Intravenous Versus Intramuscular Administration of Methylergonovine for Uterine Contraction in Cesarean Sections

Johns Hopkins University

Status and phase

Withdrawn

Early Phase 1

Conditions

Uterine Tone Disorders

Uterine Atony

Postpartum Hemorrhage

Treatments

Drug: Methylergonovine

Study type

Interventional

Funder types

Other

Identifiers

NCT03303235

IRB00120873

Details and patient eligibility

About

Insufficient uterine tone resulting in atony can potentiate hemorrhage and adverse outcomes for the parturient. Oxytocin is the first pharmacologic agent used, followed by methylergonovine, carboprost, and misoprostol. The American Congress of Obstetricians and Gynecologists (ACOG) recommends the sequential use of oxytocin, followed by methylergonovine, carboprost, misoprostol, then surgical intervention for cases of refractory uterine atony. Many studies have examined the effect and dosage of intravenous uterotonics, including oxytocin.

Although there are anecdotal reports of using intravenous bolus or rapid infusion of methylergonovine, no randomized trial has compared efficacy and side effects of these two routes of administration. Investigators hypothesize that intravenous methylergonovine reduces the time to adequate uterine tone (the tone at which the uterus is adequately contracted to prevent atony after delivery of neonate), decreases the total dose of methylergonovine to contract the uterus, and therefore produces fewer side effects of hypertension, nausea, and vomiting. Reducing the time to achieve adequate uterine tone is likely to decrease postpartum hemorrhage.

Full description

The United States is one of the few modern countries in which maternal peripartum mortality continues to rise. One of the three most important causes of maternal mortality is severe hemorrhage. Controlling postpartum uterine tone remains an important role for the obstetric anesthesiologist. Insufficient uterine tone resulting in atony can potentiate hemorrhage and adverse outcomes for the parturient. Oxytocin is the first pharmacologic agent used, followed by methylergonovine, carboprost, and misoprostol. The American Congress of Obstetricians and Gynecologists (ACOG) recommends the sequential use of oxytocin, followed by methylergonovine, carboprost, misoprostol, then surgical intervention for cases of refractory uterine atony. Many studies have examined the effect and dosage of intravenous uterotonics, including oxytocin.

Methylergonovine maleate is a semi-synthetic ergot alkaloid. Methylergonovine(200 mcg) is administered intramuscularly when oxytocin has been administered but has not contracted the uterus sufficiently. It is not without side effects, however. Due to its vasoconstrictive properties, methylergonovine has been shown to elevate blood pressures and is avoided in preeclamptic patients who may not tolerate abrupt increases in blood pressures. Although there are anecdotal reports of using intravenous bolus or rapid infusion of methylergonovine, no randomized trial has compared efficacy and side effects of these two routes of administration. Investigators hypothesize that intravenous methylergonovine reduces the time to adequate uterine tone (the tone at which the uterus is adequately contracted to prevent atony after delivery of neonate), decreases the total dose of methylergonovine to contract the uterus, and therefore produces fewer side effects of hypertension, nausea, and vomiting. Reducing the time to achieve adequate uterine tone is likely to decrease postpartum hemorrhage.

Sex

Female

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

All patients admitted for elective cesarean section
All laboring patients for planned vaginal delivery as these women may have an unplanned cesarean delivery for maternal or for fetal indications
Patients not in labor but admitted for non-elective cesarean section
Administration of oxytocin prior to administration of methylergonovine, in accordance to the ACOG guideline for postpartum hemorrhage
Obstetrician's request for methylergonovine intraoperatively to the anesthesiologist

Exclusion criteria

Fetus not considered to be of viable gestational age by obstetrical team
Patients with hypertension (either chronic or pregnancy-induced, including preeclampsia)
Patients with coronary artery disease, established and diagnosed by medical internist or cardiologist
Patients taking CYP3A4 inhibitors
Patients taking beta blockers.
Patients with contraindications to any of the uterotonic agents for whatever medical reason (allergies, for example)
Surgeon request for administration of methylergonovine earlier than per protocol due to clinical situation as abovementioned
Maternal or obstetrician refusal
Patients who require obstetrical intervention before 30 minutes has elapsed