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NCT Number: NCT03852797

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

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.

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Key information

Conditions

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

Age range

19 year–50 year

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Mount Sinai Hospital

Toronto, Ontario, M5G1X5, Canada

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Oxytocin

Drug

Oxytocin solution, 20nM concentration

Other names: pitocin

ketamine

Drug

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

Other names: ketamine HCl

Propofol

Drug

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

Etomidate

Drug

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

Primary outcomes

  1. Motility index

    Time frame: 4 hours

    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.

Secondary outcomes

  1. Amplitude of contraction

    Time frame: 4 hours

    The maximum extent of uterine muscle contraction, measured in grams (g). The analysis is undertaken by attaching myometrial strips between an isometric force transducer and the base of an organ bath chamber.

  2. Frequency of contraction

    Time frame: 4 hours

    The number of contractions in uterine muscle (myometrium) over 10 minutes, spontaneously and in response to an agonist.

    The analysis is undertaken by attaching myometrial strips between an isometric force transducer and the base of an organ bath chamber.

  3. Integrated area under response curve (AUC)

    Time frame: 4 hours

Sponsors and collaborators

Lead sponsor

Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Other

Registry information

Important dates

Study start
2019
Primary completion
2022
Study completion
2022
First posted
Feb 25, 2019
Registry last updated
Oct 25, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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