ASHEVILLE, N.C. — Peripartum hemorrhage is one of the leading causes of maternal mortality, making it important to understand the myriad options for controlling bleeding, David C. Mayer, M.D., said at the Southern Obstetric and Gynecologic Seminar.
“Unfortunately, over the decades, hemorrhage has never been moved out of the top three causes of maternal mortality,” said Dr. Mayer of the department of anesthesiology at the University of North Carolina at Chapel Hill.
Peripartum hemorrhage accounts for as much as 18% of pregnancy-related deaths in the United States, according to one estimate.
Resuscitation is the first goal in the management of peripartum hemorrhage (PPH). Make sure there is an adequate number of intravenous lines and maintain adequate volume by using crystalloids, colloids, packed red blood cells, fresh frozen plasma, or platelets, as necessary. Get baseline blood laboratory tests, including a coagulation profile, and monitor arterial blood gas levels and urinary output. Invasive monitoring with arterial or central venous lines may be necessary, as may consultation with specialists, cautioned Dr. Mayer.
There are a number of options to control bleeding: pharmacologic (such as prostaglandins), autologous blood transfusion, and selective arterial embolization. Pharmacologic therapy includes oxytocics, ergot alkaloids, prostaglandins, and recombinant activated factor VII (rFVIIa). Keep in mind almost all studies of pharmacologic therapies are based on routine elective cesarean sections.
“It may have very little applicability to a patient with an atonic uterus,” Dr. Mayer said.
Oxytocin (Pitocin) is the pharmacologic therapy that most obstetricians go to first to control bleeding. The drug can be used as prophylaxis in women who are at high risk for PPH, with doses of 10–40 U/L administered intravenously. “For uterine atony, I'm very aggressive with oxytocin, except for giving a large bolus,” Dr. Mayer said during the meeting.
He recommends using up to 40–60 U/L given intravenously. Avoid using an intravenous bolus greater than 2 IU. A bolus less than 2 IU can be effective and is unlikely to be problematic, especially if blood pressure is supported. “Just remember that if your patient is already hypotensive, it's probably not the thing to do—increasing the rate of oxytocin,” said Dr. Mayer, also of the department of obstetrics and gynecology at the university.
Ergot alkaloids—ergonovine and methylergonovine—are very effective at inducing contractions. While the exact mechanism of action is unclear, ergot alkaloids are believed to have adrenergic, dopaminergic, and tryptaminergic effects. “Most people now think that it's the adrenergic effect that causes the increased uterine contractility,” Dr. Mayer said.
However, it's also thought that the adrenergic effect is responsible for some of the concerning side effects. Ergot alkaloids produce vasoconstriction that can last for 1–4 hours. These drugs are associated with hypertension, increased central blood volume, coronary vasospasm, pulmonary edema, and cerebrovascular accidents. The dopaminergic stimulation produces nausea and vomiting that can be severe in about 20% of patients. Ergot alkaloids should be given in a very controlled manner to avoid complications such as vasospasm and decreased ejection fractions.
The range of options in the prostaglandin family could grow in the future. “We don't have the whole armamentarium that they do in Europe and I think that someday we may,” Dr. Mayer said. Prostaglandins available in the United States include carboprost (15-methyl prostaglandin F2α), misoprostol (prostaglandin E1), dinoprost (prostaglandin F2α), and dinoprostone (prostaglandin E2).
The side effect profile for these drugs is different from that of the oxytocics or ergot alkaloids. Prostaglandins do not contribute to significant vasoconstriction. One big drawback for these drugs is that they cannot be administered intravenously. Instead, prostaglandins can be administered intramuscularly and intramyometrially. Prostaglandins E1 and E2 also can be administered orally, vaginally, or rectally.
“There's nothing to suggest that there's a better drug than carboprost,” Dr. Mayer said. Carboprost (Hemabate) is 10 times more potent than the parent compound (prostaglandin F2α). It has minimal effect on the cardiovascular system. Severe bronchial constriction is the one real problem associated with carboprost, even in patients without asthma. This can result in bronchospasm, regional ventilation perfusion mismatch, and arterial desaturation. Patients receiving carboprost should be monitored with a pulse oximeter until at least an hour after the last dose. Dosing is 250 mcg given every 15 to 45 minutes, up to a maximum of 8 doses.
Both carboprost and methylergonovine are contraindicated in patients with cardiovascular and respiratory problems. Misoprostol—a synthetic oral prostaglandin E1 analog—may be one option for these patients. “Misoprostol plays a major role in [the management of] peripartum hemorrhage,” Dr. Mayer said. It is not associated with bronchospasm, has no major cardiovascular effects, and can be stored for a long time without refrigeration.