Pharmacologic intervention for managing uterine atony and related maternal hemorrhage: what is the most effective drug dose?

Abstract

Hemorrhage remains the leading cause of maternal death and accounts for approximately 34% of the 350,000 maternal deaths annually worldwide. About 120,000 deaths annually are attributed to hemorrhage. Overall worldwide, the maternal mortality ratio (MMR) is 260/100,000, with a range from less than five in developed regions to more than 1,200 /100,000 in nations with very low income. In low-income countries, hemorrhage is the leading cause of maternal death; however, the problem remains in developed countries. From 2008-2010, there were 7.8 maternal deaths per 100,000 deliveries annually in Canada. Postpartum hemorrhage (PPH) is currently the third leading cause of maternal death in Canada, with a MMR of 1.6/100,000. In the USA, the MMR is much higher at 21/100,000 deliveries in 2010, up from 13.1 in 2006. In the USA, embolic disease, preeclampsia, and hemorrhage remain leading causes of maternal death. There are many causes of postpartum hemorrhage; however, the most prevalent cause is uterine atony. It is thought to be the etiology in over 70% of all events of postpartum hemorrhage. It is difficult to determine the contribution that uterine atony makes to maternal death from hemorrhage. In a recent study in the USA reporting a large cohort of patient data from 1995-2004 (876,641 hospital admission for delivery), 25,654 cases of PPH were identified, with uterine atony accounting for 79% of these cases. The investigators of this study found a strong association between PPH and a number of serious complications, including acute renal failure, coagulopathy, and acute respiratory failure. All of these complications were likely a consequence of hypovolemia and subsequent massive transfusion. In this cohort, PPH, secondary to uterine atony, was also a significant source of maternal mortality, accounting for approximately one-fifth of all deaths in delivering patients. When evaluating trends in PPH attributable to uterine atony, these investigators identified a 27% increase in the rate of PPH from atony from 1995-2004. Disturbingly, they were unable to identify antenatal risk factors for this trend, as the increase in PPH could not be accounted for by adjusting for changes in maternal demographics, maternal comorbidity, or delivery mode. Also noteworthy in this cohort was the observation that the rates of PPH from other causes, including retained placenta and coagulopathy, remained relatively stable during the study. The investigators also noted that PPH is more common among patients delivering at hospitals in the bottom quartile for delivery volume compared with those delivering at hospitals in the top quartile, which may be a factor with overall management of hemorrhage situations. In an 11-year population-based cohort study from Ireland, similar results were found. This group reported an overall increase in the rate of PPH from 1.5% in 1999 to 4.1% in 2009; with atonic PPH increasing from 1.0% in 1999 to 3.4% in 2009. These increasing trends in rates of atonic PPH were observed across all modes of delivery, i.e., vaginal, instrumental, and emergency and elective Cesarean deliveries. In their cohort, data were collected on 649,019 childbirth hospitalizations, with a 2.6% incidence of PPH. In the patients with PPH, 75.7% were attributed to uterine atony, a number very similar to that found in the USA-based study. They noted that the incidence of atony as a cause for PPH was consistently higher among deliveries that involved induction. The lowest rates of atonic PPH were among non-induced vaginal deliveries, H. A. Muir, MD (&) Department of Anesthesiology, Duke University Hospital, Durham, NC 27710, USA e-mail: holly.muir@duke.edu