Uterine atony is the most common cause of postpartum hemorrhage. Although alternatives exist, oxytocin is the safest and best tolerated intervention, thus leading to its widespread use today.
Oxytocin is a nonapeptide hormone synthesized in the hypothalamus and secreted by the posterior pituitary gland. It is responsible for the lactation letdown reflex, uterine contraction, and water retention. Oxytocin exerts its effects via a G-protein-coupled receptor on the surface of uterine myocytes, leading to downstream synthesis of prostaglandins, and ultimately resulting in calcium release from the sarcoplasmic reticulum. All these events culminate in uterine contraction of the upper segment and subsequent relaxation. At pharmacologic doses of oxytocin, increased frequency of contraction and incomplete relaxation is observed within the uterine musculature. As gestation advances, concentrations of both oxytocin receptors and myocyte gap junctions increase, leading to increased sensitivity to oxytocin.
Not only does oxytocin play a role in uterine contraction, but this hormone is also involved in hemodynamic regulation. It can precipitate hypotension (secondary to vasodilation), especially when given as a bolus, in addition to causing a release of atrial and brain natriuretic peptides. Due to its structural similarity to vasopressin/antidiuretic hormone (ADH), oxytocin may also cause water retention and hyponatremia. It may even result in seizures and coma. For this reason, the drug should not be diluted in a hypotonic solution such as D5 ½ normal saline.
Synthetic oxytocin is an octapeptide that is the first-line routine agent for the treatment of uterine atony. It has fewer ADH-related side effects. It has a half-life of 3 minutes and does not cross the blood–brain barrier.
Given the potential side effects of oxytocin administration, it should be administered in the lowest dose possible required to achieve the desired effects. The dose and rate of intravenous (IV) infusion of oxytocin after delivery during cesarean section remain controversial. Because oxytocin administered at infusion rates less than 45 milliunits/min acts much less like an antidiuretic, it has been suggested that its administration should be restricted to lower infusion rates. Furthermore, due to its potential to cause fluid retention, lower infusion rates are particularly beneficial in patients with preeclampsia who are more prone to develop pulmonary edema. Most studies suggest administering 10–40 units oxytocin via an IV infusion, with the maximum dose 40 units to 1000 mL, over a 4–8-hour period following a Cesarean delivery in order to prevent postpartum hemorrhage.
Although there are several sets of guidelines for oxytocin usage at various institutions, deviations from these guidelines frequently occur. Such deviations may reflect a lack of robust evidence regarding the use and dosage of oxytocin to prevent uterine atony.
Ergot alkaloids (methylergonovine and ergometrine) cause generalized smooth muscle contraction. These drugs are used to treat uterine atony when oxytocin has been ineffective. Methylergonovine stimulates a-adrenergic and serotonin receptors and ...