Current Resources for Evidence‐Based Practice, January/February 2019

Abstract

Maternal mortality claims the lives of more than 300,000 woman each year, 99% of whom reside in low-resource countries. 1 The loss of life not only means the loss of a woman, a mother, a wife, a sister, but in many low-resourced countries also frequently means her newborn will face a 48-timesincreased risk of dying. 2 Postpartum hemorrhage remains the leading cause of maternal mortality worldwide. 3 Women residing in lower-resourced countries are at increased risk of severe morbidity and mortality from postpartum hemorrhage due to undernutrition and a high prevalence of anemia. The use of uterotonics, especially oxytocin, is essential for postpartum hemorrhage prevention-according to recommendations of the World Health Organization (WHO) for active management of the third stage of labor-and for postpartum hemorrhage treatment. 4 Unfortunately, maintaining the quality of oxytocin is difficult in the very same countries in most need of this valuable drug for labor induction and for prevention and treatment of postpartum hemorrhage. To maintain its effectiveness, oxytocin must be continuously stored at 2°C to 8°C (35.6°F-42.8°F) from manufacture to its administration. Additionally, as with all drugs, strict standards are needed during its manufacture to maintain sterility, potency, and freedom from contaminants. Problems with the quality of oxytocin supplies in middle-and low-income countries are well documented. A systematic review of these studies found that a mean of 45.6% of samples failed testing, with one-third containing less than 90% of the oxytocin concentration labelled. 5 A WHO study of drug quality at central storage sites in such countries found that 64% of the oxytocin samples failed testing. 6 A recent qualitative study in 3 lower-resourced countries about the stability of oxytocin found low knowledge that oxytocin was heat sensitive, as well as difficulties maintaining required storage temperatures because of electricity and refrigeration issues. 7 Therefore, the release of the results of the CHAMPION trial, a double-blind large multicenter trial, which compared the heat-stable uterotonic, carbetocin, with oxytocin, is exciting because of its potential impact on so many women's lives. 8 This noninferiority trial was designed to demonstrate that carbetocin was not worse than oxytocin in preventing postpartum hemorrhage. The trial took place at 29 sites in 10 lowand middle-income countries and enrolled 29,645 women. This study compared oxytocin 10 units with carbetocin 100 mcg, both given intramuscularly. Although carbetocin does not need to be refrigerated, its ampules were refrigerated to maintain blinding as to whether oxytocin (requiring refrigeration) or carbetocin was being administered. Women with sin-gleton pregnancies and who were less than 6 cm dilated were eligible for the study. There were 2 primary outcomes: 1) blood loss of at least 500 mL or need for a second uterotonic within one hour and 2) blood loss greater than 1000 mL. Blood loss was measured using a blood collection drape pl...

Current Resources for Evidence‐Based Practice, January/February 2019

“…In the January/February 2019 Current Resources for Evidence‐Based Practice column, Barger presents an excellent summary of the recent CHAMPION trial on heat‐stable carbetocin. The original article Barger describes also provides data from numerous studies identifying the poor quality of oxytocin as a serious problem in many countries and implies that the new heat‐stable carbetocin will solve the problem.…”