute inversion of the uterus that occurred through the uterine incision at the time of Caesarean section are described. These represent only the sixth and seventh cases reported in the literature at this time. The implications for the anaesthetist are discussed.

Topics: Acute Disease; Adult; Anesthesia, Epidural; Anesthesia, General; Anesthesia, Obstetrical; Cesarean Section; Female; Humans; Hypotension; Intraoperative Complications; Oxytocin; Pregnancy; Uterine Diseases

A case of an allergic reaction to synthetic oxytocin administered during cesarean section is reported. Epinephrine was more effective in improving the severe hypotension than ephedrine. The incidence of anaphylactoid reaction to oxytocin is very low, but this potential problem must always be kept in mind in daily obstetric practice.

Topics: Adult; Anaphylaxis; Cesarean Section; Epinephrine; Female; Humans; Hypotension; Oxytocin; Pregnancy

Nitroprusside-induced hypotension evokes ACTH secretion which is primarily mediated by enhanced secretion of immunoreactive corticotropin-releasing factor (irCRF) into the hypophysial-portal circulation. Portal plasma concentrations of neither arginine vasopressin nor oxytocin are significantly altered in this paradigm. Application of a delayed feedback signal, in the form of a 2-h systemic corticosterone infusion in urethane-anesthetized rats with pharmacological blockade of glucocorticoid synthesis, is without effect on the resting secretion of arginine vasopressin and oxytocin at any corticosterone feedback dose tested. Resting irCRF levels are suppressed only at the highest corticosterone infusion rate, which resulted in systemic corticosterone levels of 40 micrograms/dl. Suppression of irCRF secretion in response to nitroprusside-induced hypotension is observed and occurs at a plasma corticosterone level between 8-12 micrograms/dl. These studies provide further evidence for a strong central component of the delayed feedback process which is mediated by modulation of irCRF release.

Topics: Adrenocorticotropic Hormone; Animals; Arginine Vasopressin; Corticosterone; Corticotropin-Releasing Hormone; Germ-Free Life; Glucocorticoids; Hypotension; Male; Nitroprusside; Oxytocin; Pituitary Gland; Portal Vein; Rats; Rats, Inbred Strains

In anesthetized and conscious domestic hens i.v. injections of LTC4 (1 and 3 micrograms/hen) and LTD4 (0.1-10 micrograms/hen) induced a pronounced hypotension, initially interrupted by a small, upward pressure deflection. No significant changes in HR, ECG-characteristics, or hematocrit were observed. It is concluded that neither plasma leakage nor myocardial ischemia are likely to contribute significantly to the hypotension. Only experiments with LTD4 in conscious hens suggest a mediator function of cyclooxygenase products since the LTD4-induced hypotension was attenuated by IND. The failure of developing reflex tachycardia rather points to an impairment with manifestation of reflex mechanisms.

Topics: Anesthesia; Animals; Blood Pressure; Cardiovascular System; Chickens; Consciousness; Dose-Response Relationship, Drug; Electrocardiography; Female; Heart Rate; Hypotension; Indomethacin; Injections, Intravenous; Oxytocin; SRS-A

Topics: Anesthesia, Conduction; Anesthesia, Obstetrical; Drug Synergism; Female; Humans; Hypotension; Oxytocin; Pregnancy; Vasoconstrictor Agents

Topics: Amniotic Fluid; Angiotensin II; Animals; Dogs; Female; Humans; Hypotension; Ischemia; Kidney; Nephrectomy; Norepinephrine; Oxytocin; Pre-Eclampsia; Pregnancy; Rabbits; Renin; Sodium; Uterus

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

Fatal myocardial infarction occurring in a neonate is reported. The patient presented with a clinical picture of cardiogenic shock simulating a hypoplastic left heart syndrome. Etiology of the myocardial infarction is uncertain for the coronary arteries were patent, anatomically and histologically normal, and there was no significant associated cardiac defect. The possible etiologies in relationship to myocardial infarction in the neonatal period are presented.

Topics: Acute Kidney Injury; Angiocardiography; Cardiac Catheterization; Diagnosis, Differential; Electrocardiography; Female; Heart Failure; Humans; Hypotension; Infant, Newborn; Infant, Newborn, Diseases; Myocardial Infarction; Myocardium; Oliguria; Oxytocin; Pregnancy; Shock, Cardiogenic; Wolff-Parkinson-White Syndrome

Topics: Adult; Anesthesia; Anesthesia, Epidural; Bupivacaine; Female; Fetal Heart; Heart Rate; Humans; Hypotension; Labor, Induced; Oxytocin

Oxytocin, 5 to 10 units, is frequently given as a bolus injection following term delivery or elective termination of pregnancy. It is not general knowledge that this has any untoward effects. In the present study in young, healthy women undergoing elective termination of pregnancy, mean arterial blood pressure decreased approximately 30% and the total peripheral resistence 50%, 40 seconds after injection. However, heart rate increased 30% and stroke volume 25%, so that the cardiac output was elevated more than 50% above control. Oxytocin given as a dilute solution produced no circulatory change; hence, we suggest that this drug be administered in such fashion rather than by bolus injection.

Topics: Abortion, Induced; Adolescent; Adult; Blood Pressure; Cardiac Output; Chlorobutanol; Female; Heart Rate; Humans; Hypotension; Infusions, Parenteral; Injections, Intravenous; Oxytocin; Pregnancy; Vascular Resistance

Topics: Adult; Anesthesia, Intravenous; Anesthesia, Obstetrical; Blood Pressure; Female; Heart Rate; Humans; Hypotension; Oxytocin; Pregnancy

Topics: Abortion, Induced; Adult; Bradycardia; Cervix Uteri; Female; Heart Rate; Humans; Hypotension; Hypothermia; Infusions, Parenteral; Meperidine; Oxytocin; Pregnancy; Prostaglandins; Rupture; Stimulation, Chemical; Uterus

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

Topics: Aprotinin; Blood Coagulation Disorders; Cesarean Section; Cyanosis; Embolism, Amniotic Fluid; Female; Fibrinogen; Humans; Hypotension; Infusions, Parenteral; Oxytocin; Plasminogen; Polyhydramnios; Posture; Pregnancy; Pregnancy Complications, Cardiovascular; Shock; Syndrome; Uterine Hemorrhage; Vena Cava, Inferior

Topics: Animals; Diuresis; Hypotension; Male; Oxytocin; Potassium; Rats; Sodium; Water-Electrolyte Balance

Topics: Action Potentials; Adrenal Glands; Anesthesia; Animals; Electrophysiology; Estrus; Female; Hypercapnia; Hypophysectomy; Hypotension; Hypothalamus; Hypoxia; Methohexital; Neurons; Organ Size; Ovary; Oxytocin; Periodicity; Pituitary Gland; Pregnancy; Rats; Urethane; Uterus

Topics: Abortion, Spontaneous; Abortion, Therapeutic; Adolescent; Adult; Blood Vessels; Constriction; Dilatation; Electrocardiography; Ergonovine; Female; Fingers; Forearm; Humans; Hypertension; Hypotension; Oxytocin; Plethysmography; Posture; Pregnancy; Pulmonary Edema; Receptors, Adrenergic

Topics: Anesthesia, Epidural; Anesthesia, Obstetrical; Electrocardiography; Female; Fetal Heart; Heart Rate; Humans; Hypotension; Lidocaine; Oxytocin; Posture; Pregnancy

Topics: Animals; Catheterization; Dogs; Female; Fetus; Hemorrhage; Hyponatremia; Hypotension; Maternal-Fetal Exchange; Nephrectomy; Norepinephrine; Oxytocin; Peritoneal Dialysis; Placenta; Pregnancy; Pregnancy Complications; Renin; Uterus

Topics: Blood Pressure; Ergonovine; Female; Humans; Hypertension; Hypotension; Injections, Intramuscular; Injections, Intravenous; Male; Methylergonovine; Oxytocin; Postpartum Hemorrhage; Postpartum Period; Pregnancy

Topics: Anesthesia; Anesthesia, Obstetrical; Chlorpromazine; Female; Fetal Heart; Fetus; Heart Rate, Fetal; Humans; Hypotension; Labor, Obstetric; Meperidine; Oxytocin; Pharmacology; Pregnancy

Topics: Female; Halothane; Hypotension; Nephritis; Oxytocin; Pregnancy; Pregnancy Complications; Pregnancy Complications, Infectious; Shock; Surgical Procedures, Operative; Toxicology