Sodium Chloride 20% Injection (Monograph)

Drug class: Oxytocics
- Abortifacient Agents
ATC class: B05XA03
VA class: GU600
CAS number: 7647-14-5

Medically reviewed by Drugs.com on Dec 23, 2024. Written by ASHP.

Introduction

Sodium chloride 20% injection is a hypertonic injections used as an abortifacient.

Uses for Sodium Chloride 20% Injection

Injections of 20% sodium chloride are used by transabdominal intra-amniotic instillation to induce abortion late in the second trimester of pregnancy (beyond the 16th week of gestation). Following transabdominal intra-amniotic instillation of recommended dosages of 20% sodium chloride injection in second trimester pregnancies (see Dosage and Administration), abortion occurs in about 97% of patients within 72 hours.

When abortion fails to occur, the presence of uterine malformation or abnormalities (e.g., extrauterine pregnancy, ovarian cyst) should be considered; surgical intervention may be necessary. IV infusion of dilute solutions of oxytocin may be used in conjunction with intra-amniotic sodium chloride to shorten the induction-to-abortion time or to induce abortion when a patient has failed to abort within 48 hours of intra-amniotic sodium chloride administration. Oxytocin or curettage may be used as an adjunct to hypertonic sodium chloride if the placenta fails to abort spontaneously within 1 hour after delivery of the fetus; however, some clinicians maintain that oxytocin may hinder, rather than assist in, expulsion of the placenta. Because concurrent use of the 2 drugs may produce uterine contractions of such intensity that uterine rupture or cervical laceration or rupture may be more likely to occur, oxytocin usually should not be administered until the oxytocic effect of hypertonic sodium chloride has subsided completely and/or the cervix is adequately dilated, and patients should be carefully monitored.

For inducing second trimester abortions between the 12th and 16th week of gestation, most clinicians recommend dilatation and evacuation or intravaginal dinoprostone. Because the amount of amniotic fluid is small in relation to the size of the fetus and uterus between the 12th and 16th week of gestation, amniocentesis and subsequent intra-amniotic instillation of hypertonic sodium chloride may be difficult and technical failure may result. However, abortion should not be deferred until after the 16th week for purposes of administering intra-amniotic abortifacients.

Although some clinicians recommend dilatation and evacuation or, as a second choice, hypertonic abortifacients for abortions beyond the 16th week of gestation, other clinicians have preferred intra-amniotic dinoprost tromethamine, but the latter agent is no longer commercially available in the US. One multicenter study showed that when inducing second trimester abortions beyond 16-weeks’ gestation, dilatation and evacuation was associated with a lower incidence of major complications than were the intra-amniotic abortion methods; however, these results may reflect the fact that physicians performing dilatation and evacuation procedures in this study were more skilled than are most physicians performing such procedures. Conflicting reports have shown that, when used for abortion beyond 16-weeks’ gestation, the incidence of major complications with intra-amniotic dinoprost was greater than or less than intra-amniotic instillation of 20% sodium chloride injection. In addition, the fact that prostaglandin abortifacients, unlike hypertonic abortifacients, are not feticidal and some live births may occur late in the second trimester should be considered. Although use of intra-amniotic urea (augmented with IV oxytocin) is associated with higher failure rates and longer induction-to-abortion times than is intra-amniotic hypertonic sodium chloride, some clinicians believe hypertonic urea may produce a lower incidence of life-threatening adverse effects and may be safer than hypertonic sodium chloride in high-risk patients (i.e., those with cardiac, renal, or hypertensive disease).

Sodium Chloride 20% Injection Dosage and Administration

Injections of 20% sodium chloride are administered intra-amniotically. Care must be taken to ensure that the drug is administered directly into the amniotic fluid.

After performing a transabdominal tap of the amniotic sac, at least 1 mL of amniotic fluid is withdrawn and the nature of the fluid is determined. Amniotic fluid can be identified by its pH (7.4) and its ability to fern. If the fluid contains blood or if no amniotic fluid is obtained, the needle should be repositioned. Many clinicians then prefer to remove all amniotic fluid (usually 30–250 mL) to prevent sudden increases in intra-amniotic pressure when hypertonic sodium chloride is instilled and to ensure an adequate amniotic fluid concentration of sodium chloride. However, others maintain that further removal of amniotic fluid is not necessary and may increase the risks of needle displacement. A 20% solution of sodium chloride, in volumes equal to the amount of amniotic fluid removed or a maximum of 200–250 mL, is then administered slowly over a period of 20–30 minutes while observing the patient for signs and symptoms that may indicate that the drug is not being administered into the amniotic fluid. (See Cautions: Precautions and Contraindications.) Some clinicians prefer to infuse the solution over a 5- to 10-minute period to minimize the possibility of needle displacement. If adverse reactions occur at any time during administration of the drug, it should be discontinued and the condition of the patient and placement of the needle or catheter evaluated. IV infusion of a dilute solution of oxytocin may be given within 1–2 hours of hypertonic sodium chloride instillation, usually at a rate of 10–100 milliunits/minute. However, oxytocin usually should be given only after the uterine response to hypertonic sodium chloride has ceased. Instillation of sodium chloride may be repeated in 48 hours if uterine contractility, cervical effacement, and/or cervical dilation are inadequate or if abortion is not clinically imminent, providing the membranes are still intact.

In patients who fail to respond to the second dose of hypertonic sodium chloride, IV infusion of oxytocin may be given after the oxytocic action of hypertonic sodium chloride has ceased or dilatation and evacuation may be performed.

Cautions for Sodium Chloride 20% Injection

Adverse Effects

Adverse effects reported following intra-amniotic instillation of 20% sodium chloride injection include fever, flushing, pulmonary embolism, pneumonia, infection at the injection site, and cortical necrosis of the kidneys. Ascites, uterine necrosis, severe electrolyte disturbances, hypervolemia, and circulatory failure may occur if excessive sodium chloride injection is administered, overdistending the amniotic cavity.

Cervical laceration and perforation, cervicovaginal fistula, and uterine rupture have occurred during hypertonic sodium chloride-induced abortion. These effects have occurred most commonly in primigravida patients and in those receiving concomitant IV oxytocin before the cervix was adequately dilated. Placentas may be retained in some patients undergoing abortion with hypertonic sodium chloride; when abortion is delayed, the risk of retained placenta with resultant hemorrhage, fever, and infection, including endometritis and sepsis, is increased.

A mild self-limiting form of disseminated intravascular coagulation occurs frequently in patients receiving intra-amniotic hypertonic sodium chloride. Coagulation changes, including decreases in platelet counts, hematocrit, and levels of fibrinogen and factors V (proaccelerin) and VIII (antihemophilic factor) and increases in plasma volume, fibrin levels, and thrombin, prothrombin, and partial thromboplastin times, usually occur within the first 12–24 hours following intra-amniotic instillation of hypertonic sodium chloride.

Precautions and Contraindications

Intra-amniotic instillation of 20% sodium chloride injection should be performed only by physicians trained in amniocentesis, in a hospital where intensive care and surgical facilities are immediately available. Patients should be informed of the benefits and risks of hypertonic sodium chloride-induced abortions. A complete medical history and physical examination should be performed prior to administration of the drug.

When amniocentesis and subsequent intra-amniotic instillation of hypertonic sodium chloride are performed correctly, systemic absorption of sodium chloride is minimized and there is little risk of systemic effects. However, normal patients should drink at least 2 L of water on the day of the procedure to improve sodium chloride excretion. Accidental intravascular, myometrial, or intraperitoneal injection of 20% sodium chloride solutions may produce myometrial necrosis and/or hypernatremia with secondary vomiting, cerebral blood clots, cardiovascular collapse, and seizures. Maternal deaths caused by hypernatremia have been reported. Intra-amniotic instillation of hypertonic sodium chloride is usually painless; therefore, instillation of the drug should be discontinued immediately if the patient complains of symptoms that may indicate the drug is not being administered into the amniotic fluid including pain (especially a burning sensation), a sensation of heat, thirst, severe headache, mental confusion, vague distress, lower-back, pelvic or abdominal pain, tingling sensations, numbness of the fingertips, a feeling of warmth about the lips and tongue, extreme nervousness, or tinnitus. Rapid infusion of 5% dextrose injection and further supportive therapy may be necessary to prevent hypernatremic shock. So that patients remain alert and able to report adverse reactions, general anesthetics or sedatives should not be used during administration of hypertonic sodium chloride.

Patients with cervical or uterine rupture or laceration with resultant retention of the placenta and severe hemorrhage may require blood transfusions. These hazards can be minimized if the drug is not administered to patients with a history of pelvic surgery resulting in through-and-through uterine incision. Because cervical trauma can occur without symptoms, each patient should be carefully examined after the abortion is completed to detect any cervical injuries.

Induction of abortion with intra-amniotic hypertonic sodium chloride should be performed with extreme caution, if at all, in patients with cardiovascular disorders including hypertension or heart disease, epilepsy, serious renal impairment, or pelvic adhesions. The risk of hemorrhage is usually low in most patients receiving hypertonic sodium chloride but is higher in patients with blood disorders such as coagulation factor deficiencies, thrombocytopenia, or fibrinolytic defects; therefore, hypertonic sodium chloride-induced abortion is contraindicated in patients with blood disorders. The drug is also contraindicated when there is evidence of increased intra-amniotic pressure as in an actively contracting or hypertonic uterus.

Drug Interactions

IV administration of terbutaline at a rate of 5–20 mcg/minute has been reported to inhibit uterine activity initiated by intra-amniotic instillation of 20% sodium chloride. Indomethacin, in doses of 25 mg orally every 6 hours for 8 doses beginning 4–6 hours after intra-amniotic instillation of sodium chloride, has been reported to increase the time interval between intra-amniotic administration of hypertonic sodium chloride and abortion.

Pharmacology

Intra-amniotic instillation of 20% sodium chloride injection induces abortion and fetal death. Although the mechanism has not been conclusively determined, some studies indicate that the drug’s abortifacient activity may be mediated by prostaglandins released from decidual cells damaged by hypertonic solutions of sodium chloride. Hypertonic sodium chloride-induced uterine contractions are usually sufficient to cause evacuation of both the fetus and placenta; however, abortion may be incomplete in 25–40% of patients.

Sodium Chloride 20% Injection Pharmacokinetics

In one study of second trimester abortions, amniotic fluid sodium concentrations of greater than 2.2 mEq/mL were reached in 81% of patients following removal of 75–500 mL of amniotic fluid and instillation of 180–1000 mEq of sodium chloride (45–250 mL of 23% sodium chloride injection); abortion occurred within 51 hours in all of these patients. In those patients with amniotic fluid sodium concentrations of less than 2.2 mEq/mL, 20% aborted within 48 hours, 67% aborted after 2–6 days, and 13% failed to abort. It was concluded that an amniotic fluid sodium concentration of at least 2.2 mEq/mL is required to consistently induce abortion.

In one study using radiolabeled 20% sodium chloride injection, most of the drug concentrated in the decidua and the fetal part of the placenta following intra-amniotic injection. Following intra-amniotic administration of 20% sodium chloride injection, some of the drug diffuses into the maternal blood.

Chemistry

Sodium chloride occurs as cubic crystals or as a white, crystalline powder having a saline taste and is freely soluble in water and slightly soluble in alcohol. Hypertonic injections used as abortifacients usually contain 20% (3.41 mEq/mL) sodium chloride.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.