Continuing Education Activity

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.

Indications

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]

Mechanism of Action

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]

Administration

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.

Adverse Effects

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]

Contraindications

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]

Monitoring

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.

Toxicity

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]

Enhancing Healthcare Team Outcomes

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]