Syntometrine

Uses

In Antepartum:

• Induction of labor in patients with a medical indication for the initiation of labor, such as Rh problems, maternal diabetes, (pre-) eclampsia at or near term, when delivery is in the best interests of mother and fetus or when membranes are prematurely ruptured and delivery is used;
• Stimulation or reinforcement of labor, as in selected cases of uterine inertia;
• As adjunctive therapy in the management of incomplete or inevitable abortion.

In Postpartum: Oxytocin is used to produce uterine contractions during the third stage of labor and to control postpartum bleeding or hemorrhage.

Syntometrine is also used to associated treatment for these conditions: Incomplete Abortion, Inevitable abortion, Postpartum Bleeding, Reinforcement of labor

How Syntometrine works

Oxytocin plays a vital role in labour and delivery. The hormone is produced in the hypothalamus and is secreted from the paraventricular nucleus to the posterior pituitary where it is stored. It is then released in pulses during childbirth to induce uterine contractions.

The concentration of oxytocin receptors on the myometrium increases significantly during pregnancy and reaches a peak in early labor. Activation of oxytocin receptors on the myometrium triggers a downstream cascade that leads to increased intracellular calcium in uterine myofibrils which strengthens and increases the frequency of uterine contractions.

In humans, most hormones are regulated by negative feedback; however, oxytocin is one of the few that is regulated by positive feedback. The head of the fetus pushing on the cervix signals the release of oxytocin from the posterior pituitary of the mother. Oxytocin then travels to the uterus where it stimulates uterine contractions. The elicited uterine contractions will then stimulate the release of increasing amounts of oxytocin. This positive feedback loop will continue until parturition.

Since exogenously administered and endogenously secreted oxytocin result in the same effects on the female reproductive system, synthetic oxytocin may be used in specific instances during the antepartum and postpartum period to induce or improve uterine contractions.

Dosage

Syntometrine dosage

Induction or Stimulation of Labor:

• The standard solution for infusion of Oxytocin is prepared by adding the contents of one 1ml vial containing 10 units of Oxytocin to 1000 ml of infusion fluids. The combined solution containing 10 mU (1mU=0.001U) of Oxytocin/ml is rotated in the infusion bottle for thorough mixing.
• The initial dose should be 0.5-1 mU/min (equal to 3-6 ml of the dilute Oxytocin solution per hour). At 30-60 minutes intervals the dose should be gradually increased in increments of 1-2 mU/min until the desired contraction pattern has been established. Once the desired frequency of contractions has been reached and labor has progressed to 5-6 cm dilation, the dose may be reduced by similar increments.
• At term, higher infusion rates should be given with great care and rates exceeding 9-10 mU/min are rarely required.
• Before term, when the sensitivity of the uterus is lower because of a lower concentration of Oxytocin receptors, a higher infusion rate may be required.

Control of Postpartum Uterine Bleeding:

• Intravenous Infusion (Drip Method): To control postpartum bleeding, 10 to 40 units of Oxytocin may be added to the bottle, depending on the amount of infusion fluids solution remaining (maximum 40 units to 1000 ml). Adjust infusion rate to sustain uterine contraction and control uterine atony.
• Intramuscular Administration: 1 mL (10 units) of Oxytocin can be given after the delivery of the placenta.

Treatment of Incomplete or Inevitable Abortion:

• Intravenous infusion of 10 units of Oxytocin added to 500 ml of a 0.9% sodium chloride solution may help the uterus contract after a suction or sharp curettage for an incomplete, inevitable or elective abortion.
• Subsequent to intra-amniotic injection of hypertonic saline, prostaglandins, urea etc., for mid trimester elective abortion, the injection-to-abortion time may be shortened by infusion of Oxytocin at the rate of 10 to 20 mU (20 to 40 drops) per minute. The total dose should not exceed 30 units in a 12-hour period due to the risk of water intoxication.

Infusion Fluids-

• 0.9% Sodium Chloride solution
• 5% Dextrose-in-water solution
• Ringer’s solution
• Hartmann’s solution (Ringer-lactate)

Side Effects

• Hypersensitivity to the drug may result in uterine hypertonicity, spasm, titanic contraction or rupture of the uterus.
• The possibility of increased blood loss and afbrinigenemia should be kept in mind when administering the drug.
• Severe water intoxication with convulsions and coma has occurred.
• Oxytocin may occasionally cause nausea, vomiting, haemorrhage or cardiac arrhythmias, anaphylactic reaction.

Toxicity

Administration of supratherapeutic doses of exogenous oxytocin can lead to myocardial ischemia, tachycardia, and arrhythmias. High doses can also lead to uterine spasms, hypertonicity, or rupture. Oxytocin has antidiuretic properties, thus, high daily doses (as a single dose or administered slowly over 24 hours) may lead to extreme water intoxication resulting in maternal seizures, coma, and even death. The risk of antidiuresis and water intoxication in the mother appears to be greater when fluids are given orally.

Precaution

Oxytocin should not be administered in the following conditions: prematurity, borderline cephalopelvic disproportion, previous major surgery on the cervix or uterus including caesarean section, overdistention of the uterus, grand multiparity or invasive cervical carcinoma.

Interaction

Severe hypertension has been reported when Oxytocin was given three to four hours following prophylactic administration of a vasoconstrictor in conjunction with caudal-block anesthesia. Cyclopropane anesthesia may modify Oxytocin’s cardiovascular effects, so as to produce unexpected results such as hypotension. Maternal sinus bradycardia with abnormal atrioventricular rhythms has also been noted when Oxytocin was used concomitantly with cyclopropane anesthesia.

Elimination Route

Oxytocin is administered parenterally and is fully bioavailable. It takes approximately 40 minutes for oxytocin to reach steady-state concentrations in the plasma after parenteral administration.

Half Life

The plasma half-life of oxytocin ranges from 1-6 minutes. The half-life is decreased in late pregnancy and during lactation.

Clearance

In a study that observed 10 women who were given oxytocin to induce labor, the mean metabolic clearance rate was 7.87 mL/min.

Elimination Route

The enzyme oxytocinase is largely responsible for the metabolism and regulation of oxytocin levels in pregnancy; only a small percentage of the neurohormone is excreted in the urine unchanged.

Pregnancy & Breastfeeding use

Pregnancy category C. It is not known whether Oxytocin is excreted in human milk

Contraindication

This drug is contraindicated in- significant cephalopelvic disproportion; unfavorable fetal positions or presentations which are undeliverable without conversion prior to delivery, e.g., transverse lies; in obstetrical emergencies where the benefit-to-risk ratio for either the fetus or the mother favors surgical intervention; in cases of fetal distress where delivery is not imminent; hypertonic uterine patterns; hypersensitivity to the drug. Prolonged use in uterine inertia or severe toxemia is contraindicated. Oxytocin should not be used in cases where vaginal delivery is not indicated.

Acute Overdose

Overdosage with Oxytocin depends essentially on uterine hyperactivity whether or not due to hypersensitivity to this agent. Hyperstimulation with strong (hypertonic) or prolonged (tetanic) contractions, or a resting tone of 15 to 20 mm H2O or more between contractions can lead to tumultuous labor, uterine rupture, cervical and vaginal lacerations, postpartum hemorrhage, utero-placental hypoperfusion, and variable deceleration of fetal heart, fetal hypoxia, hypercapnia, or death. Water intoxication with convulsions, which is caused by the inherent antidiuretic effect of Oxytocin, is a serious complication that may occur if large doses (40 to 50 mU/minute) are infused for long periods. Management consists of immediate discontinuation of Oxytocin and symptomatic and supportive therapy.

Storage Condition

Store in between 2 to 8° C, in dark & frost free place. Keep out of the reach of children.

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