Spontaneous and Oxytocin-induced Contractility After Exposure to Intravenous Anesthetic Agents: an In-vitro Study in Human Myometrium

NCT03852797 | Completed

• 1 other identifier: 19-01
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

Poor uterine tone after the birth of a baby may cause serious bleeding (called postpartum hemorrhage or PPH). This is a major cause of maternal death worldwide. In the developed world the cesarean section rate is increasing. There are two modalities for anesthesia for cesarean section; general and regional (eg. spinal anesthetic). General anesthesia has been associated with increased blood loss compared to regional and the reasons for this may be multifactorial. Some of the anesthesia gases have been studied and there is laboratory evidence to suggest that these gases may reduce the tone of the uterus and therefore cause increased blood loss due to poor uterine tone. To date there has been little study on the intravenous anesthesia agents. These agents are usually administered to anaesthetise the patient at the start of surgery (induction of anesthesia), however they can also be used instead of the gases to keep the patient asleep using a 'total intravenous anesthesia' technique. Laboratory work in rats has suggested that high doses of these intravenous drugs might reduce uterine tone, thus increasing the risk of blood loss. Interestingly, at low doses one of these drugs (ketamine) may actually increase uterine tone. Only one of these drugs has been studied in human uterine tissue. The investigators plan to compare three anaesthesia induction agents on human uterine tissue under physiological conditions in the laboratory. This study will be the first to compare these three drugs on human tissue. The investigators plan to determine the impact of these drugs on spontaneous uterine contractility and also contractilty induced by oxytocin, which is the drug most commonly administered to help contract the uterus after birth. This is important as it will help inform anesthesiologists as to the best drug to use depending on the clinical circumstance. The investigators hypothesize that the intravenous induction agents will cause a dose dependent decrease in spontaneous uterine contractility, similar to what has been described in the rat model. The investigators also expect that exposure to high concentrations of intravenous anesthesia induction agents will cause a blunted contractile response to oxytocin.

Conditions

Postpartum Hemorrhage

Keywords

uterine contraction; oxytocin; ketamine; propofol; etomidate

Outcome Measures

Primary Outcomes (1)

• Motility index

  Motility index (MI) is a calculated outcome, based on the formula: frequency/(10 x amplitude). Frequency and amplitude are secondary outcome measures as described below. The analysis is undertaken by attaching myometrial strips between an isometric force transducer and the base of an organ bath chamber.

  4 hours

Secondary Outcomes (3)

• Amplitude of contraction

  4 hours

• Frequency of contraction

  4 hours

• Integrated area under response curve (AUC)

  4 hours

Study Arms (6)

Ketamine

ACTIVE COMPARATOR

The myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of ketamine (from 10 -7M to 10 -4M)

Drug: Ketamine

Ketamine + oytocin

ACTIVE COMPARATOR

The myometrial samples are bathed in an oxytocin solution (20nM) with increasing concentrations of ketamine (from 10 -7M to 10 -4M)

Drug: Oxytocin; Drug: Ketamine

Propofol

ACTIVE COMPARATOR

The myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of propofol (from 10 -7M to 10 -4M)

Drug: Propofol

Propofol + oytocin

ACTIVE COMPARATOR

The myometrial samples are bathed in an oxytocin solution (20nM) with increasing concentrations of propofol (from 10 -7M to 10 -4M)

Drug: Oxytocin; Drug: Propofol

Etomidate

ACTIVE COMPARATOR

The myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of etomidate (from 10 -7M to 10 -4M)

Drug: Etomidate

Etomidate + oytocin

ACTIVE COMPARATOR

The myometrial samples are bathed in an oxytocin solution (20nM) with increasing concentrations of etomidate (from 10 -7M to 10 -4M)

Drug: Oxytocin; Drug: Etomidate

Interventions

Oxytocin DRUG

Oxytocin solution, 20nM concentration

Also known as: pitocin

Etomidate + oytocin; Ketamine + oytocin; Propofol + oytocin

Ketamine DRUG

Ketamine in solution, 10-4M to 10-7M

Also known as: ketamine HCl

Ketamine; Ketamine + oytocin

Propofol DRUG

Propofol in solution, 10-4M to 10-7M

Propofol; Propofol + oytocin

Etomidate DRUG

Etomidate in solution, 10-4M to 10-7M

Etomidate; Etomidate + oytocin

Eligibility Criteria

• Age: 19 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Patients who give written consent to participate in this study
• Patients with gestational age 37-41 weeks
• Patients of 19-50 years
• Non-laboring patients, not exposed to exogenous oxytocin
• Patients requiring primary Cesarean section or first repeat Cesarean section
• Patients undergoing Cesarean section under spinal anesthesia

You may not qualify if:

• Patients who refuse to give written informed consent
• Patients who require general anesthesia
• Patients who had previous uterine surgery or more than one previous Cesarean section
• Patients with any condition predisposing to uterine atony and postpartum hemorrhage, such as abnormal placentation, multiple gestation, preeclampsia, macrosomia, polyhydramnios, uterine fibroids, bleeding diathesis, chorioamnionitis, or a previous history of postpartum bleeding
• Emergency Cesarean section in labor
• Patients on medications that could affect myometrial contractility, such as nifedipine, labetolol or magnesium sulphate.
• Patients who have been exposed to oxytocin prior or during the cesarean section.

Sponsors & Collaborators

• Samuel Lunenfeld Research Institute, Mount Sinai Hospital: lead

Study Sites (1)

Mount Sinai Hospital

Toronto, Ontario, M5G1X5, Canada

Location

MeSH Terms

Conditions

Postpartum Hemorrhage

Interventions

Oxytocin; Ketamine; Propofol; Etomidate

Condition Hierarchy (Ancestors)

Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Mrinalini Balki, MD

  MOUNT SINAI HOSPITAL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2019
• First Posted: February 25, 2019
• Study Start: March 28, 2019
• Primary Completion: January 19, 2022
• Study Completion: January 19, 2022
• Last Updated: October 25, 2022

Record last verified: 2022-10

Locations

CA (1)