ELSEVIER

European Journal of Obstetrics & Gynecology and Reproductive Biology64 (1996) 59 61

Intraumbilical vein injection of prostaglandin

D a v i d B i d e r *~'b, M o r d e c h a i

in retained placenta
L i p i t z a'b,

D u l i t z k y a'b, M o r d e c h a i G o l d e n b e r g a'b, S h l o m o S h l o m o M a s h i a c h a'b

~Department of Obstetrics and Gynecology, The Chaim Sheba Medical Center, Tel Hashomer, 52621, Israel bgaekler School of Medicine, Tel Aviv University, Tel Aviv, Israel

Received 11 November 1994; revision received 11 September 1995; accepted 21 September 1995

Abstract

A randomized protocol was used to study the effect of intraumbilical prostaglandin F2~ (Hembate, Upjohn) and oxytocin injection in women with retained placenta. Prostaglandin F2~, 20 mg, diluted to 20 ml in normal saline solution (10 women, group 1), 30 IU of oxytocin, diluted to 20 ml in normal saline solution (11 women, group 2), or 20 ml of normal saline solution alone (7 women, group 3), were injected into the umbilical vein 1 h after delivery. Nine women (group 4, controls) underwent manual removal of the retained placenta. In group 1, placental expulsion occurred in all patients and the duration of the placental expulsion after prostaglandin F2c~injection was 6.8 + 1.36 (mean + SE) min: in group 2, six placental expulsions occurred after 13.3 _+ 1.97 min (mean + SE); and in group 3, no effect was recorded after intraumbilical saline injection. We suggest that intraumbilical vein injection of prostaglandin F2~ might be a beneficial, non-surgical method for treating retained placenta. Oxytocin might reduce the incidence of manual lysis of the placenta and achieve partial success.
Keywords: Umbilical vein; Prostaglandin; Oxytocin; Retained placenta

1. Introduction

2. Patients and method

The use of intraumbilical vein injection of oxytocin to deliver a retained placenta has been evaluated in the past [1-5]. However, the effect on the third stage of normal labor [6,7] and in cases of retained placenta, is controversial. Recently, a large, multicentric study demonstrated the ineffectiveness of intraumbilical vein injection of oxytocin [8]. Heinonen and Pikhala [2] with some success used intraumbilical injections of 0.2 mg ergometrine combined with 5 IU oxytocin to treat retained placentae. Others used oxytocin alone, diluted in saline solution [8]. However, the use of intraumbilical vein injection of prostaglandin (PG) F2~ for delivering retained placentae, has not been evaluated and reported in the past. To determine whether PGF2~ injected intraumbilically would be useful for delivering a retained placenta, we enrolled all women with retained placentae over a period of 3.5 years into a randomized protocol. * Corresponding author, Tel.: + 972-3 5302697; Fax: + 972-3 5352081.

During the 3-year period ending September 1992, a total of 37 delivered, singleton-pregnancy patients had retained placentae, an incidence of 0.2%. Thirty-five full-term, and two preterm women comprised the study group. Four of the study group patients had uterine scarring and in two patients retained placenta had occurred previously. In the remaining patients there had been more than one normal delivery. Informed consent was obtained in all cases. We studied all the patients prospectively and by computerized randomization, except for three who were from the manual group because of their excessive bleeding and could therefore not be randomized. The management of the third stage of labor in our center is usually that of expectant spontaneous expulsion. After delivery of the newborn, the height of the uterine fundus and its consistency were determined, and as long as the uterus remained firm and there was no bleeding, waiting under supervision until separation of the placenta was our policy, as it is now. When signs of placental separation occur, firm contraction of the uterus is confirmed and the mother is asked to bear down. If the patient had not

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D. BMer et al, , European Jourmd o! Ohstetric,s & G~vneeology amt Reproductite Biology 64 (1996) 59-61 Table 2 Placental expulsion in the two groups lntraumbilical injection of PGF~z~ No. of cases Success rate (%) Expulsion time (min) Blood loss (ml) Oxytocin augmentation Complications: Fever Abdominal pain 10 100%, 7 _+ 1 210 + 40 6 1 3 Oxytocin Saline 11 54.5% 13 1 229_+39 5 7 0* NA*** 231_+31 4 0 0 None 9 NA 237+39 5 2 2

received oxytocin augmentation during labour, l0 IU oxytocin was injected intravenously after expulsion of the infant. A retained placenta was diagnosed when separation did not occur 1 h after delivery and umbilical cord clamping (approximately 1 cm from the introitus). We chose to wait for 1 h, which is a relatively long period, in order to eliminate the late spontaneous expulsion of placenta. After this period, 20 ml solution containing 20 mg PGF2~ (group 1), 30 units of oxytocin (group 2), or 20 ml of normal saline alone (group 3), was injected within 15 s into the umbilical vein of the cord 1 cm from the introitus just proximal to the cord clamp. A control group of patients (group 4) in whom separation of the placenta did not occur spontaneously was treated by manual removal of the placenta only with no injection. At the beginning of our study in cases of retained placentae we chose to inject 1 ampule of PGF2~ as an initial dose to investigate placental separation. The mode of intraumbilical P G F ~ injection is simpler to perform. We injected PGF2:~ after blood was drawn into the syringe and then slowly, within 15 s, injected the total amount. For each woman the length of the third stage and the delivery of the retained placenta were recorded. In group 3 patients, if placental expulsion did not occur within 30 rain either P G F ~ or oxytocin were injected randomly. The management after injection was by observation. Signs of placental separation such as a sudden gush of blood, umbilical cord protruding from the vagina, and changes in the uterine size and position, were recorded when observed. Gentle traction of the cord for final expulsion was used. Data were analyzed and evaluated with Student's t-test.
3. Results

*4 had expulsion after PGF2~ injection and 1 after oxytocin. ** Manual removal of placenta ***NA = not applicable Values are numbers of cases or mean _+ SE.

min. The rest of the patients required manual removal of the retained placentae under general anesthesia. Abdominal pains caused by uterine contractions were observed in eight of the PGF2~ group and three of the oxytocin group. Complications were minor, and included febrile morbidity in two patients: one from the PGF2~ group and one from the oxytocin group. There was no febrile morbidity in the other groups. Loss of blood occurred in two of the oxytocin group and the hemoglobin levels dropped from l lg% to 9g%. Retained placentae of nine patients (group 4), were manually removed under general anesthesia. Thirty-three of the patients had normal courses of immediate postpartum periods and were discharged from the hospital after 72 h in accordance with our routine management. Four patients were discharged 1-3 days later because of febrile morbidity (2 cases) and anemia (2 cases). These patients were managed by observation and conservative medical treatment.
4. Discussion

Table 1 summarizes the demographic data among the four groups of patients which were not statistically significant. All patients gave their informed consent for this study. Table 2 summarizes the outcome of the four groups studied. In the saline group (group 3), no expulsion was observed 30 min after the intraumbilical injection. Then PGF2c~ or oxytocin was injected. Four patients had placental expulsion: three after PGFz~ injection, and one after oxytocin injection within 5 15
Table 1 Maternal parameters of the study group PGF,z~ Age Ih) mean + SD Height Weight Parity 29.1+4.7 165.4_+7.1 46.9+3.1 all patients Oxytocin Saline Routine

30.1_+3.1 28.4_+3.9 30.8+_3.4 166.0+4.9 164.1 +5.6 166.0_+3.9 68.1 _+5.9 67.2_4_5.1 65.1 _+4.8 delivered > once (multiparas}.

Retained placenta is one of the more serious complications of the third stage of labor. Haemorrhage and infection may occur, even leading to maternal death [9]. Manual lysis of the retained placenta is the traditional treatment, and is usually performed under general anesthesia. However, the procedure may result in infection, uterine rupture, haemorrhage, or trauma to the uterine cervix, in addition to anaesthetic complications [10]. There are reports suggesting that injection of a solution containing oxytocin into the umbilical cord might reduce the need for manual removal of a retained placenta and cause spontaneous placental expulsion [1 5]. Injections into the umbilical vein were described at the beginning of this century [10]. For ten patients with retained placenta, Golan et al. [l] used a solution of 10 ml oxytocin diluted in 20 ml of saline solution. In all

D. Bider et al. / European Journal o[" Obstetrics & Gynecology and Reproductive Biology 64 (1996) 59 61 Table 3 Success Rate in Treatment of Retained Placentae According to the Literature Author No. of patients 10 18 19 72 9 14 40 14 19 11 Success rate* (%) 100 28 22 38 60 64 30 44 47 54 Advantage

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Golan et al. [1] Wilken-Jensel et al. [5] Kristiansen et al. [4] Huber et al. [8] Selinger et al. [11] Frappell et al. [12] Heinonen and Pihkala [2] Hansen et al. [13] Thiery [10] Bider [present study]

Yes No No No No No Partial No No Partial

cases of retained placentae, a recent study [8] challenged the effect of oxytocin in the treatment of retained placentae. However, PGF2~ therapy for retained placentae has not yet been evaluated. Our preliminary results are encouraging. We propose that the use of 20 mgPGF2~ injection diluted in 20 ml saline solution could be a mode of treatment before deciding on manual placental removal. This method of treating a retained placenta in the third stage of labor may reduce complications that result after manual removal. The injection mode of PGF2~ has negligible side effects and apart from a possible allergic reaction, no other precautions need to be taken.

*Treatment for retained placenta.

References
[1] Golan A, Lidor AL, Wexler S, David MP. A new method for the management of the retained placenta. Am J Obstet Gynecol 1983; 146:708 9. [2] Heinonen PK, Pikhala H. Pharmacologic management and controlled cord traction in the third stage of labor. Ann Chir Gynaecol 1985; (suppl.) 197: 31-5. [3] Hauksson A. Oxytocin injection into the umbilical vein in women with retained placenta: a questionable method (Letter). Am J Obstet Gynecol 1986; 155: 1140. [4] Kristiansen FV, Frost L, Kaspersen L, Moiler BR. The effect of oxytocin injection into the umbilical vein for the management of the retained placenta. Am J Obstet Gynecol 1987; 156: 979-80. [5] Wilken-Jensen C, Strom V, Damkjaer-Nielsen M, RosenkildeGram B. Removing a retained placenta by oxytocin - - a controlled study. Am J Obstet Gynecol 1989; 161: 155-6. [6] Young GB, Martelly PD, Greb L, Considine G, Coustan DR. The effect of intraumbilical oxytocin on the third stage of labor. Obstet Gynecol 1988; 71: 736-8. [7] Chestnut D, Wilcox L. lnfluence of umbilical vein administration of oxytocin on the third stage of labor: a randomized, doubleblind, placebo-controlled study. Am J Obstet Gynecol 1987; 157: 160 2. [8] Huber MGP, Wildschut HI J, Boer K, Kleiverda G, Hock FJ. Umbilical vein administration of oxytocin for the management of retained placenta: Is it effective? Am J Obstet Gynecol 1991; 164:1216 9. [9] Beazly JM. Complications of the third stage of labour, ln: Whitfield CR, ed. Dewhurst's textbook of obstetrics and gynaecology for postgraduates. 4th edn. Oxford: Blackwell Scientific, 1986: 409-16. [10] Carroli C. Management of retained placenta by umbilical vein injection. Br J Obstet Gynaecol 1991; 98: 348-50. [11] Selinger M, Mackenzie I, Dunlop P, James D. Intraumbilical vein oxytocin in the management of retained placenta. J Obstet Gynecol 1986: 7:115 7. [12] Frappell JM, Pearce JM, McParland P. Intraumbilical vein oxytocin in the management of retained placenta: a random, prospective, double-blind placebo-controlled study. J Obstet Gynecol 1988; 8: 322-4. [13] Hansen P, Jorgensen L, Dueholm M, Hansen S. Intraumbilikal oxytocin ved behoending af retentio placentae. Videnskab OG Praksis 1987; 149: 3318-9.

cases expulsion of the placenta occurred a few minutes after the intraumbilical injection. However, the lack of a control group, and in addition, the short upper limit for retention (15 min only), did not provide conclusive evidence. Kristiansen et al. [4], randomly studied 52 patients with retained placentae and found no influence. Heinonen and Pikhala [2] reported that 30% of their patients expelled their placentae after injection of oxytocin and ergometrine. Recently, a multicentric, randomized controlled trial involving 220 women with retained placentae [8], demonstrated a non-beneficial effect of intraumbilical vein administration of 10 IU oxytocin in 20 ml solution. No reduction of manual removal rate was obtained, and there was no decrease in the amount of blood loss. Oxytocin only induced a minor shortening of the median time interval from administration to the spontaneous expulsion of the placenta as compared with a placebo injection. Another six controlled trials addressed the question of the beneficial effect of intraumbilical oxytocin injection (5100 IU) for the treatment of retained placenta. These nine studies are summarized in Table 3 and compared with the'present study. However, we observed a beneficial effect in women aged 29-30 years of age with retained placentae who were administered 1 amp (20 mg) PGF2e in 20 ml solution intraumbilically. Moreover, PGF2~ is an extremely uterotonic drug which, in some cases, had not been previously evaluated. The upper time limit for feeling a 'retained placenta' ranged between 15-30 min after the birth of the baby. We used a long, rigorous interval of 1 h to confirm more precisely the success rate of PGF2~ by eliminating the rate of spontaneous expulsion. Despite the fact that our study demonstrated a partial effect with intraumbilical oxytocin injections in