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

NCT ID: NCT03852797

Last Updated: 2022-10-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-28
• Study Completion Date: 2022-01-19

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.

Detailed Description

There is an increasing need to fully understand the mechanisms that contribute to the higher blood loss after general anesthesia during cesarean section therefore it is important the investigators identify all pharmacological contributors to poor uterine tone. Furthermore, anesthesiologists are increasingly called upon to care for women undergoing a range of in-utero fetal surgeries which require a careful balanced anesthetic and strict control of uterine tone.

This will be the first study that compares the three commonly used intravenous anesthesia agents on human myometrium: ketamine, etomidate and propofol. This study is required to allow doctors make informed decisions about which anesthesia agent is most suitable to manage their patient depending on clinical circumstances.

The specific objective of this project is to investigate the pharmacological dose-response profiles of different anesthesia induction agents by in-vitro isometric tension measurements of contractions in gravid human myometrium. The investigators will study both spontaneous and oxytocin induced contractility.

Conditions

Postpartum Hemorrhage

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ketamine

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

Group Type: ACTIVE_COMPARATOR

Ketamine

Intervention Type: DRUG

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

Ketamine + oytocin

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

Group Type: ACTIVE_COMPARATOR

Oxytocin

Intervention Type: DRUG

Oxytocin solution, 20nM concentration

Ketamine

Intervention Type: DRUG

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

Propofol

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

Group Type: ACTIVE_COMPARATOR

Propofol

Intervention Type: DRUG

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

Propofol + oytocin

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

Group Type: ACTIVE_COMPARATOR

Oxytocin

Intervention Type: DRUG

Oxytocin solution, 20nM concentration

Propofol

Intervention Type: DRUG

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

Etomidate

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

Group Type: ACTIVE_COMPARATOR

Etomidate

Intervention Type: DRUG

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

Etomidate + oytocin

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

Group Type: ACTIVE_COMPARATOR

Oxytocin

Intervention Type: DRUG

Oxytocin solution, 20nM concentration

Etomidate

Intervention Type: DRUG

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

Interventions

Oxytocin

Oxytocin solution, 20nM concentration

Intervention Type: DRUG

Ketamine

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

Intervention Type: DRUG

Propofol

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

Intervention Type: DRUG

Etomidate

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

Intervention Type: DRUG

Other Intervention Names

pitocin; ketamine HCl

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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.

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Samuel Lunenfeld Research Institute, Mount Sinai Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mrinalini Balki, MD

Role: PRINCIPAL_INVESTIGATOR

MOUNT SINAI HOSPITAL

Locations

Mount Sinai Hospital

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

19-01

Identifier Type: -

Identifier Source: org_study_id