International Journal of Gynecology and Obstetrics (2007) 99, 105109 a v a i l a b l e a t w w w. s c i e n c e d i r e c t .

c o m

w w w. e l s e v i e r. c o m / l o c a t e / i j g o

CLINICAL ARTICLE

Intraumbilical injection of uterotonics for retained placenta

D. Habek , D. Franievi
Department of Obstetrics and Gynecology, School of Medicine, Sveti Duh General Hospital, Zagreb, Croatia Received 27 December 2006; received in revised form 6 May 2007; accepted 9 May 2007

KEYWORDS
Delivery; Intraumbilical injection; Methylergometrin; Oxytocin; Prostaglandins; Retained placenta

Abstract Objective: To assess the effect of injecting an uterotonic agent in the umbilical vein during the third stage of labor in women with retained placentas. Methods: In this prospective clinical study, 75 women with retained placentas received 20 mL of a 0.9% saline solution with either 20 IU of oxytocin (n = 54), 0.5 mg of carboprost tromethamine (n = 7), or 0.2 mg of methylergometrine (n = 14) injected in the umbilical vein after clamping. The treatment success was determined by the clinical signs of placental ablation. Results: There were no statistically significant differences among the 3 therapeutic groups regarding age, parity, risk factors, pregnancy duration, type of delivery (spontaneous, induced, or augmented), or possible early postpartum complications caused by the intraumbilical injection. The rates of therapeutic success were 76.9% in the oxytocin group, 85.7% in the synthetic prostaglandin group, and 64.2% in the methylergometrine group. Conclusion: The intraumbilical injection of uterotonics is a noninvasive, effective, and clinically safe method of shortening the third stage of labor in women with retained placentas. 2007 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

1. Introduction
Retained placenta occurs in 0.2% to 1% of vaginal deliveries. It can result from adherent placenta and various forms of invasive malplacentation such as placenta accreta, increta, or percreta. All forms of adherent placenta and invasive malpalcentation have been observed in association with uterine synechiae, endometritis, and previous abrasions or

Corresponding author. Department of Obstetrics and Gynecology, School of Medicine, Sveti Duh General Hospital Zagreb, HR-10 000 Zagreb, Croatia. Tel.: +385 1 3712 111; fax: +385 1 3745534. E-mail address: dubravko.habek@os.t-com.hr (D. Habek).

abnormalities of the uterine cavity. Active management of the third stage of labor, consisting in injecting 5 IU of oxytocin or 0.2 mg methylergometrine intramuscularly or intravenously after shoulder delivery, has resulted in a significant decrease in early and late postpartum hemorrhage and in total maternal peripartum morbidity and mortality [1,2]. After catheterizing the urinary bladder and draining the umbilical cord, treatment for retained placenta is initiated with an intravenous or intraumbilical injection of 1 or more uterotonic agents, e.g., oxytocin and/or methylergometrine, to induce strong and/or rhythmical uterine contractions. It is also recommended to perform the Dorn-Ahlfeld or Crede maneuver. If this maneuver is not performed, manual removal

0020-7292/$ - see front matter 2007 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijgo.2007.05.007

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Table 1

D. Habek, D. Franievi
Demographic characteristics of 75 women with retained placenta in the third stage of labor according to treatment drug IUV injection of 20 mL of saline solution with Oxytocin, 20 UI (n = 54) Carboprost tromethamine, 0.5 mg (n = 7) 25.2 1.4 1 (02) 2 0 1 0 39 (3741) Metilergometrin, 0.2 mg (n = 14) 24.5 6.5 1 (03) 3 1 2 0 39 (3740) P value NS NS

Age Parity Risk factors Previous Curettage Manual removal of placenta Endometritis Uterus subseptus Weeks of gestation

24.1 7.6 1 (04) 6 2 3 1 39 (3541)

NS

NS

Abbreviation: IUV, intraumbilical vein. Values are given as mean SD or median (range) unless otherwise indicated.

of the placenta under general anesthesia will be necessary [15]. The aim of the present study was to assess therapeutic success of a modified MojonGabastou [4,5] method of treating retained placenta by injecting a uterotonic agent (oxytocine, methylergometrine, or prostaglandin) in the intraumbilical vein after clamping and draining the cord.

2. Patients and methods

This prospective clinical study performed at the University Department of Obstetrics and Gynecology, Sveti Duh General Hospital, Zagreb, Croatia, and Clinical Hospital, Osijek included 75 women with retained placenta in the third stage of labor. The diagnosis of retained placenta is made when the expected pharmacokinetic effects of the administered uterotonic (5 IU of oxytocin or 0.2 mg of methylergometrine intramuscularly or

intravenously) do not occur within 30 to 45 min [7]in the absence of the clinical signs of spontaneous placental ablation (such as the Kstner, Schrder, Ahlfeld, or Klein signs), of primary postpartum bleeding, or of placental incarceration in the cervical canal. Women with multiple pregnancies or pre-eclampsia were excluded from the study, as well as those delivered vaginally after a cesarean delivery, because of the possible adverse vasoconstrictive effect of methylergometrine or the risk of uterine rupture. The 75 study participants were divided into 3 groups according to the treatment administered. Group 1 (n = 54) received 20 IU of oxytocine (Syntocynon; Novartis, USA); group 2 (n = 7) received 0.5 mg of carboprost tromethamine (Prostin 15M; Pfizer, USA); and group 3 (n = 14) received 0.2 mg of methylergometrine (Ergotyl; Lek, Slovenia). The medications were suspended in 20 mL of a 0.9% saline solution and injected in the umbilical vein after clamping. Intraumbilical vein (not

Table 2

Success rate of intraumbilical injection of uterotonic agents in the treatment of 75 women with retained placenta IUV injection of 20 mL of saline solution with Oxytocin, 20 UI (n = 54) Carboprost tromethamine, 0.5 mg (n = 7) 3 3 0 4 6 Metilergometrin, 0.2 mg (n = 14) 5 2 1 9 9 NS NS P value

Characteristic of labor/delivery

Spontaneous Induced with Oxytocin Intravaginal PgE2 gel Augmented with oxytocin Placenta expelled within 30 min of IUVI Complications Hemorrhage N 500 mL Postpartum fever Abdominal pain Manual removal of placenta Success rate

18 13 3 36 43

1 0 1 11 79.6

0 1 1 1 85.7

0 0 3 5 64.2

NS

b 0.05 in groups 1 and 3, b 0.05 in groups 2 and 3

Abbreviations: IUV, intraumbilical vein; IUVI, intraumbilical vein injection; PgE, prostaglandin E2. Values are given as number or percentage unless otherwise indicated.

Intraumbilical injection of uterotonics for retained placenta

Table 3 Succes rates of intraumbilical injection in women with retained placenta according to the uterotonic agents used Author(s) Pipingas [15] Habek [10] Heinonen and Pikhala [12] Golan [3] Bider [6] Huber [8] Weeks [20] Frappel [21] Gazvani [11] Wilken-Jensen [19] Carroli [18] Habek [17] Uterotonic agent PgF2 Oxytocin Oxytocin Oxytocin Oxytocin PgF2 Oxytocin Oxytocin Oxytocin Oxytocin Oxytocin Oxytocin Oxytocin Oxytocin No. of patients (success rate, %) 7 (77) 12 (58.3) 19 (68.4) 40 (30) 100 (all) 100 (10) 54 (11) 220 (38) 572 (76) 14 (64) 28 (46.2) 40 (100) 291 (58) 47 (80.8)

107 manuallywith the associated risks of injury to the internal and external genitalia, such as lacerations of the cervix, vagina, and perineum and uterine perforations; postpartum hemorrhage and infections; Rhesus alloimmunisation; trophoblastic or amniotic fluid embolism; and accidents during general anesthesia, such as aspiration of gastric content and anaphylactic reactions [7,8]. Efforts by generations of obstetricians to replace this traditional surgical management of retained placenta have produced pharmacological procedures. One of these is IUIU, usually with oxytocin or methylergometrine and, lately, prostaglandins [6,8,11,12,14], suspended in 20 mL of saline solution. This method causes very strong uterine contractions, resulting in iatrogenic placental rupture, or in placental ablation when the solution administered produces an effusion between the placenta and its bed. Diffuse placenta accreta, increta and/or percreta) are resistant to this treatment. Reports on the clinical use of IUIU in the active management of the third stage of labor are varied. Reddy and Carey [13] found that treatment with oxytocin significantly reduced blood loss (135 vs. 373 mL) as well as the duration of the third stage of labor (4.1 vs. 9.4 min), and thus recommended the intraumbilical route rather than the standard intramuscular and/or intravenous administration. In contrast, in a study with 2 group of 50 patients, one who received IUIU and the other only the saline solution, Young and colleagues [23] did not find a clinically significant reduction in the duration of the third stage of labor in their IUIU group. Overall, however, the results of large clinical studies investigating clinical relevance of IUIU appear to suggest that the method should be included in the current obstetric algorithms. The method was originally introduced in 1826 by Mojon [4] in Geneva, as an injection of saline solution in the intraumbilical vein, and produced high rates of uteroplacental ablation without resorting to the more invasive procedure (manual removal was considered dangerous at the time), and Gabastou [5] adopted the method in 1914 in Buenos Aires. In 1953, Sanatore [9] recommended the intraumbilical administration of pitutrine (oxytocin) for the management of retained placenta, and Heinonen and Pikhala [12] employed the method with success, using 0.2 mg of ergometrine or 5 IU of oxytocin. In contrast, Huber and coworkers [8] could not demonstrate a statistically a clinically significant benefit to the intraumbilical administration of 10 IU of oxytocine suspended in 20 mL of saline solution, as it reduced neither blood loss nor the incidence of manual placental removal during the third stage of labor in their sample of 220 patients. Likewise, the results of a recent study by Sivalingam and Surinder [16] showed no significant advantage to the intraumbilical administration of 30 IU of oxytocin suspended in 27 mL of saline compared with 30 mL of saline solution. In that study, the incidence of manual removal of the placenta was 9 in the 19 women treated with oxytocin and 10 in the 16 women who only received the saline solution. Although the incidence of manual ablation was significantly lower in the oxytocin group in that study, it did not appear to justify the inclusion of IUIU in the obstetric protocol. Although Pipingas and coworkers [15] introduced the intraumbilical infusion of oxytocin, rather than the single injection, and obtained a higher rate of success (77.7% vs.

Abbreviation: PgF2, prostaglandin F2.

intraumbilical artery) injection is a method originally described by Mojon and Gabastou [4,5]. The therapeutic effect was assessed by clinical signs of placental ablation, which include strong uterine contraction, bleeding, and descending of umbilical cord through the vulva within 30 min, followed by placental labor after cord traction. A thorough inspection of the fetal membranes and the fetal and maternal sides of the placenta was performed [610]. The KruskalWallis test was used for statistical analysis. P b 0.05 was considered significant.

3. Results
The demographic characteristics of the study participants are shown in Table 1. Peripartum assessment and the therapeutic effect of intraumbilical injection of uterotonics (IUIU) are presented in Table 2. There were no statistically significant differences among the groups regarding age, parity, risk factors (previous curettage, manual removal of placenta, endometritis, and uterus subseptus), pregnancy duration, type of delivery (spontaneous, induced, or augmented), and early postpartum complications after IUIU (there were none). Severe abdominal pains (a score of 5 on a visual analog scale) were recorded by 3 patients and were associated with a continuous uterotonic effect of methylergometrine over several hours. The therapeutic success rate of the IUIU method was 76.9% in the oxytocin group, 85.7% in the prostaglandin group, and 64.2% in the methylergometrine group, yielding a statistically significant difference between groups 1 and 3 and between groups 2 and 3 (Table 3). The best therapeutic effect was achieved in group 2 (the prostaglandin group). No complications caused by the IUIU method were recorded during the study period.

4. Discussion
When a conservative management of retained placenta and fetal membranes fails, the placenta must be removed

108 58.3%), Golan and coworkers [3] reported 100% success 5 min after the standard intraumbilical injection of oxytocin. Habek and coworkers [10] investigated the effect of a standard 20-mL intraumbilical injection on placental expulsion comparing 3 groups, one that received 20 IU of oxytocin (group 1); another that received only a saline solution (group 2); and the third one that received 0.2 mg of methylergometrine (group 3). In group 1, which included 2 patients with placenta accreta focalis who underwent curettage after placental expulsion, the success rate was 68.4%. There were no clinically significant complications attributable to the method. There were no statistically significant differences between the methods of delivery (induced or augmented vs. spontaneous labor) according to parity, gestational age, and maternal age. In another study [17], the rate of success obtained with the MojonGabastou method was 80.8%, whereas with IUIU the rates were 79.6% in the oxytocin group, 85.7% in the prostaglandin group, and 64.2% in the methylergometrine group. Bider and colleagues [6] investigated the effect of IUIU with prostaglandin PgF2 (20 mg) and oxytocin, and reported success rates of 100% using PgF2 and 54.5% using oxytocin. These results were confirmed by similar results from Gazvani and colleagues [11], who also found a statistically significant reduction in the need of manual removal of the placenta. In 2001, using comparison methods to analyze the results of randomized clinical studies published in the Cohrane database, Carroli and Bergel [18] found that the success rates of IUIU with oxytocin were significantly higher than those obtained with the intraumbilical injection of saline solution alone. A review of clinical studies investigating the clinical potential of this method suggests that an increase in the oxytocin units used as the primary therapeutic agent, combined with a greater volume of saline solution as a diluting fluid, leads to higher rates of therapeutic success. In support of this conclusion, Wilken-Jensen and associates [19] obtained a statistically significant reduction in the need of manual removal using a 3.3-IU/mL dose of oxytocin in 30 mL of saline solution. Analyzying the results of recent multicenter, randomized, controlled study conducted from the Department of Gynecology and Obstetrics of Liverpool University Hospital, Weeks and coinvestigators [20] reported that a single 50-IU oxytocin dose injected in the umbilical artery provoked placental expulsion. However, a study by Frappel and coinvestigators [21] reported that a mere 0.5 IU of oxytocin suspended in 20 mL of saline solution achieved significant results. The mechanism of action is based on a dual effect, i.e., the separation of the placenta from its bed by the sheer volume injected as well as the strong uterine contractions. None of the studies recorded any clinically significant adverse effects, such as pelvic pain from strong uterine contractions, postpartum hemorrhage, or subfebrile conditions, when PgF2 was used. An influx of oxytocin in the circulation has been reported in 40% of patients, yet without any effects on the cardiovascular system [22,23]. This finding was confirmed by Wilken-Jensen and colleagues [19] in 100 patients who received 100 IU of oxytocin intraumbilically. Thus, IUIU is noninvasive and inexpensive, and it appears to be an effective and safe method of shortening the third

D. Habek, D. Franievi stage labor in women with retained placentas. Further studies are needed to adjust the volume of the saline solution and the dosage of the uterotonic agent.

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