ratinsio plasenta

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Intraumbilical injection of three different uterotonics inthe management of retained placentajog_1499 1203..1207

Rany Harara1, Sherif Hanafy1, Mahmoud Saad Alsayed Zidan2 and Medhat Alberry1,3

1Ain-Shams University Maternity Hospital, Cairo and 2Department of Obstetrics and Gynecology, Mansoura University,Mansoura, Egypt; and 3Luton and Dunstable Hospital, NHS Foundation Trust, Luton, UK

Abstract

Aim: The aim of this work was to compare the effect of intraumbilical injection of three different uterotonicsolutions in the management of retained placenta.

Materials and Methods: This study was conducted in Ain-Shams University Maternity Hospital, Cairo, Egypt.A total of 78 women with retained placenta (>30 min after delivery of the fetus) were included in the study and

subdivided into three groups. Each group was injected with a different type of uterotonic into the umbilicalvein after clamping it using the Pipingas technique. Uterotonics used were either 20 IU oxytocin dissolved in30 mL saline (n = 26), ergometrine 0.2 mg dissolved in 30 mL saline (n = 27) or misoprostol 800 mg dissolved in30 mL saline (n = 25).

Results: The overall success rate of spontaneous placental separation within 30 min after intraumbilicalinjection of uterotonics was 56/78 (71.79%). The success rate was higher with misoprostol when compared tooxytocin and ergometrine but the difference was not significant (20/25 [80%], 19/26 [73.08%], 17/27 [62.96%],respectively, P > 0.05). The injection-to-separation interval was significantly shorter in the misoprostol groupthan in the oxytocin and ergometrine groups (7.0 2.2 min, 13.14 3.76 min, 22.5 4.37 min, respectively,P < 0.001).

Conclusion: Intraumbilical injection of uterotonics, namely oxytocin, ergometrine and dissolved misoprostolin saline, are closely effective in the management of retained placenta, with misoprostol being slightly more

effective. This method may have a role in minimizing the need for manual removal of the placenta and itsadverse sequelae.

Key words: obstetric complications, obstetrics diagnosis, placental pathology, post-partum care, post-partumhemorrhage.

Introduction

Postpartum hemorrhage (PPH) is one of the mostcommon causes of maternal mortality worldwide andremains as the commonest cause of maternal mortalityin developing countries, including Egypt. The World

Health Organization (WHO) estimated that 25% of585 000 maternal deaths worldwide were due to severeperipartum hemorrhage, with a further 20 millionmothers per year suffering significant morbidity fromthis cause.1

The third stage of labor lasts 1015 min on average,and is generally considered to be prolonged after30 min. Even with active management of thethird stage,about 3% of cases have a prolonged third stage oflabor.2,3 Retained placenta may result from simplyadherent placenta or various forms of morbidly adher-

ent placenta, including placenta accreta, increta, or per-creta. All formsof simply or morbidly adherent placentahave been observed in association with intrauterineadhesions,endometritis, previous uterine operations orabnormalities of the uterine cavity.3 Active management

Received: June 23 2010.Accepted: October 18 2010.Reprint request to: Mr Medhat Alberry, Luton and Dunstable Hospital, Luton LU4 0DZ, UK. Email: [email protected]

doi:10.1111/j.1447-0756.2010.01499.x J. Obstet. Gynaecol. Res. Vol. 37, No. 9: 12031207, September 2011

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of the third stage of labor, by injecting 5 IU of oxytocinor 0.2 mg methyl-ergometrine intramuscularly aftershoulder delivery, has resulted in a significant reduc-tion in incidence of retained placenta and a significantdecrease of early and late post-partum hemorrhage andin total maternal peripartum morbidity and mortality.4

Manual removal of retained placenta appears tobe the management of choice for retained placenta.However, it is associated with higher risk ofendometritis, hemorrhage and traumatic perforationof the uterine wall. In addition, it requires the use ofeither general or regional anesthesia.5 Effective medicaltreatment of the retained placenta is based on stimulat-ing contraction of the underlying myometrium thathas sufficient strength to induce separation of theplacenta.6 Oxytocin, ergometrine, and prostaglandinsare all capable of inducing sustained myometrialcontractions.

Recent studies have shown that uterotonic agentsadministered via umbilical vein injection may be effec-tive in management of retained placenta7 and a WHOpublication even recommended this treatment as a firstline of treatment for retained placenta.8 Despite thisrecommendation, the method is yet to make its wayinto routine practice, probably because of the lackof a large randomized controlled trial to determinewhich uterotonic to use and at what dosage.8 The latestCochrane Review concluded that umbilical vein injec-tion of saline solution plus oxytocin appears to beeffective in the management of retained placenta.9

Methods

This study was conducted at Ain-Shams UniversityMaternity Hospital (18 000 deliveries/year). A total of2512 women between 18 and 40 years of age wererecruited into the study over a 12-month period (April2008 to March 2009). Deliveries less than 20 weeksgestation, multiple pregnancies, hypertensive disor-ders with pregnancy, and vaginal birth after cesareanwere excluded. A total of 78 cases had a prolongedthird stage of labor. The diagnosis of retained placenta

was made when signs of spontaneous placental sepa-ration had not occurred within 30 min after delivery ofthe fetus, despite administration of uterotonics (5 IUof oxytocin + 0.2 mg methyl ergometrine [ergometrine]i.m.) after delivery of the anterior shoulder. Gentleuterine massage is performed routinely after deliveryof the fetus, before a diagnosis of retained placenta ismade.

The 78 included women were randomly divided intothree groups: group I (n = 26) received 20 IU oxytocinin 30 mL saline; group II (n = 27) received ergometrine0.2 mg in 30 mL saline; and group III (n = 25) receivedmisoprostol 800 mg dissolved in 30 mL saline.Randomization was performed using a computer-generated randomization system. When spontaneousseparation of the placenta had not occurred within25 min, the solution for injection was prepared inthe last 5 min. If placental separation spontaneouslyoccurred in the last 5 min the solution was discarded.We used the Pipingas technique10 for injection of theuterotonics in the umbilical vein. Patients characteris-tics are shown in Table 1.

A size-10 nasogastric suction catheter was insertedalong the umbilical vein. If resistance was felt, the cath-eter was retracted by 12 cm and then advanced as faras possible. The prepared solution was then injected

after clamping of the cord. If spontaneous placentalseparation failed to occur within 30 min after injection,or significant bleeding occurred, manual removal of theplacenta was performed. The primary outcome was thesuccess of spontaneous separation or expulsion ofthe placenta. Misoprostol tablets were highly soluble insaline. Misoprostol tablets are supplied in blister packsand whilst not sterile, the preparation of solutionsunder aseptic conditions and their injection only ontothe umbilical cord makes transmission of infectionto the mother unlikely.3 The number of cases withsuccessful placental separation in each group and the

injectionseparation time interval were recorded.Collected data were spread on an Excel sheet. Statis-tical analysis was performed using spss. Range, meanand standard deviation were used as descriptive statis-tics for parametric data; range, median and interquar-tile range were used for non-parametric data. anovawas used to compare the means of the three groups.The c2-test was used to compare the categorical data ofthe three groups.

Results

The mean age of included women was 23.43

3.34 years (range: 1835 years). Mean gestational agewas 38.23 2.3 weeks (range: 2642 weeks). Medianparity was 1 (range: 04; interquartile range: 02). Themean birthweight was 3020.23 438.2 g (range: 10004000 g). The mean placental weight was 482 53.2 g(range: 280550 g). The mean cord length was51.3 2.7 cm (range: 4555 cm). The mean cathetertip-to-placenta distance was 10.02 2.12 cm (range:

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812 cm). Those parameters and the number of previ-ous uterine evacuations or curettages in the threegroups were not significantly different.

Overall, spontaneous placental separation occurredin 56 (71.79%) women, while manual removal of theplacenta was indicated in 22 (28.21%) women. Womenin the misoprostol treatment group had the highestsuccess rate compared to women in either the oxytocin

or ergometrine groups (20/25 [80%], 19/26 [73.08%],17/27 [62.96%], respectively, P > 0.05) (Table 2). Thisdifference was not statistically significant. The meaninjection-to-separation time interval was significantlyshorter in the misoprostol group compared to theoxytocin and ergometrine groups (7.0 2.2 min,13.14 3.76 min, 22.5 4.37 min, respectively, P 0.0522.4 3.8 25.7 6.1 26.3 5.2 NS

Parity 1 (02) 1 (03) 1 (04)>

0.05NSNo. of previous uterine curettages 1 (01) 1 (02) 1 (02) >0.05

NSGestational age (weeks) 3241 2642 3242 >0.05

39.2 2.7 37.6 5.2 38.0 4.1 NSFetal weight (g) 22003800 10004000 17504000 >0.05

3520 484.3 2990 996.1 3201 827.2 NSPlacental weight (g) 350550 280550 350550 >0.05

495.5 54.8 477 84.4 473 73.7 NSCord length (cm) 4555 4854 4855 >0.05

50.2 2.6 51.09 2.7 51.4 2.2 NSCatheter tip to placenta (cm) 812 912 812 >0.05

10 2.6 10.9 2.1 9.9 2.3 NS

*Analysis using one-way anova. Data presented as range, mean standard deviation or median (range). NS, not significant.

Table 2 Difference between study groups concerning successful spontaneous placental separation

No. of women Oxytocingroup (n = 26)

Ergometrinegroup (n = 27)

Misoprostolgroup (n = 25)

P*

Spontaneous placental separation n (%) 19 (73.08%) 17 (62.96%) 20 (80%) >0.05

*Analysis using c2-test.

Table 3 Difference between study groups concerning injection-to-separation interval

Spontaneous placental separation Oxytocin group(n = 19/26)mean SD

Ergometrinegroup (n = 17/27)mean SD

Misoprostolgroup (n = 20/25)mean SD

P*

Injection-to-spontaneous separation interval (min) 13.1 3.76 22.5 4.37 7.0 2.2


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included women had a morbidly adherent placenta orpostpartum hemorrhage. There were no cases of mater-nal side-effects after administration of any of the threeuterotonic agents. Even the theoretical risk of closureof the uterine cervix and its subsequent entrapmentof the placenta was not encountered in any of theincluded cases.

Discussion

Manual removal of the placenta is associated with lac-erations of the genital tract, uterine perforation, andpostpartum hemorrhage. Other complications includeinfections, Rhesus alloimmunization, trophoblastic oramniotic fluid embolism, and complications of generalor regional anesthesia.11 Intraumbilical injection ofuterotonics, such as oxytocin, methyl-ergometrine andpossibly prostaglandins suspended in saline solution

may provide a suitable alternative. This method causespotent uterine contractions, resulting in the separationof the placenta. Morbidly adherent placentae areusually resistant to this line of management.12

This work showed that various intraumbilical injec-tions of uterotonics (misoprostol 800 mg dissolved in30 mL saline, oxytocin 20 IU in 30 mL saline and ergo-metrine 0.2 mg in 30 mL saline) were comparably effec-tive in treating retained placenta. Misoprostol had arelatively higher success rate. The misoprostol grouphad a significantly shorter mean injection-to-separationtime interval compared to the other two groups. In

2001, Habek et al. studied 31 women with retained pla-centa, comparing the efficacy of oxytocin 20 IU (n = 19),ergometrine 0.2 mg (n = 4), both dissolved in 20 mLsaline (n = 8), to saline alone. They found the efficacyof oxytocin to be 13/19 (68.4%), of saline alone to be1/8 (12.5%), and of ergometrine to be 0/4 (0%).13

The effect of oxytocin, ergometrine and syntheticprostaglandin (carboprost tromethamine 0.5 mg) onwomen with retained placenta was compared on alarger sample of 75 women. The results of this study, tosome extent, are comparable to our work. They foundthat the success rate with oxytocin injected intraumbili-cally was 41/54 (76.9%), the success rate of ergometrine

was 9/14 (64.2%), and that of carboprost tromethaminewas 6/7 (85.7%).4 The efficacy of oxytocin was evidentin a number of other trials, with a range of efficacy of54.55%,7 58.3%,10 to 76%.14 This relatively wide range isprobably related to the variable sample sizes. Carroliand Bergel in a Cochrane systematic review of 12 trialsshowed that oxytocin has significantly higher efficacywhen compared to saline alone.9

Ergometrine was tested in a number of trials,showing a lower efficacy compared to oxytocin. Onlyone trial showed that ergometrine is not effective intreating retained placenta.13 Intraumbilical injection ofprostaglandins was also shown to be a promising tech-nique in the management of retained placenta. Severalstudies achieved a success rate of placental separationranging between 77% and 100% using different typesof prostaglandins.3,7,10 The intraumbilical injection ofuterotonics is a non-invasive, effective, and clinicallysafe method of shortening the third stage of laborin women with retained placentas. However, surgicalintervention remains an important line of managementof retained placenta.

Intraumbilical injection of uterotonics, namely oxy-tocin, methergine and dissolved misoprostol saline,seem to have close efficacy in the management ofretained placenta, with misoprostol being slightly more

effective. This method may have a role in minimizingthe need for manual removal of the placenta and itsadverse sequelae. More work looking into the cost-effectiveness of its use will be required.

References

1. WHO. Revised 1990 Estimates of Maternal Mortality: A NewApproach by WHO and UNICEF. Geneva: World HealthOrganization, 1996.

2. Dombrowski MP, Bottoms SF, Saleh AAA et al. Obstetrics:Third stage of labor: Analysis of duration and clinical practice.

Am J Obstet Gynecol 1995; 172: 12791284.3. Rogers MS, Yuen PM, Wong S. Avoiding manual removal ofplacenta: Evaluation of intra-umbilical injection of uterotonicsusing the Pipingas technique for management of adherentplacenta. Acta Obstet Gynecol Scand 2007; 86: 4854.

4. Habek D, Franicevic D. Intraumbilical injection of uterotonicsfor retained placenta. Int J Gynecol Obstet 2007; 99: 105109.

5. Ely JW, Rijhsinghani A, Bowdler NC et al. The associationbetween manual removal of the placenta and postpartumendometritis following vaginal delivery. Obstet Gynecol 1995;86: 10021006.

6. Krapp M, Baschat AA, Hankeln M et al. Gray scale and colorDoppler sonography in the third stage of labor for avoidingmanual removal of placenta 53 early detection of failed pla-cental separation. Ultrasound Obstet Gynecol 2000; 15: 138142.

7. Bider D, Dulitzky M, Goldenberg M et al. Intraumbilical veininjection of prostaglandin F2alpha in RP. Eur J Obstet GynecolReprod Biol 1996; 64: 5956.

8. Purwar MB. Practical recommendations for umbilical veininjection for management of retained placenta. In: Gulmezo-glu AM, Villar J (eds). The WHO Reproductive Health Library,Vol. 4. Geneva: World Health Organization, 2001; 114119.

9. Carroli G, Bergel E. Umbilical vein injection for managementof retained placenta (Review). Cochrane Database Syst Rev2001; (4): CD001337. DOI: 10.1002/14651858.CD001337.

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10. Pipingas A, Gulmezoglu AM, Mitri FF, Hofmeyr GJ. Umbili-cal vein injection for retained placenta: Clinical feasibilitystudy of a new technique. East Afr Med J 1994; 71: 396397.

11. Wilken-Jensen C, Strom V, Nielsen MD, Rosenkilde-Gram B.Removing a placenta by oxytocin: A controlled study. Am JObstet Gynecol 1989; 161: 155156.

12. Huber MGP, Wildschut HI, Boer K, Kleiverda G, Hoek FJ.Umbilical vein administration of oxytocin for the manage-

ment of retained placenta: Is it effective? Am J Obstet Gynecol1991; 164: 12161219.

13. Habek D, Hrgovic Z, Ivanisevic M, Delmis J. Treatment of aretained placenta with intraumbilical oxytocin injection. Zen-tralbl Gynakol 2001; 123: 415417.

14. Weeks A, Mirembe FM. The retained placenta new insightsinto an old problem. Eur J Obstet Gynecol Reprod Biol 2002; 102:109110.

Medical management of retained placenta

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