The Relaxant Effect of Nitroglycerin on Oxytocin Desensitized Human Myometrium

Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Status: Completed

Conditions: Postpartum Hemorrhage

Treatments: Drug: Nitroglycerin; Drug: Oxytocin

Study type: Interventional

Funder types: Other

Identifiers

NCT03408054

18-01

Details and patient eligibility

About

Oxytocin causes myometrial contraction via the oxytocin receptor (OTR). Desensitization of the OTR after exposure to oxytocin has been demonstrated in previous studies. The resultant need for a higher oxytocin dose to cause adequate uterine contraction in vivo has also been demonstrated in laboring women having received oxytocin for labor augmentation.

Achieving rapid uterine relaxation can be invaluable for maternal and fetal wellbeing in some acute obstetric emergency settings. Nitroglycerin has become a commonly used agent for achieving rapid uterine relaxation amongst obstetric anesthesiologists.

Previous studies have concluded that oxytocin can be used to re-establish uterine tone following nitroglycerin mediated relaxation. However, no studies to date have looked at the effects of nitroglycerin mediated relaxation of uterine muscle that has undergone oxytocin receptor desensitization. Nor has the response to oxytocin re-exposure and return of contractility in desensitized myometrium (following nitroglycerin) been examined.

The investigators hypothesize that nitroglycerin will reduce and inhibit uterine contractions in both oxytocin pre-treated myometrium, as well as untreated myometrium in a dose dependent fashion, but that myometrium that has undergone OTR desensitization will require less nitroglycerin for contractions to abate.

The investigators also expect that the dose of oxytocin required to re-establish equivalent contractions will be higher in the myometrial samples which have undergone nitroglycerin mediated relaxation.

Full description

Oxytocin and nitroglycerin have opposing actions on the myometrium. The pharmacological properties of quick onset and offset of action of nitroglycerin have made this the preferred drug to be used in acute scenarios where uterine relaxation is necessary.

As nitroglycerin causes changes to intracellular calcium levels and the ability uterine muscle to engage in effective contraction, it is plausible that the effects of nitroglycerin may interfere with subsequent uterine contractility and action of oxytocin.

The situation where a difficult fetal extraction is encountered at cesarean section may be in two broad groups of patients. Those pre-exposed to oxytocin and those with an oxytocin naïve myometrium. Given the large observational variation in dosages of nitroglycerin usage seen in the literature we feel it is vital to investigate whether pre-exposure to oxytocin impacts on the ability of nitroglycerin to relax uterine smooth muscle. Furthermore, once the uterus has relaxed following nitroglycerin exposure, is there a need for higher doses of oxytocin to be administered in order to re-engage the uterus in effective contraction? And is this requirement further exacerbated by the phenomenon of oxytocin receptor desensitization? These clinically important questions will be addressed by the design of this in vitro myometrial study.

Enrollment: 17 patients

Sex: Female

Ages: 16 to 40 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Patients who give written consent to participate in this study
• Patients with gestational age 37-41 weeks
• Non-laboring patients, not exposed to exogenous oxytocin
• Patients requiring primary Cesarean delivery or first repeat Cesarean delivery 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 delivery
• 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 with medical/pregnancy related conditions, such as diabetes, preeclampsia and essential hypertension

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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17 participants in 4 patient groups

Control group

No Intervention group

Description:

No oxytocin desensitization (pretreatment), no nitroglycerin

Oxytocin desensitized - no nitroglycerin

Active Comparator group

Description:

Pretreated with oxytocin, no nitroglycerin exposure

Treatment:

Drug: Oxytocin

Oxytocin desensitized - plus nitroglycerin

Active Comparator group

Description:

Pretreated with oxytocin followed by nitroglycerin exposure

Treatment:

Drug: Oxytocin

Drug: Nitroglycerin

Non oxytocin desensitized - plus nitroglycerin

Active Comparator group

Description:

No oxytocin pretreatment, followed by nitroglycerin exposure

Treatment:

Drug: Nitroglycerin