Effects of Ephedrine, Phenylephrine, Norepinephrine and Vasopressin on Contractility of Human Myometrium and Umbilical Vessels: An In-vitro Study

NCT04053478 | Recruiting

• 1 other identifier: 19-04
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

Brief Summary

Hypotension is one of the most common adverse effects of spinal anesthesia for cesarean deliveries, affecting as many as 55-90% of mothers. Hypotension during cesarean deliveries can have detrimental effects on the mother and neonate. Various vasopressors, such as ephedrine, phenylephrine and more recently norepinephrine, have been used for the prevention and treatment of hypotension at cesarean deliveries. Ephedrine was historically considered as the gold standard vasopressor for the management of hypotension during cesarean deliveries. This was based on studies in animal models that showed preserved uteroplacental circulation with ephedrine and not with phenylephrine. However, multiple studies in the past several decades have shown that phenylephrine compared with ephedrine results in a more favorable fetal acid-base status. Consequently, the use of phenylephrine for blood pressure management during cesarean deliveries increased. Recently, norepinephrine was introduced in the obstetrical practice for the management of hypotension at cesarean deliveries, due to its ability to maintain maternal cardiac output better than phenylephrine. Studies have also investigated the use of vasopressin to limit hypotension during CD. There have been case reports of successful vasopressin usage to treat post-spinal hypotension after CD in patients with advanced idiopathic pulmonary arterial hypertension as well as severe mitral stenosis with pulmonary hypertension. Its effect was associated with hemodynamic stability without evidence of harm to the mother or child. However, much controversy still exists surrounding the choice of vasopressor in the obstetric population, in large part due to their varying efficacies, and maternal and fetal effects. Vasopressors used for the treatment of hypotension during cesarean deliveries can have significant direct or indirect effects on the perfusion of uteroplacental and umbilical vessels. Reduction of uteroplacental perfusion and constriction of umbilical vessels can result in fetal acidosis, however, the mechanisms for these effects are unclear. The investigators hypothesize that ephedrine, phenylephrine and norepinephrine and vasopressin have variable effects on the contractility of pregnant myometrium and umbilical arteries due to their variable actions on adrenergic alpha (α) and beta (β) receptors, as well as vasopressin1 and vasopressin2 receptors located in these tissues.

Conditions

Hypotension

Keywords

vasopressor; ephedrine; phenylephrine; norepinephrine; umbilical arteries; uterine contraction; fetal acidosis; vasopressin

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 (12)

Myometrium + Ephedrine

EXPERIMENTAL

The myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of ephedrine

Drug: Ephedrine

Myometrium + Phenylephrine

EXPERIMENTAL

The myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of phenylephrine

Drug: Phenylephrine

Myometrium + Norepinephrine

EXPERIMENTAL

The myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of norepinephrine

Drug: Norepinephrine

Myometrium + Vasopressin

EXPERIMENTAL

The myometrial samples are bathed in physiological salt solution (PSS) with increasing concentrations of vasopressin

Drug: Vasopressin

Umbilical artery + Ephedrine

EXPERIMENTAL

The umbilical artery samples are bathed in physiological salt solution (PSS) with increasing concentrations of ephedrine

Drug: Ephedrine

Umbilical artery + Phenylephrine

EXPERIMENTAL

The umbilical artery samples are bathed in physiological salt solution (PSS) with increasing concentrations of phenylephrine

Drug: Phenylephrine

Umbilical artery + Norepinephrine

EXPERIMENTAL

The umbilical artery samples are bathed in physiological salt solution (PSS) with increasing concentrations of norepinephrine

Drug: Norepinephrine

Umbilical artery + Vasopressin

EXPERIMENTAL

The umbilical artery samples are bathed in physiological salt solution (PSS) with increasing concentrations of vasopressin

Drug: Vasopressin

Umbilical vein + Ephedrine

EXPERIMENTAL

The umbilical vein samples are bathed in physiological salt solution (PSS) with increasing concentrations of ephedrine

Drug: Ephedrine

Umbilical vein + Phenylephrine

EXPERIMENTAL

The umbilical vein samples are bathed in physiological salt solution (PSS) with increasing concentrations of phenylephrine

Drug: Phenylephrine

Umbilical vein + Norepinephrine

EXPERIMENTAL

The umbilical vein samples are bathed in physiological salt solution (PSS) with increasing concentrations of norepinephrine

Drug: Norepinephrine

Umbilical vein + Vasopressin

EXPERIMENTAL

The umbilical vein samples are bathed in physiological salt solution (PSS) with increasing concentrations of vasopressin

Drug: Vasopressin

Interventions

Ephedrine DRUG

Ephedrine in solution, at applicable concentrations based on literature

Myometrium + Ephedrine; Umbilical artery + Ephedrine; Umbilical vein + Ephedrine

Phenylephrine DRUG

Phenylephrine, at applicable concentrations based on literature

Myometrium + Phenylephrine; Umbilical artery + Phenylephrine; Umbilical vein + Phenylephrine

Norepinephrine DRUG

Norepinephrine, at applicable concentrations based on literature

Myometrium + Norepinephrine; Umbilical artery + Norepinephrine; Umbilical vein + Norepinephrine

Vasopressin DRUG

Vasopressin, at applicable concentrations based on literature

Myometrium + Vasopressin; Umbilical artery + Vasopressin; Umbilical vein + Vasopressin

Eligibility Criteria

• Age: 19 Years - 40 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 19-40 years
• Non-laboring patients, not exposed to exogenous oxytocin
• Patients requiring elective primary or first repeat caesarean delivery
• Patients undergoing caesarean delivery under spinal anesthesia

You may not qualify if:

• Patients who refuse to give written informed consent
• Patients who require general anesthesia
• Patients in labor and those receiving oxytocin for induction of labor
• Emergency caesarean delivery in labor
• Patients who have had previous uterine surgery or \>1 previous caesarean delivery
• Patients with any condition predisposing to uterine atony
• Patients on medications that could affect myometrial contractility, such as insulin, nifedipine, labetolol or magnesium sulfate.

Sponsors & Collaborators

• Samuel Lunenfeld Research Institute, Mount Sinai Hospital: lead

Study Sites (1)

Mount Sinai Hospital

Toronto, Ontario, M5G1X5, Canada

RECRUITING

MeSH Terms

Conditions

Hypotension; Diabetes Insipidus

Interventions

Ephedrine; Phenylephrine; Norepinephrine; Vasopressins

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pituitary Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Phenethylamines; Ethylamines; Ethanolamines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Mrinalini Balki, MD

  MOUNT SINAI HOSPITAL

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mrinalini Balki, MD

CONTACT

416-586-4800; mrinalini.balki@uhn.ca

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: August 8, 2019
• First Posted: August 12, 2019
• Study Start: July 8, 2019
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: March 7, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)