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

How's the Tone? Intravenous Versus Intramuscular Administration of Methylergonovine for Uterine Contraction in Cesarean Sections

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.

Study Overview

• Status: Withdrawn
• Conditions: Postpartum Hemorrhage; Uterine Atony; Uterine Tone Disorders
• Intervention / Treatment: Drug: Methylergonovine

Detailed 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.

• Study Type: Interventional
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IV Methergine; IV methylergonovine group -IM 0.9% NaCl (1 ml)) + IV methylergonovine (2 mcg/ml) infusion (100 ml)	Drug: Methylergonovine; IV vs IM; Other Names: methergine
Active Comparator: Conventional; IM methylergonovine group -200 mcg IM methylergonovine (1 ml) + IV 0.9% NaCl infusion (100 ml)	Drug: Methylergonovine; IV vs IM; Other Names: methergine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to achieve "adequate" uterine tone	Our primary objective is to determine the time to achieve "adequate" uterine tone with either intramuscular (IM) dose versus intravenous (IV) dose methylergonovine, when oxytocin has failed to do so in cesarean sections.	10 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose that achieves "adequate" uterine tone	Determining dose that achieves "adequate" uterine tone as defined by obstetricians on a qualitative numerical scale defined prior to the study (0 to 10 with 0 being inability of uterus to contract (i.e. uterine atony) to 10 being fully contracting uterus; "adequate" would be >5 on the scale)	3 minutes
Need for additional uterotonic agents	Quantifying need for additional uterotonic agents as outlined by the postpartum hemorrhage guidelines set forth by ACOG	3 minutes
Frequency of side effects of methylergonovine	Determining frequency of side effects of methylergonovine, including blood pressure changes, especially if elevated >20% preoperative level), headache, nausea, and vomiting	30 minutes
Need for vasopressors	To determine if the patient requires a vasopressor (including phenylephrine, ephedrine, epinephrine, norepinephrine or vasopressin)?	3 minutes
Estimated blood loss	Utilizing estimated blood loss by suction canister + estimated weight of blood on surgical lap	2 hours
Computed blood loss	Calculating changes in hematocrit (Hct preop - Hct postop)	2 hours

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Karen Lindeman, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2020
• Primary Completion (Anticipated): October 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: September 26, 2017
• First Submitted That Met QC Criteria: October 2, 2017
• First Posted (Actual): October 5, 2017

Study Record Updates

• Last Update Posted (Actual): August 3, 2020
• Last Update Submitted That Met QC Criteria: July 30, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: methylergonovine
• Additional Relevant MeSH Terms: Pathologic Processes; Pregnancy Complications; Obstetric Labor Complications; Puerperal Disorders; Uterine Hemorrhage; Dystocia; Hemorrhage; Postpartum Hemorrhage; Uterine Inertia; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Methylergonovine
• Other Study ID Numbers: IRB00120873

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes