Obstetrics and Gynecology International 5 Table 3: Clinical data for management of retained placenta by treatment group (per protocol population, PP). Nitroglycerin (n = 51) Placebo (n = 54) 19 (37.3) n = 48 474 (470) 250.0 (50; 2200) n = 48 1020 (604) 925 (200; 2500) 23 (45.1) 11 (20.4) n = 53 569 (468) 400 (0; 1800) n = 53 1091 (662) 950 (150; 3000) 25 (46.3) P-value 0.056 0.31 0.58 0.90 Relative Risk (RR) 95% CI 1.83 (0.97; 3.46) 0.97 (0.64; 1.48) Variable Placental detachment n (%) Blood loss after treatment (mL) Mean (SD) Median (range) Total blood loss (mL) Mean (SD) Median (range) Total blood loss ≥1000 mL n (%) Side eﬀect Headache (VAS scale 1–10) Mean (SD) Median (range) Palpitations (VAS scale 1–10) Mean (SD) Median (range) Nitroglycerin (n = 55) n = 34 0.9 (1.6) 0.0 (0; 6) n = 29 0.4 (1.1) 0.0 (0; 5) Per protocol population (PP): randomized patients who all received 1 mg nitroglycerin or placebo tablets. Table 4: Maternal side eﬀects following medical treatment (ITT group). Placebo (n = 56) P value n = 33 0.5 (1.3) 0.0 (0; 6) n = 32 0.2 (0.5) 0.0 (0; 2) 0.08 0.36 Intention to treat group, ITT: all randomized patients, including 4 patients who did not receive study medication and 2 patients who only received 0.5 mg nitroglycerin. attached to the myometrium [15]. In the present study ultrasonography was not performed routinely to distinguish between the diﬀerent types of retained placenta. However, none of the women was diagnosed with placenta accreta. A signiﬁcant drop in both systolic and diastolic blood pressure as well as a signiﬁcant increase in pulse rate was registered following administration of nitroglycerin (Figure 1). However, in all women the hemodynamic eﬀects were transient and nitroglycerin-induced uterine relaxation did not aggravate vaginal hemorrhage. These ﬁndings conﬁrm previous studies which have shown that sublingual admin- istration of 1 mg nitroglycerin in women with retained placenta and normal blood loss is a safe procedure [6, 7]. Many of the women reported side eﬀects, especially headache and palpitations of mild or moderate intensity (Table 4). However, no statistical diﬀerence was registered regarding frequency and intensity of side eﬀects between the nitroglycerin and the placebo group. The high number of reported side eﬀects may be due to the fact that the women were informed about possible adverse eﬀects of nitroglycerin before giving informed consent. Sequential treatment with oxytocin and nitroglycerin is supposed to initiate uterine contractions followed by transient uterine relaxation, thereby promoting placental detachment. In the present study three factors that could possibly aﬀect the outcome of the method negatively were identiﬁed following discussions with midwives and cross- checking of the medical records: (1) oxytocin infusion in the third stage was continued after administration of nitroglycerin; (2) breastfeeding of the newborn child/nipple stimulation was continued after administration of nitroglyc- erin; (3) abdominal uterine massage to promote contractions was performed after administration of nitroglycerin. Clearly, all these factors could possibly counteract the relaxing eﬀect of nitroglycerin. One weakness of the present study is that only obste- tricians with no experience of the method were involved in the study. On the other hand, the study describes a real-life clinical scenario when a new method is being introduced. It was simply not possible to carry out a multicenter study involving only obstetricians with great experience of the method. The fact that placenta was removed in almost half of the women following administration of nitroglycerin in the two hospitals with some experience of the method is encouraging. Clearly, a large prospective randomized placebo-controlled study performed by obstetricians who have experience of the method would be of interest. 5. Conclusion This study showed an increased release of retained placenta following sequential administration of oxytocin and nitro- glycerin compared to oxytocin and placebo. However, the diﬀerence in success rate did not reach statistical signiﬁcance. A tendency that clinical experience of the method could be of importance for removal of placenta was registered. Nitroglycerin did not cause any adverse eﬀects of clinical importance. Acknowledgments This study was supported by grants from the Foundation of Gothenburg Medical Society and Regional Research Sources (FoU), Sweden. Special thanks to Mr. Nils-Gunnar Pehrsson and Mr. Mattias Molin for the statistical support.