In Vitro Evaluation of Spontaneous and Oxytocin-induced Contractility of Pregnant Human Myometrium During Exposure to Dexmedetomidine

In Vitro Evaluation of Spontaneous and Oxytocin-induced Contractility of Pregnant Human Myometrium During Exposure to Dexmedetomidine

In Vitro Evaluation of Spontaneous and Oxytocin-induced Contractility of Pregnant Human Myometrium During Exposure to Dexmedetomidine

Postpartum hemorrhage (PPH) remains to be one of the leading causes of maternal morbidity and mortality. It has been noted that an increasing number of PPH is attributed to the increased incidence of uterine atony. Myometrial contraction is affected by the choice of anesthetic technique and medications during cesarean delivery (CD). It has been proven that exposure to oxytocin during labor results in a decrease in myometrial contractions. Dexmedetomidine is a drug which has been used in obstetric practice due to its desirable effects such as decreasing pain, reduced elevation in blood pressure and heart rate, sedation, and diminished anesthetic requirement. It has been used as an adjunct during spinal or epidural anesthesia during CD and even during general anesthesia for some obstetric surgeries. The use of dexmedetomidine has been continuously rising due to its favorable effects. Its use as an adjunct in general anesthesia for obstetrical surgeries has been shown to have promising advantages. During this pandemic, dexmedetomidine has been utilized largely as a sedative in critically ill and intubated patients. This does not exclude critically ill pregnant patients who may also need to deliver urgently. Thus, it is important to investigate its effect on uterine contractility on this particular group of patients. The investigators hypothesize that dexmedetomidine causes a dose-dependent increase in contractility of the pregnant human myometrium, both spontaneous and oxytocin-induced.

The myometrial samples are bathed in increasing concentrations of dexmedetomidine (from 10 -9M to 10 -4M).

The myometrial samples are pre-treated with oxytocin (10-5M) for 2 hours, and then in increasing concentrations of dexmedetomidine (from 10 -9M to 10 -4M).

The myometrial samples are pre-treated with oxytocin (10-5M) for 2 hours, and then bathed in oxytocin at 20nM.

The myometrial samples are pre-treated with oxytocin (10-5M) for 2 hours, and then bathed in oxytocin at 20nM along with dexmedetomidine (10-9M to 10-4M)

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.

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.

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.

Inclusion Criteria: Pregnant patients scheduled for elective CD under regional anesthesia at 37-41 weeks of gestational age will be included in this study. Only patients for primary CD or repeat CD (1x) will be included in this study since excessive uterine scarring from multiple CD may affect the contractility of myometrial sample. Exclusion Criteria: patient refusal emergency CD general anesthesia placenta accreta spectrum disorder any condition predisposing the patient to uterine atony (e.g. polyhydramnios, multiple gestation) patients taking medications affecting myometrial contractions(labetalol, magnesium etc.).