7.4.2 Risks of using oxytocin during labour
– Maternal risk: uterine rupture, especially in a scarred uterus, but in a unscarred uterus as well, particularly if it is overdistended (multiparity, polyhydramnios, multiple pregnancy) or if there is major foeto-pelvic disproportion.
– Foetal risk: foetal distress due to uterine hypertony (uterine contraction without relaxation).
7.4.3 Contra-indications to the use of oxytocin during labour
– Obvious foeto-pelvic disproportion, including malpresentation (brow, transverse, etc.). – Complete placenta praevia. – Spontaneous uterine hypertony. – Foetal distress. – Two or more prior caesarean sections. – Prior classical caesarean section (vertical uterine incision).
– Absence of indication.
7.4.4 Situations requiring special precautions
– Prior single low transverse caesarean section. – Grand multiparity (5 deliveries or more).
– Overdistended uterus.
These factors increase the risk of uterine rupture. Oxytocin may be used provided the following precautions are respected: 1. maximum infusion rate of 30 drops/minute for 5 IU in 500 ml (i.e. 15 milli-units per minute); 2. assess maternal and foetal status before every dosage increase; 3. interval of at least 30 minutes between dose increases;
4. do not increase dosage (possibly even decrease dosage) if satisfactory uterine contractions and progress of cervical dilation.
7.4.5 Conditions for oxytocin use
– Given the risk to both mother and foetus, use of oxytocin during labour requires: • close maternal monitoring (check for hyperstimulation, dystocia and imminent rupture at least every 30 minutes); • close foetal monitoring (check for decelerations in heart rate at least every 30 minutes); • proximity to an operating theatre, in order to perform prompt caesarean section if needed.
– Position the patient on her left side.
In the event of foetal distress, uterine hyperkinesia (more than 5 contractions in 10 minutes) or uterine hypertony (absence of uterine relaxation): stop the oxytocin.
After delivery, however, there is no risk of uterine rupture or foetal distress, and oxytocin can be used more readily.
Table 7.2 - Use of oxytocin
| During labour | |||
| Labour induction | • On vaginal exam, assess cervical dilation and effacement, and engagement (Bishop score ≥ 6, Table 7.1). |
| • Appearance and quality of contractions, uterine relaxation. • Foetal heart rate. • General condition of the mother. • Cervical dilation. Rupture the membranes as soon as possible. |
| Correction of dynamic dystocia | • Cervix at least 5 cm on vaginal exam. • Spontaneous or artificial rupture of membranes. • No foeto-pelvic disproportion. | As for labour induction. | • Resumption or augmentation of contractions, uterine relaxation. • Foetal heart rate. • General condition of the mother. • Cervical dilation. |
| No contractions 15 minutes after the birth of first twin | Verify that presentation is vertical (not transverse). | • Start or resume oxytocin infusion. | • Resumption or augmentation of contractions, uterine relaxation. |
| Note: outside of labour, oxytocin is use as below | |||
| Haemorrhage due to uterine atony | • First, manually remove the placenta, if needed. | IV infusion over 2 hours of 20 IU in 1 litre of Ringer lactate or 0.9% sodium chloride (160 drops/minute). At the same time, give 5 to 10 IU by slow IV injection; repeat if necessary until the uterus becomes firm and contracted (max. 60 IU total dose). | • Heart rate, blood pressure, blood loss. |
| After caesarean section | 10 IU by slow IV injection after clamping the cord then IV infusion over 2 hours of 20 IU in 1 litre of Ringer lactate or 0.9% sodium chloride (160 drops/minute). | Uterine retraction. |
|
| Prevention of postpartum haemorrhage | Verify that there is no second twin. | 5 to 10 IU by slow IV or IM injection, before or after the third stage, depending on staff expertise. |
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Oxytocin is indicated and approved by the FDA for two specific time frames in the obstetric world: antepartum and postpartum. In the antepartum period, exogenous oxytocin is FDA-approved for strengthening uterine contractions with the aim of successful vaginal delivery of the fetus. There are three situations during the antepartum period, which indicate the use of oxytocin. These include mothers with preeclampsia, maternal diabetes, premature rupture of the membranes, mothers with inactive uteri that require stimulation into labor, and mothers with inevitable or incomplete abortions in their second trimester. Postpartum, oxytocin is FDA-approved when it is time to deliver the placenta during the third stage of labor and control postpartum hemorrhage. This activity outlines the indications, mechanism of action, methods of administration, significant adverse effects, contraindications, monitoring, and toxicity of oxytocin so providers can direct patient therapy to optimal outcomes where oxytocin has therapeutic benefit.
Objectives:
Identify the indications for the therapeutic use of oxytocin.
Describe the mechanism of action of oxytocin that gives it its therapeutic effects.
Review the potential adverse events and contraindications to using oxytocin.
Outline the importance of collaboration and communication among interprofessional team members to improve outcomes and treatment efficacy for patients who might benefit from therapy with oxytocin.
Oxytocin is indicated and approved by the FDA for two specific time frames in the obstetric world: antepartum and postpartum. In the antepartum period, exogenous oxytocin is FDA-approved for strengthening uterine contractions with the aim of successful vaginal delivery of the fetus. There are three situations during the antepartum period in which oxytocin is indicated:
For mothers who have preeclampsia, maternal diabetes, premature rupture of the membranes
For mothers with inactive uteri that require stimulation to start labor
For mothers with inevitable or incomplete abortions in their second trimester
In regards to the postpartum period, oxytocin is FDA-approved when it is time to deliver the placenta during the third stage of labor and control postpartum hemorrhage. A former version of oxytocin in the United States included an intranasal formula to encourage postpartum milk ejection. Other non-FDA-approved indications for exogenous oxytocin include treatment of delayed orgasm, inducing sexual arousal, and treatment of autism. Oxytocin has long been known as a hormone that plays a role in social behaviors and bonding. Because women release oxytocin during sexual intercourse, it is thought to play a role in bonding. Autism is not known to be caused by lower levels of oxytocin when compared to non-autistic people; however, previous studies have shown that giving oxytocin to children with autism seems to spark social skills. Further studies and larger sample sizes are needed.[1][2][3]
Oxytocin is an oligopeptide hormone that contains nine amino acyl residues, or in other words, a nonapeptide hormone. It is one of the two hormones stored and released from the posterior pituitary gland but created in the hypothalamus. It is specifically released from the paraventricular nucleus of the hypothalamus into the posterior pituitary gland for later use. This specific part of the posterior pituitary gland that stores oxytocin is called the pars nervosa, also known as the neural or posterior lobe. Most hormones create negative feedback loops after they are released, but oxytocin is one of the few that exhibit positive feedback loops, i.e., that the release of oxytocin leads to actions that stimulate even more of a release of oxytocin. This feedback contrasts with antidiuretic hormone (ADH), also known as vasopressin (the second and only other hormone stored and released from the posterior pituitary), which exhibits a negative feedback loop after release. Less of this hormone will be released after it exhibits its effect on the body.[4]
Exogenous oxytocin causes the same response in the female reproductive system as that of endogenous oxytocin. Both types of oxytocin stimulate uterine contractions in the myometrium by causing G-protein coupled receptors to stimulate a rise in intracellular calcium in uterine myofibrils. Oxytocin receptor activation causes many signals that stimulate uterine contraction by increasing intracellular calcium levels, which is where positive feedback comes into play. When oxytocin is released, it stimulates uterine contractions, and these uterine contractions, in turn, cause more oxytocin to be released; this is what causes the increase in both the intensity and frequency of contractions and enables a mother to carry out vaginal delivery completely. The head of the fetus pushes against the cervix, the nerve impulses from this action travel to the mother’s brain, which activates the posterior pituitary to secrete oxytocin. This oxytocin is then carried through the blood to the uterus to increase uterine contractions further, and the cycle continues until parturition.[5][4][5]
Not only does oxytocin stimulate uterine contractions, but it also causes contractions of the myoepithelial cells in the female breasts. This activity occurs in the alveolar ducts. Such contractions are what force milk from these ducts into even larger sinuses, which enable milk expulsion. Positive feedback is also relevant to this milk-ejection reflex. A baby attempting to latch on to his mother’s breast signals oxytocin secretion into the blood in the same manner as vaginal delivery, except, instead of uterine contractions, milk is ejected from the breast. The oxytocin makes its way to the brain at the same time to increase more oxytocin secretion.[6]
Lastly, oxytocin also has both antidiuretic and vasodilatory effects, increasing cerebral, coronary, and even renal blood flow.[7][8]
An injected form of oxytocin is administered intravenously using the drip method in the setting of delayed and potentially complicated labor. The same route of administration is indicated for both incomplete and inevitable abortions as well. Lastly, in the case of persistent uterine bleeding after giving birth, oxytocin may be given either intramuscularly or intravenously.[9][10]
Dosing for labor induction/augmentation:
0.5 to 2 milliunits/minute IV, with increases of 1 to 2 milliunits every 15 to 40 minutes until there is an established contraction pattern.
Dosing for postpartum hemorrhage:
Prophylactic dosing: 10 units IM once following placental delivery.
Therapeutic dosing: 60 to 200 milliunits/minute IV.
Common side effects of oxytocin administration include the following: erythema at the site of injection, intensified contractions, more frequent contractions, nausea, vomiting, stomach pain, and loss of appetite. Serious adverse effects that require monitoring after oxytocin administration include cardiac arrhythmias, seizures, anaphylaxis, confusion, hallucinations, extreme increase in blood pressure, and blurred vision.[11]
Specific contraindications to oxytocin include hypersensitivity to the hormone itself or any part of its synthetic version and vaginal deliveries that are in themselves contraindicated. These include the patient having an active genital herpes infection, vasa previa, complete placenta previa, invasive cervical cancer, and prolapse or presentation of the umbilical cord). Other contraindications to administering oxytocin include the fetus in an abnormal position (most notably including a transverse lie) and the fetus exhibiting distress when delivery is not about to happen. Antepartum usage of oxytocin is also contraindicated for women with pelvises not large enough to handle an infant passing through her birth canal and for when the woman's uterus is either hyperactive or hypertonic.[12]
It is essential to monitor patient fluids (both intake and outtake) while administering oxytocin and the frequency of uterine contractions, patient blood pressure, and heart rate of the unborn fetus.
An inappropriate dosage of oxytocin can lead to dangerous tachycardia, arrhythmias, and myocardial ischemia. High dosages of oxytocin can cause uterine rupture, hypertonicity, and spasms. When oxytocin is given to women in the first or second stages of labor or to women to cause induction of labor, uterine rupture, maternal subarachnoid hemorrhages, maternal death, and even fetal death can result. If oxytocin is given in dosages too large or even slowly during 24 hours, the medication can exhibit an antidiuretic effect resulting in extreme water intoxication; this can result in coma, seizures, and even death of the mother. Note that patients who receive fluids orally are at higher risk for water intoxication and antidiuretic effects when given exogenous oxytocin.[13][14]
Oxytocin is primarily used by the obstetrician and labor and delivery nurses. Its use and monitoring require the efforts of an interprofessional healthcare team that includes clinicians, specialists, obstetric nurses, and pharmacists. Clinicians who do prescribe this hormone should be familiar with its side effects. An inappropriate dosage of oxytocin can lead to dangerous tachycardia, arrhythmias, and myocardial ischemia. High dosages of oxytocin can cause uterine rupture, hypertonicity, and spasms. When oxytocin is given to women in the first or second stages of labor or to women to cause induction of labor, uterine rupture, maternal subarachnoid hemorrhages, maternal death, and even fetal death can result. If oxytocin is given in dosages too large or even slowly during 24 hours, the medication can exhibit an antidiuretic effect resulting in extreme water intoxication. This excessive dosing can result in coma, seizures, and even death in the mother.; hence, the pharmacist needs to check the dosage ordered carefully. Note that patients who receive fluids orally are at higher risk for water intoxication and antidiuretic effects when given exogenous oxytocin. When used at therapeutic doses, the drug is safe and effective.[15][16] [Level 5]
Review Questions
1.
Sentilhes L, Madar H, Ducarme G, Hamel JF, Mattuizzi A, Hanf M. Outcomes of operative vaginal delivery managed by residents under supervision and attending obstetricians: a prospective cross-sectional study. Am J Obstet Gynecol. 2019 Jul;221(1):59.e1-59.e15. [PubMed: 30807764]
2.Saccone G, Della Corte L, Maruotti GM, Quist-Nelson J, Raffone A, De Vivo V, Esposito G, Zullo F, Berghella V. Induction of labor at full-term in pregnant women with uncomplicated singleton pregnancy: A systematic review and meta-analysis of randomized trials. Acta Obstet Gynecol Scand. 2019 Aug;98(8):958-966. [PubMed: 30723915]
3.Saccone G, Della Corte L, D'Alessandro P, Ardino B, Carbone L, Raffone A, Guida M, Locci M, Zullo F, Berghella V. Prophylactic use of tranexamic acid after vaginal delivery reduces the risk of primary postpartum hemorrhage. J Matern Fetal Neonatal Med. 2020 Oct;33(19):3368-3376. [PubMed: 30704334]
4.Li XH, Matsuura T, Xue M, Chen QY, Liu RH, Lu JS, Shi W, Fan K, Zhou Z, Miao Z, Yang J, Wei S, Wei F, Chen T, Zhuo M. Oxytocin in the anterior cingulate cortex attenuates neuropathic pain and emotional anxiety by inhibiting presynaptic long-term potentiation. Cell Rep. 2021 Jul 20;36(3):109411. [PubMed: 34289348]
5.Ellis JA, Brown CM, Barger B, Carlson NS. Influence of Maternal Obesity on Labor Induction: A Systematic Review and Meta-Analysis. J Midwifery Womens Health. 2019 Jan;64(1):55-67. [PMC free article: PMC6758543] [PubMed: 30648804]
6.Perkinson MR, Kim JS, Iremonger KJ, Brown CH. Visualising oxytocin neurone activity in vivo: The key to unlocking central regulation of parturition and lactation. J Neuroendocrinol. 2021 Nov;33(11):e13012. [PubMed: 34289195]
7.Sapolsky RM. Doubled-Edged Swords in the Biology of Conflict. Front Psychol. 2018;9:2625. [PMC free article: PMC6306482] [PubMed: 30619017]
8.Viteri OA, Sibai BM. Challenges and Limitations of Clinical Trials on Labor Induction: A Review of the Literature. AJP Rep. 2018 Oct;8(4):e365-e378. [PMC free article: PMC6306280] [PubMed: 30591843]
9.Gallos ID, Papadopoulou A, Man R, Athanasopoulos N, Tobias A, Price MJ, Williams MJ, Diaz V, Pasquale J, Chamillard M, Widmer M, Tunçalp Ö, Hofmeyr GJ, Althabe F, Gülmezoglu AM, Vogel JP, Oladapo OT, Coomarasamy A. Uterotonic agents for preventing postpartum haemorrhage: a network meta-analysis. Cochrane Database Syst Rev. 2018 Dec 19;12:CD011689. [PMC free article: PMC6388086] [PubMed: 30569545]
10.Bhargava R, Daughters KL, Rees A. Oxytocin therapy in hypopituitarism: Challenges and opportunities. Clin Endocrinol (Oxf). 2019 Feb;90(2):257-264. [PubMed: 30506703]
11.Simpson KR. Considerations for Active Labor Management with Oxytocin: More May Not be Better. MCN Am J Matern Child Nurs. 2020 Jul/Aug;45(4):248. [PubMed: 32604188]
12.Ghorbani Z, Mirghafourvand M. The efficacy and safety of intravaginal oxytocin on vaginal atrophy: A systematic review. Post Reprod Health. 2021 Mar;27(1):30-41. [PubMed: 32814499]
13.Zhang H, Liu H, Luo S, Gu W. Oxytocin use in trial of labor after cesarean and its relationship with risk of uterine rupture in women with one previous cesarean section: a meta-analysis of observational studies. BMC Pregnancy Childbirth. 2021 Jan 06;21(1):11. [PMC free article: PMC7786988] [PubMed: 33407241]
14.Pursche T, Diedrich K, Banz-Jansen C. Blood loss after caesarean section: depending on the management of oxytocin application? Arch Gynecol Obstet. 2012 Sep;286(3):633-6. [PubMed: 22569708]
15.Smorti M, Ponti L, Tani F. The effect of maternal depression and anxiety on labour and the well-being of the newborn. J Obstet Gynaecol. 2019 May;39(4):492-497. [PubMed: 30773960]
16.Charles D, Anger H, Dabash R, Darwish E, Ramadan MC, Mansy A, Salem Y, Dzuba IG, Byrne ME, Breebaart M, Winikoff B. Intramuscular injection, intravenous infusion, and intravenous bolus of oxytocin in the third stage of labor for prevention of postpartum hemorrhage: a three-arm randomized control trial. BMC Pregnancy Childbirth. 2019 Jan 18;19(1):38. [PMC free article: PMC6339323] [PubMed: 30658605]